A 2-year-old boy with progressive familial intrahepatic cholestasis (PFIC) underwent a left lateral segment liver transplant from a living donor. He developed a recurrent stricture at the biliary-enteric anastomosis despite multiple cholangioplasties and internal-external biliary drains. Five years post-transplant, due to worsening cholangitis and advanced graft fibrosis, the team decided to place two biodegradable biliary stents using a "kissing-stent" technique to maintain ductal patency. What is the primary advantage of using biodegradable stents in this setting?

A: They prevent the recurrence of biliary strictures permanently.

B: They eliminate the need for immunosuppressive therapy.

C: They reduce the need for permanent external drains, enhancing quality of life.

D: They avoid the risk of restenosis at the biliary-enteric anastomosis.

C: They reduce the need for permanent external drains, enhancing quality of life.

Explanation:
Biodegradable biliary stents provide temporary support to maintain biliary patency while naturally degrading over time, reducing the need for external drains. This approach enhances patient comfort and quality of life, particularly in pediatric patients with complex biliary anatomy and recurrent strictures. Although not a permanent solution, they delay the need for retransplantation and can reduce the frequency of interventions.

Reference:
Malik A, Ng VL, Sayed BA, Siddiqui A, Parra DA.
Biodegradable biliary stents placement using a “kissing-stent” technique for management of a recalcitrant stricture post-live donor liver transplant.
Pediatric Transplantation. 2024;28. doi:10.1111/petr.14725.

A 25-year-old male with methylmalonic acidemia (MMA) presented with chronic liver dysfunction and metabolic instability after prior kidney transplantation for end-stage kidney disease (ESKD). Imaging revealed a large hepatic tumor in the right lobe, and serum alpha-fetoprotein (AFP) levels were markedly elevated. Given his MMA and tumor presence, he underwent living-donor liver transplantation (LDLT) using a left lobe graft from his mother. Which of the following considerations most supports LDLT as the preferred treatment for this patient?

A: It improves enzyme activity to stabilize MMA-related metabolic dysfunction.

B: It reduces the patient's dependence on immunosuppression.

C: It enables direct surgical resection of hepatic metastases.

D: It is a definitive cure for MMA and prevents all future metabolic crises.

A: It improves enzyme activity to stabilize MMA-related metabolic dysfunction.

Explanation:
In patients with MMA, LDLT can enhance propionyl-CoA catabolism, stabilizing metabolic function by providing enzyme activity from the donor liver. Although not a cure for MMA, liver transplantation helps reduce episodes of metabolic decompensation and improves quality of life. LDLT is especially considered when liver neoplasms like hepatocellular carcinoma are present, as it addresses both the metabolic disorder and liver pathology. MMA patients still require careful monitoring for metabolic stability post-transplant.

Reference:
Malik A, Ng VL, Sayed BA, Siddiqui A, Parra DA.
Living-donor liver transplantation for methylmalonic acidemia patient with hepatocellular carcinoma: A case report and literature review.
Pediatric Transplantation. 2024;28. doi:10.1111/petr.14719.

A 9-year-old girl presented with symptoms of obstructive jaundice, including dark urine, light-colored stools, and pruritus. Imaging revealed multiple liver masses, including a 4-cm lesion near the porta hepatis. Extensive evaluation, including PET/CT, endoscopic ultrasound, and capsule endoscopy, did not reveal an extrahepatic primary tumor. Biopsy confirmed a well-differentiated neuroendocrine tumor (NET) of WHO Grade I, presumed to be primary to the biliary tract. Due to unresectable tumor location and ongoing cholestasis, she underwent a deceased donor liver transplant. What is the primary justification for liver transplantation in pediatric patients with unresectable primary biliary tract NET?

A: It allows for complete tumor resection and symptom control.

B: It minimizes the need for long-term somatostatin analogs.

C: It prevents recurrence by enhancing systemic chemotherapy.

D: It reduces the risk of biliary cirrhosis without immune suppression.

A: It allows for complete tumor resection and symptom control.

Explanation:
Liver transplantation provides curative potential for pediatric patients with unresectable primary NETs when standard surgical options are inadequate. It allows complete tumor removal and management of symptoms like cholestasis, especially in rare cases involving primary biliary tract NETs. Given the tumor’s well-differentiated nature and lack of extrahepatic spread, liver transplant is a viable option to improve long-term outcomes in select cases.

Reference:
Rai A, Sproule L, Larman T, et al.
Liver transplant for primary biliary tract neuroendocrine tumor in a nine-year-old girl.
Pediatric Transplantation. 2024;28. doi:10.1111/petr.14732.

A 14-year-old girl with a history of biliary atresia underwent her third liver transplant due to recurrent cholangitis and biliary fibrosis from bile reflux. Her complex surgical history included prior choledochoduodenostomy and short-gut syndrome, which limited traditional biliary reconstruction options. During her third transplant, a gastric sleeve tubular graft from the greater curvature of the stomach was repurposed as a Roux limb for biliary drainage. What is the primary advantage of using a gastric sleeve as an "extra-anatomical" Roux limb in complex biliary reconstructions?

A: It reduces the likelihood of future liver graft rejection.

B: It provides a longer Roux limb option in patients with limited bowel length.

C: It enables spontaneous intestinal adaptation in short-gut syndrome.

D: It prevents portal vein thrombosis by improving venous return.

B: It provides a longer Roux limb option in patients with limited bowel length.

Explanation:
In pediatric liver transplantation, especially for patients with short-gut syndrome or extensive surgical history, standard Roux-en-Y jejunal limb reconstruction may not be feasible. Using a gastric sleeve as an "extra-anatomical" Roux limb provides a suitable conduit for biliary drainage when bowel length is limited, maintaining adequate blood supply through the preserved gastric mesentery. This approach can reduce the risks associated with bile reflux and recurrent cholangitis in complex cases.

Reference:
Hakeem AR, Gee H, Attia M, Raj Prasad K.
Gastric sleeve as an extra-anatomical roux for biliary reconstruction in a pediatric third liver transplant.
Pediatric Transplantation. 2024;28. doi:10.1111/petr.14769.

An 8-week-old infant with fulminant liver failure of unknown etiology was urgently listed as Status 1A for liver transplantation. The only available donor liver was from a 3.5-year-old child, located 1939 nautical miles away. Due to the distance and size discrepancy, the transplant team opted for an in situ split liver procurement rather than a backtable reduction. The recipient’s hepatectomy was started ahead of the organ's arrival to minimize cold ischemic time, totaling 510 minutes. Post-operatively, the graft functioned well, aiding the infant’s recovery. Which of the following is a primary advantage of in situ split liver procurement in this case?

A: It allows for the preservation of both lobes for dual recipients.

B: It reduces cold ischemic time, minimizing graft dysfunction risk.

C: It simplifies the surgical technique for pediatric recipients.

D: It decreases logistical challenges during organ transport.

B: It reduces cold ischemic time, minimizing graft dysfunction risk.

Explanation:
In situ split liver procurement is especially beneficial when donor distance is significant, as it reduces cold ischemic time by splitting the liver at the donor site rather than on a backtable. This method helps maintain graft viability and minimizes the risk of primary non-function, which is critical for critically ill pediatric patients requiring expedited organ transplantation.

Reference:
Kwon YK, Valentino PL, Saarela KM, et al.
Pushing the Limits of In Situ Split Liver Procurement to Overcome Donor Distance and Graft Size Challenges for 8-Week-Old Pediatric Recipient.
Pediatric Transplantation. 2024;28. doi:10.1111/petr.14848.

A 3-week-old male neonate, born prematurely and weighing 4.5 kg, was diagnosed with pediatric acute liver failure (PALF) secondary to a suspected viral infection. His condition met King's College criteria for liver transplantation (LT), but no deceased donor organs were available. An altruistic living donor provided a left lateral segment liver graft, which underwent in-situ hyperreduction to achieve a graft-to-recipient weight ratio (GRWR) of 3.5%. The transplant was performed successfully despite ABO incompatibility. Postoperative challenges included biliary stricture and sinusoidal congestion, managed with biliary interventions and immunosuppression adjustments. What is the primary benefit of hyperreducing a left lateral segment liver graft in a small pediatric recipient?

A: Enhanced biliary drainage with reduced risk of bile duct stricture

B: Prevention of large-for-size syndrome and abdominal compartment syndrome

C: Elimination of the need for immunosuppressive therapy in ABO-incompatible cases

D: Improved vascular anastomosis by reducing graft size

B: Prevention of large-for-size syndrome and abdominal compartment syndrome

Explanation:
Hyperreduction of a left lateral segment graft ensures appropriate size matching, reducing the risk of large-for-size syndrome, which can lead to graft perfusion issues, vascular complications, and abdominal compartment syndrome. This is particularly important in small pediatric recipients where standard-sized grafts exceed optimal GRWR limits. While hyperreduction does not eliminate the need for immunosuppression, it facilitates a safer transplantation process with fewer technical complications.

Reference:
Van der Schyff F, Britz RS, Strobele B, et al.
Hyperreduced left lateral living donor liver transplant in a 4.5 kg child—A first in Africa.
Pediatr Transplant. 2023;27:e14536. doi:10.1111/petr.14536.

A 1-year-old boy with a malignant rhabdoid tumor (MRT) of the liver presented with a large hepatic mass infiltrating the three main hepatic veins, leaving only segments S1 and S6 unaffected. The tumor was initially managed with four courses of cisplatin-pirarubicin chemotherapy, which significantly reduced its size but still rendered conventional liver resection unfeasible. The patient underwent associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a bridging therapy to living donor liver transplantation (LDLT). Post-transplant, the patient remained recurrence-free at 15 months. What is the primary advantage of using the ALPPS technique in this clinical scenario?

A: Complete eradication of microscopic tumor cells through vascular isolation

B: Enhanced liver hypertrophy allowing for safe two-stage resection

C: Immediate reduction of portal hypertension and liver function improvement

D: Elimination of the need for adjuvant chemotherapy post-transplantation

B: Enhanced liver hypertrophy allowing for safe two-stage resection

Explanation:
The ALPPS technique facilitates rapid hypertrophy of the future liver remnant (FLR), enabling safe resection in cases where conventional liver resection is unfeasible due to insufficient liver reserve. This staged approach was critical for managing the advanced hepatic MRT in this patient, allowing for subsequent LDLT. While ALPPS does not directly treat portal hypertension or obviate the need for chemotherapy, it expands the pool of patients eligible for curative liver resection or transplantation.

Reference:
Uesato Y, Ono S, Kawamata F, et al.
Associating liver partition and portal vein ligation for staged hepatectomy as bridging therapy for liver transplantation in an infant with an advanced hepatic rhabdoid tumor.
Pediatr Transplant. 2023;27:e14559. doi:10.1111/petr.14559.

A 9-year-old boy with alpha-1 antitrypsin deficiency (A1ATD), diagnosed at 4 months of age with the ZZ phenotype, presented with decompensated liver disease. Evaluation revealed jaundice, ascites, coagulopathy, and portal hypertension. He underwent living donor liver transplantation (LT) using a graft from his maternal aunt, who was heterozygous for the MZ phenotype with a serum alpha-1 antitrypsin (A1AT) level of 84 mg/dL. Postoperatively, the recipient’s A1AT levels normalized within 3 months, and he demonstrated excellent liver function at 26 months follow-up. What is the primary rationale for utilizing a heterozygous donor in this case?

A: MZ heterozygous donors are unaffected by A1ATD-related liver dysfunction.

B: Heterozygous grafts guarantee long-term immunity to liver-related A1AT complications.

C: Limited availability of deceased donor grafts necessitated alternative solutions.

D: MZ phenotype donors produce elevated A1AT levels compensating for recipient deficiency.

C: Limited availability of deceased donor grafts necessitated alternative solutions.

Explanation:
The shortage of deceased donor grafts often necessitates the use of living donors, even if they carry heterozygous mutations, as seen in this case. MZ donors typically have near-normal liver function and are suitable if they demonstrate adequate preoperative A1AT levels and lack histological evidence of liver disease. The use of heterozygous donors expands the donor pool, offering timely transplantation and survival benefits for critically ill patients. However, long-term monitoring for potential graft-related issues remains essential.

Reference:
Sood V, Lee EJ, Raghu V, et al.
Liver transplantation for alpha-1 antitrypsin deficiency (A1ATD) using a heterozygous donor: Outcomes and review of the literature.
Pediatr Transplant. 2023;27:e14488. doi:10.1111/petr.14488.

A 14-year-old boy with autoimmune hepatitis and severe portal hypertension underwent liver transplantation (LT) using a graft procured from a 13-year-old donor with a donor-to-recipient weight ratio (D/RW) of 1.6. Pre-transplant evaluation revealed a graft-recipient weight ratio (GRWR) of 4.6% and a graft weight to right anteroposterior distance (GW/RAP) of 105 g/cm, indicating a large-for-size (LFS) mismatch. To optimize graft-recipient size matching, an ex situ right posterior sectionectomy (RPS) was performed, reducing graft weight by 20%. The patient experienced no delayed graft function or vascular complications post-transplant. What is the primary benefit of performing ex situ RPS in cases of LFS mismatch?

A: Reduction of portal hyperperfusion to prevent small-for-size syndrome

B: Avoidance of anterior and posterior graft compression in the abdominal cavity

C: Improved biliary drainage through enhanced anatomical alignment

D: Elimination of the need for immunosuppressive therapy

B: Avoidance of anterior and posterior graft compression in the abdominal cavity

Explanation:
Ex situ right posterior sectionectomy (RPS) reduces both graft volume and three-dimensional dimensions (anteroposterior thickness and cranio-caudal length), facilitating a better fit within the recipient’s abdominal cavity. This adjustment minimizes the risk of LFS complications such as compression-related vascular and biliary dysfunction. While portal hyperperfusion is relevant in small-for-size grafts, RPS addresses mismatches caused by excessive graft size. Immunosuppressive therapy remains necessary in all transplant cases, regardless of graft modifications.

Reference:
Rossignol G, Muller X, Dubois R, et al.
Optimizing graft-recipient size matching in adolescent liver transplantation: Don't forget ex situ right posterior sectionectomy.
Pediatr Transplant. 2023;27:e14510. doi:10.1111/petr.14510.

A 2-year-old girl with a history of liver transplantation for unresectable choledochal cyst presented 19 months post-transplant with persistent stridor, requiring intubation. Examination revealed edematous, hyperplastic supraglottic tissues and a flaccid mass prolapsing into the airway. Biopsies confirmed eosinophilic laryngitis and associated eosinophilic esophagitis (EE). She was managed with laser ablation, high-dose oral corticosteroids, and swallowed fluticasone, leading to symptom resolution. However, reducing tacrolimus to prevent airway recurrence resulted in graft rejection requiring retransplantation. What was the most likely factor contributing to the development of eosinophilic laryngitis in this patient?

A: Tacrolimus-induced Th1 to Th2 immune shift

B: Persistent Epstein–Barr virus (EBV) viremia

C: Chronic allograft rejection with mucosal inflammation

D: Dietary allergens triggering systemic eosinophilia

A: Tacrolimus-induced Th1 to Th2 immune shift

Explanation:
Tacrolimus is known to selectively suppress Th1 lymphocytes, which shifts the immune response toward Th2 predominance, promoting atopy and eosinophilic inflammation. This patient exhibited multiple risk factors for de novo atopy post-transplant, including young age, high tacrolimus exposure, and elevated peripheral eosinophil counts. While dietary triggers and EBV can exacerbate eosinophilic inflammation, they were not primary factors in this case. Reduction of tacrolimus successfully controlled airway pathology but resulted in graft rejection, highlighting the challenge of balancing immunosuppression.

Reference:
Rajasekaran V, McCaffer C, Bishop J, et al.
Late airway complications following pediatric liver transplantation: A case series.
Pediatr Transplant. 2023;27:e14473. doi:10.1111/petr.14473.

A 12-year-old girl with citrin deficiency (CD) and liver cirrhosis underwent living donor liver transplantation (LDLT) using a hybrid surgical procedure. The approach included hand-assisted laparoscopic mobilization of the liver, midline incision extension for explantation, and direct-vision graft implantation. The donor was her 22-year-old cousin, providing a left lobe graft with a graft-to-standard liver volume ratio of 58.8%. Post-transplant, the patient exhibited restored secondary sexual characteristics and normal liver function. What is the primary advantage of the hybrid surgical approach in pediatric LDLT?

A: Improved vascular anastomosis through robotic assistance

B: Enhanced cosmetic outcomes with reduced wound complications

C: Complete elimination of intraoperative bleeding risk

D: Increased graft perfusion due to pneumoperitoneum

B: Enhanced cosmetic outcomes with reduced wound complications

Explanation:
The hybrid approach for LDLT combines laparoscopic mobilization with a limited midline incision, avoiding extensive abdominal muscle disruption. This results in lower rates of wound-related complications and improved cosmetic outcomes, particularly beneficial in pediatric patients. While the procedure does not eliminate bleeding risks or involve robotic assistance, it provides a balance between minimally invasive techniques and surgical precision.

Reference:
Kosaka T, Soyama A, Fujita T, et al.
A hybrid procedure of living donor liver transplantation for a pediatric patient with citrin deficiency.
Pediatr Transplant. 2023;27:e14485. doi:10.1111/petr.14485.

A 33-year-old woman, who underwent living donor liver transplantation (LT) at age 16 for biliary atresia, presented with sudden abdominal pain, distension, and nausea. Imaging revealed bowel dilation, a suspected intestinal obstruction, and dilated intrahepatic bile ducts. Laparotomy identified a large (4.2 cm) gallstone causing obstruction near the jejunojejunal anastomosis. Enterotomy was performed, and the stone was removed. The patient recovered without complications and was discharged on postoperative day 12. Component analysis revealed a calcium bilirubinate stone. What is the most likely factor contributing to gallstone formation in this patient?

A: Chronic cholangitis due to recurrent biliary infections post-LT

B: Impaired bile flow in the Roux-en-Y afferent limb due to poor peristalsis

C: Absence of prophylactic antibiotics post-LT for enteric reconstruction

D: Long-term use of tacrolimus leading to biliary stasis

B: Impaired bile flow in the Roux-en-Y afferent limb due to poor peristalsis

Explanation:
The Roux-en-Y reconstruction used during LT creates an afferent limb that may become a blind loop with low peristaltic activity, predisposing to bile stasis and stone formation. Over time, deposition of bile constituents, combined with bacterial infection, promotes the growth of pigment stones. The patient did not have a history of recurrent cholangitis or antibiotic prophylaxis issues. While tacrolimus may influence bile flow, it is not a primary factor in this context.

Komine R, Sakamoto S, Uchida H, et al.
Gallstone ileus at 17 years after living donor liver transplantation: A case report.
Pediatr Transplant. 2023;27:e14517. doi:10.1111/petr.14517.

A 16-year-old boy underwent deceased-donor liver transplantation for autoimmune hepatitis. Four months later, he presented with fever, right upper quadrant pain, and elevated liver enzymes. Imaging revealed a large hepatic mass compressing the bile duct and portal vein. Cultures of purulent fluid from the mass were positive for Escherichia coli. Despite antibiotic therapy, he developed nodular skin lesions near the surgical scar. Biopsies from the skin and liver mass showed histiocytes containing Michaelis-Gutmann bodies (MGB), diagnostic of malakoplakia. Treatment with a nine-month course of doxycycline and cefdinir led to complete resolution of the lesions without reducing immunosuppression. What is the pathophysiological hallmark of malakoplakia?

A: Granulomatous inflammation caused by impaired lysosomal function in macrophages

B: Excessive T-cell activation leading to mass-forming lesions in immunodeficient hosts

C: Chronic fibrosis due to prolonged bacterial antigen exposure in transplant recipients

D: Autoimmune destruction of tissue macrophages by anti-phagocytic antibodies

A: Granulomatous inflammation caused by impaired lysosomal function in macrophages

Explanation:
Malakoplakia results from defective macrophage bactericidal activity due to low cyclic guanosine monophosphate (cGMP) levels, impairing lysosomal function. This defect allows bacteria to persist within macrophages, leading to the deposition of calcium and iron, forming Michaelis-Gutmann bodies, which are pathognomonic for the condition. Treatment includes prolonged targeted antibiotic therapy guided by culture and susceptibility, as surgical options may not always be feasible in immunocompromised patients.

Reference:
Gerard A, Mesa H, Danziger-Isakov L, et al.
Successful treatment of malakoplakia of the liver and skin in a pediatric liver transplant patient.
Pediatr Transplant. 2023;27:e14492. doi:10.1111/petr.14492.

A male infant with Fanconi anemia (FA), due to a FANCD2 mutation, presented with neonatal jaundice and conjugated hyperbilirubinemia progressing to cryptogenic liver cirrhosis. At 8 months of age, he underwent liver transplantation (LT) with a split liver graft, followed by hematopoietic stem cell transplantation (HSCT) at 19 months for bone marrow failure. The sequential approach was chosen to address life-threatening liver disease first and minimize HSCT-related hepatic toxicity. Post-HSCT complications included grade III acute Graft-versus-Host Disease (GvHD), recurrent sepsis, and biliary stent infection, which were managed successfully. What is the primary rationale for performing LT before HSCT in this patient?

A: Prevent exacerbation of bone marrow failure by preexisting liver disease

B: Minimize the risk of conditioning regimen-induced liver graft failure

C: Facilitate earlier engraftment by improving nutritional status

D: Avoid the need for immunosuppressive therapy during HSCT

B: Minimize the risk of conditioning regimen-induced liver graft failure

Explanation:
In patients with FA and concurrent severe liver disease, LT is prioritized to stabilize hepatic function before subjecting the patient to HSCT. The conditioning regimens required for HSCT can exacerbate preexisting liver disease, leading to potentially fatal complications. By resolving the hepatic dysfunction first, the patient can tolerate HSCT with reduced risk of liver-related morbidity. This strategy reflects a multidisciplinary approach to managing complex comorbidities in FA.

Reference:
Di Stasio F, Bravi M, Bonanomi S, et al.
Successful sequential liver and hematopoietic stem cell transplantation in a patient with Fanconi anemia.
Pediatr Transplant. 2023;27:e14503. doi:10.1111/petr.14503.

A 4-year-old boy who underwent liver transplantation (LT) for familial intrahepatic cholestasis presented with fever, dyspnea, and cough five months post-transplant. Examination revealed lymphadenopathy, splenomegaly, violaceous macules on the surgical scar, anemia, and thrombocytopenia. Laboratory studies showed elevated EBV and HHV8 viral loads. Initial diagnoses of post-transplant lymphoproliferative disease (PTLD) and hemophagocytic lymphohistiocytosis (HLH) were considered but ruled out after a lymph node biopsy confirmed Kaposi sarcoma (KS). Immunosuppressive therapy was adjusted by switching from tacrolimus to sirolimus, with clinical improvement and no recurrence after nine years of follow-up. What is the primary mechanism by which sirolimus benefits patients with post-transplant KS?

A: Direct antiviral activity against HHV8

B: Immunosuppression with antineoplastic properties

C: Induction of T-cell tolerance to HHV8

D: Restoration of natural killer cell function

B: Immunosuppression with antineoplastic properties

Explanation:
Sirolimus is an mTOR inhibitor with dual effects: immunosuppression to prevent organ rejection and antineoplastic activity that inhibits angiogenesis and tumor cell proliferation. These properties are particularly beneficial in managing KS, a tumor linked to HHV8 infection and immunosuppression. Unlike tacrolimus, sirolimus reduces the risk of KS progression without compromising graft function.

Reference:
Cordeiro C, Ferreira S, Nobre S, et al.
Kaposi sarcoma in three pediatric liver transplantation recipients.
Pediatr Transplant. 2023;27:e14469. doi:10.1111/petr.14469.

A 15-year-old girl with a history of biliary atresia and two previous liver transplants was admitted with life-threatening gastrointestinal (GI) bleeding. Imaging revealed extensive portal vein thrombosis (PVT) extending to the intrahepatic branches and significant portal hypertension. Endoscopic banding of esophageal varices, intravenous octreotide, and coagulation optimization failed to stabilize her condition. A multidisciplinary team opted for transjugular intrahepatic portosystemic shunt with portal vein recanalization (TIPS-PVR) using a combined transsplenic and transjugular approach. The procedure successfully reduced portal pressure and resolved the GI bleeding without complications. What key factor contributed to the success of TIPS-PVR in this complex post-liver transplantation scenario?

A: Use of a covered stent with controlled expansion to minimize hepatic encephalopathy risk

B: Recanalization of intrahepatic and extrahepatic portal veins using transhepatic access

C: Surgical intervention to bypass thrombosed portal segments prior to TIPS

D: Administration of long-term anticoagulation to prevent recurrent thrombosis

A: Use of a covered stent with controlled expansion to minimize hepatic encephalopathy risk

Explanation:
Using a controlled-expansion polytetrafluoroethylene (PTFE) stent allowed for precise regulation of shunt diameter, reducing the risk of hepatic encephalopathy by limiting excessive portosystemic shunting. The trans splenic approach enabled effective recanalization of thrombosed portal veins, facilitating TIPS placement. The minimally invasive procedure provided a critical alternative to surgical shunting, which carries higher morbidity. Long-term anticoagulation, though important, was a secondary consideration after the immediate resolution of GI bleeding.

Reference:
de Assis AM, de Carvalho Melo JA Jr, Kawakami WY, et al.
Life-threatening variceal bleeding after liver transplantation and extensive portal vein thrombosis: Desperate times call for desperate measures.
Pediatr Transplant. 2023;27:e14555. doi:10.1111/petr.14555

A 5-year-old girl with methylmalonic acidemia underwent a split liver transplantation with a left lobe graft. Postoperatively, she developed bilious output in her surgical drain on day 9. Imaging studies, including a hepatobiliary iminodiacetic acid (HIDA) scan, confirmed a bile leak but failed to localize the precise source. The patient was taken for surgical exploration. Despite prolonged observation under high magnification, the bile leak could not be visually identified. Indocyanine green (ICG) fluorescence imaging was subsequently utilized, revealing a pinpoint bile leak along the cut surface of the liver, which was successfully repaired. What is the primary mechanism by which ICG fluorescence imaging facilitated the identification of the bile leak in this patient?

A: Enhanced contrast of the bile duct anatomy through direct injection into the biliary system

B: Real-time visualization of bile excretion via near-infrared fluorescence following hepatic clearance

C: Identification of vascular perfusion abnormalities associated with the leak site

D: Visualization of bile leaks using radiotracer uptake within the biliary tree

B: Real-time visualization of bile excretion via near-infrared fluorescence following hepatic clearance

Explanation:
ICG fluorescence imaging involves intravenous administration of ICG, which is exclusively taken up by hepatocytes and excreted into the bile. Using near-infrared fluorescence, ICG enables real-time visualization of bile excretion, allowing precise localization of leaks. In this case, it proved invaluable in identifying the small bile leak along the cut liver surface when conventional visual inspection under magnification failed. This technology does not directly visualize bile duct anatomy or use radiotracer uptake as in HIDA scans.

Reference:
Lemoine CP, Lautz TB, Superina R.
Indocyanine green fluorescence imaging as an adjunct for the localization of a bile leak after split liver transplantation.
Pediatr Transplant. 2023;27:e14431. doi:10.1111/petr.14431.

A 3-year-old boy presented with jaundice, choluria, pale stools, abdominal pain, and fever. Imaging revealed a large hilar mass (76 × 80 × 63 mm) involving segments VI and VII of the liver, with invasion of the inferior vena cava (IVC) and portal vein, as well as intrahepatic bile duct dilation. Histological findings from biopsy showed spindle cell proliferation with chronic inflammatory infiltrates, consistent with inflammatory myofibroblastic tumor (IMT). The mass was deemed unresectable due to its proximity to vital structures, and the patient underwent living donor liver transplantation (LDLT) with a left lateral segment graft from his mother. Complex vascular reconstruction using cadaveric iliac vein grafts for the IVC and portal vein was performed. What was the primary advantage of choosing LDLT in this case?

A: Availability of a size-matched graft for vascular reconstruction

B: Enhanced ability to treat systemic complications of IMTs

C: Ability to achieve complete tumor resection with free margins

D: Potential for spontaneous tumor resolution without surgery

C: Ability to achieve complete tumor resection with free margins

Explanation:
LDLT was selected to enable radical tumor resection and ensure free margins, critical for a favorable prognosis in IMTs, especially in cases involving critical structures like the hepatic hilum and IVC. The tumor’s benign nature and lack of effective chemotherapy options further supported surgical intervention. The success of the procedure also depended on complex vascular reconstruction, highlighting the role of LDLT as a curative strategy for advanced hilar IMTs.

Reference:
Costa CM, Neto JS, Benavidez MR, et al.
Liver transplantation for hilar inflammatory myofibroblastic tumor: Case report and review of the literature.
Pediatr Transplant. 2023;27:e14445. doi:10.1111/petr.1

A 6-year-old child with a history of bilateral lung transplantation (BLTx) at age 2 due to ABCA3 transporter deficiency presents with progressive hypoxemic respiratory failure four years post-transplant. Despite empiric treatments, her lung function does not improve, leading to prolonged veno-venous extracorporeal membrane oxygenation (ECMO) support as a bridge to re-transplantation. Which of the following strategies is most beneficial for optimizing outcomes during ECMO support in pediatric patients awaiting lung re-transplantation?

A: High-dose sedation to reduce stress and oxygen demand

B: Frequent use of neuromuscular blockade to facilitate ECMO management

C: Implementation of early rehabilitation with minimal sedation

D: Complete bed rest to prevent further lung injury

C: Implementation of early rehabilitation with minimal sedation

Explanation:
Early rehabilitation and physical activity during ECMO, with optimized sedation protocols, help maintain physical conditioning and reduce deconditioning, which are critical for improving pre-transplant status and post-transplant outcomes. This approach requires a multidisciplinary team and family involvement. High-dose sedation or bed rest can lead to significant deconditioning, worsening outcomes. Neuromuscular blockade may only be used in specific situations and is not standard for optimizing outcomes.

Reference:
Herrera-Camino A, Sweet SC, Pendino R, et al.
Lung Re-transplantation after prolonged veno-venous extracorporeal membrane oxygenation (ECMO) in a child with chronic lung allograft dysfunction.
Pediatric Transplantation. 2024;28:e14579. doi:10.1111/petr.14579.

A 12-month-old female with a history of severe bronchopulmonary dysplasia and pulmonary hypertension underwent heart-lung transplantation (HLT) following a period of veno-venous extracorporeal membrane oxygenation (ECMO). On the 13th postoperative day, a chest CT revealed herniation of the right lower lobe across the midline. What is the most appropriate initial management approach for this complication?

A: Conservative monitoring with serial imaging

B: High-dose corticosteroids to reduce inflammation

C: Immediate surgical exploration and repositioning of the herniated lung

D: Bronchoscopic airway stenting to alleviate compression

C: Immediate surgical exploration and repositioning of the herniated lung

Explanation:
ung herniation following HLT is a rare but potentially life-threatening complication due to the risk of vascular compromise and airway obstruction. Early recognition through imaging and prompt surgical correction is essential to prevent irreversible damage and maintain lung function. Conservative measures or non-surgical options are not sufficient in cases involving structural displacement.

Reference:
Kim D, Choi KH, Kim H, Lee JH, Kim Y, Byun J-H.
Right lower lung midline herniation as a rare complication in an infant with heart-lung transplantation: A case report.
Pediatric Transplantation. 2024;28:e14656. doi:10.1111/petr.14656.

A 17-year-old female with idiopathic pulmonary arterial hypertension underwent bilateral lung transplantation and was maintained on tacrolimus, azathioprine, and prednisone. During routine surveillance bronchoscopy at 6 months post-transplant, her bronchoalveolar lavage (BAL) culture grew *Irpex lacteus*, an uncommon environmental fungus. She remained asymptomatic and treatment was deferred. However, 20 months post-transplant, she presented with progressive respiratory symptoms, hypoxia, and a drop in FEV1 to 42% predicted. Imaging revealed new nodular opacities and peripheral consolidations. What is the most important consideration in deciding to initiate antifungal treatment in cases like this?

A: The patient's age at the time of transplantation

B: The presence of pre-existing colonization by atypical fungi

C: Immediate onset of hypoxic episodes post-transplant

D: Resistance of Irpex lacteus to most antifungal agents

B: The presence of pre-existing colonization by atypical fungi

Explanation:
In immunocompromised patients such as lung transplant recipients, pre-existing colonization with atypical fungi like *Irpex lacteus* can progress to invasive fungal disease (IFD), particularly when coupled with declining clinical status and immunosuppressive therapy. Though initially asymptomatic, worsening respiratory function and imaging findings should prompt consideration for antifungal treatment. The risk of IFD must be balanced against potential treatment side effects.

Reference:
Atwood DT, Köhler JR, Vargas SO, et al.
Identification of Irpex and Rhodotorula on surveillance bronchoscopy in a pediatric lung transplant recipient: A case report and review of literature of these atypical fungal organisms.
Pediatric Transplantation. 2024;28:e14759. doi:10.1111/petr.14759.

A 13-year-old boy with end-stage kidney disease (ESKD) due to steroid-resistant nephrotic syndrome developed encapsulating peritoneal sclerosis (EPS) after 10 years of automated peritoneal dialysis (APD). The patient initially presented with intermittent abdominal pain and chronic constipation, progressing to vomiting and subacute intestinal obstruction. A CT scan confirmed EPS, revealing peritoneal thickening and calcification without bowel obstruction. He was transitioned to hemodialysis and treated with steroids and tamoxifen before undergoing a successful deceased donor kidney transplant. What is the main rationale for initiating tamoxifen in the management of EPS?

A: It promotes rapid resolution of bowel obstructions.

B: It decreases TGF-β production, reducing fibrotic processes.

C: It acts as a direct anti-inflammatory agent in peritoneal tissue.

D: It enhances the immunosuppressive effect of corticosteroids.

B: It decreases TGF-β production, reducing fibrotic processes.

Explanation:
Tamoxifen is a selective estrogen receptor modulator that has shown benefits in EPS by inhibiting TGF-β production, a key mediator in fibrotic changes within the peritoneum. This helps control the fibrotic process and mitigate encapsulation. The use of tamoxifen in conjunction with steroids targets both the inflammatory and fibrotic components of EPS.

Reference:
Al Riyami MS, Altalebi A, Al Hashmi S, et al.
Improvement of encapsulating peritoneal sclerosis after medical treatment and successful deceased donor kidney transplant in a child: A case report.
Pediatric Transplantation. 2024;28:e14867. doi:10.1111/petr.14867.

A 3-year-old boy with a history of end-stage kidney disease (ESKD) due to urethral atresia has been on peritoneal dialysis since birth. A multidisciplinary team decides on a kidney transplant. The donor is a 28-year-old woman whose right pelvic kidney, identified as having two short renal veins and a short ureter, was procured robotically. The surgical plan involved complex venous reconstruction using a deceased donor's iliac vein system to extend the renal veins and anastomose them to the recipient's vasculature. The patient experienced immediate graft function with serum creatinine levels of 0.5 mg/dL three months post-transplant and no vascular complications. What is the main advantage of using iliac vein grafts in pediatric renal transplantation with complex vascular anatomy?

A: They reduce the likelihood of surgical infection.

B: They allow extension of short renal veins, minimizing dissection.

C: They eliminate the need for post-operative immunosuppression.

D: They enable the use of arterial clamps for better control during surgery.

B: They allow extension of short renal veins, minimizing dissection.

Explanation:
In pediatric kidney transplantation involving anatomical challenges like short renal veins, utilizing iliac vein grafts can extend the renal veins effectively. This minimizes the extent of surgical dissection required, preventing transplant-related bleeding and lymphatic complications while facilitating a secure anastomosis. The technique supports graft function without increasing the risk of venous thrombosis or technical complications.

Reference:
Lledo E, Tabbara MM, Alvarez A, et al.
Venous vascular reconstruction of a robotically procured right kidney with two renal veins transplanted into a pediatric recipient.
Pediatric Transplantation. 2024;28:e14646. doi:10.1111/petr.14646.

A 6-year-old boy with end-stage renal disease secondary to nephronophthisis underwent kidney transplantation from his father, who was blood type O+. The recipient was blood type A+. On postoperative day 11, he developed fever, abdominal pain, diarrhea, and hematochezia. Laboratory tests revealed a sudden drop in hemoglobin, elevated lactate dehydrogenase, undetectable haptoglobin, and a positive direct antiglobulin test (DAT). These findings, combined with strongly positive anti-A antibodies in the eluate, confirmed passenger lymphocyte syndrome (PLS). Despite initial conservative treatment, he required therapeutic plasma exchange (TPE) and segmental colectomy for ischemic colitis. What is the most likely mechanism linking PLS to ischemic colitis in this patient?

A: Direct cytotoxicity of anti-A antibodies on intestinal endothelial cells

B: Activation of complement-mediated vascular thrombosis in mesenteric veins

C: Disseminated intravascular coagulation (DIC) triggered by severe hemolysis

D: Direct invasion of the bowel wall by donor-derived lymphocytes

C: Disseminated intravascular coagulation (DIC) triggered by severe hemolysis

Explanation:
Passenger lymphocyte syndrome (PLS) involves hemolytic anemia caused by donor-derived lymphocytes producing antibodies against recipient red blood cell antigens. In this case, hemolysis and a hypercoagulable state led to DIC, which contributed to venous-origin ischemic colitis. This complication emphasizes the systemic effects of severe hemolysis in PLS. While anti-A antibodies may activate complement, no direct cytotoxic or invasive mechanisms were observed in the colon.

Reference:
Yeom GE, Lim SH, Kim JH, et al.
Gastrointestinal involvement of passenger lymphocyte syndrome followed by minor ABO-incompatible renal transplantation: A case report.
Pediatr Transplant.. 2023;27:e14556. doi:10.1111/petr.14556.

A 7-year-old boy with Schimke immuno-osseous dysplasia (SIOD) underwent kidney transplantation (KT) after developing steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis. Post-transplant, he was treated with low-dose tacrolimus monotherapy and maintained stable graft function (eGFR 80 mL/min/1.73m²). However, he experienced recurrent viral infections and thrombocytopenia due to bone marrow suppression. Despite normal kidney function, his condition required weekly platelet transfusions, and hematopoietic stem cell transplantation (HSCT) was considered. What is the primary benefit of sequential HSCT after KT in patients with SIOD?

A: Prevention of extra-renal complications, such as vascular abnormalities

B: Resolution of defective cellular immunity while maintaining graft function

C: Enhanced renal allograft survival through improved immune tolerance

D: Elimination of the need for lifelong immunosuppressive therapy

B: Resolution of defective cellular immunity while maintaining graft function

Explanation:
Sequential HSCT after KT addresses the underlying cellular immune deficiency in SIOD, reducing the risk of recurrent infections and cytopenias while preserving kidney graft function. HSCT replenishes hematopoietic and immune systems, offering systemic benefits for this multisystem disease. Although it may stabilize some extra-renal complications, it primarily targets the immunological dysfunction, without eliminating the need for immunosuppression entirely.

Reference:
Woo HA, Kim SH, Ahn YH, et al.
Clinical course of post-kidney transplant Schimke immuno-osseous dysplasia.
Pediatr Transplant. 2023;27:e14605. doi:10.1111/petr.14605.

A 16-year-old girl with end-stage renal disease (ESRD) secondary to granulomatosis with polyangiitis (GPA) underwent kidney transplantation. She had a history of rituximab therapy for c-ANCA vasculitis 13 months before transplant. Post-transplant immunosuppressive therapy included antithymocyte globulin (ATG), tacrolimus, mycophenolate mofetil, and prednisone. One month later, she developed progressive polyarthritis involving multiple joints. MRI revealed synovitis, myositis, and joint effusions. Synovial fluid cultures were negative, but 16S rRNA PCR identified Ureaplasma parvum. She was treated with a 12-week course of levofloxacin with full symptom resolution. Which factor most likely predisposed her to invasive Ureaplasma infection?

A: T-cell depletion due to anti-thymocyte globulin

B: Persistent hypogammaglobulinemia after rituximab therapy

C: Subtherapeutic tacrolimus levels early post-transplant

D: Absence of prophylactic antibiotics targeting atypical organisms

B: Persistent hypogammaglobulinemia after rituximab therapy

Explanation:
The patient’s prior rituximab therapy resulted in prolonged hypogammaglobulinemia, leaving her vulnerable to infections with fastidious organisms like Ureaplasma parvum. Although ATG and tacrolimus contributed to immmunosuppression, her inability to recover adequate humoral immunity was the key predisposing factor. Prophylactic antibiotics do not routinely cover Ureaplasma, and the infection's onset was not related to early subtherapeutic tacrolimus levels.

Reference:
Schwartz S, Aldrich A, Kessler E, et al.
Disseminated Ureaplasma polyarthritis in a renal transplant recipient
Pediatr Transplant. 2023;27:e14538. doi:10.1111/petr.14538.

A 16-year-old girl with a history of kidney transplantation for focal segmental glomerulosclerosis presented three years post-transplant with right lower quadrant graft pain and hematuria. Imaging revealed severe external compression of the transplant renal vein due to graft engorgement, with a venous pressure gradient of 12 mmHg. An endovascular stent was placed, reducing the pressure gradient to 2 mmHg. Post-stenting, she developed hematuria progressing to anuria, with ultrasound confirming obstructive clot formation in the renal pelvis. Cystoscopy and placement of a nephroureteral JJ stent restored urine output and resolved symptoms. What is the most likely mechanism of acute anuria after stent placement in this patient?

A: Migration of the stent causing renal vein thrombosis

B: Acute ureteral obstruction due to clot formation in the collecting system

C: Increased venous pressure leading to renal artery compression

D: Hemodynamic instability from excessive blood loss during stent deployment

B: Acute ureteral obstruction due to clot formation in the collecting system

Explanation:
Acute anuria in this patient was caused by obstruction of the renal pelvis due to clot formation, a known complication of stent placement. This may result from venous stasis or mechanical irritation during the procedure. The placement of a JJ stent effectively relieved the obstruction, restoring urine output and preventing further graft damage. While venous pressure changes or stent migration can complicate such interventions, these were not observed in this case.

Reference:
Reis J, Bogart AM, Healey PJ, et al.
Transplant renal vein stent placement complicated by obstructive hematuria: A case report.
Pediatr Transplant. 2023;27:e14607. doi:10.1111/petr.14607.

A 16-year-old boy with end-stage renal disease secondary to lupus nephritis underwent deceased-donor kidney transplantation. The donor was CMV-positive, while the recipient was CMV-negative. Four months post-transplant, he presented with elevated serum creatinine (4.0 mg/dL), reduced eGFR (18 mL/min/1.73m²), and nephrotic-range proteinuria. Biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) with extensive podocyte foot process effacement. CMV viremia was detected (7,238 IU/mL), while CMV staining on biopsy was negative. Antiviral therapy with valganciclovir and reduced immunosuppression resolved proteinuria and improved renal function. What is the most likely mechanism of CMV-associated collapsing FSGS in this patient?

A: Direct cytopathic effect of CMV in glomerular epithelial cells

B: CMV-mediated immune activation leading to podocyte injury

C: Graft dysfunction secondary to CMV-induced vasculitis

D: Reactivation of latent lupus nephritis in the graft

B: CMV-mediated immune activation leading to podocyte injury

Explanation:
CMV-associated collapsing FSGS is proposed to occur through immune-mediated mechanisms rather than direct viral invasion, as suggested by negative CMV staining and absence of viral inclusions on biopsy. CMV infection triggers systemic immune activation, leading to cytokine release and podocyte injury, culminating in collapsing FSGS. This mechanism differs from recurrent lupus nephritis, which was excluded in this case. Timely antiviral therapy and adjusted immunosuppression were pivotal in reversing renal dysfunction.

Reference:
Parr MFE, Hidalgo G, Goldstein MJ, et al.
CMV-associated collapsing focal segmental glomerulosclerosis after kidney transplant in a pediatric patient
Pediatr Transplant. 2023;27:e14535. doi:10.1111/petr.14535.

Two pediatric donors aged 3 and 4 years with anuric acute kidney injury (AKI) donated four kidney grafts that were transplanted into four adult recipients. Donor 1, a 4-year-old, had a baseline serum creatinine of 0.5 mg/dL, rising to 4.4 mg/dL at procurement after 24 hours of anuria. Donor 2, a 3-year-old, was on continuous venovenous hemodiafiltration and ECMO. The recipients were carefully selected to exclude those with severe comorbidities or high immunologic risk. All kidneys were transplanted as single grafts, and all recipients achieved delayed but complete graft function without surgical complications. What is the primary factor contributing to the successful use of these pediatric kidneys with AKI in adult recipients?

A: Advanced immunosuppressive protocols preventing rejection

B: High regenerative capacity of pediatric kidneys with acute injury

C: Routine use of en-bloc transplantation to improve outcomes

D: Pre-transplant histological evaluation of all pediatric grafts

B: High regenerative capacity of pediatric kidneys with acute injury

Explanation:
Pediatric kidneys have a remarkable regenerative potential due to their lack of chronic structural damage and high cellular adaptability. These features enable successful transplantation even when donors exhibit acute kidney injury (AKI), including anuric states. Selecting low-risk adult recipients further enhanced outcomes. The kidneys were transplanted as single grafts rather than en-bloc, demonstrating their capacity for functional recovery despite AKI. Pre-transplant histological evaluation was not performed, highlighting the reliance on clinical judgment and donor history.

Reference:
Koch M, Kraus D, Boedecker-Lips S, et al.
Successful transplantation of four kidney grafts from two small pediatric donors with anuric acute renal failure into adult recipients.
Pediatr Transplant. 2023;27:e14542. doi:10.1111/petr.14542.

A 17-year-old male with a history of a deceased donor kidney transplant for atypical hemolytic uremic syndrome (aHUS) presented 18 months post-transplant with progressive weight loss of 8 kg over six months. Routine spirometry revealed a restrictive lung pattern, and high-resolution computed tomography (HRCT) showed bilateral diffuse ground-glass opacities. Bronchoscopy with bronchoalveolar lavage (BAL) confirmed Pneumocystis jirovecii pneumonia (PJP) through Gomori-methenamine-silver staining. The patient was treated with a six-week course of trimethoprim-sulfamethoxazole (TMP-SMX), resulting in improved lung function and weight gain. What is the most likely risk factor contributing to late-onset PJP in this patient?

A: Suboptimal prophylaxis with TMP-SMX during the first 6 months post-transplant

B: Ongoing immunosuppressive therapy combined with eculizumab for aHUS

C: CMV co-infection leading to opportunistic fungal proliferation

D: Pre-existing obstructive lung disease misdiagnosed as asthma

B: Ongoing immunosuppressive therapy combined with eculizumab for aHUS

Explanation:
This patient’s immunosuppressive regimen, including tacrolimus, mycophenolate mofetil, prednisone, and eculizumab (a complement inhibitor), created a highly immunosuppressed state, predisposing him to late-onset PJP. Although TMP-SMX was appropriately used for prophylaxis during the initial 6 months, long-term immunosuppression significantly increased the risk of opportunistic infections. CMV infection was ruled out, and his restrictive lung pattern was secondary to PJP, not asthma.

Reference:
Grewal M, Srivastava R, Ang JY, et al.
Unique presentation of late-onset Pneumocystis pneumonia in a pediatric kidney transplant recipient.
Pediatr Transplant. 2023;27:e14576. doi:10.1111/petr.14576.

A 10-year-old girl with Schimke immuno-osseous dysplasia (SIOD) and end-stage renal disease (ESRD) underwent living-related kidney transplantation from her ABO-compatible mother. Her T-cell deficiency and risk of infections necessitated a modified immunosuppressive protocol using basiliximab induction, low-dose mycophenolate mofetil (MMF), and tacrolimus. MMF was discontinued at 8 weeks post-transplant due to neutropenia, and she was maintained on tacrolimus monotherapy. Five years later, after developing neurological symptoms possibly linked to tacrolimus, she was switched to everolimus monotherapy. Seven years post-transplant, she exhibited excellent graft function and no significant infections or rejection episodes. What is the primary benefit of low-dose immunosuppression in this patient?

A: Enhanced prevention of opportunistic infections and malignancies

B: Improved graft perfusion through reduced endothelial damage

C: Elimination of the need for antiviral prophylaxis post-transplant

D: Rapid recovery of naïve T-cell populations after transplantation

A: Enhanced prevention of opportunistic infections and malignancies

Explanation:
Patients with SIOD have a predisposition to T-cell deficiency, increasing their risk for opportunistic infections and post-transplant lymphoproliferative disease (PTLD). The use of a low-dose immunosuppressive regimen, including tacrolimus monotherapy, minimizes immunosuppression-related complications while maintaining graft function. This approach is critical in managing patients with SIOD, where standard immunosuppressive regimens can significantly elevate morbidity and mortality risks.

Reference:
Finsen SH, Tepel M, Neland M, et al.
Successful low-dose immunotherapy after kidney transplantation in a 10-year-old girl with Schimke immuno-osseous dysplasia
Pediatr Transplant. 2023;27:e14495. doi:10.1111/petr.14495.

A 4-year-old girl with a history of idiopathic nephrotic syndrome (INS) presented with recurrence of steroid-resistant nephrotic syndrome (SRNS) immediately after kidney transplantation from a deceased donor. Despite treatment with tacrolimus, mycophenolate mofetil, methylprednisolone pulses, daily immunoadsorption, and obinutuzumab, she exhibited persistent massive proteinuria. A global B-cell targeting strategy was adopted, adding daratumumab, an anti-CD38 monoclonal antibody, to her regimen. Proteinuria resolved by day 99 post-transplantation, and she remained in remission 18 months post-transplant under maintenance therapy. What is the primary mechanism by which daratumumab contributed to her remission?

A: Direct inhibition of T-cell-mediated autoimmunity

B: Neutralization of circulating nephrin autoantibodies

C: Depletion of long-lived plasma cells producing pathogenic antibodies

D: Enhanced removal of immune complexes via complement activation

C: Depletion of long-lived plasma cells producing pathogenic antibodies

Explanation:
Daratumumab targets CD38, a surface marker on plasma cells, leading to their depletion and reducing the production of long-lived pathogenic antibodies. This approach is particularly effective in cases like post-transplant SRNS where conventional therapies fail. Plasma cells are key contributors to the production of autoantibodies, such as those targeting nephrin in INS, and their depletion significantly improves outcomes. This targeted therapy is distinct from the effects of traditional immunosuppression and B-cell depletion alone.

Reference:
Delbet J-D, Hogan J, Parmentier C, et al.
Successful global anti-B-cell strategy with daratumumab in a patient with post-transplant nephrotic syndrome recurrence unresponsive to immunoadsorption and obinutuzumab
Pediatr Transplant. 2023;27:e14544. doi:10.1111/petr.14544

A 2-year-old girl with renal dysplasia underwent deceased donor kidney transplantation with a 4/6 HLA mismatch. Postoperative complications included ureteral stenosis and posterior reversible encephalopathy syndrome, prompting a switch from tacrolimus to everolimus-based immunosuppression. By post-transplant day (PTD) 36, she developed stage 1 acute kidney injury and mixed rejection (T-cell mediated rejection [TCMR] grade 1B and antibody-mediated rejection [AMR]), confirmed by biopsy and donor-specific antibodies (DSAs) against HLA-DQ (MFI 4100). Initial AMR treatment with bortezomib, plasmapheresis, and rituximab failed due to toxicities, including thrombocytopenia and neuropathy. She was transitioned to carfilzomib, receiving six doses with fluid and N-acetylcysteine prehydration to mitigate nephrotoxicity. This approach led to complete DSA eradication and baseline creatinine restoration. What is the most likely mechanism of carfilzomib’s efficacy in this patient?

A: Direct inhibition of complement activation at the C1q level

B: Suppression of plasma cell antibody production through proteasome inhibition

C: Blocking of cytokine signaling in memory T cells

D: Elimination of alloreactive T-cell populations via apoptosis induction

B: Suppression of plasma cell antibody production through proteasome inhibition

Explanation:
Carfilzomib, a second-generation proteasome inhibitor, reduces antibody production by targeting plasma cells, which are responsible for the persistence of DSAs in AMR. This approach is particularly useful in cases refractory to first-line treatments like bortezomib due to its higher specificity and reduced neuropathy risk. While it does not directly block complement or target memory T cells, its efficacy lies in disrupting the pathogenic antibody response central to AMR.

Reference:
Cody EM, Varnell C Jr, Lazear D, et al.
Carfilzomib-based antibody mediated rejection therapy in pediatric kidney transplant recipients.
Pediatr Transplant. 2023;27:e14534. doi:10.1111/petr.14534.

A 15-year-old girl with end-stage renal disease (ESRD) secondary to lupus nephritis underwent a living-donor kidney transplant from her 29-year-old HLA-haploidentical uncle. The donor experienced perioperative hypotension and bleeding, raising concerns for ischemia-reperfusion injury (IRI). Post-transplant, the patient developed severe delayed graft function (DGF), marked by 17 days of anuria and histological findings of acute cellular rejection (Banff 2A), vascular wall necrosis, and mild antibody-mediated rejection (ABMR) without donor-specific HLA antibodies. She had a history of prior COVID-19 infection and demonstrated elevated non-HLA autoantibodies, including anti-angiotensin II type 1 receptor (AT1R) and endothelin type A receptor (ETAR). Intensive anti-rejection therapy was initiated, leading to improved graft function. What is the most likely contributing factor to the severity of this patient’s post-transplant complications?

A: Inadequate immunosuppression post-transplant

B: Development of HLA donor-specific antibodies

C: Heterologous immunity due to prior viral infections

D: Graft rejection due to ABO incompatibility

C: Heterologous immunity due to prior viral infections

Explanation:
The patient’s history of COVID-19 infection and seropositivity for multiple viruses likely contributed to the activation of memory T cells with cross-reactivity to alloantigens, a phenomenon known as heterologous immunity. This may have exacerbated the alloimmune response and contributed to the rapid onset of rejection. Additionally, high levels of non-HLA autoantibodies (AT1R and ETAR) likely aggravated the rejection process. There were no donor-specific HLA antibodies or ABO incompatibility identified, and immunosuppression protocols were appropriately intensified to manage the rejection.

Reference:
Al Attas RA, Alshami A, Mohamed N, et al.
Severe delayed graft function in a living-related kidney transplant recipient due to combination of alloimmunity, autoimmunity, and heterologous immunity: A case report.
Pediatr Transplant. 2023;27:e14424. doi:10.1111/petr.14424.

An 11-year-old girl with severe dilated cardiomyopathy (DCM) and pulmonary hypertension, managed on chronic milrinone therapy and anticoagulated with apixaban for a central-line related thrombus, was listed for heart transplantation. After 80 days, an HCV-positive donor heart was offered, involving a prolonged travel time estimated at 4.5 hours and a donor-to-recipient weight ratio of 2.1. The transplant center used a total cardiac volume (TCV) assessment and an extracorporeal organ care system to mitigate risks associated with size mismatch and ischemic time. The patient successfully underwent transplantation and showed normal cardiac function post-operatively, with rapid seroconversion to HCV negativity after antiviral treatment. What key strategy was critical in accepting this donor heart despite the associated risks?

A: Pre-operative use of reversal agents for anticoagulation

B: Implementation of extracorporeal heart preservation for prolonged ischemic times

C: Routine use of enoxaparin instead of apixaban for thrombosis prevention

D: Avoidance of antiviral treatment for post-transplant infections

B: Implementation of extracorporeal heart preservation for prolonged ischemic times

Explanation:
The use of the extracorporeal organ care system (OCS) was essential in maintaining the viability of the donor heart during the extended travel time, reducing cold ischemic time to 51 minutes and supporting warm perfusion for 428 minutes. This approach, combined with careful donor evaluation and antiviral treatment post-transplant, allowed successful outcomes despite donor HCV status and size mismatch concerns.

Reference:
Torpoco Rivera DM, Hollander SA, Almond C, et al.
An integrated program to expand donor utilization in pediatric heart transplantation: Case report of successful transplant with multiple donor risk factors.
Pediatric Transplantation. 2024;28:e14584. doi:10.1111/petr.14584.

An 11-year-old girl with dilated cardiomyopathy and pulmonary hypertension is bridged to heart transplantation with milrinone. Due to the limited donor pool, an HCV NAT-positive donor heart becomes available. After extensive counseling, her family consents to proceed. Post-transplant, she is immediately started on glecaprevir/pibrentasvir therapy and achieves a sustained virologic response with undetectable HCV viral load by post-op day 8. At her 1-year follow-up, she shows stable graft function without rejection. Which of the following is a primary benefit of using HCV NAT-positive donor hearts in pediatric transplantation?

A: It eliminates the need for antiviral therapy.

B: It expands the donor pool, reducing waitlist mortality.

C: It increases immunity against HCV-related complications post-transplant.

D: It decreases the risk of coronary allograft vasculopathy.

B: It expands the donor pool, reducing waitlist mortality.

Explanation:
Utilizing HCV NAT-positive donor hearts, combined with prompt initiation of direct-acting antiviral (DAA) therapy, safely broadens the donor pool and reduces waitlist times in pediatric heart transplantation. While antiviral therapy is required, studies show excellent outcomes with DAAs, enabling HCV-negative recipients to maintain good graft function and viral suppression. This approach is essential in high-risk cases with limited donor availability.

Reference:
Kushner LE, Puckett L, Lee J, et al.
Utilization of Hepatitis C Virus-Infected Donor Hearts in Two Children and Two Young Adults: Initial Experience at a Pediatric Transplant Center.
Pediatric Transplantation. 2024;28. doi:10.1111/petr.14879.

A 21-month-old girl underwent orthotopic heart transplantation (OHT) for hypoplastic left heart syndrome. Five months post-transplant, she developed Epstein-Barr virus (EBV)-positive post-transplant lymphoproliferative disorder (PTLD), presenting with mesenteric lymphadenopathy and abdominal symptoms. Despite reduction of immunosuppression and six weeks of rituximab therapy, her PTLD persisted, and EBV titers remained elevated. She then received EBV-directed T-cell therapy, which led to a reduction in viral load. What is the main mechanism of action for EBV-directed T-cell therapy in treating refractory EBV-PTLD?

A: Direct cytotoxic effect on EBV-positive B cells

B: B-cell depletion through CD20 binding

C: Stimulation of EBV-specific T cells to target infected cells

D: Enhancement of systemic antibody production against EBV

C: Stimulation of EBV-specific T cells to target infected cells

Explanation:
EBV-directed T-cell therapy provides cytotoxic T cells that specifically recognize and eliminate EBV-infected B cells, addressing cases of rituximab-refractory PTLD. This therapy aims to restore immune surveillance against EBV by delivering T cells programmed to target EBV antigens, thus reducing viral burden and lymphoma progression in immunosuppressed patients.

Reference:
Work E, Gupta D, Slayton WB, et al.
Epstein Barr virus-directed T-cell therapy for refractory EBV-PTLD in a toddler post Orthotopic heart transplantation.
Pediatric Transplantation. 2024;28. doi:10.1111/petr.14707.

A 5-year-old boy with congenital core myopathy presented with restrictive cardiomyopathy (RCM) associated with compound heterozygous mutations in the titin (TTN) gene. Despite preserved biventricular systolic function early in life, he developed severe diastolic dysfunction and a respiratory infection that led to cardiopulmonary failure, requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). After 11 months on the transplant waiting list, he underwent successful heart transplantation. Postoperatively, he achieved normal cardiac function and improved motor performance despite ongoing mild respiratory insufficiency. What is the most important factor supporting the decision for heart transplantation in patients with neuromuscular disorders?

A: Reduced risk of transplant-related complications in neuromuscular disorders

B: Stable skeletal and respiratory muscle function over time

C: Immediate reversal of restrictive pulmonary syndrome post-transplant

D: High likelihood of spontaneous cardiac recovery in congenital myopathies

B: Stable skeletal and respiratory muscle function over time

Explanation:
In patients with neuromuscular disorders, heart transplantation is considered when the cardiac phenotype is disproportionately severe compared to skeletal and respiratory muscle involvement. Stable neuromuscular function supports the decision to transplant, as progressive weakness or respiratory insufficiency could limit post-transplant outcomes. This patient demonstrated stable motor development despite significant cardiac dysfunction, making him a suitable candidate. Transplant-related complications and spontaneous cardiac recovery are less predictable and were not central to the decision-making process.

Reference:
Wacker J, Di Bernardo S, Lobrinus JA, et al.
Successful heart transplant in a child with congenital core myopathy and delayed-onset restrictive cardiomyopathy due to recessive mutations in the titin (TTN) gene.
Pediatr Transplant. 2023;27:e14561. doi:10.1111/petr.14561.

A 9-year-old girl, 9 months post-heart transplantation, presented with frontal headache, vomiting, and mild left hemiparesis. Imaging revealed a right frontoparietal lesion with cerebral edema and midline shift. A biopsy of the lesion confirmed tuberculoma, with histopathology showing granulomatous inflammation and positivity for Bacillus Calmette–Guérin (BCG) antibody. She was started on standard anti-tuberculosis treatment, including rifampicin, isoniazid, pyrazinamide, and ethambutol, with close monitoring of tacrolimus levels. The patient remained asymptomatic at discharge, 22 days after admission. What was the most critical factor leading to the development of tuberculoma in this patient?

A: Subclinical tuberculosis reactivation due to immunosuppression

B: Inadequate pre-transplant screening for latent tuberculosis

C: Delayed initiation of corticosteroid therapy for neuroinflammation

D: Use of rifampicin interfering with tacrolimus metabolism

A: Subclinical tuberculosis reactivation due to immunosuppression

Explanation:
Immunosuppression following solid organ transplantation, particularly with calcineurin inhibitors like tacrolimus, significantly increases the risk of reactivating latent tuberculosis, leading to opportunistic infections such as cerebral tuberculoma. While pre-transplant latent tuberculosis screening is essential, this patient had no reported history or screening for latent TB. Rifampicin was managed effectively with tacrolimus dose adjustments, minimizing interactions. The presentation and progression underscore the need for high clinical suspicion and rapid treatment initiation.

Reference:
Oliveira PC, Corbi MJA, Siqueira AWS, et al.
Brain tuberculoma in a pediatric heart transplant recipient.
Pediatr Transplant. 2023;27:e14496. doi:10.1111/petr.14496.

A neonate with a de novo FBN1 gene duplication was diagnosed with neonatal Marfan syndrome after presenting with hypotonia, abnormal facial features, and severe valvar regurgitation. By 10 months of age, she developed progressive mitral and tricuspid valve dysfunction requiring surgical repair. Postoperatively, she experienced profound biventricular dysfunction and was placed on a biventricular assist device (BiVAD). After eight months of BiVAD support and nutritional rehabilitation, she underwent heart transplantation (HTx) at 22 months of age. Her postoperative course included immunosuppression with tacrolimus and mycophenolate mofetil, but she developed early-onset coronary allograft vasculopathy (CAV) 3.8 years post-transplant. What was the primary role of BiVAD support in this patient?

A: Prevention of coronary allograft vasculopathy

B: Enabling physical and nutritional rehabilitation as a bridge to transplant

C: Restoration of aortic valve function in the setting of severe dilation

D: Long-term cardiac support eliminating the need for transplantation

B: Enabling physical and nutritional rehabilitation as a bridge to transplant

Explanation:
The use of BiVAD support provided critical circulatory stabilization and facilitated extensive nutritional and physical rehabilitation, which were essential for improving candidacy for heart transplantation in this patient with neonatal Marfan syndrome. This strategy addressed the severe heart failure and multisystem deconditioning commonly associated with this condition, enabling a successful transplant. While BiVAD did not directly address CAV or long-term cardiac function, it served as an effective bridge to transplantation.

Reference:
Laks JA, Lynch A, Honjo O, et al.
Heart transplantation in neonatal Marfan syndrome: Saving life in a rare and fatal condition.
Pediatr Transplant. 2023;27:e14560. doi:10.1111/petr.14560.

A 10-year-old girl with a history of orthotopic heart transplantation at 2 weeks of life for pulmonary atresia with an intact ventricular septum presented with recurrent gastrointestinal (GI) symptoms, including diarrhea and feeding intolerance, 9.5 years post-transplant. Despite adjustments to her immunosuppressive regimen and trials of various therapies, including steroids and mesalamine, her symptoms persisted, and colonoscopy showed erythema, nodularity, and focal active colitis. Histological analysis demonstrated chronic duodenitis, mild chronic gastritis, and an unusual presence of Russell bodies in the GI tract, indicative of immune-mediated bowel disease. Due to worsening symptoms and steroid-associated complications, basiliximab was initiated, leading to clinical stabilization and improved GI symptoms. What was the primary mechanism by which basiliximab provided benefit in this patient?

A: Direct eradication of gastrointestinal pathogens

B: Inhibition of IL-2 receptor signaling on activated T cells

C: Suppression of tumor necrosis factor-alpha (TNF-α) activity

D: Reduction of intestinal permeability through epithelial repair

B: HSCT provides curative potential for refractory lymphomas with a possible underlying immune deficiency.

Explanation:
HSCT is considered in pediatric cases of refractory or recurrent lymphoma, particularly when there is an aggressive disease course and potential immunodeficiency. It allows for immune reconstitution and eradication of lymphoma cells through graft-versus-lymphoma effects. In this case, the patient’s lymphoma did not respond to conventional chemotherapy, and HSCT offered curative potential.

Reference:
Memon S, Almudayfir Z, Elbashir E, et al.
A Rare Case of Refractory Nodal Marginal Zone Lymphoma in a Child, Successfully Cured by Allogeneic Stem Cell Transplant.
Pediatric Transplantation. . 2024;28. doi:10.1111/petr.14835.

A 31-month-old boy with a history of hyperactive airway disease and recurrent infections presented with lymphadenopathy and splenomegaly. He was diagnosed with Epstein-Barr virus (EBV)-positive nodal marginal zone lymphoma (NMZL), which did not respond to five cycles of R-CHOP chemotherapy. A PET/CT scan revealed persistent hypermetabolic lymphadenopathy, and he was declared as having relapsed/refractory disease. After additional cycles of bortezomib-based therapy, he underwent a successful allogeneic hematopoietic stem cell transplant (HSCT) from a matched sibling donor. Which of the following best explains the rationale for HSCT in this patient?

A: NMZL typically resolves with HSCT in adults, so it was used in this pediatric case.

B: HSCT provides curative potential for refractory lymphomas with a possible underlying immune deficiency.

C: HSCT is effective in all cases of pediatric non-Hodgkin lymphoma (NHL), regardless of disease type.

D: HSCT allows the reduction of chemotherapy in pediatric patients with nodal lymphomas.

B: Inhibition of IL-2 receptor signaling on activated T cells

Explanation:
Basiliximab is a chimeric monoclonal antibody targeting the CD25 subunit of the IL-2 receptor on activated T cells, thereby reducing T-cell activation and proliferation. In this patient, basiliximab addressed the immune dysregulation underlying her bowel disease, which was refractory to conventional treatments. While it does not target pathogens directly or TNF-α, its ability to modulate T-cell responses made it effective in managing her condition.

Reference:
Kiskaddon AL, Wilsey M, Gonzalez-Gomez I, et al.
Basiliximab therapy for immune-mediated bowel disease in a pediatric heart transplant patient.
Pediatr Transplant. 2023;27:e14443. doi:10.1111/petr.14443.

An 8-year-old boy with refractory T-cell acute lymphoblastic leukemia (R/R T-ALL) relapsed after his first allogeneic hematopoietic stem cell transplantation (allo-HSCT). He had persistent minimal residual disease (MRD) and high CD7 expression despite multiple rounds of chemotherapy. CD7 CAR T-cell therapy was administered as a bridging strategy to a second allo-HSCT. Which of the following outcomes best describes the result of CD7 CAR T-cell therapy in this patient?

A: Complete remission without any adverse events.

B: Initial remission followed by severe graft-versus-host disease.

C: Complete remission with manageable Grade 1 cytokine release syndrome (CRS).

D: Partial remission with severe multiorgan failure.

E: No response, leading to disease progression.

C: Complete remission with manageable Grade 1 cytokine release syndrome (CRS).

Explanation:
In the presented case, the patient achieved complete remission after CD7 CAR T-cell therapy, which served as a successful bridge to a second allo-HSCT. The treatment led to Grade 1 CRS, characterized by mild symptoms such as fever, but these were managed effectively without severe complications. This approach provided durable remission and a significant survival benefit.

Reference:
Fanqiao M, Chen X, Ren X, Li L, Wu T.
CD7 CAR T bridging to allo-HSCT in R/R T-ALL: A case report.
Pediatric Transplantation. . 2024;28. doi:10.1111/petr.14367.

A 2.5-month-old girl diagnosed with RAG1 immunodeficiency underwent unrelated cord blood hematopoietic stem cell transplantation (HCT). The immediate post-transplant course was unremarkable, but 3 months later, she developed severe Grade IV gut, skin, and liver graft-versus-host disease (GVHD), managed with ruxolitinib after steroid and mycophenolate failure. As her immunosuppression tapered and enteral feeding resumed, she experienced repeated episodes of vomiting, diarrhea, lethargy, and hypotension, leading to three PICU admissions. Extensive evaluations for sepsis and infections were negative. What should be considered as a potential diagnosis for her condition?

A: Acute intestinal obstruction

B: Sepsis-related shock

C: Severe food protein-induced enterocolitis syndrome (FPIES)

D: GVHD recurrence involving the gut

C: Severe food protein-induced enterocolitis syndrome (FPIES)

Explanation:
Severe FPIES is a non–IgE-mediated food allergy that can present with vomiting, diarrhea, lethargy, and hypotension, often mistaken for sepsis. In this case, the patient experienced these symptoms post-HCT, unrelated to infections or GVHD recurrence. Awareness of FPIES as a differential diagnosis in post-transplant patients with immune dysregulation is essential for reducing morbidity.

Reference:
Alonso García L, Panesso Romero M, García Macías E, Segarra Cantón O, Diaz de Heredia Rubio C.
Severe food protein-induced enterocolitis syndrome after hematopoietic stem cell transplantation: Pediatric case report.
Pediatric Transplantation. . 2024;28:e14810. doi:10.1111/petr.14810.

A 2.5-year-old boy born to consanguineous parents presented at 8 months with developmental delay, hydrocephaly, nystagmus, and severe bone sclerosis on imaging. Genetic testing identified a homozygous pathogenic mutation in the CA2 gene, confirming intermediate autosomal recessive osteopetrosis with renal tubular acidosis (RTA). Due to worsening bone marrow hypocellularity and anemia, he underwent allogenic hematopoietic stem cell transplantation (HSCT) from his mother as a full-matched related donor. Which of the following best explains the role of HSCT in the management of CA2-related osteopetrosis?

A: It directly reverses renal tubular acidosis by correcting CA2 enzyme deficiency.

B: It halts osteopetrosis progression by providing functional osteoclasts derived from donor cells.

C: It promotes rapid cerebral calcification resolution in patients with CA2 mutations.

D: It eliminates the need for immunosuppressive therapy in osteopetrosis.

B: It halts osteopetrosis progression by providing functional osteoclasts derived from donor cells.

Explanation:
HSCT is essential for treating osteopetrosis associated with CA2 deficiency as it enables the generation of functional osteoclasts, which can restore normal bone resorption and prevent further skeletal abnormalities. Although HSCT does not fully resolve RTA, it significantly improves bone density and reduces disease symptoms. This approach is critical for patients with severe, progressive forms of osteopetrosis.

Reference:
Shamsian BS, Momtazmanesh N, Saneifard H, et al.
Allogenic hematopoietic stem cell transplantation in an Iranian patient with osteopetrosis caused by carbonic anhydrase II deficiency: A case report.
Pediatric Transplantation. 2024;28. doi:10.1111/petr.14689.

A 5-month-old girl with bilateral intraocular retinoblastoma and a pineal trilateral tumor was diagnosed with high-risk trilateral retinoblastoma. She received six cycles of multiagent chemotherapy, including vincristine, carboplatin, etoposide, and cyclophosphamide, followed by tandem high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT). The first conditioning regimen included carboplatin, etoposide, and thiotepa, while the second utilized cyclophosphamide and thiotepa. Peripheral blood stem cells were collected and infused after each HDC cycle. Tumor regression was achieved post-transplant; however, relapse occurred 10 months later, and she succumbed to progressive disease following craniospinal radiotherapy. What is the primary benefit of tandem HDC-ASCT in managing high-risk trilateral retinoblastoma?

A: Complete eradication of central nervous system metastases

B: Sequential dose escalation with distinct chemotherapeutic agents

C: Preservation of functional vision in bilateral retinoblastoma

D: Long-term control of extraocular disease with minimal toxicity

B: Sequential dose escalation with distinct chemotherapeutic agents

Explanation:
Tandem HDC-ASCT allows for increased chemotherapy intensity by delivering sequential high-dose regimens using different agents, which enhances tumor control in high-risk pediatric cancers like trilateral retinoblastoma. While it does not guarantee CNS metastasis eradication or vision preservation, the approach improves disease-free survival compared to single HDC. Relapse in this patient highlights the need for multimodal therapy and underscores the aggressive nature of trilateral retinoblastoma.

Reference:
Toret E, Ozdemir ZC, Zengin Ersoy G, et al.
Tandem high-dose chemotherapy followed by autologous stem cell transplantation: An infant with trilateral retinoblastoma.
Pediatr Transplant. 2023;27:e14504. doi:10.1111/petr.14504.

An 18-month-old girl with a newly diagnosed primitive neuroectodermal tumor (PNET) received her first varicella vaccine (MMRV) one day prior to diagnosis. Chemotherapy was initiated 20 days post-vaccination, followed by three courses of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). On day one post-HSCT, she developed dermatomal herpes zoster (HZ), progressing to meningoencephalitis by day six. Polymerase chain reaction (PCR) confirmed Oka strain varicella vaccine in cerebrospinal fluid (CSF) at high viral loads (5.24 log10 copies/mL). She was treated with acyclovir and foscarnet, showing neurological recovery in five days without sequelae. What is the most likely factor contributing to this early reactivation of the vaccine strain?

A: Insufficient antibody production following the varicella vaccine

B: Short interval between live vaccine administration and immunosuppression

C: Delayed initiation of antiviral prophylaxis post-transplant

D: Lack of protective T-cell immunity against wild-type varicella zoster virus

B: Short interval between live vaccine administration and immunosuppression

Explanation:
The early initiation of intensive chemotherapy only 20 days after the live-attenuated varicella vaccine likely impaired the development of a robust immune response, predisposing the patient to vaccine strain reactivation. Prophylactic antiviral treatment was not initiated earlier because the patient met criteria for starting antivirals only post-HSCT. T-cell-mediated immunity plays a critical role in controlling varicella reactivation, but the timing of immunosuppression in this case disrupted the balance, leading to complications.

Reference:
Coralie R, Chebel Z, Renaud C, et al.
Varicella vaccine meningoencephalitis in a child receiving autologous bone marrow transplantation.
Pediatr Transplant. 2023;27:e14562. doi:10.1111/petr.14562.

A 16-year-old girl with serine/threonine kinase 4 (STK4) deficiency underwent hematopoietic stem cell transplantation (HSCT) due to a history of recurrent infections, eczema, and high-grade B-cell lymphoma in partial remission. Conditioning included rituximab, busulfan, and fludarabine, with GVHD prophylaxis using sirolimus, mycophenolate mofetil (MMF), and short-term methotrexate. Post-transplant, she developed low-grade GVHD, sclerotic chronic GVHD (cGVHD), and transient kidney impairment, which resolved after extracorporeal photopheresis (ECP) and immunosuppressive adjustments. One year post-HSCT, she demonstrated complete donor chimerism and normalized CD4+ T-cell counts. Which feature of her management was critical in balancing disease control with minimizing GVHD risk?

A: Myeloablative conditioning using busulfan and fludarabine

B: Use of rituximab for B-cell depletion in conditioning

C: Switching from sirolimus to cyclosporine A and later to MMF

D: Extracorporeal photopheresis for chronic GVHD

B: Use of rituximab for B-cell depletion in conditioning

Explanation:
Rituximab, an anti-CD20 monoclonal antibody, was used to deplete B cells, which not only helped control her pre-HSCT lymphoma but also reduced the risk of cGVHD by targeting donor B cells that can contribute to alloreactivity. Although other interventions, such as adjusting immunosuppression and ECP, were pivotal in managing GVHD, rituximab's inclusion in the conditioning regimen played a central role in balancing disease control and GVHD risk in this high-risk STK4-deficient patient.

Reference:
Uygun V, Keleş S, Daloğlu H, et al.
Hematopoietic stem cell transplantation in serine/threonine kinase 4 (STK4) deficiency: Report of two cases and literature review.
Pediatr Transplant. 2023;27:e14439. doi:10.1111/petr.14439.

A 13-year-old girl with a history of type 1 diabetes, diagnosed at age 4, presented with hypoglycemic unawareness and hypersensitivity to insulin preparations, including reactions ranging from urticaria to life-threatening anaphylaxis. She also experienced severe glycemic lability, with blood glucose levels fluctuating between 40 and 500 mg/dL, and had an HbA1c of 7.6%. Despite extensive medical management, including continuous subcutaneous insulin infusion, antihistamines, and topical steroids, her hypersensitivity reactions persisted, leading to generalized painful rashes, chronic abdominal pain, and significant impairment in cognitive and social development. Following a pancreas transplant alone (PTA), she achieved euglycemia without the need for exogenous insulin, her hypersensitivity reactions resolved completely, and her quality of life improved dramatically, with accelerated cognitive and social milestones. What is the most likely explanation for the success of PTA in this patient?

A: Pancreas transplantation eliminates the autoimmune process of type 1 diabetes.

B: It provides endogenous insulin secretion, avoiding hypersensitivity reactions caused by exogenous insulin components.

C: Immunosuppression directly resolves insulin hypersensitivity.

D: Euglycemia post-transplant reduces the burden of chronic rejection and improves pancreatic function.

B: It provides endogenous insulin secretion, avoiding hypersensitivity reactions caused by exogenous insulin components.

Explanation:
This patient's hypersensitivity reactions were linked to preservatives in exogenous insulin formulations, such as polysorbates and metacresol. By providing endogenous insulin secretion, the pancreas transplant resolved her hypersensitivity reactions and stabilized her glycemic control, leading to significant quality-of-life improvements. While the autoimmune process of type 1 diabetes remains active, the transplanted pancreas can function effectively under immunosuppression. Immunosuppression prevents graft rejection but does not directly treat hypersensitivity, and euglycemia does not directly impact chronic rejection risk.

Reference:
Adamusiak AM, Ramanathan K, Moe T, et al.
Effective treatment of diabetes, improved quality of life and accelerated cognitive development after pancreas transplantation in a child with type 1 diabetes and allergy to manufactured insulin preparations.
Pediatr Transplant. 2023;27:e14447. doi:10.1111/petr.14447.

An 8-year-old boy with a history of isolated intestinal transplantation presented with fever, vomiting, and increased stool output. Histology from biopsies confirmed moderate acute cellular rejection (ACR), with prominent apoptotic bodies in the crypts. Intestinal ultrasound (IUS) revealed bowel wall thickening (5.2 mm), increased vascularity (Limberg score 3), and mesenteric inflammation (score 2). After treatment with methylprednisolone, repeat IUS showed normalized bowel wall thickness and vascularity, correlating with histological improvement. Based on these findings, what is the most likely role of IUS in managing intestinal transplant recipients?

A: Replacement for histological diagnosis of ACR

B: Non-invasive tool for initial detection and response monitoring of ACR

C: Diagnostic confirmation of mesenteric vascular occlusion in transplant rejection

D: Primary imaging modality for viral enteritis in transplant recipients

B: Non-invasive tool for initial detection and response monitoring of ACR

Explanation:
Intestinal ultrasound (IUS) is a promising non-invasive tool for detecting and monitoring acute cellular rejection (ACR) in intestinal transplant recipients. It can identify changes such as bowel wall thickening, increased vascularity, and mesenteric inflammation, which correlate with histological findings. While IUS does not replace biopsy for definitive diagnosis, it provides a practical adjunct for tracking treatment responses, particularly in pediatric patients, reducing the need for repeated invasive procedures.

Reference:
Couper MR, Valamparampil J, Thyagarajan M, et al.
Intestinal ultrasound may be a useful tool in monitoring acute rejection following intestinal transplantation.
Pediatr Transplant. 2023;27:e14574. doi:10.1111/petr.14574.

A 6-year-old boy with megacystis-microcolon-intestinal hypoperistalsis (MMIHS) underwent isolated intestinal transplantation (IT) due to growth failure despite total parenteral nutrition. Five years later, he experienced refractory rejection leading to allograft removal. At age 13, he received a multivisceral transplant (MVT) including the liver, stomach, pancreas, small intestine, and right kidney. Immunosuppression included rabbit anti-thymocyte globulin (rATG) induction and tacrolimus maintenance. Fourteen years post-transplant, he self-discontinued tacrolimus and remained rejection-free. Immunological testing revealed donor-specific hyporesponsiveness, including low frequencies of inflammatory T-cytotoxic memory cells and no donor-specific antibodies (DSAs). Which factor most likely contributed to the development of operational tolerance in this patient?

A: Reduced antigen presentation by donor B cells and monocytes

B: High levels of circulating donor-specific antibodies

C: Persistent donor chimerism in the blood and lymph nodes

D: Complete absence of viral immune responses post-transplant

A: Reduced antigen presentation by donor B cells and monocytes

Explanation:
Operational tolerance was associated with donor-specific hyporesponsiveness in T-cytotoxic memory cells and reduced antigen presentation by donor B cells and monocytes. Additionally, the absence of DSAs and intact immunity to cytomegalovirus (CMV) and Epstein–Barr virus (EBV) supported a balanced immune state. Persistent donor chimerism was not observed in this case, and antiviral immunity was maintained. These findings suggest that reduced antigen presentation and donor-specific T-cell apoptosis contributed significantly to tolerance development.

Reference:
Remaley L, Ashokkumar C, Soltys KA, et al.
Operational tolerance after intestine re-transplantation in childhood and immunological correlates.
Pediatr Transplant. 2023;27:e14455. doi:10.1111/petr.14455.

A 16-month-old boy who suffered severe anoxic brain injury was declared brain-dead and became a potential organ donor. During the hospital stay, the donor underwent routine testing for SARS-CoV-2, with initial negative results from nasopharyngeal swabs. However, at autopsy, both nasopharyngeal swabs and plasma samples tested positive for SARS-CoV-2 RNA. The liver, heart, and en-bloc kidneys were transplanted into three recipients. None of the recipients developed symptoms or evidence of SARS-CoV-2 transmission, and their graft functions remained excellent during follow-up. Based on this case, what is the most likely explanation for the absence of viral transmission?

A: SARS-CoV-2 cannot survive transplantation procedures.

B: SARS-CoV-2 infection in non-lung tissues is non-infectious.

C: SARS-CoV-2 RNA detection does not always indicate active infection.

D: Recipients' immunosuppressive therapies prevent SARS-CoV-2 replication.

C: SARS-CoV-2 RNA detection does not always indicate active infection.

Explanation:
Detection of SARS-CoV-2 RNA in donor tissues or fluids, especially outside the respiratory tract, does not confirm the presence of live, infectious virus. This case demonstrates that pediatric non-lung organ donors with SARS-CoV-2 RNA may not pose a significant risk of transmission to recipients, provided there is no evidence of systemic infection or organ dysfunction. The absence of clinical or laboratory signs of transmission further underscores the importance of careful donor evaluation.

Reference:
Clark JD, et al.
SARS-CoV-2 RNA positive pediatric organ donors: A case report.
Pediatr Transplant. 2023;27:e14452. doi:10.1111/petr.14452.

A 13-year-old girl with end-stage renal disease secondary to a solitary dysplastic kidney underwent a kidney transplant from a SARS-CoV-2-positive deceased donor. The donor had mild COVID-19 symptoms 4 weeks prior to donation and a cycle threshold (Ct) value of 33.4, suggesting a low viral load. The recipient, vaccinated with two doses of mRNA COVID-19 vaccine, was SARS-CoV-2 anti-spike IgG positive pre-transplant. The patient received induction immunosuppression with alemtuzumab and perioperative intravenous immunoglobulin (IVIg). No SARS-CoV-2 transmission occurred, and her renal function remained stable (estimated GFR of 83.3 mL/min/1.73m²) at 86 days post-transplant. What factors most likely contributed to the safety of using a SARS-CoV-2-positive donor in this case?

A: The donor's low Ct value and absence of recent symptoms

B: Pre-transplant SARS-CoV-2 vaccination and recipient antibody positivity

C: Use of IVIg and alemtuzumab to mitigate immune activation

D: Absence of any history of symptomatic COVID-19 in the recipient

B: Pre-transplant SARS-CoV-2 vaccination and recipient antibody positivity

Explanation:
The recipient's vaccination status and pre-existing anti-spike IgG antibodies likely reduced the risk of donor-derived SARS-CoV-2 transmission and severe post-transplant disease. The donor's low viral load (high Ct value) further minimized the risk of transmission. IVIg was administered as a precautionary measure, but the recipient's immunity played a central role in the favorable outcome. This case highlights the importance of assessing donor viral load and recipient immunity when considering organs from SARS-CoV-2-positive donors.

Reference:
Pizzo H, Soni PR, Nadipuram S, et al.
Utilization of SARS-CoV-2-positive donors in pediatric renal transplantation.
Pediatr Transplant. 2023;27:e14451. doi:10.1111/petr.14451.