Transplant medicine

Transplant medicine US Medical PG Question 1: A research team develops a new monoclonal antibody checkpoint inhibitor for advanced melanoma that has shown promise in animal studies as well as high efficacy and low toxicity in early phase human clinical trials. The research team would now like to compare this drug to existing standard of care immunotherapy for advanced melanoma. The research team decides to conduct a non-randomized study where the novel drug will be offered to patients who are deemed to be at risk for toxicity with the current standard of care immunotherapy, while patients without such risk factors will receive the standard treatment. Which of the following best describes the level of evidence that this study can offer?

• A. Level 1
• B. Level 3 (Correct Answer)
• C. Level 5
• D. Level 4
• E. Level 2

Transplant medicine Explanation: ***Level 3*** - A **non-randomized controlled trial** like the one described, where patient assignment to treatment groups is based on specific characteristics (risk of toxicity), falls into Level 3 evidence. - This level typically includes **non-randomized controlled trials** and **well-designed cohort studies** with comparison groups, which are prone to selection bias and confounding. - The study compares two treatments but lacks randomization, making it Level 3 evidence. *Level 1* - Level 1 evidence is the **highest level of evidence**, derived from **systematic reviews and meta-analyses** of multiple well-designed randomized controlled trials or large, high-quality randomized controlled trials. - The described study is explicitly stated as non-randomized, ruling out Level 1. *Level 2* - Level 2 evidence involves at least one **well-designed randomized controlled trial** (RCT) or **systematic reviews** of randomized trials. - The current study is *non-randomized*, which means it cannot be classified as Level 2 evidence, as randomization is a key criterion for this level. *Level 4* - Level 4 evidence includes **case series**, **case-control studies**, and **poorly designed cohort or case-control studies**. - While the study is non-randomized, it is a controlled comparative trial rather than a case series or retrospective case-control study, placing it at Level 3. *Level 5* - Level 5 evidence is the **lowest level of evidence**, typically consisting of **expert opinion** without explicit critical appraisal, or based on physiology, bench research, or animal studies. - While the drug was initially tested in animal studies, the current human comparative study offers a higher level of evidence than expert opinion or preclinical data.

Transplant medicine US Medical PG Question 2: A 22-year-old man is brought to the emergency department by ambulance 1 hour after a motor vehicle accident. He did not require any circulatory resuscitation at the scene, but he was intubated because he was unresponsive. He has no history of serious illnesses. He is on mechanical ventilation with no sedation. His blood pressure is 121/62 mm Hg, the pulse is 68/min, and the temperature is 36.5°C (97.7°F). His Glasgow coma scale (GCS) is 3. Early laboratory studies show no abnormalities. A search of the state donor registry shows that he has registered as an organ donor. Which of the following is the most appropriate next step in evaluation?

• A. Evaluation of brainstem reflexes (Correct Answer)
• B. Brain MRI
• C. Electroencephalography
• D. Cerebral angiography
• E. Apnea test

Transplant medicine Explanation: ***Evaluation of brainstem reflexes*** - In a patient with a **Glasgow Coma Scale (GCS) of 3** and no response to noxious stimuli/sedation, assessment of **brainstem reflexes** is a critical step in determining brain death. - This evaluation includes checking for pupillary light reflex, corneal reflex, vestibulo-ocular reflex (doll's eyes), oculocephalic reflex, and gag/cough reflexes to ascertain the complete absence of brainstem function. *Brain MRI* - While a brain MRI can provide detailed anatomical information regarding brain injury, it is **not the primary diagnostic test** for determining brain death. - Brain death is a **clinical diagnosis** based on the irreversible loss of brain and brainstem function, which can be confirmed rapidly by clinical examination. *Electroencephalography* - **EEG** measures electrical activity in the brain and can show electrocerebral silence, which is consistent with brain death. - However, EEG is **not always required** for the diagnosis of brain death and is often used as a confirmatory test in specific situations, such as when clinical examination is inconclusive or legal requirements necessitate it. *Cerebral angiography* - **Cerebral angiography** can demonstrate the absence of cerebral blood flow, which is a criterion for brain death. - This is an **invasive procedure** and is generally reserved for situations where clinical examination tests are difficult to perform or interpret (e.g., severe facial trauma, drug intoxication), and is not the initial step. *Apnea test* - The **apnea test** is a critical component of the brain death evaluation, confirming the absence of spontaneous breathing response to hypercapnia. - It is performed **after the absence of brainstem reflexes** has been established and all confounding factors (e.g., hypothermia, hypotension, sedatives) have been ruled out.

Transplant medicine US Medical PG Question 3: A 50-year-old man presents to a clinic with oliguria. Four weeks ago, he had a kidney transplant. Postoperative follow-up was normal. He is currently on cyclosporine and admits that sometimes he forgets to take his medication. On physical examination, the vital signs include: temperature 37.1°C (98.8°F), blood pressure 165/110 mm Hg, heart rate 80/min, and respiratory rate 16/min. There is mild tenderness on renal palpation. His serum creatinine level is 4 mg/dL, well above his baseline level after the transplant. Which of the following best describes the histological finding if a biopsy is taken from the transplanted kidney?

• A. Lymphocytic infiltration of graft vessels and endothelial damage (Correct Answer)
• B. Thrombosis and occlusion of vessels
• C. Atherosclerosis on angiography
• D. Necrosis with granulation tissue
• E. Thickening of blood vessels, fibrosis of graft vessels, and parenchymal atrophy

Transplant medicine Explanation: ***Lymphocytic infiltration of graft vessels and endothelial damage*** - The patient's presentation with **oliguria**, elevated **creatinine**, and **hypertension** following a recent kidney transplant, especially with a history of non-adherence to **cyclosporine** (an immunosuppressant), strongly indicates **acute rejection**. - Histologically, acute rejection is characterized by **lymphocytic infiltration** of the graft vessels (often referred to as **vasculitis** or **endotheliitis**) and associated **endothelial damage**. *Thrombosis and occlusion of vessels* - This finding is more characteristic of **hyperacute rejection**, which typically occurs within minutes to hours of transplantation, not weeks later. - Hyperacute rejection is mediated by **pre-formed antibodies** and leads to severe, rapid graft failure due to widespread intravascular thrombosis. *Atherosclerosis on angiography* - While post-transplant patients can develop accelerated atherosclerosis (a form of **chronic rejection**), it is typically a long-term complication developing months to years after transplantation. - The acute presentation with rapid creatinine elevation is not typical for primary atherosclerosis. *Necrosis with granulation tissue* - **Necrosis** with **granulation tissue** is a general healing response to significant tissue injury or inflammation. - While some cellular necrosis can occur in severe rejection, it's not the defining feature, and granulation tissue indicates a more prolonged, subacute process rather than the primary histological hallmark of acute rejection. *Thickening of blood vessels, fibrosis of graft vessels, and parenchymal atrophy* - These are classic features of **chronic rejection**, which manifests months to years after transplantation as a gradual decline in graft function. - **Chronic rejection** involves progressive damage leading to vasculopathy, interstitial fibrosis, and tubular atrophy, rather than the acute inflammatory cellular infiltrate seen here.

Transplant medicine US Medical PG Question 4: A 14-year-old boy has undergone kidney transplantation due to stage V chronic kidney disease. A pre-transplantation serologic assessment showed that he is negative for past or present HIV infection, viral hepatitis, EBV, and CMV infection. He has a known allergy for macrolides. The patient has no complaints 1 day after transplantation. His vital signs include: blood pressure 120/70 mm Hg, heart rate 89/min, respiratory rate 17/min, and temperature 37.0°C (98.6°F). On physical examination, the patient appears to be pale, his lungs are clear on auscultation, heart sounds are normal, and his abdomen is non-tender on palpation. His creatinine is 0.65 mg/dL (57.5 µmol/L), GFR is 71.3 mL/min/1.73 m2, and urine output is 0.9 mL/kg/h. Which of the following drugs should be used in the immunosuppressive regimen in this patient?

• A. Belatacept
• B. Sirolimus
• C. Omalizumab
• D. Daclizumab
• E. Basiliximab (Correct Answer)

Transplant medicine Explanation: **Basiliximab** - **Basiliximab** is a **monoclonal antibody** that targets the **IL-2 receptor (CD25)** on activated T cells, preventing their proliferation and inducing immunosuppression. - It is commonly used as **induction therapy** in kidney transplant recipients due to its good safety profile, especially in pediatric patients, without the nephrotoxicity associated with calcineurin inhibitors, minimizing acute rejection risks immediately post-transplant. *Belatacept* - **Belatacept** works by co-stimulation blockade, binding to **CD80 and CD86** on antigen-presenting cells to prevent T-cell activation. - It is typically reserved for patients who cannot tolerate calcineurin inhibitors due to **nephrotoxicity** or require a steroid-sparing regimen, which is not indicated as an immediate need in this patient. *Sirolimus* - **Sirolimus** is an **mTOR inhibitor** that works by blocking T-cell proliferation and B-cell differentiation. - It is associated with several side effects, including **delayed wound healing**, **thrombocytopenia**, and **hyperlipidemia**, which are undesirable in the immediate post-transplant period, especially in a growing adolescent. *Omalizumab* - **Omalizumab** is an **anti-IgE monoclonal antibody** primarily used for allergic asthma and chronic spontaneous urticaria. - It has no role in **immunosuppression for organ transplantation** as its mechanism of action is unrelated to preventing graft rejection. *Daclizumab* - **Daclizumab** is another **monoclonal antibody** that also targets the **IL-2 receptor (CD25)**, similar to basiliximab. - However, daclizumab has been **withdrawn from the market** due to serious adverse effects including severe liver injury and autoimmune encephalitis, making it unavailable for clinical use in transplantation.

Transplant medicine US Medical PG Question 5: A 58-year-old man is brought to the emergency department because of confusion, weight loss, and anuria. He has chronic kidney disease, hypertension, and type 2 diabetes mellitus. He was diagnosed with acute lymphoblastic leukemia at the age of 8 years and was treated with an allogeneic stem cell transplantation. He is HIV-positive and has active hepatitis C virus infection. He drinks around 8 cans of beer every week. His current medications include tenofovir, emtricitabine, atazanavir, daclatasvir, sofosbuvir, insulin, amlodipine, and enalapril. He appears lethargic. His temperature is 36°C (96.8°F), pulse is 130/min, respirations are 26/min, and blood pressure is 145/90 mm Hg. Examination shows severe edema in his legs and generalized muscular weakness. Auscultation of the lung shows crepitant rales. Laboratory studies show positive HCV antibody and positive HCV RNA. His HIV viral load is undetectable and his CD4+ T-lymphocyte count is 589/μL. Six months ago, his CD4+ T-lymphocyte count was 618/μL. An ECG of the heart shows arrhythmia with frequent premature ventricular contractions. Arterial blood gas analysis on room air shows: pH 7.23 PCO2 31 mm Hg HCO3- 13 mEq/L Base excess -12 mEq/L The patient states he would like to donate organs or tissues in the case of his death. Which of the following is an absolute contraindication for organ donation in this patient?

• A. HIV infection
• B. Childhood leukemia (Correct Answer)
• C. Alcoholism
• D. No absolute contraindications
• E. Acute kidney injury

Transplant medicine Explanation: ***Correct: Childhood leukemia*** - **History of hematologic malignancy** (including acute lymphoblastic leukemia) is an **absolute contraindication** for solid organ donation according to UNOS and OPTN guidelines. - Even though this patient was treated 50 years ago with allogeneic stem cell transplantation, the concern for **residual malignant cells** or **transmission to immunosuppressed recipients** makes this an absolute exclusion. - Unlike solid tumors (which may be acceptable after long disease-free intervals), **leukemias and lymphomas carry lifelong exclusion** from organ donation due to their systemic nature and potential for dormant cells. *Incorrect: Acute kidney injury* - **Acute kidney injury (AKI)** is NOT an absolute contraindication for organ donation. - While the kidneys themselves may not be suitable for transplantation, other organs (heart, liver, lungs, corneas) could still be viable. - Each organ is assessed individually for suitability. *Incorrect: HIV infection* - **Well-controlled HIV infection** (undetectable viral load, stable CD4 count >200) is no longer an absolute contraindication. - Under the **HOPE Act (HIV Organ Policy Equity Act)**, organs from HIV-positive donors can be transplanted into HIV-positive recipients. - This patient has excellent viral control (undetectable VL, CD4 589), making HIV not an absolute barrier. *Incorrect: Alcoholism* - **Alcohol use disorder** alone is not an absolute contraindication for organ donation. - The suitability depends on individual organ assessment (e.g., liver function, cardiac health). - This patient drinks 8 beers/week, which is moderate consumption and doesn't preclude donation of undamaged organs. *Incorrect: No absolute contraindications* - This patient **does have an absolute contraindication**: his history of hematologic malignancy (acute lymphoblastic leukemia). - Despite the long time since treatment, hematologic cancers remain absolute exclusions for organ donation.

Transplant medicine Flashcard 1 of 3

Question: What type of graft is from self? _____

Answer: Autograft

Transplant medicine Flashcard 2 of 3

Question: Patients who have undergone _____ surgery can sometimes manifest with symptoms of hypoparathyroidism and hypocalcemia.

Answer: Thyroid

Transplant medicine Flashcard 3 of 3

Question: In a renal transplant a patient presenting with fever and leakage of urine into the pelvic cavity 5 - 10 days following the transplant most likely has _____

Answer: distal ureteral ischemia