Immunology demystified: A guide for transplant hepatologists.

Liver transplantation has become standard practice for treating end-stage liver disease. The success of the procedure relies on effective immunosuppressive medications to control the host's immune response. Despite the liver's inherent capacity to foster tolerance, the early post-transplant period is marked by significant immune reactivity. To ensure favorable outcomes, it is imperative to identify and manage various rejection types, encompassing T-cell-mediated, antibody-mediated, and chronic rejection. However, the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidence-based criteria. Given that the majority of patients will require lifelong immuno suppression as the mechanisms underlying operational tolerance are still being investigated, healthcare providers must possess an understanding of immune responses, rejection mechanisms, and the pathways targeted by immunosuppressive drugs. This knowledge enables customization of treatments and improved patient care, even though a consensus on an optimal immunosuppressive regimen remains elusive.

Are treatment options used for adult-onset type 2 diabetes mellitus (equally) available and effective for children and adolescents?

Youth-onset type 2 diabetes mellitus (T2DM), influenced by an increase in obesity, is a rising problem worldwide. Pathophysiological mechanisms of this early-onset T2DM include both peripheral and hepatic insulin resistance, along with increased hepatic fasting glucose production accompanied by inadequate first and second-phase insulin secretion. Moreover, the incretin effect is reduced. The initial presentation of type 2 diabetes can be dramatic and symptoms may overlap with those of type 1 diabetes mellitus. Therefore, immediate therapy should address hyperglycemia and associated metabolic derangements irrespective of ultimate diabetes type, while further therapy adjustments are prone to patients' phenotype. New agents with proven glycemic and beyond glycemia benefits, such as Glucagon-like polypeptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors, used in the adult population of T2DM patients, might become increasingly important in the treatment armamentarium. Moreover, metabolic surgery is an option for markedly obese (body mass index > 35 kg/m2) children and adolescents suffering from T2DM who have uncontrolled glycemia and/or serious comorbidities when lifestyle and pharmacologic interventions fail. In this mini-review, we will discuss the potential of treatment options considering new data available from randomized control trials, including individuals with adult-onset type diabetes mellitus.

Metformin and pancreatic neuroendocrine tumors: A systematic review and meta-analysis.

BACKGROUND: Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant. In this perspective, metformin is emerging as a molecule of interest. Retrospective studies have described metformin, a widely used agent for the treatment of patients with type 2 diabetes mellitus (T2DM), to be effective in modulating different tumor-related events, including cancer incidence, recurrence and survival by inhibiting mTOR phosphorylation. This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET. AIM: To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and post-treatment outcomes of pNET. METHODS: A systematic review of the published literature was undertaken, focusing on the role of T2DM and metformin in insurgence and prognosis of pNET, measured through outcomes of tumor-free survival (TFS), overall survival and progression-free survival. RESULTS: A total of 13 studies (5674 patients) were included in this review. Analysis of 809 pNET cases from five retrospective studies (low study heterogeneity with I² = 0%) confirms the correlation between T2DM and insurgence of pNET (OR = 2.13, 95%CI = 1.56-4.55; P < 0.001). The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients (hazard ratio = 1.84, 95%CI = 0.78-2.90; P < 0.001). The study heterogeneity was intermediate, with I² = 51%. A few studies limited the possibility of performing pooled analysis in the setting of metformin; therefore, results were heterogeneous, with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET. CONCLUSION: T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients. Unfortunately, a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients.

BACKGROUND: Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019 (COVID-19) but its full correlation with COVID-19 infection remains unknown. AIM: To identify acute pancreatitis' occurrence, clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19. METHODS: A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19. Data were obtained from hospital electronic medical records. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab. RESULTS: Four hundred and eight out of 1432 (28.49%) patients who received a renal allograft developed COVID-19 disease. The analyzed cohort included 321 patients (57% males). One hundred and fifty patients (46.7%) received at least one dose of the anti-SARS-CoV-2 vaccine before the infection. One hundred twenty-five (39.1%) patients required hospitalization, 141 (44.1%) developed pneumonia and four patients (1.3%) required mechanical ventilation. Treatment included immunosuppression modification in 233 patients (77.1%) and remdesivir in 53 patients (16.6%), besides the other supportive measures. In the study cohort, only one transplant recipient (0.3%) developed acute pancreatitis during acute COVID-19, presenting with abdominal pain and significantly elevated pancreatic enzymes. She survived without complications with a stable kidney allograft function. CONCLUSION: Although rare, acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients. The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

Association of Atraumatic Splenic Rupture and Acute Pancreatitis: Case Report with Literature Review.

Atraumatic splenic rupture is an uncommon complication of acute pancreatitis. This article presents a case of a 35-year-old patient presenting with acute pancreatitis who subsequently developed a splenic vein thrombosis and splenic rupture requiring a laparotomy and splenectomy. This rare but life-threatening complication requires prompt recognition and management in patients with pancreatitis who develop sudden hemodynamic instability.