Noonan syndrome (NS) is a genetic disorder caused by mutations in the RAS/MAPK signaling pathway, typically characterized by unique physical features, congenital heart defects, and short stature. Osteoporosis (OP), although uncommon in NS, can significantly impact patients' quality of life. We report the case of a 60s-year-old male with NS who experienced progressive osteoporosis over seven years. Dual-energy X-ray absorptiometry (DEXA) scans revealed a marked decline in bone mineral density (BMD) accompanied by multiple fractures. Despite normal vitamin D and parathyroid hormone intact levels, the patient’s BMD continued to deteriorate, leading to vertebral compression fractures that necessitated surgical intervention. This case highlights the importance of early osteoporosis screening and prompt management in NS patients to prevent severe complications. Further research is warranted to explore the mechanisms underlying bone fragility in NS and to develop targeted therapeutic strategies.

Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene, leading to deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). This results in impaired bone and dental mineralization, causing a wide range of clinical manifestations, from perinatal lethality to mild adult-onset forms. We report a case of a 40-year-old female with a history of joint pain, multiple fractures, dental issues, and bipolar disorder, who was diagnosed with adult-onset HPP. Laboratory investigations revealed persistently low alkaline phosphatase (ALP) levels and elevated vitamin B6. Genetic testing confirmed a pathogenic ALPL mutation. The patient was initiated on enzyme replacement therapy (ERT) with asfotase alfa, resulting in significant symptom improvement. This case highlights the importance of recognizing HPP in adults with unexplained musculoskeletal symptoms and underscores the role of genetic testing in the diagnosis and management of this condition.

Background: Heart transplantation (HT) remains the definitive therapy for end-stage heart failure, yet rejection and cardiac allograft vasculopathy (CAV) continue to limit long-term outcomes. Beyond donor-specific HLA antibodies, non-HLA antibodies, particularly anti-angiotensin II type 1 receptor antibodies (AT1R-Abs), have been implicated in allograft injury, but published findings are heterogeneous. Aim: The aim of this study is to systematically evaluate the evidence linking AT1R gene expression and anti-AT1R antibodies with key post-heart transplant outcomes. Methods: We conducted a systematic review in accordance with PRISMA guidelines. Scopus, PubMed, Web of Science, and the Cochrane Library were searched (December 2025) for cohort and case–control studies evaluating AT1R gene expression and/or AT1R-Ab status in HT recipients and their association with post-transplant outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the NIH Quality Assessment Tool. Results: Twelve studies encompassing 951 recipients met the inclusion criteria. Five studies evaluated AT1R mRNA expression, reporting variable patterns: several observed reduced AT1R/AT2R transcription after transplantation without clear clinical correlation, whereas others associated higher donor or recipient AT1R expression with transplant coronary artery disease and recurrent rejection. AT1R-Ab prevalence varied widely and appeared to increase after mechanical circulatory support, with substantial seroconversion reported during LVAD support in initially antibody-negative patients. Associations between AT1R-Ab and acute cellular rejection and antibody-mediated rejection were inconsistent across studies, and survival findings were inconclusive; however, some reports linked elevated AT1R-Abs to poorer long-term freedom from adverse events. Evidence regarding CAV was mixed, with signals of increased vasculopathy risk in some cohorts but not others. Conclusions: Current evidence suggests a potential role for AT1R expression and AT1R-Abs in cardiac allograft dysfunction, including rejection phenotypes and vasculopathy. Larger prospective studies with harmonized testing strategies are needed to define clinically meaningful AT1R-Ab cutoffs and clarify their utility in risk stratification and targeted therapeutic trials.

Background and Aim: This network meta‐analysis addresses the limited dose‐specific comparative evidence by evaluating different doses of tirzepatide (TZP) versus dulaglutide (DULA) for glycemic control, weight loss, and safety in type 2 diabetes mellitus (T2DM). Methods: Following PRISMA and Cochrane guidance, we searched major databases for RCTs comparing TZP and DULA in adults with T2DM. Efficacy outcomes included body weight change (Weeks 12 and 16) and mean HbA1c change (Weeks 12 and 24). Safety outcomes included mortality, cardiovascular events, and adverse events (AEs). SUCRA ranking was used and analysis performed in RStudio (v4.5.1). Results: Four RCTs comprising 14,348 participants contributed to a seven‐node network. However, Nicholls et al. 2025 had the majority of sample size ( n = 13,165). TZP 15 mg achieved the greatest reduction in body weight at Week 16 (mean difference [MD] vs. TZP 5 mg: −2.68 kg; 95% CI −4.98 to −0.38), while TZP 1 mg (MD: 4.39 kg; 95% CI 1.28 to 7.51) and DULA 0.75 mg (MD: 3.10 kg; 95% CI 0.25 to 5.96) were associated with smaller reductions relative to TZP 5 mg. TZP 15 mg also produced the largest HbA1c reduction at Week 24 (MD vs. TZP 5 mg: −0.40%; 95% CI −0.62 to −0.19), compared with TZP 10 mg (MD: −0.23%; 95% CI −0.44 to −0.02) and DULA 1.5 mg (MD: 0.67%; 95% CI 0.25 to 1.09). No significant differences were observed between treatments for all‐cause mortality or major cardiovascular events. Gastrointestinal AEs were more frequent with higher TZP doses, especially TZP 15 mg vs. TZP 5 mg for nausea, while serious AEs and severe hypoglycemia were similar across doses. Conclusion: Higher TZP doses potentially improve efficacy, while lower TZP/DULA doses enhance tolerability, supporting individualized T2DM care. However, these findings should be interpreted cautiously because several comparisons are indirect, many participants had not reached their maintenance dose, several safety outcomes were based on limited event counts, and significant inconsistency was observed for early body‐weight outcomes.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enhancing immune surveillance against tumors. However, their use in kidney transplant recipients presents a significant challenge due to the risk of immune-mediated graft rejection. This retrospective case series highlights four kidney transplant recipients treated with ICIs for various malignancies, revealing the complex interplay between oncologic outcomes and transplant function. Two of four patients developed severe acute kidney injury (AKI), leading to dialysis-dependent graft loss despite high-dose corticosteroid therapy. One patient exhibited partial renal recovery following transient dialysis. In contrast, another patient maintained stable graft function despite prolonged ICI therapy. Oncologic outcomes varied, with two patients achieving significant tumor regression, while others experienced disease progression. These cases underscore the need for careful immunosuppressive management and close monitoring when administering ICIs in transplant recipients. The findings emphasize the importance of individualized treatment strategies to optimize both cancer control and graft survival.