Sultanah Aminah Hospital

The ASC4OPT non-comparative phase 3b study (NCT04948333) evaluates asciminib once daily (QD) or twice daily (BID) in chronic myeloid leukemia in chronic phase (CML-CP) treated with ≥2 tyrosine kinase inhibitors (TKIs). This study enrolled 169 patients not in major molecular response (MMR), with unsatisfactory response (intolerant, warning or failure) as defined by European LeukemiaNet (ELN) 2020 criteria. Patients intolerant to their most recent TKI and in MMR at baseline (n = 30) were also enrolled. The primary endpoint was the MMR rate at Week 48 for patients not in MMR at baseline. Results showed an overall MMR rate of 39.4% at Week 48 (40 mg BID, 43.4%; 80 mg QD, 35.4%) and 43.6% at Week 96 (40 mg BID, 45.8%; 80 mg QD, 41.5%) in patients not in MMR at baseline. Among 40 patients who had their asciminib dose escalated to 200 mg QD, 17.5% were in MMR at Week 96. Most patients in MMR at baseline remained in MMR at 48 and 96 weeks (93.3% and 86.7%, respectively). Safety for both dosing regimens was consistent with that of previous studies. Findings support asciminib as a potential standard of care for patients with CML-CP who have not responded optimally to prior TKI therapy.

KEY POINTS:Patients with IgA nephropathy and proteinuria are at risk of kidney failure despite use of guideline-recommended renin-angiotensin system and sodium-glucose cotransporter 2 (SGLT2) inhibition. Atrasentan reduces proteinuria in IgA nephropathy, but its efficacy as adjunct to renin-angiotensin system and SGLT2 inhibition has not been rigorously tested. Atrasentan provided a clinically meaningful reduction in proteinuria in adults with IgA nephropathy treated with renin-angiotensin system and SGLT2 inhibitors. BACKGROUND:Atrasentan, a highly selective endothelin-A receptor antagonist, is approved for proteinuria reduction in adults with IgA nephropathy. Renin-angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are guideline recommended, yet the additional benefit of atrasentan has not been rigorously determined. METHODS:We performed a randomized, double-blind, placebo-controlled crossover study of atrasentan in adults with IgA nephropathy, eGFR ≥30 ml/min per 1.73 m 2 , and urinary protein >0.5 g/d while on maximal, stable RASi and SGLT2i. Participants were randomized 1:1 to either sequence AB or sequence BA (0.75 mg atrasentan [A] once daily during period 1 and matching placebo [B] during period 2, or vice versa), with a 12-week washout period in between. The primary end point was the change in urinary protein-to-creatinine ratio (UPCR) to week 12. The secondary end point was the change in UPCR to week 24. Safety end points included the type, incidence, severity, seriousness, and relatedness of adverse events (AEs). RESULTS:We recruited 54 participants with mean age 48 years (SD 12), 43% female, mean (SD) eGFR 63 (22) ml/min per 1.73 m 2 , and median UPCR 1.0 g/g (Q1-Q3, 0.7-1.4). Treatment with atrasentan versus placebo resulted in a difference in geometric mean percentage change in UPCR at week 12 of -25.3% (95% confidence interval, -36.8 to -11.7; P < 0.001). The treatment difference in UPCR between atrasentan versus placebo during treatment period 2 at week 24 was -26.4% (95% confidence interval, -45.8 to -0.0). There was one unrelated serious adverse event. Fluid retention events were uncommon, and none required hospitalization. There were no study drug discontinuations due to treatment-related adverse events and no deaths. CONCLUSIONS:Atrasentan provided a clinically meaningful reduction in proteinuria in adults with IgA nephropathy and proteinuria ≥0.5 g/d treated with RASi and SGLT2i therapy. Atrasentan was well tolerated, and no new safety signals emerged. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:NCT05834738 .

IntroductionSurgery-related muscle loss (SRML) is common after major upper gastrointestinal (GI) surgery and is associated with worse recovery and survival, and prehabilitative parenteral nutrition (PN) has been proposed to attenuate it, yet data from Southeast Asian populations are absent. We set out to characterise perioperative muscle change and to test whether the amount of protein and energy delivered per kilogram body weight was associated with muscle preservation.MethodsWe conducted a single-centre observational cohort study of 115 adults who underwent elective major upper GI surgery at Hospital Sultanah Aminah, Johor Bahru, and received 800 kcal/day premixed prehabilitative PN (38 g amino acids), as a supplement to oral or enteral intake, for 7 days before surgery. Body composition was measured by segmental bioimpedance analysis (InBody 770) at admission and on postoperative days (PODs) 3, 7, 30, and 90. The primary outcome was clinically relevant SRML, defined as a decrease in skeletal muscle mass (SMM) of 10% or more from admission to POD 7; 111 patients had an evaluable POD 7 measurement.ResultsPatients had a median age of 61 years, 58.3% were male, 70.4% had malignant disease, and 19.1% were underweight; median total protein delivery (PN plus oral or enteral intake) was 1.4 g/kg/day. From admission to POD 7, SMM decreased by a mean of 2.6%, phase angle by 6.2% and body mass index by 3.1% (all p < 0.001). Clinically relevant SRML occurred in 18 of 111 evaluable patients (16.2%). Protein delivered per kilogram was not associated with the change in SMM (Spearman rho = 0.05, p = 0.59), and energy per kilogram showed only a weak, non-significant trend (Spearman rho = 0.16, p = 0.09). In exploratory multivariable models limited by only 18 events, only a higher baseline SMM predicted greater relative loss, and no delivery variable predicted SRML.DiscussionIn a real-world prehabilitative PN cohort, clinically relevant muscle loss was relatively infrequent, but protein delivery was not independently associated with muscle preservation, consistent with anabolic resistance during surgical stress. The single-arm design precludes causal inference, and the narrow range of protein exposure may have left the study underpowered to detect a dose-response relationship. Controlled studies with contemporaneous non-PN comparators, wider exposure contrasts and functional endpoints are required.

Background: Tuberculous pleural effusion (TBE) and malignant pleural effusion (MPE) are the most common causes of exudative pleural effusion in tuberculosis-endemic regions. This study evaluates transthoracic ultrasound (TUS) features of TBE vs. MPE and incorporates clinical and pleural fluid (Pf) parameters into a machine learning-based random forest (RF) model for differentiation. Methods: This prospective observational study was conducted over 6 months across six tertiary hospitals in Malaysia, involving patients undergoing diagnostic medical thoracoscopy (MT). Diagnostic confidence for TBE and MPE was determined based on final thoracoscopic diagnosis. Logistic regression and RF models were applied to predefined clinical, imaging, and laboratory variables. Results: Among 187 recruited patients, 132 (70 TBE and 62 MPE) subjects with at least moderate diagnostic confidence were analyzed. On TUS, TBE was more likely to be non-hyperechoic, complex, and loculated, with the presence of fibrin and less pleural thickening, while MPE showed hyperechoic effusion and hemidiaphragm nodules. Independent predictors for TBE included younger age [adjusted odds ratio (aOR) =0.94], presence of fibrin (aOR =2.86), lower Pf lactate dehydrogenase (LDH) (aOR =0.996), and higher Pf adenosine deaminase (ADA) (aOR =1.10). Without Pf ADA, these parameters, along with the absence of hemidiaphragm nodules (aOR =0.33), remained significant for TBE prediction. The RF model outperformed logistic regression (92.6% vs. 87.9% accuracy), even without Pf ADA. Conclusions: TUS parameters can aid in differentiating TBE from MPE. The RF model demonstrated superior diagnostic performance, offering a potential point-of-care tool, even in the absence of Pf ADA.