Search Results (10,402)

Background: Current guidelines recommend mitral valve (MV) repair over replacement for active native valve endocarditis. However, traditional techniques involving radical debridement and prosthetic patch reconstruction may limit repair feasibility and long-term durability. This study evaluates the long-term clinical outcomes of an alternative approach utilizing a limited resection and non-patch technique in patients presenting with active native MV endocarditis. Methods: Consecutive patients with definite active native MV endocarditis who underwent surgical treatment between January 2016 and December 2021 were retrospectively reviewed. From this cohort, all patients managed with MV repair using a limited resection strategy without patch plasty were selected and compared to patients undergoing MV replacement after radical resection. The prespecified primary endpoints were overall mortality, the incidence of recurrent endocarditis, and the rate of reoperation during five-year follow-up. The Cox proportional hazards model was used to identify predictors of overall mortality and adverse events (composite of death, recurrence, and/or reoperation). Results: Out of 128 patients with active native MV endocarditis, 75 patients successfully underwent MV repair via the limited resection and non-patch technique and 53 patients received MV replacement. Five-year mortality rates were 43% in the repair group and 52% in the replacement group, p = 0.31. Six patients developed recurrent endocarditis in the repair group, while one patient developed it in the replacement group. Reoperation was necessary in five cases in the repair group, while one patient in the replacement group required reoperation due to paravalvular leakage. Surgical strategy was not associated with mortality or adverse events. Staphylococcal endocarditis was a strong predictor of overall mortality (HR: 2.2 (1.3–3.7)) and adverse events (HR: 2.2 (1.0–4.9)). Conclusions: A limited resection approach for active native MV endocarditis appears to be a feasible surgical strategy to enhance valve reparability, particularly in non-staphylococcal cases. Conversely, staphylococcal endocarditis remains a potent independent risk factor associated with increased mortality and adverse events. Full article

Background: Left ventricular thrombus (LVT) is a serious complication associated with cardiomyopathy and impaired left ventricular (LV) systolic function. Patients with a resolved LVT remain at risk for recurrence and subsequent thromboembolism. However, the factors influencing the recurrence of LVT are not yet fully understood. The aim of this study was to identify the risk factors and clinical outcomes related to LVT recurrence and to improve follow-up strategies and treatment options. Methods and results: We retrospectively investigated patients confirmed to have a resolved LVT by transthoracic echocardiography from January 2018 to April 2021 at Zhongshan Hospital Fudan University. All patients received anticoagulant therapy for more than 6 months and underwent at least two follow-up transthoracic echocardiograms. No statistically significant differences were observed in baseline characteristics between the LVT recurrence and non-recurrence groups, including gender, age, diabetes, hyperlipidemia, renal function, previous stroke history, other underlying medical conditions, ejection fraction, or left ventricular diameter. Patients in the recurrence group exhibited a higher prevalence of previous myocardial infarction and percutaneous coronary intervention compared to the non-recurrence group (84.6% vs. 61.1%, p = 0.03; 76.9% vs. 52.8%, p = 0.03). Additionally, patients in the recurrence group tended to have more ventricular aneurysms (50.0% vs. 22.2%, p = 0.008) and larger previous thrombus sizes (27.7 ± 12.6 vs. 21.4 ± 9.1 mm, p = 0.008) compared to those in the non-recurrence group. Multivariate logistic regression analysis indicated that the longitudinal diameter of the LVT was an independent risk factor for LVT recurrence (OR 1.058, 95% CI 1.003–1.115, p = 0.04). ROC curve analysis revealed an area under the curve of 0.647 for the longitudinal diameter of the LVT, with an optimal cut-off value of 23.5 mm, a sensitivity of 62%, and a specificity of 64%. After a follow-up duration of 3.0 ± 2.5 years, the incidence of non-fatal myocardial infarction and major adverse cardiovascular events (MACEs) in the recurrence group was significantly higher than that in the non-recurrence group [non-fatal myocardial infarction: 3 (11.5%) vs. 1 (1.4%), p = 0.02; MACE: 7 (26.9%) vs. 7 (9.7%), p = 0.01]. No statistically significant differences were found in bleeding events, systemic embolism, or all-cause death between the two groups. Conclusions: Our study indicates that a history of myocardial infarction, the presence of ventricular aneurysm, and a larger thrombus diameter are significant factors influencing LVT recurrence. Furthermore, the longitudinal diameter of the thrombus is identified as an independent risk factor for recurrence following resolution. The threshold for LVT diameter requiring extended anticoagulation and the required duration of anticoagulation need to be confirmed in future studies. Full article

Gastric cancer is one of the malignancies with the highest incidence and mortality worldwide. Helicobacter pylori (H. pylori) infection is the primary driving factor in its development. The progression of gastric mucosal malignancy follows the Correa cascade model: “chronic non-atrophic gastritis → chronic atrophic gastritis (CAG) → intestinal metaplasia (IM) → dysplasia (Dys) → gastric cancer.” Currently, clinical management faces major challenges, including increasing antibiotic resistance in H. pylori, limited pharmacological options for gastric precancerous lesions, and treatment resistance and toxicity in established gastric cancer. This review synthesizes current evidence on BBR, COP, EPI, PAL, and JAT and organizes their reported actions into a three-tier intervention framework. At the first tier, etiologic and inflammatory interception, individual alkaloids suppress H. pylori persistence through direct antibacterial injury, urease inhibition, and modulation of bacterial virulence and antibiotic susceptibility, while attenuating infection-driven inflammatory and immune responses. At the second tier, modulation of precancerous mucosal progression, preclinical studies indicate that these compounds can ameliorate gastric glandular injury and may attenuate biological processes associated with progression toward intestinal metaplasia and dysplasia. At the third tier, antitumor and adjunctive intervention in established gastric cancer, alkaloids inhibit proliferation, induce cell-cycle arrest and apoptosis, suppress invasion and metastasis, and regulate non-coding RNA and epigenetic networks; BBR-centered preclinical studies further suggest potential chemosensitizing and supportive effects. This review integrates the five alkaloids BBR, COP, EPI, PAL, and JAT and systematically elucidates their mechanisms of action across the pathological continuum from H. pylori infection and chronic inflammation to precancerous lesions and ultimately gastric cancer. It establishes a stage-oriented, compound-specific analytical framework to clarify the pharmacological positioning of these compounds, identify priorities requiring further validation, and guide future mechanistic and translational research. Full article

Botrytis cinerea is a major fungal pathogen of grapevine responsible for gray mold, causing significant economic losses worldwide. Under specific environmental conditions, controlled development of Botrytis cinerea may lead to “noble rot,” a quality-enhancing attribute of premium wines; however, the same fungus can rapidly develop into destructive gray mold, causing significant grape losses. Consequently, the challenge is not necessarily the complete eradication of the pathogen, but the regulation of its development to prevent uncontrolled disease progression while preserving grape quality. The present study investigated the potential of using essential oils extracted from selected aromatic plants using ultrasound-assisted hydrodistillation (UAHD) as eco-friendly biocontrol agents against Botrytis cinerea. The extraction process was optimized by evaluating the effects of biomass particle size, ultrasonic power, and distillation time on essential oil yield. Antifungal activity was assessed through in vitro poisoned food and disk diffusion assays and validated in vivo on artificially inoculated grape berries by evaluating disease incidence, disease severity, treatment efficacy, and weight loss. Ultrasound pretreatment increased essential oil yield by up to 29.58% compared with conventional hydrodistillation, with optimal conditions achieved using 1 cm biomass, 150 W ultrasonic power, and 85 min distillation. Oregano, thyme, sage, and lemon balm essential oils achieved 100% inhibition of Botrytis cinerea mycelial growth at the tested concentrations, whereas lavender essential oil showed 95.03% inhibition at 0.125% and complete inhibition at 0.25%. In vivo, essential oil formulations markedly reduced gray mold development, with the 2.0% formulation providing the highest treatment efficacy and the lowest disease severity. These findings show that UAHD-derived essential oils represent promising sustainable alternatives for the management of Botrytis cinerea in viticulture. However, these findings represent preliminary evidence obtained under controlled in vitro conditions, necessitating further validation in real-world applications. Full article

Background: Fragility fractures of the pelvis (FFP) are increasingly encountered in older adults, yet early deterioration is difficult to anticipate because fracture instability interacts with frailty and systemic vulnerability. We developed and validated an admission-based multimodal framework to predict 90-day treatment failure (TF90) before definitive management. Methods: This multicentre retrospective prediction study included 1684 consecutive patients aged ≥65 years with FFP treated at five tertiary hospitals. TF90 was defined as persistent fracture-related pain or immobility, delayed conversion to operative stabilisation, secondary displacement, FFP-related unplanned readmission, revision or unplanned reoperation, or all-cause mortality within 90 days. Only predictors available within 24 h of admission and before the definitive treatment decision were eligible, including CT-defined fracture morphology, frailty, clinical characteristics and routine laboratory biomarkers; DXA and specialised bone metabolism measurements were evaluated separately in an extended model. Four prespecified models were developed in 985 patients, temporally validated in 520 patients and evaluated in a completely held-out Centre E internal–external validation cohort of 179 patients, with additional leave-one-centre-out internal–external cross-validation. Results: TF90 occurred in 307 patients (18.2%) and increased from 8.1% in FFP I to 37.1% in FFP IV. Higher risk was associated with advanced age, greater frailty, impaired prefracture mobility, bilateral posterior ring injury, greater displacement, systemic inflammation, hypoalbuminaemia and renal dysfunction. In temporal validation, AUROCs were 0.732 for the simple logistic model, 0.763 for the core logistic model, 0.759 for the core random forest and 0.755 for the extended random forest. Neither greater algorithmic complexity nor specialised skeletal measurements provided reproducible incremental value. A development-derived high-risk stratum had a TF90 incidence of 32.2% and contained 70.0% of all events. At the fixed threshold of 0.209, sensitivity was 71.3%, specificity 70.0% and negative predictive value 93.1%. Conclusions: Pretreatment integration of pelvic ring mechanics, frailty and routinely available systemic biomarkers enables clinically relevant enrichment of older patients at risk of TF90. The model is best positioned to support intensified surveillance and structured reassessment rather than determine operative treatment. Independent prospective external validation, recalibration and clinical impact evaluation are required before routine implementation. Full article

Objective: Open surgical repair (OSR) remains an important treatment for abdominal aortic aneurysm (AAA), but its invasiveness contributes to substantial perioperative risk. Although Enhanced Recovery After Surgery (ERAS) pathways have improved outcomes across several surgical specialties, evidence supporting their use in open aortic surgery, particularly in Chinese clinical settings, remains limited. We, therefore, evaluated the association between adherence to a locally adapted ERAS pathway and early perioperative outcomes after elective OSR for AAA. Methods: This single-center retrospective cohort study included 182 patients who underwent elective OSR for AAA. Patients who received at least 70% of the 30 ERAS elements were assigned to the ERAS group (n = 93), whereas those who received less than 70% were assigned to the control group (n = 89). A total of 152 patients remained after 1:1 matching of the two groups using propensity score. Quantile regression and logistic regression models were used to evaluate the impact of the ERAS protocol on postoperative length of stay, 30-day mortality, ICU admission rate, hospital cost, major complications, and readmission. Results: After matching, baseline and aneurysm characteristics were generally comparable between groups. The ERAS group demonstrated a significantly reduced risk of major complications (OR = 0.33; 95% CI 0.16–0.71; p = 0.004) and postoperative nausea and vomiting (OR = 0.10; 95% CI 0.01–0.80; p = 0.030). The time to postoperative bowel movement was 1 day earlier in the ERAS group (p < 0.001). The incidence of postoperative cardiac complications was significantly lower in the ERAS group (2.6% vs. 11.8%; p = 0.028). Pulmonary complications were also markedly reduced in the ERAS group (1.3% vs. 19.7%; p < 0.001). The ERAS group was associated with a reduction in postoperative length of hospital stay by 2 days (p < 0.001) and a decrease in hospital cost by 8065 RMB (p < 0.001). Conclusions: Higher adherence to a locally adapted ERAS pathway was associated with fewer major complications, faster bowel recovery, shorter postoperative hospitalization, and lower hospital costs after elective open AAA repair. These findings support prospective multicenter evaluation and further context-specific implementation of ERAS in open aortic surgery. Full article

Objective: To investigate the impact of asymptomatic high-risk status for ischemic stroke on patients with abdominal aortic aneurysm undergoing endovascular aortic repair (EVAR). Methods: Eligible patients with abdominal aortic aneurysm who underwent EVAR between January 2011 and December 2021 were enrolled in this retrospective cohort study. Propensity score matching (PSM) was used to balance baseline characteristics between the cerebrovascular high-risk group and the standard control group. The impact of cerebrovascular high-risk status on short- and long-term outcomes was assessed using Cox proportional hazards regression and generalized linear models, with results presented as hazard ratios (HRs), odds ratios (ORs), and corresponding 95% confidence intervals (CIs). Results: A total of 1080 patients were included (299 high-risk, 781 standard). During the 13-year follow-up period, ischemic stroke occurred in 45 patients (15.1%) in the high-risk group (HR, 7.01; 95% CI, 4.11–11.94; p < 0.001). The high-risk group also had a higher incidence of major adverse cardiovascular and cerebrovascular events (MACCEs), which occurred in 129 patients (43.1%) (HR, 1.78; 95% CI, 1.43–2.24; p < 0.001). These findings remained consistent across inverse probability of treatment weighting (IPTW) and propensity score matching combined with multivariable generalized linear model (PSM+MVA-GLM) analyses. Conclusions: Although no significant increase in perioperative cerebrovascular adverse events was observed in asymptomatic patients with a preoperative cerebrovascular high-risk status, their worse long-term prognosis appears to be associated with this risk status. This association highlights the need for rigorous cardiovascular and cerebrovascular risk management in this vulnerable population after surgery. Full article

Background: Survival after early breast cancer has improved to the point where reproductive health is no longer a peripheral concern in young survivors but a routine one. This review synthesizes current evidence on oncologic safety, obstetric and neonatal outcomes, fertility preservation, breastfeeding, and psychosocial survivorship to develop a counseling framework that clinicians can apply in practice. Methods: This narrative review was informed by a structured literature search of PubMed/MEDLINE, Embase, and the Cochrane Library covering studies published from January 2000 to July 2026, with greater analytic weight given to studies published from 2010 onward to ensure the synthesis reflects contemporary treatment standards. Relevant evidence was identified and narratively synthesized according to the clinical and reproductive aspects of pregnancy after breast cancer. No formal risk-of-bias assessment or quantitative synthesis was undertaken. Results: On the currently available evidence, pregnancy after breast cancer is not associated with an increased risk of recurrence. This holds in hormone receptor-positive disease and in BRCA1/2 carriers, and it is supported prospectively by the POSITIVE trial, whose preplanned update at a median follow-up of 71 months found a five-year incidence of breast cancer-free interval events of 12.3% against 13.2% in matched external controls. Obstetric and neonatal risks are higher than in the general obstetric population, although the pooled effect sizes are small to moderate: odds ratios are approximately 1.14 for cesarean delivery, 1.45 for preterm birth, 1.50 for low birth weight, and 1.16 for small-for-gestational-age birth. The excess concentrates in pregnancies conceived within the first one to two years after diagnosis and attenuates thereafter. Fertility preservation techniques appear both effective and oncologically safe. Fertility-related distress, by contrast, is common and does not reliably resolve once treatment ends. Conclusions: Oncologic risk alone is not a reason to advise against pregnancy after breast cancer. Early oncofertility referral, multidisciplinary planning, and risk-adapted obstetric surveillance remain the priorities. Because the evidence base is predominantly observational, these conclusions describe what the current data show rather than establishing safety definitively. Full article

Background/Objectives: Pregnancy is associated with profound hormonal, hemodynamic, and metabolic changes that may affect the auditory and vestibular systems. However, evidence regarding pregnancy-related audiological disturbances remains limited due to the low incidence of these conditions and the scarcity of dedicated studies. The study aimed to identify the most commonly reported audiological changes occurring during pregnancy and the postpartum period with an emphasis on sudden sensorineural hearing loss (SSNHL), its risk factors, clinical presentation, and treatment methods. Methods: A literature search was conducted in PubMed, Embase, Web of Science, and Google Scholar from database inception to November 2025 using combinations of the keywords “pregnancy”, “hearing loss”, and “audiological changes”. The review is based on twenty-four original articles that met the preselected criteria. Results: Current evidence does not support pregnancy as an independent risk factor for SSNHL; the prevalence in obstetric patients is lower than in the control groups. Most cases occur during the third trimester or the postpartum period. Pre-pregnancy obesity and elevated blood pressure were identified as potential risk factors. Higher income levels and rural residency are associated with an increased incidence of SSNHL, whereas gestational diabetes, pre-eclampsia, and pregnancy-related weight gain showed no consistent association with SSNHL. Audiometric studies demonstrated mild, predominantly low-frequency, hearing threshold elevations that were generally transient and resolved after delivery. Tinnitus, nausea, aural fullness, dizziness, and vertigo were the most common ear-related complaints. Most of these disorders resolve spontaneously, but some studies suggest steroid treatment should be introduced. Intratympanic corticosteroid therapy was the most frequently investigated treatment for SSNHL and was associated with favorable hearing outcomes in most reported cases. Limited evidence suggests that Dextran 40 may improve hearing outcomes when used as an adjunctive therapy. Conclusions: Potentially transient cochleovestibular impairment during pregnancy and the postpartum period should not be underestimated and requires further evaluation. Pregnancy-related physiological adaptations may contribute to transient auditory and vestibular disturbances, particularly during late pregnancy and the postpartum period. Although current evidence does not indicate an increased risk of SSNHL during pregnancy, prompt recognition and management remain important to prevent long-term hearing impairment. Further high-quality studies are required to clarify the underlying mechanisms and establish evidence-based treatment recommendations for pregnant patients with SSNHL. Full article

Endovascular aortic aneurysm repair (EVAR) has become the first-line treatment for abdominal aortic aneurysms (AAA); however, its long-term durability is affected by Type II endoleak. This narrative review describes the evolution of sac filling techniques and concepts developed to address this complication. In selected cases of diagnosed Type II endoleaks, early therapeutic sac filling, while clinically indicated, is frequently constrained by difficult access, variable success rates, and recurrence. Consequently, prophylactic sac filling during primary EVAR has been adopted as an alternative approach, with reported high technical success and reduced endoleak incidence. The subsequent Nellix Endovascular Aneurysm Sealing (EVAS) system, although early results showed technical feasibility, was associated with graft migration, endobag separation, and reintervention at long-term follow-up, leading to its withdrawal from the market. Currently, devices based on shape memory polymer (SMP) provide early observations of decreased endoleaks and sac regression. This review outlines the transition from reactive management to preventive strategies, and, more recently, to patient-specific, material-based approaches, while showcasing emerging strategies that may influence long-term EVAR outcomes. However, these novel approaches remain under investigation, and larger controlled studies with extended follow-up are required to establish their clinical utility. Full article

Background/Objective: Ovarian hyperstimulation syndrome (OHSS) is a severe complication during controlled ovarian hyperstimulation. Ascites and consecutive hemoconcentration may lead to potentially life-threatening complications like thromboembolic events and the need for intensive care. The use of diuretics is widely used to treat ascites in non-OHSS patients. The aim of this study was to assess whether the use of furosemide in the treatment of OHSS was associated with a higher rate of complications compared to the literature. Methods: In this retrospective cohort study, 502 cases treated from January 2005 to June 2023 for OHSS at the Medical University of Vienna were evaluated regarding the distribution of OHSS severity, average duration of treatment, types and frequency of complications associated with antidiuretic treatment, and predictive factors for paracentesis. Results: The median AMH levels were 5.7 ng/mL. An antagonist protocol was used in 80% of stimulations. Human Chorionic Gonadotropin trigger was used in 80% of stimulations, with 71.7% of cases being early-onset. The incidence dropped from 8.4% (2006 to 2016) to 3.3% (from 2015 to 2023). The median duration of inpatient treatment was seven days, with about 75% of patients receiving furosemide as a diuretic treatment. Ascites drainage was necessary in 27.9%. None of our patients developed a thromboembolic complication following the furosemide treatment. Conclusions: During the study period, the incidence of OHSS declined, most probably as a result of advances in ovarian stimulation protocols and freezing strategies. In moderate to severe OHSS, standardized diuretic treatment with furosemide was not associated with additional thromboembolic complications as long as patients remain normovolemic. Full article

Infective endocarditis (IE) continues to represent a major challenge for global health systems. In 2019, its annual incidence was estimated at 13.8 cases per 100,000 individuals, contributing to approximately 66,300 deaths worldwide. Due to its high morbidity and mortality rates, enhancing preventive measures has become a priority in both clinical practice and ongoing research efforts. Since the publication of the 2015 ESC Guidelines for the management of IE, several pivotal studies have emerged, prompting a re-evaluation and potential update of the existing recommendations. One growing concern is the increasing antibiotic resistance among oral streptococci, particularly to macrolides such as azithromycin and clarithromycin, which now show higher resistance levels than penicillin. Changes in national antibiotic stewardship programs may have inadvertently contributed to a rise in IE incidence, in part due to altered prophylactic practices. At the same time, advances in diagnostic modalities—including more widespread and targeted use of echocardiography in patients with positive blood cultures for organisms like Enterococcus faecalis, Staphylococcus aureus, and various streptococci—have likely improved detection rates. Additionally, innovations in imaging, particularly computed tomography (CT) and nuclear medicine techniques, have enhanced the diagnosis of IE, especially among patients with prosthetic heart valves or implantable cardiac devices. This has allowed for better characterization of patient populations, aiding in the refinement of diagnostic criteria and therapeutic approaches. Furthermore, updated antibiotic treatment protocols, informed by EUCAST’s antimicrobial susceptibility data, have helped tailor antimicrobial regimens to current resistance trends. The combination of improved diagnostic sensitivity and evolving microbial resistance patterns has also led to an increased number of patients being considered for cardiac surgery as part of their treatment pathway. This review seeks to synthesize the latest findings and guideline revisions, offering an integrated overview of recent progress in the diagnosis, medical treatment, and surgical management of infective endocarditis. It will also explore current therapeutic strategies and operative indications in light of the most recent evidence. Full article

Background/Objectives: Comparator selection can change disproportionality findings when multidrug therapies are represented by report-level listings rather than verified treatment histories. We evaluated a proxy-comparator framework for cardiometabolic reporting with long-acting cabotegravir/rilpivirine (CAB/RPV), including sensitivity to comparator definition and reporting context. Methods: We conducted a disproportionality analysis of publicly available individual case safety reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), restricted to study-defined markets and the period from the first quarter of 2022 through the second quarter of 2025. Reports were classified as CAB/RPV, regimen-only (a complete oral regimen listing alone), or regimen-plus (that listing plus other antiretrovirals). Three contrasts assessed 3-point and expanded major adverse cardiovascular events (MACE), diabetes, dyslipidemia, and hypertension using inverse probability weighting and adjusted reporting odds ratios (aRORs). Post-review analyses examined demographic completeness, reporter source, geography, and tenofovir disoproxil fumarate (TDF) inclusion. No binary signal threshold, case-by-case review, or causality adjudication was used. Results: The cohorts comprised 10,082 CAB/RPV, 4434 regimen-plus, and 14,559 regimen-only reports. In the internal oral contrast, regimen-plus showed statistically supported upward disproportionality for 3-point MACE (aROR 1.88, 95% confidence interval 1.44–2.15), expanded MACE (1.88, 1.47–2.40), and dyslipidemia (3.03, 2.39–3.84). CAB/RPV estimates were below 1 versus both proxies, although CAB/RPV versus regimen-plus lacked acceptable balance. Sensitivity analyses changed estimates and diagnostics; TDF inclusion left the CAB/RPV versus regimen-plus dyslipidemia estimate essentially unchanged but altered proxy-comparator findings. Conclusions: Proxy-comparator construction influenced cardiometabolic reporting patterns; reporting-context analyses qualified their interpretation. These hypothesis-generating findings do not establish incidence, clinical risk, causal effects, comparative safety, or a protective effect. Full article

Pneumocystis jirovecii pneumonia (PCP) prophylaxis is established in people with human immunodeficiency virus (HIV), but guidance for non-HIV, non-malignant immunocompromised adults remains fragmented. We searched eight databases and registries through 18 May 2026 (PROSPERO CRD420261396046). Because the evidence did not support a clinically exchangeable network, we evaluated four linked routes: comparative effectiveness, active-regimen safety, trimethoprim-sulfamethoxazole (TMP-SMX) discontinuation burden, and descriptive second-line evidence. Fifty-four full-length peer-reviewed reports were included. The primary effectiveness synthesis comprised 27 studies, 34,473 participants, and 243 PCP events. Compared with no prophylaxis, standard-dose TMP-SMX (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.18–0.48; low certainty) and low-dose TMP-SMX (OR 0.08, 95% CI 0.03–0.18; low certainty) were associated with lower PCP incidence. Lower-intensity TMP-SMX strategies were associated with fewer treatment-limiting discontinuations than standard/conventional-dose TMP-SMX (OR 0.234, 95% CI 0.145–0.377). Across 33 TMP-SMX studies/cohorts, the pooled discontinuation proportion was 12.3% (95% CI 9.4–15.9%). Breakthrough PCP occurred in 0.5% of 1056 second-line recipients. TMP-SMX had the clearest protective association; however, low-dose evidence did not establish superiority or non-inferiority, and second-line data did not permit comparative estimates or regimen ranking. Full article

Enlicitide (MK-0616) is an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for the treatment of hypercholesterolemia. We conducted the first systematic review and meta-analysis evaluating the efficacy and safety of enlicitide across randomized controlled trials enrolling adults with hypercholesterolemia or heterozygous familial hypercholesterolemia (HeFH). The primary outcome was the baseline-to-endpoint percentage change in low-density lipoprotein cholesterol (LDL-C); secondary outcomes included apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein(a) [Lp(a)], and safety. Four randomized controlled trials involving 3894 participants were included. Enlicitide achieved a substantial reduction in LDL-C (mean difference [MD]: −55.78 percentage points; 95% confidence interval [CI]: −61.15 to −50.42; p < 0.0001; I² = 99.58%), with sustained efficacy demonstrated in the newly available 52-week Phase 3 CORALreef data. Significant reductions were also observed in ApoB (MD: −47.95 pp; 95% CI: −51.22 to −44.67), non-HDL-C (MD: −49.42 pp; 95% CI: −54.23 to −44.60), and Lp(a) (MD: −22.70 pp; 95% CI: −28.62 to −16.78). The pooled incidence of any adverse event was not statistically significant (event rate: 0.21; p = 0.087), and treatment discontinuation due to adverse events was uncommon (event rate: 0.007). Enlicitide demonstrated substantial lipid-lowering efficacy with an acceptable safety profile. The ongoing CORALreef Outcomes trial will determine whether these lipid improvements translate into reductions in major adverse cardiovascular events. Full article