Citations

ABSTRACT Objectives Xylitol, a low‐permeability sugar alcohol, is recommended for treating chronic rhinosinusitis (CRS) due to its ability to decrease liquid salt concentration at the airway surface. This study investigated the efficacy of xylitol nasal irrigation for the management of CRS and its postoperative care. Methods We analysed 7 studies with 263 participants after reviewing the studies that were retrieved from PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to December 2024. Those comparing changes in endoscopic score, Sinonasal Outcome Test (SNOT), Nasal Obstruction Symptom Evaluation (NOSE), olfactory dysfunction, and CRS‐related visual analogue scale from baseline to post‐treatment between xylitol and normal saline nasal irrigation groups were analysed. Results Nasal irrigation with xylitol significantly improved sinonasal well‐being in CRS patients compared to irrigation with saline (SMD 0.6253, 95% CI [0.0067; 1.2438]; I 2 = 0.0%). Patients who underwent endoscopic sinus surgery showed substantial SNOT improvement (SMD 3.1284, 95% CI [0.5229; 5.7338]; I 2 = 86.1%), while no significant changes were observed in non‐ESS patients (SMD 0.2571, 95% CI [−0.4872; 1.0014]). The xylitol group also showed significant improvements in NOSE (SMD 0.5976, 95% CI [0.2297; 0.9656]; I 2 = 49.3%) and SNOT scores (SMD 0.3608, 95% CI [0.0724; 0.6493]; I 2 = 49.1%). However, there were no significant changes in endoscopic scoring (SMD 0.1309, 95% CI [−0.1777; 0.4396]; I 2 = 0.0%), olfaction (SMD −0.0292, 95% CI [−0.3633; 0.3050]; I 2 = 0.0%), or saccharine clearance time (SMD 0.3816, 95% CI [−0.3816; 1.1449]; I 2 = 61.6%). Xylitol irrigation was well tolerated, with minimal, transient side effects and no significant adverse events. Conclusion Nasal irrigation with xylitol significantly improves the subjective management of CRS and postoperative care compared to saline irrigation but does not alter objective outcomes.

ABSTRACT Background Treating Mycobacterium avium complex (MAC) infection pre‐lung transplant (LT) can be challenging to treat, given prolonged therapy and side effects. The impact of pre‐transplant MAC treatment on recurrence and outcomes post‐LT remains unclear, especially in patients with interstitial lung disease (ILD) who have a median survival of less than 2 years. Methods We performed a retrospective cohort study of adult LT patients at the Mayo Clinic who had positive MAC sputum cultures pre‐LT. The cohort was stratified and compared based on the type of treatment (complete, partial, or no treatment) for MAC pulmonary infection. The primary outcome was MAC recurrence post‐LT, and secondary outcomes were mortality, FEV‐1, and FVC at 1‐year post‐LT. Results Among the cohort of 47 patients, 9 (19.1%) were partially treated and 11 (23.4%) were completely treated for MAC infection pre‐LT. Post‐transplant MAC pulmonary infection recurrence occurred in eight (17%) of the total cohort, with four (14.8%) in the non‐treated, four (44.4%) in the partially‐treated, and none (0%) in the completely treated patients ( p = 0.026). There was no difference in mortality in patients who had MAC recurrence post‐transplantation (13% vs. 9.7%, p > 0.9) and those who were completely or partially treated, compared to non‐treated (0% vs. 13% vs. 13%, p > 0.9). The FEV1 and FVC at 1‐year post‐LT did not differ by the pre‐transplant treatment or post‐transplant MAC recurrence status. Conclusion The role of treatment for MAC infection pre‐transplant is questionable, especially in patients with diseases like ILD who may not have enough wait time to complete therapy.

BACKGROUND Predictive biomarkers to guide chemotherapy decisions for metastatic castration–resistant prostate cancer (mCRPC) are lacking. Preclinical studies indicate that circulating tumor cell (CTC) studies of chromosomal instability (CTC-CIN) can predict taxane resistance. METHODS The CARD trial randomized individuals with mCRPC progressing within a year of treatment with an androgen receptor pathway inhibitor (ARPI; enzalutamide or abiraterone acetate plus prednisolone/prednisone) to cabazitaxel or the alternative ARPI. As a preplanned biomarker analysis, CTCs were isolated from blood samples obtained at baseline, cycle 2, and the end of treatment. Associations between baseline CTC and CTC-CIN counts with imaging-based progression-free survival (ibPFS), overall survival (OS), time to prostate-specific antigen (PSA) progression, RECIST 1.1 objective response rate (ORR), and PSA 50 response rate were assessed. RESULTS High baseline CTC-CIN counts significantly associated with worse OS after adjustment for confounding variables (median OS, 15.3 vs. 8.9 months; univariate HR, 2.16; 95% CI, 1.52–3.06; P < 0.001; multivariate HR, 1.56; 95% CI, 1.01–2.43; P = 0.047). Detectable CTC-CIN counts at baseline may predict a lack of ibPFS and OS benefit when comparing cabazitaxel with ARPI. CONCLUSION This preplanned analysis of biomarker data from the CARD trial confirms that CTC-CIN counts are a clinically useful prognostic and predictive biomarker of taxane resistance in mCRPC. Detectable CTC-CIN at baseline defines a patient subpopulation with unmet clinical needs in which alternative therapeutics should be tested. TRIAL REGISTRATION ClinicalTrials.gov number NCT02485691. FUNDING Funded by Sanofi and Epic Sciences.

Objective: To determine associations between central adiposity, cognitive function, and randomized menopausal hormone therapy (MHT) in a reanalysis of the Kronos Early Estrogen Prevention Study-Cognitive and Affective (KEEPS-Cog) sub-study participants. Methods: KEEPS randomized 727 women (ages 42-58) who were <36 months postnatural menopause to oral conjugated equine estrogens (o-CEE), transdermal 17-β-estradiol (t-E2), or placebo for 48 months. Participants with diabetes, body mass index >35 kg/m 2 , coronary artery calcium score >50 Agatston Units, and other cardiometabolic disease risk indicators were excluded from enrollment. In the ancillary KEEPS-Cog study, cognitive tests were completed at baseline, 18-, 36-, and 48-month post-randomization. In these analyses, cognitive variables were summarized as four cognitive domain-specific factor scores: verbal learning and memory, auditory attention and working memory, visual attention and executive function, and speeded language and mental flexibility. Waist-hip-ratio (WHR), an indicator of central adiposity, was measured at screening (baseline) and modeled as a covariate in linear latent growth models assessing associations of MHT with cognitive functions at baseline and over time. Results: Higher baseline WHR was associated with poorer performance on all domain-specific cognitive outcomes at baseline and with changes in visual attention and executive function across time. Models including interaction effects were not significant for either o-CEE x WHR or t-E2 x WHR. Conclusion: Central adiposity is a risk factor for domain-specific cognitive decline, and thus, cognitive health effects should be investigated in early postmenopausal women, even in women with low cardiovascular risk statuses.

Background. Assessment tools in surgical education help identify improvement areas for trainees. We developed and present validity evidence for a novel Transplant Operative Assessment Tool to optimize technical feedback for surgical trainees in transplantation. Methods. The Transplant Operative Assessment Tool assesses learners on anatomy, technical skills, judgment, and communication. Performance is rated across 5 competency levels. Content validity evidence included a construct map using existing literature and expert cognitive interviews. Ratings were used to develop an item response theory calibration, which was then used to evaluate the tool and provide validity evidence. Results. Eighty-two assessments for 28 trainees (16 residents, 12 fellows) were completed by 25 faculty surgeons across 4 programs. Fifty-six kidney transplants, 13 liver transplants, and 13 donor nephrectomies were assessed. The mean assessment completion time was 4.1 ± 4.3 min. Internal structure validity was evaluated by calculating item infit (range, 0.86–1.15), indicating a strong model fit and confirming a high quality of items. Internal consistency was also high (Cronbach’s alpha = 0.94). There was a positive correlation between ratings and training level ( P < 0.01), indicating strong discriminatory power. Warm ischemia time for transplant operations did not correlate with performance ( P = 0.16). Conclusions. These data provide validity evidence for a novel operative assessment tool. This instrument can measure performance, monitor progress, document competency, and has the potential to provide valuable feedback.

Background and Aims: With rapid changes in the management landscape of chronic hepatitis B (CHB), this technical systematic review addresses 4 critical Population, Intervention, Comparator, Outcome (PICO) questions to provide guidance to the formulation of recommendations to the 2025 AASLD practice guideline for management of CHB. Approach: The review was reported in accordance with PRISMA guidelines. Outcomes were evaluated across 4 key PICOs: (1) antiviral therapy for prevention of horizontal HBV transmission in high-risk groups, (2) antiviral therapy versus observation for persons in the immune-tolerant phase, (3) discontinuation versus continuation of nucleos(t)ide analogue therapy in HBeAg-negative individuals with undetectable HBV DNA, and (4) hepatocellular carcinoma (HCC) surveillance in non-cirrhotic individuals with HBsAg clearance or co-infections with HCV, HDV, or HIV. Results: For PICO 1, limited evidence suggests antiviral therapy may reduce horizontal transmission risk, though with low certainty. PICO 2 analyses reveal uncertain benefits of treating persons in the immune-tolerant phase, with very low certainty due to heterogeneity and bias. PICO 3 analyses demonstrate that discontinuing antiviral therapy in persons who are HBeAg negative with undetectable HBV DNA increases HBsAg loss rates (OR: 12.65, 95% CI: 1.58–101.51) but carries moderate risks of virologic relapse (OR: 47.17, 95% CI: 2.79–797.35) and clinical flares. PICO 4 analyses on several cohort studies showed that in patients co-infected with HCV, HBV, or HIV, the annual incidence of HCC was higher than the level where screening becomes cost-effective, suggesting that regular liver cancer screening could be beneficial for these patients. Conclusions: Despite low certainty, the findings support shared decision-making in high-risk horizontal transmission scenarios or in treating individuals in the immune tolerance phase, caution in discontinuing antiviral therapy in virologically suppressed individuals without HBsAg loss, and tailored HCC surveillance for those with co-infection or cirrhosis.

Background and Aims: Accumulating data related to prevention, surveillance and treatment of chronic hepatitis B (CHB) provided the impetus for this updated guideline, using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Methods: The guideline was developed in compliance with the National Academy of Medicine standards. The guideline panel developed structured questions following the Population, Intervention Comparison, Outcomes (PICO) framework. The panel addressed 6 PICO questions covering prevention (maternal to infant transmission and horizontal transmission), surveillance for liver cancer (among hepatitis B surface antigen positive (HBsAg) persons co-infected with hepatitis C virus, hepatitis D virus and/or human immunodeficiency viruses and after HBsAg loss) and treatment (HBsAg positive persons in immune-tolerant or indeterminate phases as well as withdrawal of antiviral therapy), providing evidence-based recommendations on these topics. Four systematic reviews of the literature were conducted, and two existing systematic reviews were utilized to support the recommendations in this practice guideline. Conclusions: This evidence-based guideline provides updated recommendations to optimize the care of persons with CHB.

Aims Native vertebral osteomyelitis (NVO) and infective endocarditis (IE) are increasingly seen as interconnected conditions, sharing similar risk factors — such as advanced age and immunosuppression — and overlapping microbial profiles, notably Staphylococcus aureus and streptococci. When these infections occur together, they present distinct challenges in diagnosis and treatment, which can obscure clear outcomes and mortality estimates. Therefore, we aimed to systematically assess the combined mortality associated with concurrent NVO and IE and to detail the clinical characteristics of affected patients. Methods We conducted a systematic review following the PRISMA framework, searching MEDLINE, Embase, the Cochrane Library, and Scopus for relevant studies published between 1970 and October 2023. Studies included were those reporting mortality outcomes for at least ten adult patients with both NVO and IE. Two independent reviewers screened the literature, extracted data, and evaluated study quality using a modified Newcastle-Ottawa Scale. We then performed a random-effects meta-analysis to pool in-hospital, 1-month, 1-year, and 3-year mortality rates. Results A total of 16 studies (12 retrospective, 3 prospective, and 1 mixed design) involving 641 patients (mean age 67.1 years) with concomitant NVO and IE were included. The pooled in-hospital mortality rate was 10.0% (95% CI: 5.2–14.7%), with mortality rates of 5.6% (95% CI: 2.2–9.0%) at 1 month, 12.1% (95% CI: 5.3–18.8%) at 1 year, and 14.5% (95% CI: 4.3–24.8%) at 3 years. There was significant heterogeneity among studies (I² ranging from 46% to 86%). Common comorbidities included diabetes (24.6%), renal failure (17.3%), and immunosuppression (11.1%). The predominant pathogens identified were streptococci (31.3%), S. aureus (27.3%), and enterococci (13.7%). Approximately 40.6% of patients underwent surgical intervention, though its effect on mortality remains inconclusive. Overall, the certainty of the estimates was limited by imprecision and impossibility of perform subgroup analysis. Conclusion The coexistence of NVO and IE is associated with significant mortality, emphasizing the need for earlier diagnosis, coordinated multidisciplinary management, and standardized treatment protocols. Future prospective, high-quality studies are crucial to determine optimal diagnostic and surgical strategies for managing this complex clinical scenario.