Citations

Key Points Serum glycerol-3-phosphate (G3P) levels were significantly associated with higher fibroblast growth factor 23 levels in ESKD. Pathway and mediation analyses identified the pentose phosphate pathway as the top mediator of the relationship between serum G3P and fibroblast growth factor 23. The role of G3P in ESKD provides new insights into potential therapeutic targets for CKD-mineral and bone disorder. Background Fibroblast growth factor 23 (FGF23) is a key regulator of mineral metabolism that is independently associated with mortality in patients with ESKD. Glycerol-3-phosphate (G3P), a byproduct of glycolysis that can be derived from injured kidneys, stimulates FGF23 production. We aimed to determine if serum G3P is associated with FGF23 levels in patients with ESKD and identify potential molecular pathways that mediate their relationship. Methods We conducted a cross-sectional study of 99 nondiabetic patients with ESKD on hemodialysis. We used linear regression to examine the association between G3P terciles and log-transformed C-terminal FGF23 levels, adjusting for demographics, coronary artery disease, serum calcium, phosphorus, and parathyroid hormone. Mann–Whitney U tests compared 247 serum metabolite levels between the first and third FGF23 terciles; significant metabolites ( P < 0.01) were selected for pathway enrichment analyses. Top pathway scores were used in mediation analyses. Results The median age of participants was 54 years (interquartile range [IQR], 44–63), 38% were women, 71% self-identified as Black, and 27% had coronary artery disease. The median FGF23 level was 777 (interquartile range, 222–1310) RU/ml. In adjusted analyses, compared with participants with the lowest G3P tercile, those with the highest G3P tercile had a 95% higher FGF23 level (95% Confidence Interval, 6% to 260%; P = 0.04). Of the 27 metabolites significantly associated with FGF23 levels, pathway enrichment analysis identified the pentose phosphate pathway as the top hit (impact score=0.33, false discovery rate-adjusted P value = 0.01). The pentose phosphate pathway mediated the relationship between G3P and FGF23, resulting in a 62% change in the β coefficient. Conclusions In nondiabetic patients with ESKD on hemodialysis, serum G3P positively correlated with serum C-terminal FGF23, and this relationship was mediated by the pentose phosphate pathway. Exploring the pentose phosphate pathway could yield critical mechanistic insights into the regulation of FGF23, enhancing our understanding of its broader biologic functions.

Objective: To compare postoperative complications between staged versus unstaged tympanoplasty and subtotal petrosectomy (STP) in adults undergoing cochlear implants with noncholesteatoma chronic otitis media (NCCOM) and tympanic membrane perforation. Databases reviewed: PubMed/MEDLINE, Cochrane CENTRAL, Embase, CINAHL, Web of Science, WHO Global Index Medicus, ClinicalTrials.gov, and WHO ICTRP. Materials and methods: A systematic search of databases was conducted by a research librarian from inception through November 18, 2024. Eligible studies for inclusion must have reported on adult cochlear implant recipients undergoing surgical management of NCCOM with perforation. Using a random effects model, complication rates were pooled and compared between staged and unstaged surgeries using relative risk (RR) with 95% CI. Results: Of 1265 studies identified, 19 met inclusion criteria (n = 84). Fifty three (63.1%) patients underwent unstaged surgery. Amongst all patients, STP was performed more than tympanoplasty (72.6%, 61/84 vs 27.4%, 23/84), and the overall complication rate was 11.9% (10/84). There was no significant difference in complication rates between combined staged and unstaged surgeries [RR: 1.13 (95% CI, 0.18-7.04)] as well staged and unstaged tympanoplasty [RR: 0.34 (95% CI, 0.11-0.1.01)]. However, complication rates were lower for staged than unstaged STP [RR: 0 (95% CI, 0.0-0.07)]. Conclusion: Staged and unstaged surgery for NCCOM and cochlear implant may result in comparable complication rates, however the wide CIs for RR statistics in comparisons between combined staged and unstaged procedures as well as staged and unstaged tympanoplasty indicate a need for similar studies of larger populations.

ABSTRACT Light chain multiple myeloma (LCMM) is a subtype of multiple myeloma (MM) characterized by the exclusive production of immunoglobulin light chains and accounts for 15%–20% of newly diagnosed MM. A comprehensive comparison of LCMM with MM producing intact immunoglobulin (non‐LCMM) remains limited. In this retrospective study, we described distinct clinical and cytogenetic features and assessed long‐term outcomes in 852 LCMM patients diagnosed between 01/01/2004 and 12/31/2022, compared with non‐LCMM controls matched for age, sex, and year of diagnosis. On univariable analysis, LCMM patients were more likely to present with elevated creatinine (> 2 mg/dL), beta‐2‐microglobulin ≥ 5.5 mg/L, elevated LDH, hypercalcemia, t(11;14), del(13q), and t(6;14). Conversely, IMS‐IMWG high‐risk disease, hyperdiploidy, t(4;14), and serum albumin < 3.5 g/dL were less common. On multivariable analysis, elevated creatinine (OR: 5.1, 95% CI: 1.2–27, p = 0.04), t(11;14) (OR: 2.6, 95% CI: 1.3–5.2, p = 0.006), and del(13q) (OR: 4.1, 95% CI: 2.1–8.2, p < 0.001) were independently associated with LCMM, while IMS‐IMWG high‐risk disease (OR: 0.3, 95% CI: 0.1–0.8, p = 0.02) and hyperdiploidy (OR: 0.3, 95% CI: 0.1–0.7, p = 0.002) were less frequent. Despite these differences, progression‐free survival with frontline treatment (HR: 0.97, 95% CI: 0.84–1.11, p = 0.63) and overall survival (HR: 0.99, 95% CI: 0.87–1.13, p = 0.94) were similar between LCMM and non‐LCMM patients. This study highlights the distinct clinical and cytogenetic features of LCMM, marked by higher rates of renal failure, t(11;14), and del(13q), lower prevalence of IMS‐IMWG high‐risk disease, and comparable survival outcomes.

Objective: To estimate the relative risk of meningitis after repair of spontaneous lateral skull base cerebrospinal fluid (CSF) leaks through meta-analysis of published studies. Databases Reviewed: PubMed, Medline, Embase, Cochrane, SCI-EXPANDED, ESCI, Epistemonikos, and WHO Global Index Medicus were queried for terms including and related to meningitis, CSF leak, surgery, and spontaneous from inception to April 02, 2024. Methods: Prospective and retrospective studies in any language reporting either preoperative or postoperative rates of meningitis in adults with spontaneous lateral skull base CSF leaks were included. Two reviewers independently screened 2,564 studies and extracted data and evaluated risk of bias in 57 studies that met inclusion criteria. A random effects generalized linear mixed model was used to pool and compare logit transformed risk of meningitis before and after repair. Results: Of 1,310 patients who met inclusion criteria, 1,239 underwent CSF leak repair. Fifty-two studies reported rates of preoperative meningitis, and 27 studies reported rates of postoperative meningitis. Twenty-two studies with a total of 511 patients reported both rates. The average follow-up period of 17 studies reporting duration of follow-up was 23.1 months. The preoperative pooled risk of meningitis was 0.16 (95% CI: 0.13–0.25, I 2 = 40.57%). The postoperative pooled risk was considerably lower at 0.01 (95% CI: 0.01–0.14, I 2 = 4.16%). With substantial heterogeneity (I 2 = 62.94%), we observed a relative risk of meningitis after repair of 0.02 (95% CI: 0.00–0.79, p = 0.04). Conclusion: Surgical repair of spontaneous lateral skull base CSF leaks may significantly reduce the risk of adult meningitis.

Objective: Assess the impact of adult cochlear implantation on the disability and quality of life (QOL) of communication partners (CP) of cochlear implant (CI) recipients. Databases reviewed: PubMed, MEDLINE, Embase, Cochrane CENTRAL, Science Citation Index Expanded, and Emerging Sources Citation Index were searched. Methods: This study was reported following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Articles included reported on disability or QOL measures of CP of adult CI recipients. Study selection included retrospective, prospective, and randomized controlled studies in English language. Three reviewers independently screened studies for inclusion, extracted data, and evaluated risk of bias. Outcomes included both qualitative and quantitative pre-CI and post-CI measures of CP disability or QOL. Results: Of 1615 screened articles, 9 studies utilizing quantitative and qualitative measures with 504 CP met inclusion criteria. Four of 6 studies assessing only post-CI CP QOL, demonstrated self-reported improvement, while one demonstrated worse CP QOL compared with the general population and one identified CP and CI recipient qualities that correlated with CP QOL scores. Two studies assessing pre-CI to post-CI CP QOL also reported improvements. One study assessing only pre-CI CP QOL suggested that CPs had worse QOL than normal hearing controls. Duration of CI recipient hearing loss did not impact CP QOL in any study. Conclusions: Though homogenous data on the QOL of CPs of CI recipients and the relationship between CI recipient and CP factors is limited, studies suggest that CPs of CI recipients may have worse QOL than the general population but, cochlear implantation may improve CP QOL.

Purpose Genitourinary syndrome of menopause (GSM) describes the symptoms and physical changes that result from declining estrogen and androgen concentrations in the genitourinary tract during the menopausal transition. This guideline provides information to clinicians regarding identification, diagnosis, counseling, and treatment for patients with GSM to optimize symptom control and quality of life while minimizing adverse events. Methods The systematic review used in the creation of this guideline is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality and funded by the Patient Centered Outcomes Research Institute. The EPC synthesized effectiveness and/or harms outcomes from 68 publications. An additional 66 articles evaluating 46 nonhormonal interventions were described in an evidence map. Results Clinicians diagnose GSM based on symptoms, with or without related physical findings, and after ruling out other etiologies or co-occurring pathologies. There is a large body of evidence examining the use of hormonal and nonhormonal treatment options to manage the symptoms of GSM; however, the local low-dose vaginal estrogen has the most robust evidence base. Conclusion The strategies defined in this document were derived from evidence-based and consensus-based processes. Given that there is insufficient information to recommend one hormonal therapy over another, this guideline is not meant to support a stepwise progression through different hormonal approaches. The clinician should make treatment decisions in the context of shared decision-making, considering patient goals and preferences, using the evidence of efficacy and adverse events of each possible intervention as a guide.

Abstract Synchronous squamous cell carcinoma (SCC) and chronic lymphocytic leukemia (CLL) in the parotid gland is rare, with limited evidence on personalized treatment. We report a 75-year-old male with prior cutaneous SCC who presented with a hypermetabolic parotid mass and cervical lymphadenopathy; fine needle aspiration confirmed SCC. Surgery revealed poorly differentiated SCC and CLL in multiple lymph nodes. He underwent radiotherapy but developed regional SCC relapse without systemic CLL symptoms. Recurrence in the ear required extensive surgical resection and reconstruction. Genetic profiling showed high tumor mutational burden (&gt;50 mutations/Mb) and mutations in ARID1B, CDKN2A, MSH2, PMS2, and TP53. He received six cycles of cemiplimab followed by cetuximab-based targeted therapy, based on rising circulating DNA levels. This case emphasizes the value of genetic profiling and tools like TMB, FISH, and immunohistochemistry for risk stratification and personalized treatment in managing advanced or complex parotid malignancies, including synchronous SCC and CLL, to optimize patient outcomes.