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PURPOSE Low-grade serous carcinoma (LGSOC) of the ovary, fallopian tube, or peritoneum is a hormonally driven, relatively chemoresistant malignancy with limited treatment options in the recurrent setting. Given frequent estrogen receptor (ER) expression and dysregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6)–p16–Rb pathway, features shared with hormone receptor–positive breast cancer, dual endocrine, and CDK4/6 inhibition is a biologically rational strategy. This phase II trial evaluated ribociclib plus letrozole in recurrent LGSOC. METHODS This open-label, single-arm, multicenter phase II study enrolled women with measurable, recurrent LGSOC. Patients received ribociclib (600 mg orally, once daily, days 1-21 of a 28-day cycle) and letrozole (2.5 mg orally, once daily). The primary end point was investigator-assessed objective response rate (ORR) per RECIST 1.1. Secondary end points included clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS Of 74 patients screened, 51 were enrolled and 49 treated. The confirmed ORR was 30.6% (90% CI, 19.9 to 43.2), including one complete and 14 partial responses. Among responders, the median duration of response was 21.2 months. The CBR was 84% (90% CI, 72.5 to 91.6). The median PFS was 14.5 months (90% CI, 10.1 to 28.8), and the median OS was 44.5 months (90% CI, 31.8 to not reached). The most common grade ≥3 adverse event (AE) was neutropenia (47%), managed with dose modifications. Three grade 5 events (6%) occurred but were unrelated to treatment. Treatment discontinuation because of AEs occurred in 4%. No dose-limiting toxicities were observed. CONCLUSION Ribociclib plus letrozole met the primary end point, achieving meaningful response rates and durable disease control in recurrent LGSOC. The safety profile was consistent with prior CDK4/6 inhibitor studies. This combination represents a therapeutic option in this rare and genomically distinct subtype.

Abstract The benefit of rituximab maintenance after first-line (1L) bendamustine-rituximab (BR) in patients with mantle cell lymphoma (MCL) remains uncertain, with inconsistent results from the phase 2 MAINTAIN trial and several retrospective studies. We conducted a large retrospective study at 27 US and Canadian academic centers to examine the benefit of rituximab maintenance after BR. A total of 911 patients received 1L BR between 2010 and 2020, and 703 had an objective response and no evidence of disease progression at the 3-month post-BR landmark. Among those, 394 (56%) received rituximab maintenance and 309 (44%) did not, with largely similar baseline patient and disease characteristics. In the landmark analysis, rituximab maintenance was associated with improved event-free survival (EFS; median, 49.9 vs 29.7 months; P< .001) as well as overall survival (OS; median, 109.5 vs 74.2 months; P< .001). The EFS and OS benefits were observed across most of the subgroups. EFS and OS differences were statistically significant in those who achieved a complete response to 1L BR (n = 590; median EFS, 62.7 vs 31.1 months [P< .001]; median OS, 136.1 vs 75.3 months [P< .001]), but the analysis among those who achieved a partial response to 1L BR was limited by the small sample size. These results provide additional evidence for the survival benefit of rituximab maintenance after BR in MCL and support its use in clinical trial design and routine practice.

This cohort study evaluates the use of definitive rhinectomy and adjuvant radiotherapy with or without chemotherapy for patients who declined rhinectomy or had unresectable disease.

Abstract Background These recommendations provide guidance on the optimal timing for transitioning from intravenous to oral antibiotics in patients with complicated urinary tract infection (cUTI), especially in presence of associated Gram-negative bacteremia. Methods The panel's recommendations are based upon evidence derived from systematic literature reviews which focused on comparative benefits and harms of transitioning to oral therapy versus continuing parenteral therapy of the total duration of treatment, including publications since 2000. These recommendations adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Results The guidelines panel suggests transitioning to oral antibiotics in patients with cUTI who are clinically improving, able to take medication, and for whom an effective oral option is available, rather than continuing parenteral therapy for the remaining treatment duration, regardless of the presence of associated Gram-negative bacteremia. An effective oral option needs to be active against the causative pathogen and achieve therapeutic levels in the urine and relevant tissue. Conclusions Parenteral and oral antibiotics used to complete treatment courses for cUTI provide similar efficacy and adverse events, especially in the context of shorter duration of therapy. This recommendation places a high value on reducing avoidable intravenous catheter-related adverse events, costs, and resources, as well as taking into account practical aspects of antibiotic administration.

Abstract Background These recommendations provide guidance on the optimal duration of antibiotics in patients with complicated urinary tract infection (cUTI), especially in presence of associated Gram-negative bacteremia. Methods The panel's recommendations are based upon evidence derived from systematic literature reviews which focused on comparative benefits and harms of shorter (5–7 days) vs prolonged (10–14 days) duration of antibiotics, including publications since 2000. These recommendations adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Results The guidelines panel suggests that patients with cUTI who are improving on effective therapy can be treated with shorter duration of antimicrobials (either 5–7 days of a fluoroquinolone or 7 days of a non-fluoroquinolone) rather than longer courses of antibiotics, regardless of the presence of associated Gram-negative bacteremia. An effective antimicrobial agent achieves therapeutic levels in the urine and relevant tissue and is active against the causative pathogen. However, men with febrile UTI in whom acute bacterial prostatitis is suspected may benefit from a longer treatment duration (10–14 days), and a short courses of oral beta lactams may require higher doses for efficacy. Conclusions Shorter durations of antibiotics for cUTI provide similar efficacy as longer courses, except in men with febrile UTI in whom acute bacterial prostatitis is suspected. This recommendation places a high value on antibiotic stewardship considerations as well as reducing the burden of antimicrobial administration from a healthcare perspective and reducing the burden of taking antibiotics from a patient perspective.

Abstract Background These recommendations address the empiric choice of antibiotics in suspected complicated urinary tract infection (cUTI). Issues to balance include the need for appropriate initial empiric antimicrobial therapy, the patient's severity of illness, and antimicrobial stewardship concerns. Methods The panel's recommendations are based upon evidence derived from systematic literature reviews that focused on comparative benefits and harms of classes of antibiotics approved for cUTI, starting with publications from 2008 onwards, and our review of predictors of resistance in uropathogens included references identified since 2000. These recommendations adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Results The guidelines panel suggests initially selecting among preferred empiric antibiotic choices rather than alternative options, stratified for the patient's severity of illness and antimicrobial stewardship considerations. When choosing among these antibiotics for a specific patient, the guideline panel suggests a 4-step process to account for changing resistance patterns and individualized patient needs. The steps are: (1) assess the severity of illness (for initial prioritization of antibiotics), (2) consider patient-specific risk factors for resistant uropathogens (for optimization of coverage), (3) evaluate other patient-specific considerations (to reduce the risk of adverse events), and (4) for patients with sepsis, consult a relevant local antibiogram if available (to further improve the likelihood of giving appropriate empiric therapy). Lastly, the guideline panel suggests selecting definitive effective therapy with a targeted spectrum based on the result of the urine culture. Conclusions Many of the classes of antibiotics approved to treat cUTI demonstrate similar efficacy as other classes of antibiotics in randomized controlled trials. Bacterial resistance prevalence is always changing, and new antibiotics will be developed. In this context, the guidelines panel provides recommendations for choosing empiric antibiotic therapy for cUTI that will help clinicians decide among available antibiotic options at the point of care.

Background: The use of spinal cord stimulation (SCS) for managing severe refractory chronic pain has expanded considerably due to positive statistical evidence regarding its use; however, the statistical robustness of the underlying randomized controlled trials (RCTs) requires further scrutiny. One such tool that can be used for this purpose is the fragility index, which quantifies how many individual outcome events must be altered for an outcome to lose statistical significance. Thus the index can be used quantitatively to assess the stability and robustness of an RCT’s conclusions, with higher values indicating increased trial stability. This study assesses the fragility of pain outcomes across RCTs investigating SCS for chronic pain to better understand the quality and robustness of evidence. Methods: A systematic search was conducted for RCTs assessing SCS for any chronic pain indication. The primary outcome was an evaluation of the trial-specific fragility index for the prespecified pain primary outcomes of RCTs. Secondary outcomes included an evaluation of fragility for (1) specified indications for SCS therapy, (2) reported pain outcomes appearing in three or more RCTs, (3) the presence/absence of a conflict of interest, and (4) comparisons of SCS to conservative management or different SCS waveform modalities. Results: A total of 30 RCTs were included. The median (interquartile range [IQR]) fragility index across the primary outcome of all trials was 5.45 (3.00 to 11.45). There was no statistical difference between the (1) types of outcomes (dichotomous vs. continuous; P = 0.710), (2) primary versus secondary pain outcomes ( P = 0.771), or (3) presence versus absence of trial conflict of interest ( P = 0.753). Indications with a median (IQR) fragility score greater than three included persistent spinal pain syndrome type 2 with a score of 8.00 (2.80 to 12.60), painful diabetic neuropathy with a score of 6.00 (3.00 to 11.80), complex regional pain syndrome with a score of 7.20 (4.62 to 81.50), mixed etiologies with a score of 9.00 (3.00 to 38.00), and other etiologies with a score of 3.00 (1.00 to 8.55). Conclusions: This study suggests that the majority of RCTs investigating primary pain outcomes after SCS therapy are robust with relatively high fragility scores. Reporting the fragility of outcomes in trials can provide a more comprehensive assessment of trial robustness and can further aid clinicians in interpreting trial results and making informed treatment decisions.

Abstract Objectives The aim of this work was to develop an American Headache Society position statement addressing diagnostic screening for migraine among girls and women. Background Despite its high prevalence and substantial negative impacts, migraine is underdiagnosed and undertreated. Diagnostic screening for migraine enables more patients to receive timely, appropriate, and effective management. Methods Development of this position statement followed the rules established by the American Headache Society Guidelines Committee. The published literature was reviewed to determine if migraine meets criteria for when disease screening is justified, to guide recommendations for screening tools, and to determine subpopulation(s) for which migraine screening is indicated. After author consensus was reached, the position statement was reviewed and approved by the American Headache Society Board of Directors. Results Migraine fulfills established criteria for conditions in which screening is appropriate since it is highly prevalent, results in significant morbidity, and exerts substantial economic and social costs. Migraine incidence and prevalence are exceptionally high among girls and women during adolescence and through menopause. Furthermore, there are valid and reliable diagnostic screening methods (e.g., ID Migraine) and effective treatments that reduce migraine symptoms and disease impact. Conclusion Yearly diagnostic screening for migraine should be included as part of women's preventive healthcare services, particularly from adolescence to menopause.