2 Minute Medicine Rewind October 5th, 2026
Gepotidacin and Early Symptom Improvement in Uncomplicated Urinary Tract Infection
1. Gepotidacin leads to rapid clinical response in female patients with uncomplicated urinary tract infections (UTIs) and is generally well-tolerated.
Evidence Rating Level: 2 (Good)
uUTIs are exceedingly common in women, with an incidence of 50% to 60%, and severely disrupt patients’ lives due to physical and mental burden. While antibiotic treatment is typically empiric, up to 17% of patients with uUTIs experience treatment failure. As antimicrobial resistance rises, so does the need for novel antibiotic agents. Gepotidacin is a novel, first-in-class triazaacenaphthylene oral antibacterial that inhibits bacterial DNA replication. While it has been approved in some countries for the treatment of uUTIs in specific populations, it is unclear how quickly patients experience improvement with gepotidacin. This phase 3b, open-label, single-arm, multicenter nonrandomized clinical trial included nonpregnant female patients 12 years or older with a body weight of 40 kg or more who presented with 2 or more clinical symptoms of uUTI (dysuria, frequency, urgency, or lower abdominal or suprapubic pain) and had evidence of urinary nitrites or pyuria. 97 patients (mean age [SD], 45.7 [16.4] years) received oral gepotidacin (1500 mg) twice daily for 5 days, and 90 patients (mean age [SD], 46.1 [16.4] years) were clinically evaluable. The clinical symptom score (CSS; range, 0-12), a composite of each uUTI symptom scored from 0-3 (higher = more severe), was assessed at 7 time points (0 hours, 24 hours, 48 hours, 72 hours, 96 hours, day 10, day 28). At 24 hours, 49 participants (54.4%; 95% CI, 43.6%-65.0%) in the clinically evaluable population had clinical symptom improvement. The number of participants with clinical symptom improvement at 48, 72, and 96 hours was 71 of 89 (79.8%; 95% CI, 69.9%-87.6%), 81 of 90 (90.0%; 95% CI, 81.9%-95.3%), and 77 of 89 (86.5%; 95% CI, 77.6%-92.8%), respectively. Clinical symptom resolution was 3 of 90 participants (3.3%) at 24 hours, 48 of 89 participants (53.9%) at 96 hours, and 81 of 90 (90.0%) at day 10. No participants required an additional nonstudy antimicrobial up to day 10. 58 adverse events (AEs) were experienced by 27 of the 97 participants (28%), with the most common being diarrhea (16 [16%]), flatulence (6 [6%]), dizziness (5 [5%]), abdominal pain (4 [4%]), headache (3 [3%]), abdominal discomfort (2 [2%]), and nausea (2 [2%]). There were no severe AEs, and three participants experienced drug-related AEs leading to study drug discontinuation.
1. A single course of 3 Gy low-dose radiotherapy (LDRT) significantly improved short-term responder rate in patients with knee osteoarthritis (OA) compared to sham radiation, while a single course of 0.3 Gy LDRT did not.
Evidence Rating Level: 1 (Excellent)
OA is an increasingly prevalent degenerative disorder that most frequently affects the knee. Although it is a leading cause of global disability and escalating healthcare costs, there is a notable treatment gap between conservative therapies and joint replacement surgery. LDRT is a non-invasive alternative for pain reduction that works through anti-inflammatory mechanisms such as polarizing macrophages towards an anti-inflammatory phenotype, modulating regulatory T cells, and reducing the production of reactive oxygen species, nitric oxide, and pro-inflammatory cytokines. While data show the overall absolute risk for radiation-induced solid tumors is low, apprehension regarding secondary malignancies remains a barrier to wider adoption. This study focused on dose optimization and implementation of a single-course LDRT strategy. This is a multicenter, single-blind, sham-controlled, randomized trial that included participants aged 50-85 years with a diagnosis of primary knee OA, a baseline walking visual analog scale (VAS) pain score between 50 and 90 mm at the time of screening, and a willingness to discontinue all current analgesic medications, except for prescribed rescue medication. 114 participants were randomized to sham RT (n = 39; mean [SD] age, 67.6 [6.7] years; 71.8% female), total 0.3 Gy LDRT (n = 37; mean [SD] age, 69.4 [7.3] years; 78.4% female), and total 3 Gy LDRT (n = 38; mean [SD] age, 67.3 [6.9] years; 76.3% female). Treatments were delivered in six fractions (two fractions per week) to the most symptomatic knee. The primary endpoint was the Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responder rate at 4 months after LDRT. At 4 months, the 0.3 Gy group responder rate did not differ significantly from sham (58.3% vs. 41.7%; p=0.168). The 3 Gy group had a significantly higher responder rate at 4 months (70.3% vs. 41.7%; p=0.021) and 8 months (76.5% vs. 45.5%; p = 0.013), but not at 12 months (66.7% vs. 50.0%; p > 0.05). There were no significant changes between groups in Western Ontario and McMaster Universities Osteoarthritis Index subscales, Patient Global Assessment, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), and MRI-based parameters. No treatment toxicities or local reactions were reported.
Sex Differences in Mortality Among Patients With Hepatocellular Carcinoma
1. In patients with hepatocellular carcinoma, male sex was associated with significantly higher mortality compared to female sex, but the relationship was heterogeneous across liver disease etiologies.
Evidence Rating Level: 2 (Good)
Liver cancer is the sixth most common cancer, with HCC accounting for 75-90% of cases. There is an abundance of research that demonstrates males have a disproportionate incidence of HCC compared with females. However, there is limited data on the association of sex with HCC mortality. Some studies have found female sex to be independently associated with lower mortality, whereas other studies have found no association. This retrospective cohort study included patients aged 18 years or older with HCC between January 1, 2000, and December 31, 2023 across 17 centers from Japan, South Korea, Spain, Taiwan, and the US. Primary study outcomes were the incidence of overall, liver-related, and non-liver-related mortality. Of the initial cohort of 10 178 patients, 8594 (mean [SD] age, 63.3 [10.9] years; 27.7% female) were included. There were 5644 Asian [65.7%], 458 Black [5.3%], 615 Hispanic [7.2%], and 1784 White [20.8%]. In the full cohort, male sex was associated with increased overall mortality (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.05-1.23]; P = .002). This association remained in subgroup analysis, with males having increased overall mortality in Asian (aHR, 1.22 [95% CI, 1.10-1.36]; P < .001), cirrhosis (aHR, 1.18 [95% CI, 1.08-1.29]; P < .001), and viral (aHR, 1.15 [95% CI, 1.05-1.26]; P = .004) subgroups. Additionally, males had significantly higher aHR in liver disease caused by alcohol (aHR, 1.90 [95% CI, 1.02-3.54]; P = .04), hepatitis B (aHR, 1.22 [95% CI, 1.01-1.47]; P = .04), and hepatitis C (aHR, 1.13 [95% CI, 1.02-1.26]; P = .03), but not in metabolic dysfunction–associated steatotic liver disease.
1. In adults with migraines unsuitable for triptans, rimegepant can provide rapid-onset and lasting symptom relief.
Evidence Rating Level: 1 (Excellent)
While triptans are a cornerstone of the acute treatment of migraine, there are numerous instances when their use is unsuitable, for example, when there is inadequate response, intolerability, or a contraindication. Calcitonin gene-related peptide receptor antagonists have been shown to be efficacious and safe in acute migraine management, with a recently randomized, placebo-controlled trial (NCT05509400) showing rimegepant to have significantly increased migraine pain relief. However, the full time course of rimegepant’s effect is unknown but important to establish, as quick onset of effect is commonly preferred by patients with migraine. The objective of the present study was to evaluate the full time course of rimegepant effect from 15 min to 48 hours post-dose based on data from NCT05509400. NCT05509400 was a phase 4, multinational, randomized, double-blind, placebo-controlled study that included adults 18 years and older with ≥ 1-year history of migraine attacks, migraine attacks lasting an average of 4–72 h if untreated, an average of 4–14 migraine days per month, and unsuitable for triptan use (intolerance (30.5%) and/or lack of efficacy (84.9%) to at least 2 triptans or the documented presence of a contraindication (9.1%)). 570 participants were randomized to rimegepant 75 mg (n = 286; mean [SD] age, 43.1 [11.8] years; 88.5% female) one dose or placebo (n = 284; mean [SD] age, 42.6 [11.5] years; 90.1% female). Participants recorded migraine headache pain intensity prior to dosing and at 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, and 48 h post-dose. Improvements of ≥ 5% for rimegepant over placebo with p ≤ 0.05 [difference (95% CI)] were first observed at 1 h for pain relief [8.6% (1.3%, 15.8%); p = 0.0201], and 1.5 h for pain freedom [6.2% (1.5%, 11.0%); p = 0.0103] and return to normal function [7.1% (1.1%, 13.1%); p = 0.0210]. Rimegepant significantly improved pain relief, pain freedom, and return to normal function at all subsequent time points, with significance remaining at 48 hours. These results suggest that in patients with migraines unsuitable for triptans, rimegepant can provide symptom relief within 1-2 hours that remains for up to 48 hours.
1. In adult patients undergoing sleeve gastrectomy, dexmedetomidine offers a similar analgesic effect compared to remifentanil while significantly reducing the incidence of postoperative nausea and vomiting and intraoperative bradycardia.
Evidence Rating Level: 1 (Excellent)
Bariatric surgery is an established and effective therapeutic option for patients with obesity refractory to lifestyle modification and pharmacotherapy. As the incidence of bariatric surgery rises, it is essential to optimize perioperative analgesia. Although remifentanil is widely used because of its rapid offset and potent analgesic properties, it is associated with opioid-induced hyperalgesia and an increased incidence of PONV. Dexmedetomidine is a α₂-adrenergic agonist that provides analgesic effects without respiratory depression. However, few studies have compared remifentanil and dexmedetomidine in head-to-head trials. This prospective, parallel-group, double-blind randomized controlled trial included patients aged 18-60 years with body mass index (BMI) ≥ 35 kg/m2 and scheduled for a primary laparoscopic sleeve gastrectomy. 98 patients were randomized to the dexmedetomidine (n = 45; mean [SD] age, 40.5 [8.8] years; 51.1% female) or remifentanil (n = 42; mean [SD] age, 41.6 [7.5] years; 66.7% female) groups. Patients in the dexmedetomidine group received an intravenous loading dose of 1μ g/kg (IBW) administered as a slow infusion over 10 minutes prior to surgery, followed by a continuous maintenance infusion at 0.5 μ g/kg/h until the end of the procedure. Patients in the remifentanil group received a continuous intravenous infusion at 0.25 μ g/kg/min until the end of the procedure. There were no significant differences in postoperative visual acuity scale scores at 2, 6, 12, and 24 hours post-surgery. The incidences of PONV (26.8% vs. 58.3%; p = 0.005) and intraoperative bradycardia (4.4% vs. 19.0% ; p = 0.031) were significantly lower in the dexmedetomidine group compared to the remifentanil group. There were no significant differences in the incidences of intraoperative hypotension and duration of post-anesthesia care unit stay.
Image: PD
©2026 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.
