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2 Minute Medicine Rewind January 12th, 2026
Ethosuximide and Irritable Bowel Syndrome–Related Abdominal Pain: A Randomized Clinical Trial
1. Ethosuximide was not superior to placebo for the treatment of abdominal pain in adults with irritable bowel syndrome.
Evidence Rating Level: 1 (Excellent)
Previous research suggested that increased activity or expression of T-type channels, particularly the Cav3.2 subtype, in the colonic mucosa contributes to visceral hypersensitivity in irritable bowel syndrome (IBS). The Cav3.2 channel is involved in pain transduction, and limited research has found that its inhibition alleviates pain. This study thus investigated the analgesic effect of the Cav3.2 channel blocker, ethosuximide, in IBS-related abdominal pain. This multicenter, double-blinded, randomized clinical trial was conducted between February 2018 and February 2022 and included adults with IBS (meeting Rome IV criteria). Participants were randomized to receive either ethosuximide or a placebo for 12 weeks and followed up for 3 weeks. The primary outcome responder rate, defined as a reduction of at least 30% in mean weekly abdominal pain intensity from baseline and a Subject Global Assessment (SGA) score of at least 4 out of 5 (i.e., considerably relieved or completely relieved). Of the 124 patients randomized (mean [SD] age, 4.7 [14.9] years; 72 [58.1%] women), 64 were in the ethosuximide group and 60 in the placebo group. Responder rates did not differ significantly between groups (17/64 [26.6%] for ethosuximide vs 14/60 patients [23.3%] for placebo; relative risk, 1.14; 95% CI, 0.61-2.11). Compared to placebo, ethosuximide was less well tolerated, with higher discontinuation rates and induced more adverse events. Overall, this study found that ethosuximide was not superior to placebo for the treatment of abdominal pain in adults with IBS and was associated with reduced tolerability. These findings do not support the use of ethosuximide for managing IBS-related pain.
1. Compared to placebo, edaravone dexborneol improved functional independence at 90 days in patients with acute ischaemic stroke who underwent endovascular thrombectomy.
Evidence Rating Level: 1 (Excellent)
Edaravone dexborneol is a novel multitarget brain cytoprotective agent that has shown efficacy in patients with acute ischaemic stroke without reperfusion therapy. It is unclear whether edaravone dexborneol provides additional benefits in patients undergoing reperfusion therapy. This study thus examined the efficacy and safety of edaravone dexborneol in improving functional outcomes among patients with acute ischaemic stroke undergoing endovascular thrombectomy. This multicentre, double blind, randomised controlled trial was conducted in China between March 2022 and May 2023. Patients aged 18-80 years were included if they had a clinically diagnosed acute ischaemic stroke and planned endovascular thrombectomy. Patients were randomly assigned 1:1 to receive edaravone dexborneol (37.5 mg) or placebo before endovascular thrombectomy, twice daily for a consecutive period of 10-14 days. The primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0-2 (range 0 [no symptoms] to 6 [death]), and serious adverse events. In total, 690 patients were included in the edaravone dexborneol group (median [IQR] age = 67.0 [57.0-73.0] years, male [%] = 435 [63.0]) and 672 in the placebo group (median [IQR] age = 67.0 [58.0-73.0]) years, male [%] = 436 [64.9]). Due to loss to follow-up, 1360 patients were included in the intent-to-treat analysis. At 90 days, 379 (55.0%) of 689 patients in the edaravone dexborneol group and 333 (49.6%) of 671 patients in the placebo group achieved functional independence. Patients who received edaravone dexborneol were 11% more likely to achieve functional dependence than those who received a placebo (risk ratio 1.11, 95% confidence interval (CI) 1.00 to 1.23; risk difference 5.4%, 95% CI 0.1% to 10.7%). Patients with mismatch at admission (NIHSS score ≥10 and ASPECTS ≥9 or NIHSS score ≥20 and ≥7) were more likely to achieve functional independence when treated with edaravone dexborneol compared to placebo (55.5% (178/321) versus 42.9% (134/312); risk ratio 1.29, 1.10 to 1.52; risk difference 13.0%, 5.6% to 20.3%; P for interaction=0.003). Overall, this study found that compared to placebo, edaravone dexborneol improved functional independence at 90 days in patients with acute ischaemic stroke who underwent endovascular thrombectomy, particularly for those with clinical imaging mismatch present at admission. These findings highlight the potential of edaravone dexborneol as an adjunctive therapy with reperfusion treatment. Future studies should validate these findings in other populations with larger sample sizes.
1. Nearly one in three people with cystic fibrosis experienced a nephrolithiasis during their lifetime.
2. The degree of exocrine pancreatic insufficiency control was not associated with nephrolithiasis.
3. Potential risk factors for nephrolithiasis include small bowel resection, alcohol use, and low BMI.
Evidence Rating Level: 2 (Good)
People with cystic fibrosis are more likely to develop calcium oxalate nephrolithiasis than the general population. While exocrine pancreatic insufficiency (EPI) is a primary risk factor, the relationship between the degree of EPI control and risk of nephrolithiasis is unclear. This study thus examined the association between the degree of EPI control and incidence and lifetime prevalence of nephrolithiasis in CF. This retrospective cohort study enrolled adults with CF from a medical center in Ohio, USA, between July 1, 2018, and June 30, 2023. The primary outcome was nephrolithiasis events, defined as the occurrence of nephrolithiasis identified on abdominal imaging. Of the 332 patients with cystic fibrosis included in the study, 107 [32%] had at least one nephrolithiasis event during their lifetime (mean [SD] age = 38.8 [13.3], male [%] = 58 [52.4]) and 225 had no history of nephrolithiasis (mean [SD] age = 36.8 [13], male [%] = 112 [49.8]). The overall incidence of any nephrolithiasis event was 34 cases per 1,000 person-years. While the lifetime prevalence was higher in patients with EPI (32%) than without EPI (24%), no significant difference in prevalence was observed according to the degree of EPI control. Small bowel resection (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.0–9.0), alcohol use (OR 1.7, 95% CI 1.0–2.9), and lower BMI (OR 0.9, 95% CI 0.9–1.0) were associated with nephrolithiasis independent of EPI status. Overall, this study found that nearly one in three people with cystic fibrosis experienced nephrolithiasis during their lifetime, and that degree of exocrine pancreatic insufficiency control was not associated with nephrolithiasis. Potential risk factors for nephrolithiasis include small bowel resection, alcohol use, and low BMI. Future prospective studies are needed to confirm the study findings.
Metformin, Maternal Glycemic Control, and Neonatal Hypoglycemia After Antenatal Steroids: A Randomised Clinical Trial
1. Metformin was associated with lower mean maternal glucose values and a lower rate of neonatal hypoglycemia in preterm infants compared to the control group.
Evidence Rating Level: 1 (Excellent)
Pregnant women at risk of preterm delivery commonly receive antenatal corticosteroid (ACS), particularly betamethasone, to reduce complications of prematurity. However, ACS administration can lead to maternal hyperglycemia, which can contribute to ACS-induced neonatal hypoglycemia. Metformin is commonly used to manage maternal hyperglycemia during pregnancy in women with gestational diabetes. It is unclear whether treating maternal hyperglycemia with metformin reduces the risk of neonatal hypoglycemia in preterm infants. This study thus examined the impact of metformin treatment after betamethasone administration on maternal glycemic control and the incidence of neonatal hypoglycemia in preterm infants. This multicenter, randomized clinical trial conducted from July 1, 2020, to June 30, 2024, in Israel, included pregnant women receiving betamethasone from 24.0 to 36.5 gestational weeks due to increased preterm delivery risk. Participants were randomized 1:1 to metformin (425 mg 3 times daily before meals and 850-1700 mg at 10 pm) or no treatment. The treatment lasted up to 48 hours after the first betamethasone dose (12mg). The primary outcomes were mean maternal glucose values up to 48 hours from the first betamethasone injection and the rate of neonatal hypoglycemia in preterm deliveries (<37 gestational weeks). Out of the 169 women included (mean [SD] age = 29.7 [5.4] years), 91 were in the metformin group, and 96 women were in the control group. Compared to the control group, the metformin group had lower mean (SD) maternal total and postprandial glucose values (121 [15] vs 127 [17] mg/dL; P = .01; and 129 [22] vs 138 [26] mg/dL; P = .009, respectively). The metformin group also had a lower neonatal hypoglycemia rate (10 [21%] vs 23 [40%]; P = .04) and 47% lower neonatal hypoglycemia risk (relative risk, 0.53; 95% CI, 0.28-0.99) compared to the control group. Mild adverse effects were reported by 12 women. Overall, this study found metformin to be safe and effective in lowering betamethasone-induced maternal hyperglycemia and risk of neonatal hypoglycemia in preterm infants. These findings indicate a potential role for metformin in managing adverse metabolic effects associated with antenatal corticosteroid use among pregnant women. Future research should confirm these findings and determine the best dose and timing in relation to ACS treatment.
1. Surgery-induced weight loss was associated with lower cancer incidence and mortality rates in women with obesity, but not men.
Evidence Rating Level: 2 (Good)
Obesity is a risk factor for cancer, and surgery-induced weight loss has been associated with reduced cancer risk and mortality. Although prior studies have found sex differences in surgery-induced weight loss and cancer risk, long-term studies are lacking. This study thus examined the relationship between surgery-induced weight loss and long-term cancer outcomes. This study was a post-hoc analysis of a prospective, controlled intervention trial that recruited patients (37-60 years old) with obesity who underwent bariatric surgery and matched controls who received standard nonsurgical obesity-related care between September 1, 1987, and January 31, 2001, in Sweden. Obesity was defined as body mass index (BMI) ≥34 kg/m2 for men and ≥38 kg/m2 for women. The primary outcomes were cancer events and cancer-related deaths. In total, 2007 patients were in the bariatric surgery group, while 2,040 patients were in the control group. In both groups, about 71% of the group were women. Median follow-up was 26.8 years (interquartile range (IQR) [22.9, 29.6]) in the surgery group and 24.9 years (IQR [18.7, 28.8]) in the control group. Bariatric surgery was associated with a 22% lower overall cancer incidence rate in women (adjusted hazard ratio (HRadj) = 0.78; 95% confidence interval (CI) [0.67, 0.90]), but not in men (sex–treatment interaction p = 0.013). Among women, bariatric surgery was also associated with 22% lower overall cancer mortality rate, although this was borderline statistically significant (HRadj = 0.78 (95% CI [0.61, 1.00]). The associations between surgery and female-specific cancer incidence, as well as female-specific cancer-related mortality, were stronger in women with high baseline insulin levels (insulin-treatment interaction p = 0.021 and 0.039, respectively). Overall, this study found that bariatric surgery was associated with lower cancer incidence and mortality rates in women with obesity, but not men, with stronger associations for female-specific cancers among women with higher baseline insulin levels.
Image: PD
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