2 Minute Medicine Rewind September 28, 2026
Probiotics and Risk of Death, Necrotizing Enterocolitis, and Sepsis in Very Preterm Infants
1. Probiotic supplementation was associated with a lower risk of death and/or necrotizing enterocolitis in very preterm infants.
Evidence Rating Level: 2 (Good)
Specific probiotics have been shown to reduce the incidence of necrotizing enterocolitis (NEC) and all-cause mortality in preterm infants; however, population-based clinical evidence is limited. In 2020, a national recommendation in Sweden was issued to provide probiotics to very preterm infants in neonatal intensive care units. This study examined the association between probiotic supplementation and risk of death, NEC, and/or culture-proven sepsis in very preterm infants. This cohort study included very preterm infants (28 weeks 0 days’ to 31 weeks 6 days’ gestation) live born in Sweden from January 1, 2017, through December 31, 2024. The daily probiotic supplementation included 1 billion colony-forming units of freeze-dried Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus given after birth to postmenstrual week 34. The primary outcomes were composites of death and/or NEC (Bell stage 2-3), death and/or surgical NEC (Bell stage 3), and death and/or culture-proven sepsis. Among 4695 infants analyzed (mean [SD] gestational age, 30.2 [1.1] weeks; 2145 female [45.7%]), 1571 (33.5%) were in the probiotics group and 3124 infants (66.5%) were in the no probiotics group. Following the national probiotic supplementation guideline in 2020, probiotic uptake increased from 0% before 2020 to 16.9% in 2020 and to a mean (SD) of 64.8% (4.7%) in 2021 to 2024. The probiotic group had a 72% lower risk of death and/or NEC (adjusted relative risk [aRR], 0.28 [95% CI, 0.14-0.56]) compared to no probiotic supplementation. When analyzed separately, the probiotic group had an 84% lower risk of death (aRR, 0.16 [95% CI, 0.06-0.45]) and 75% lower risk of NEC (aRR, 0.25 [95% CI, 0.10-0.61]) compared to the no-probiotic group. About 42.3% (credible interval, 16.1%-100%) of the observed mortality reduction was mediated via reduced NEC incidence. Risk of culture-proven sepsis was similar in both groups (ARR, 1.22 [95% CI, 0.78-1.90]). Overall, this study found that probiotic supplementation was associated with a lower risk of death and/or NEC in very preterm infants. These findings support the use of probiotic supplementation in very preterm infants in Sweden.
Posttraumatic Stress Disorder, Health-Related Social Needs, and Cognitive Outcomes in US Veterans
1. Among US Veterans, posttraumatic stress disorder (PTSD) and health-related social needs (HRSNs) were independently associated with a higher hazard of incident mild cognitive impairment, Alzheimer disease, or AD-related dementias, and those with both PTSD and HRSNs had the highest hazard.
Evidence Rating Level: 2 (Good)
Health-related social needs (HRSNs) are individual-level social circumstances, including housing instability, financial problems, and food insecurity. Posttraumatic stress disorder (PTSD) and HRSNs have been associated with cognitive decline; however, their joint associations with mild cognitive impairment (MCI), Alzheimer disease (AD), and AD-related dementias (ADRD) are unclear. This study thus examined the independent and joint associations of PTSD and HRSNs with incident MCI, AD, and ADRD among US veterans. This retrospective cohort study analyzed data from the National Veterans Health Administration (VHA) between 2015 and 2024 and included veterans aged 55 to 100 years with no prior diagnosis of MCI, AD, or ADRD. The primary outcome was a composite of incident MCI, AD, or ADRD. Among the 3,817,970 veterans included in the study (mean [SD] age, 70.3 [9.1] years; 3,664,349 [96.0%] male), 270,282 (7.1%) developed MCI, AD, or ADRD with median (IQR) follow-up of 8.84 (5.02-9.03) years. The hazard of incident MCI, AD, or ADRD was 33% higher among veterans with PTSD (adjusted hazard ratio [aHR], 1.33; 95% CI, 1.32-1.35) and 117% higher among those with HRSNs (aHR, 2.17; 95% CI, 2.13-2.20). Compared with veterans with neither PTSD or HRSNs, the hazard of incident MCI, AD, or ADRD was 114% higher among those with HRSNs only (aHR, 2.14; 95% CI, 2.11-2.17), 13% higher among those with PTSD only (aHR,1.13; 95% CI, 1.07-1.19), and 187% higher among those with both PTSD and HRSNs (aHR, 2.87; 95% CI, 2.82-2.92). Overall, this study found that among US veterans, PTSD and HRSNs were independently associated with a higher hazard of incident MCI, AD, or ADRD, and those with both PTSD and HRSNs had the highest hazard. These findings suggest that US veterans with both PTSD and HRSNs may represent a clinically vulnerable group.
1. Long-term gonadotropin-releasing hormone agonist (GnRH-a) protocol was associated with higher odds of positive pregnancy outcomes for women with endometriosis undergoing frozen embryo transfer (FET), compared with GnRH-antagonist (GnRH-ant), and mild-ovarian stimulation protocols.
Evidence Rating Level: 2 (Good)
In vitro fertilization (IVF) is one of the most effective treatments for infertility associated with endometriosis. A key component of IVF is ovarian stimulation. Previous studies have compared the effectiveness of various ovarian stimulation protocols for fresh embryo transfer in women with endometriosis; however, the effectiveness of these protocols for frozen embryo transfer (FET) is unclear. This study thus examined the efficacy of three different controlled ovarian stimulation (COS) protocols: long-term gonadotropin-releasing hormone agonist (GnRH-a), GnRH-antagonist (GnRH-ant), and mild ovarian stimulation, in endometriosis patients undergoing FET. This retrospective study included women (<40 years) with stage III–IV endometriosis who received one of the three COS protocols during January 1, 2015, to December 31, 2022. The primary outcome was live birth rate. Among the 636 patients included, 118 received GnRH-a, 295 received GnRH-ant, and 223 received mild-ovarian stimulation protocols. Compared to the GnRH-a group, the GnRH-ant group had lower odds of live birth (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.47–0.83), whereas the mild-ovarian stimulation group had no significant difference in odds of live birth (OR 0.87, 95% CI 0.65–1.16). Compared to the GnRH-a group, both GnRH-ant and mild-ovarian stimulation groups had a lower rate of high morphological grade embryos (GnRH-ant: OR 0.73, 95% CI 0.55–0.98; mild: OR 0.69, 95% CI 0.51–0.94) and lower biochemical pregnancy rate (GnRH-ant: OR 0.62, 95% CI 0.47–0.83; mild: OR 0.73, 95% CI 0.54–0.98). Overall, this study found that compared to GnRH-ant and mild-ovarian stimulation protocols, the GnRH-a protocol was associated with higher odds of positive pregnancy outcomes for women with endometriosis undergoing FET. These findings suggest that the GnRH-a protocol may be a more effective ovarian stimulation option for this population, and the mild-ovarian stimulation protocol may serve as an alternative when considering only live birth rate.
1. Among older adults with atrial fibrillation, higher homocysteine and C-reactive protein levels, poorer cognitive performance, and greater nutritional risk were independently associated with frailty.
Evidence Rating Level: 2 (Good)
Frailty affects about 40% of patients with atrial fibrillation (AF). While previous studies have examined individual factors related to frailty, research examining frailty status together with factors such as AF treatment patterns, inflammatory and metabolic markers, and cognitive and nutritional status is lacking. This study thus compared various clinical factors associated with frailty among robust, pre-frail, and frail patients. This retrospective cohort study included patients >60 years with AF admitted to a hospital (index admission) in China between January 2018 and December 2024. The primary outcome was frailty status at index admission. Among the 198 patients included, 28 (14.1%) were robust, 68 (34.3%) pre-frail, and 102 (51.5%) were frail. In total, 52 (26.3%) patients were newly diagnosed with AF, and 146 (73.7%) had pre-existing AF. Across the robust, pre-frail, and frail groups, functional and cognitive abilities decreased, nutritional risk increased, and homocysteine and C-reactive protein levels increased (all P < 0.001). In multivariable analyses, higher homocysteine levels (adjusted odds ratio (aOR) per 5-μmol/L increase, 1.34; 95% CI 1.09–1.65), higher C-reactive protein levels (adjusted OR per 5-mg/L increase, 1.15; 95% CI 1.02–1.31), lower cognitive scores (aOR per 1-point increase Montreal Cognitive Assessment score, 0.63; 95% CI 0.49–0.81), and higher Nutritional Risk Screening 2002 scores (aOR per 1-point increase, 2.28; 95% CI 1.58–3.28) were independently associated with frailty. Overall, this study found that among older adults with AF, higher homocysteine and C-reactive protein levels, poorer cognitive performance, and greater nutritional risk were independently associated with frailty. These findings highlight the importance of multidimensional frailty assessments to help identify vulnerable patients with AF.
1. Prognostic associations of anthropometric indices varied according to clinical outcomes. The body roundness index showed the highest discrimination for atherosclerotic cardiovascular disease, body mass index for all-cause mortality, and waist circumference for atrial fibrillation.
Evidence Rating Level: 2 (Good)
Body mass index (BMI), waist circumference (WC), and the body roundness index (BRI) are the three most commonly used anthropometric indices for obesity and have been associated with cardiovascular and metabolic disorders and mortality. However, whether prognostic associations of these indices differ depending on specific clinical outcomes is unclear. This study thus compares the prognostic associations of BMI, WC, and BRI across multiple cardiovascular and mortality outcomes. This retrospective cohort study included Korean adults (aged ≥55 years) from the National Health Insurance Service database who underwent health screening between 2009 and 2012 and had no prior history of myocardial infarction (MI), stroke, heart failure or AF at baseline. Participants were followed for up to 10 years. The primary outcomes were atherosclerotic cardiovascular disease (ASCVD), all-cause mortality, and atrial fibrillation (AF). Among the 1,199,633 adults included (mean [SD] age, 63.5 [7.3] years, 566,526 male [47.2%], mean BMI = 24.04 ± 3.02 kg/m2, mean WC = 82.4 ± 8.3 cm, mean BRI = 82.4 ± 8.3 cm), 9.6% developed ASCVD and 4.7% developed AF. The cumulative incidence was 10.9 for all-cause mortality and 4.2% for cancer-related mortality. For ASCVD, BRI showed the highest area under the curve (AUC: 0.553), followed by WC (0.540), and BMI (0.512; P < 0.05 for all). For all-cause mortality, BMI showed the highest AUC (0.595), attributed to an inverse association in the underweight group, followed by BRI (0.595) and WC (0.506; P < 0.05 for all). For incident AF, WC showed the highest AUC (0.567), followed by BRI (0.550) and BMI (0.527). Non-linear (U-shaped or J-shaped) relationships were observed for most outcomes. Overall, this study found that the prognostic associations of anthropometric indices varied according to clinical outcomes, with BRI showing the highest discrimination for ASCVD, BMI for all-cause mortality, and WC for AF. These findings highlight the importance of considering the specific clinical outcome when selecting an anthropometric index for obesity-related risk assessment.
Image: PD
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