A Systematic Review And Meta-Analysis

[Posted 17/May/2022]

AUDIENCE: Emergency Medicine, Pediatric

KEY FINDINGS: The present systematic review and meta-analysis showed that POCUS had high sensitivity and specificity for identifying testicular torsion in paediatric patients although the risk of bias was high in the studies analysed.

BACKGROUND: Previous studies have examined the utility of ultrasonography performed by radiologists for diagnosing paediatric testicular torsion. While point-of-care ultrasound (POCUS) is used in paediatric emergency medicine, its diagnostic accuracy is still unknown. The present systematic review and meta-analysis aimed to clarify the accuracy of POCUS in diagnosing testicular torsion in children.

DETAILS: Following the Preferred Reporting Items for Systematic Review and Meta-analysis of Diagnostic Test Accuracy guidelines, a systematic review was performed. Any study investigating the diagnostic accuracy of POCUS for paediatric testicular torsion was extracted. The primary outcome was the assessment of the diagnostic accuracy of POCUS for paediatric testicular torsion. The pooled sensitivity and specificity were calculated. Quality analysis was conducted using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Four studies enrolling 784 patients in total were included. The pooled sensitivity, specificity, and positive and negative likelihood ratios of POCUS were 98.4% (95% CI: 88.5% to 99.8%), 97.2% (95% CI: 87.2% to 99.4%), 34.7 (95% CI: 7.4 to 164.4) and 0.017 (95% CI: 0.002 to 0.12), respectively. Risk-of-bias assessment using QUADAS-2 revealed that two of the studies had a high risk of bias in patient selection.

Copyright © BMJ Publishing Group Ltd and the College of Emergency Medicine. All rights reserved.

Source: Mori, T., Ihara, T., Nomura, O. (2022). Diagnostic Accuracy Of Point-Of-Care Ultrasound For Paediatric Testicular Torsion: A Systematic Review And Meta-Analysis. Emergency Medicine Journal . 2022; e212281. Published: May 6, 2022. DOI: 10.1136/emermed-2021-212281.

[Posted 23/Sep/2026]

AUDIENCE: Cardiology, Oncology, Internal Medicine

KEY FINDINGS: In this large real-world cohort of patients with early-stage HER2-positive breast cancer, biosimilar trastuzumab use increased markedly between 2018 and 2024 without a statistically significant difference in heart failure risk compared with reference trastuzumab. Overall heart failure occurred in 5.9% of the study population. Comorbidity burden and older age were associated with higher heart failure risk, emphasizing the importance of cardiovascular risk assessment during HER2-directed therapy. Because this was a retrospective claims-based study, longer follow-up and additional real-world studies are needed to further evaluate long-term cardiac outcomes.

BACKGROUND: Trastuzumab is an important treatment for HER2-positive breast cancer, but cardiac dysfunction, including heart failure, remains a recognized safety concern. Biosimilar trastuzumab products have expanded treatment access and may reduce costs, although real-world data comparing their cardiac safety with the reference product remain limited. This study evaluated the uptake of biosimilar trastuzumab and compared heart failure risk between patients receiving biosimilar and reference trastuzumab in routine clinical practice.

DETAILS: The investigators analyzed patients aged ≥18 years with breast cancer who received trastuzumab between 2018 and 2024 using the IQVIA PharMetrics Plus Closed Health Plan Claims database. Patients who underwent breast cancer surgery within the first year after diagnosis were considered to have early-stage disease. Individuals with a heart failure diagnosis before breast cancer surgery were excluded. Trastuzumab products were identified using Healthcare Common Procedure Coding System Level II codes, while heart failure was identified using International Classification of Diseases codes. The analysis used multivariable cause-specific Cox proportional hazards regression to evaluate the association between trastuzumab type and subsequent heart failure risk. The study included 5,135 patients, of whom 43.9% received reference trastuzumab.

Use of biosimilar trastuzumab increased substantially during the study period, from 0% in 2018 to 71.3% in 2024 (P<0.001). Overall, heart failure occurred in 5.9% of patients, including 5.5% of those receiving reference trastuzumab and 6.3% of those receiving biosimilar trastuzumab (P=0.26). After adjustment for relevant factors, there was no statistically significant difference in heart failure risk between biosimilar and reference trastuzumab (adjusted HR, 1.16; 95% CI, 0.92-1.46). In contrast, patients with a Charlson Comorbidity Index score ≥2 had a higher heart failure risk than those with a score of 0 (adjusted HR, 1.52; 95% CI, 1.11-2.08). Older age was also associated with greater risk: compared with patients aged 18-54 years, the adjusted HR was 1.61 (95% CI, 1.19-2.19) for those aged 65-74 years and 1.95 (95% CI, 1.29-2.96) for those aged ≥75 years.

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Source: Jackson, I., Zhang, N., Sullivan, M., et al. Real-World Cardiotoxicity of Biosimilar versus Reference Trastuzumab in Early HER2-Positive Breast Cancer. JACC: CardioOncology. Published: September 10, 2026. DOI: 10.1016/j.jaccao.2026.07.009.

[Posted 21/Sep/2026]

AUDIENCE: Emergency Medicine, Pediatrics

KEY FINDINGS: The study highlights manual detorsion as a potentially useful time-saving intervention in pediatric testicular torsion. Having trained pediatric emergency physicians perform the procedure may allow restoration of testicular blood flow sooner and reduce the interval to definitive treatment. Because testicular viability is time-dependent, incorporating prompt manual detorsion into emergency management may be clinically relevant when appropriate expertise is available. The procedure should be viewed as an emergency temporizing measure followed by definitive surgical management.

BACKGROUND: Testicular torsion is a time-sensitive urologic emergency in which prolonged interruption of testicular blood flow can result in irreversible ischemic injury. Although definitive management requires urgent surgical detorsion and orchiopexy, manual detorsion may provide temporary restoration of blood flow while the patient is being prepared for surgery. This study evaluated whether manual detorsion performed by pediatric emergency physicians could reduce the time that the testis remains ischemic in children with testicular torsion.

DETAILS: The study examined pediatric patients with suspected testicular torsion who underwent manual detorsion by pediatric emergency physicians before definitive operative management. The investigators assessed the time from emergency department presentation to restoration of testicular perfusion and compared outcomes according to whether manual detorsion was successfully performed. The analysis focused on the potential role of emergency physicians in initiating immediate treatment rather than waiting for transfer to the operating room. Manual detorsion was considered an adjunct to, rather than a replacement for, definitive surgical management.

Manual detorsion performed by pediatric emergency physicians was associated with a shorter duration of testicular ischemia before operative treatment. Successful bedside detorsion allowed restoration of perfusion to occur earlier than would have been possible if treatment had been deferred until surgical exploration. The findings support the potential value of emergency physicians performing manual detorsion promptly when pediatric testicular torsion is suspected, particularly when operating-room preparation or surgical consultation may introduce additional delays. Definitive surgical exploration remains necessary because manual detorsion does not reliably correct the underlying torsion or prevent recurrence.

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Source: Rivera, T., Lozano, J., Maniaci, V., et al. Manual Detorsion by Pediatric Emergency Physicians Shortens Ischemia Time in Pediatric Testicular Torsion. Academic Emergency Medicine. 2026; 33(9): e70412. Published: September, 2026. DOI: 10.1111/acem.70412.

[Posted 18/Sep/2026]

AUDIENCE: General Surgery, Pediatrics, Emergency Medicine

KEY FINDINGS: The study demonstrates substantial international variation in pediatric trauma laparotomy pathways, particularly in prehospital delays, access to senior surgical and anesthesia providers, and available resources. Although crude 30-day mortality was 8% overall, children treated in lower-HDI settings had nearly sixfold higher adjusted odds of postoperative death than those in upper-HDI settings. The findings highlight disparities across the entire trauma-care pathway rather than differences attributable solely to operative management. The authors emphasize the need for trauma systems specifically designed around the physiological, surgical, and developmental needs of children.

BACKGROUND: Traumatic injury is a major cause of death and disability among children and adolescents worldwide, yet pediatric trauma systems and access to specialized care vary substantially between countries. This international study examined differences in injury patterns, treatment pathways, operative care, and postoperative outcomes among children requiring emergency laparotomy after traumatic injury.

DETAILS: The study was a planned post-hoc analysis of the international, multicentre, prospective GOAL-Trauma cohort, which collected data between April 1 and December 31, 2024. Patients aged 18 years or younger with blunt or penetrating trauma who underwent laparotomy within 5 days of presentation were eligible. Hospitals were grouped according to the Human Development Index (HDI) of their setting. A total of 237 pediatric patients from 85 hospitals across 32 countries met the inclusion criteria. Of these, 110 patients were treated in lower-HDI settings, 89 in middle-HDI settings, and 38 in upper-HDI settings. The investigators assessed differences in time to presentation, decision-making and surgery, perioperative interventions, staffing, injury severity, and 30-day in-hospital mortality.

The timing of trauma care differed substantially across HDI groups. Median time from injury to presentation, decision to operate, and operation itself was significantly longer in lower-resource settings, with the greatest variation occurring before hospital arrival. Overall median time from injury to operation was 7.4 hours (IQR 3.5-18.8). There were also major differences in the resources available during surgery. A consultant or attending general surgeon was the most senior surgeon present for 59% of cases in lower-HDI settings, compared with 78% in middle-HDI and 97% in upper-HDI settings. Similarly, a consultant or attending anesthetist was present in 35%, 62%, and 95% of cases, respectively. The overall crude 30-day in-hospital mortality was 8% (19 of 237 patients). After adjustment for relevant factors, children treated in the lower-HDI group had substantially higher postoperative mortality than those in the upper-HDI group, with an adjusted odds ratio of 5.69 (95% CI 1.58-20.44; P=0.0079).

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Source: Aziz, R., Bath, M. F., Abdelmohsen, S. M., et al. Global variation in injury patterns, interventions, and post-operative outcomes for children and adolescents undergoing trauma laparotomy: an international cohort study. The Lancet Child & Adolescent Health. 2026; 10(7): 505-514. Published: May 7, 2026. DOI: 10.1016/S2352-4642(26)00069-6.

[Posted 17/Sep/2026]

AUDIENCE: Ob/Gyn, Infectiouos Disease, Internal Medicine

KEY FINDINGS: In this large US observational analysis, publication of randomized trial evidence in 2016 was followed by a substantial increase in adjunctive azithromycin use during unscheduled cesarean delivery and a relative reduction in postpartum infections. The study provides evidence that clinical trial findings were subsequently incorporated into routine practice beyond the original trial setting. Because this was an observational difference-in-differences analysis rather than a new randomized trial, the findings demonstrate an association between adoption of the intervention and changes in infection rates rather than establishing causality.

BACKGROUND: Unscheduled cesarean delivery is associated with a higher risk of postpartum infection. A 2016 clinical trial showed that adding azithromycin to standard antibiotic prophylaxis could reduce postoperative infections in patients undergoing unscheduled cesarean delivery. This study evaluated whether use of adjunctive azithromycin increased after publication of that trial and whether postpartum infection rates subsequently changed in routine US practice.

DETAILS: Investigators conducted a difference-in-differences analysis using Epic Cosmos data from 2013 through 2024. The analysis included pregnant individuals who received prenatal care, experienced labor, and delivered a live singleton infant at 24 to 43 weeks' gestation. Cesarean deliveries served as the treatment group and vaginal deliveries as the comparison group, allowing changes occurring after publication of the 2016 trial to be assessed relative to trends in vaginal births.

The study included 1,663,441 deliveries, comprising 202,234 cesarean births and 1,461,207 vaginal births. The primary outcomes were perioperative azithromycin administration and postpartum infection occurring within 6 weeks of delivery. The investigators compared births from January 1, 2013, through September 28, 2016, with those occurring from January 1, 2017, through December 31, 2024.

Before publication of the 2016 trial, azithromycin was administered during 2.2% of cesarean births compared with 0.01% of vaginal births. During 2017-2024, use increased to 39.6% of cesarean births and 0.04% of vaginal births. The adjusted difference-in-differences estimate for cesarean births was 37.6 percentage points (95% CI, 33.1 to 42.2). Postpartum infection after cesarean delivery declined from 9.2% during the pre-2016 period to 8.0% during 2017-2024. Among vaginal births, infection rates changed from 2.0% to 2.7%, producing an adjusted difference-in-differences estimate of -2.0 percentage points (95% CI, -2.6 to -1.4) for cesarean births. The findings therefore showed that, following publication of the randomized trial, adjunctive azithromycin use increased substantially among patients undergoing unscheduled cesarean delivery while postpartum infection rates decreased relative to the comparison group.

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Source: Freret, T. S., Litman, E., Wen, T., et al. Adoption of Adjunctive Azithromycin for Unscheduled Cesarean Delivery and Postpartum Infections. JAMA. 2026; Published: September 14, 2026. DOI: 10.1001/jama.2026.15010.

[Posted 15/Sep/2026]

AUDIENCE: Cardiology, Oncology, Hematology

KEY FINDINGS: The findings identify ERRα downregulation as an early and potentially causal component of anthracycline-induced cardiac injury. Formononetin improved cardiac energy metabolism and function in experimental models while retaining, and potentially enhancing, doxorubicin's anticancer activity in breast cancer organoids. The study therefore suggests that pharmacologic activation of ERRα could represent a future strategy for simultaneously addressing anthracycline cardiotoxicity and cancer treatment. However, the evidence remains preclinical, and clinical studies are required to determine whether these findings translate into cardioprotection in patients receiving anthracycline chemotherapy.

BACKGROUND: Anthracyclines such as doxorubicin are effective anticancer agents, but their use can be limited by anthracycline-induced cardiotoxicity (AIC). Early metabolic disturbances in cardiac muscle may contribute to the development of cardiac dysfunction. This study investigated the role of estrogen-related receptor α (ERRα), a regulator of cardiac energy metabolism, in AIC and evaluated whether pharmacologic activation of ERRα with formononetin could provide cardiac protection while maintaining anticancer activity.

DETAILS: The investigators used a porcine model of anthracycline cardiotoxicity to examine changes in ERRα over time and cardiomyocyte-specific gain- and loss-of-function mouse models to assess its functional role. Mechanistic experiments, including ChIP-qPCR, reporter assays, and microscale thermophoresis, were used to investigate how formononetin interacts with the ERRα pathway. Cardiac tissue from patients who had received chemotherapy was also examined, while human breast cancer patient-derived organoids were used to evaluate potential effects on tumor activity. ERRα expression was reduced in hearts from the porcine AIC model and in cardiac tissue from patients treated with chemotherapy. In pigs, the reduction occurred at the 6-week subclinical stage, before overt cardiac dysfunction developed. Increasing ERRα expression specifically in cardiomyocytes enhanced mitochondrial metabolic programs and fatty-acid oxidation and preserved systolic function after doxorubicin exposure, whereas ERRα reduction worsened metabolic dysfunction and cardiac impairment.

Drug screening identified formononetin as a selective ERRα activator. In mouse and pig models, formononetin increased ERRα activity, improved cardiac mitochondrial metabolism, and reduced anthracycline-associated cardiac injury. Mechanistic experiments indicated that formononetin interacts with the ERRα/PGC-1α complex and promotes its stability, supporting activation of downstream metabolic pathways.

Importantly, formononetin also demonstrated anticancer activity in human breast cancer patient-derived organoids. Treatment with formononetin alone reduced organoid viability and proliferation, while combining formononetin with doxorubicin produced greater antitumor effects.

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Source: Wang, X., Ling, G., Wei, Y., et al. Natural ERRα Activator Formononetin Ameliorates Anthracycline Cardiotoxicity via Metabolic Improvement. Circulation Research. 2026; 139(7): e329042. Published: September 11, 2026. DOI: 10.1161/CIRCRESAHA.126.329042.