A Large Multisite Cohort Study

[Posted 6/Jun/2022]

AUDIENCE: General Surgery, Ob/Gyn

KEY FINDINGS: Although the risk for uterine perforation with IUD insertion 4 days to 6 weeks or less post partum is nearly seven times that of insertion non-post partum, perforation remains an incredibly rare event for all clinical time points. Despite a slight increased risk of perforation with breastfeeding at IUD insertion, the benefits of breastfeeding and effective contraception generally outweigh risks and should have little clinical impact. Therefore, IUD insertion timing should be based on individual desire for IUD contraception and patient convenience to assure an IUD insertion can occur. Careful follow-up of individuals at higher risk of uterine perforation is warranted.

BACKGROUND: Reports of perforation risk related to intrauterine devices (IUDs) inserted immediately post partum and among non-post-partum individuals are scarce, and previous studies with only 12-month follow-ups underestimate the risk. Breastfeeding at IUD insertion and insertion within 36 weeks post partum have been associated with increased risk of uterine perforation. The aim of these analyses was to compare the incidence and risks of IUD-related uterine perforations by non-post-partum and post-partum intervals at IUD insertion, and among post-partum individuals, to assess the impact of breastfeeding on these outcomes.

DETAILS: Performed a multisite cohort study in the USA, using electronic health records (EHR). Study sites were three health-care systems and a site that used data from a health-care information exchange. The study population included individuals who were aged 50 years or younger and had an IUD insertion between Jan 1, 2001, and April 30, 2018. Individuals were excluded if they had not been in the health-care system for at least 12 months before IUD insertion. The primary outcome for this analysis was any IUD-related uterine perforation diagnosis for the first IUD insertion in this time period. Both complete and partial IUD-related perforations were identified. Chart abstraction was done to validate EHR-based algorithms or confirm perforations. The crude rate and cumulative incidence of uterine perforation were evaluated by non-post-partum and post-partum intervals at IUD insertion in the full cohort, and by breastfeeding status in a subcohort of post-partum individuals. Cox models estimated crude and adjusted hazard ratios (aHRs). Data from 326,658 individuals in the full cohort and 94,817 individuals in the post-partum subcohort were analysed. In the full cohort, we identified 1008 uterine perforations (51.2% complete), with the 5-year cumulative incidence being the lowest in the non-post-partum group (0.29%, 95% CI 0.26-0.34). The aHR for the post-partum interval relative to non-post partum ranged from 2.73 (95% CI 1.33-5.63; 0 to 3 days post partum) to 6.71 (4.80-9.38; 4 days to >=6 weeks post partum). The post-partum subcohort of individuals with breastfeeding information had 673 uterine perforations (62% complete), with a 5-year cumulative incidence of 1.37% (95% CI 1.24-1.52) and an increased risk with breastfeeding (aHR 1.37, 95% CI 1.12-1.66).

Copyright © Elsevier Ltd. All rights reserved.

Source: Reed, S. D., Zhou, X., Ichikawa, L., et al. (2022). Intrauterine Device-related Uterine Perforation Incidence And Risk (Apex-Iud): A Large Multisite Cohort Study. The Lancet. 2022; 399(10341): 2103-2112. Published: June 4, 2022. DOI: 10.1016/S0140-6736(22)00015-0.

A randomised, open-label, phase 4 clinical trial

[Posted 22/Jan/2026]]

AUDIENCE: Infectious Disease, Family Medicine

KEY FINDINGS: Artemether-lumefantrine was associated with a higher risk of recurrent malaria than other antimalarial combinations tested, and K13 mutations were associated with delayed parasite clearance. Changes in first-line therapy for uncomplicated malaria must be considered in response to suboptimal efficacy of artemether-lumefantrine.

BACKGROUND: Anti-malarial artemisinin-based combination therapies (ACTs) might be losing efficacy in east Africa, with the spread of artemisinin partial resistance and reduced partner drug activity. Our trial aimed to measure the efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine in three sites in Uganda.

DETAILS: This randomised, open-label, phase 4 clinical trial was carried out at three sites in the Agago, Arua, and Busia districts of Uganda. Children aged 6 months to 10 years with uncomplicated Plasmodium falciparum malaria were randomly assigned to receive either artemether-lumefantrine (20 mg artemether; 120 mg lumefantrine; twice a day for 3 days) in all sites or dihydroartemisinin-piperaquine (40 mg dihydroartemisinin and 320 mg piperaquine, once a day for 3 days) in Agago, artesunate-amodiaquine (25 mg artesunate and 67.5 mg amodiaquine for children <9 kg or 50 mg artesunate and 135 mg amodiaquine for children >=9 kg, once a day for 3 days) in Busia; and artesunate-pyronaridine (60 mg artesunate and 180 mg pyronaridine for children >15 kg or 20 mg artesunate and 60 mg pyronaridine for children <15 kg, once a day for 3 days) in Arua, with follow-up to 42 days. Participants were not blinded to group assignments; however, investigators and those assessing outcome were masked. The primary outcome was parasitaemia, assessed by microscopy, either uncorrected or PCR-corrected to distinguish recrudescence from new infection. All participants who received the treatment per protocol and were not lost to follow-up were included in the primary outcome. All participants who were randomly allocated to treatment groups were included in the safety analyses. This study is registered with the Pan African Clinical Trials Registry, number PACTR202301796134887, and is complete. Between Nov 7, 2022, and March 24, 2023, 808 participants (437 [54%] female) were enrolled and assigned to treatment groups; 15 (2%) were lost to follow-up and 793 (98%) completed follow-up. The uncorrected adequate clinical and parasitological response for artemether-lumefantrine was 87 (51.8%; 95% CI 44.0-59.5) of 168 participants in Arua, 88 (51.8%; 44.0-59.4) of 170 and Busia, and 131 (79.4%; 72.3-85.1) of 165 in Agago. This response for artemether-lumefantrine was lower than that of the other ACTs at all sites: 97 (98.0%; 92.2-99.6) of 99 for dihydroartemisinin-piperaquine in Agago, 95 (99.0%; 93.5-99.9) of 96 for artesunate-amodiaquine in Busia, and 73 (73.7%; 63.8-81.8) of 99 for artesunate-pyronaridine in Arua. PCR-corrected 28-day efficacies were 88 (81.5%; 72.6-88.1) of 108 for artemether-lumefantrine and 95 (100%; 95.2-100.0) of 95 for artesunate-amodiaquine in Busia; 131 (97.0%; 92.1-99.0) of 135 for artemether-lumefantrine and 97 (100%; 95.3-100.0) of 97 for dihydroartemisinin-piperaquine in Agago; and 87 (82.1%; 73.2-88.6) of 106 for artemether-lumefantrine and 73 (92.4%; 83.6-96.9) of 79 for artesunate-pyronaridine in Arua. All regimens were well tolerated. The most common adverse events were upper respiratory tract infection, diarrhoea, and anaemia. None of the reported adverse events were attributed to the study drugs. There were two serious adverse events, both cases of severe malaria in Arua, one in each of the treatment groups. Parasite clearance half-lives were prolonged with parasites carrying the PfK13 Cys469Tyr (median 4.2 h; IQR 3.4-4.9) and Ala675Val (4.9 h; 3.4-5.7) mutations compared with wild-type parasites (2.8 h; 2.3-3.6; p<0.0001).

Copyright © Elsevier Ltd. All rights reserved.

Source: Kamya, M. R., Nankabirwa, J. I., Ebong, C., et al. Efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in children aged 6 months to 10 years in Uganda: a randomised, open-label, phase 4 clinical trial. The Lancet Infectious Diseases. 2026; 26(1): 67-68. Published: January, 2026. DOI: 10.1016/S1473-3099(25)00407-4.

[Posted 21/Jan/2026]

AUDIENCE: Neurology, Cardiology, Internal Medicine

KEY FINDINGS: Among patients with high-grade stenosis without recent symptoms, the addition of stenting led to a lower risk of a composite of perioperative stroke or death or ipsilateral stroke within 4 years than intensive medical management alone. Carotid endarterectomy did not lead to a significant benefit.

BACKGROUND: Improvements in medical therapy, carotid-artery stenting, and carotid endarterectomy call into question the preferred management of asymptomatic carotid stenosis. Whether adding revascularization to intensive medical management would provide greater benefit than intensive medical management alone is unclear.

DETAILS: Authors conducted two parallel, observer-blinded clinical trials that enrolled patients with high-grade (>=70%) asymptomatic carotid stenosis across 155 centers in five countries. The stenting trial compared intensive medical management alone (medical-therapy group) with carotid-artery stenting plus intensive medical management (stenting group); the endarterectomy trial compared intensive medical management alone (medical-therapy group) with carotid endarterectomy plus intensive medical management (endarterectomy group). The primary outcome was a composite of any stroke or death, assessed from randomization to 44 days, or ipsilateral ischemic stroke, assessed during the remaining follow-up period up to 4 years. A total of 1245 patients underwent randomization in the stenting trial and 1240 in the endarterectomy trial. In the stenting trial, the 4-year incidence of primary-outcome events was 6.0% (95% confidence interval [CI], 3.8 to 8.3) in the medical-therapy group and 2.8% (95% CI, 1.5 to 4.3) in the stenting group (P=0.02 for the absolute difference). In the endarterectomy trial, the 4-year incidence of primary-outcome events was 5.3% (95% CI, 3.3 to 7.4) in the medical-therapy group and 3.7% (95% CI, 2.1 to 5.5) in the endarterectomy group (P=0.24 for the absolute difference). From day 0 to 44, in the stenting trial, no strokes or deaths occurred in the medical-therapy group and seven strokes and one death occurred in the stenting group; in the endarterectomy trial, three strokes occurred in the medical-therapy group and nine strokes occurred in the endarterectomy group.

Copyright © Massachusetts Medical Society. All rights reserved.

Source: Brott, T. G., Howard, G., Lal, B. K., et al. Medical Management and Revascularization for Asymptomatic Carotid Stenosis. NEJM. 2025; 394(3): 219-231. Published: November, 2025. DOI: 10.1056/NEJMoa250880.

Tissue Sensor Implementation in a Clinical System

[Posted 20/Jan/2026]

AUDIENCE: General Surgery, Nephrology, Internal Medicine

KEY FINDINGS: The developed optical guidance system provides real-time feedback during laser lithotripsy, improving safety and precision by reducing the risk of accidental tissue damage. The proposed technology is expected to enhance outcomes in minimally invasive urological laser procedures.

BACKGROUND: Purpose of this study is to develop an optical feedback system compatible with a commercial surgical laser for automatically distinguishing between urinary stones and soft tissues during laser lithotripsy, thereby enhancing procedural safety.

DETAILS: The system, based on diffuse reflectance spectroscopy (DRS), was implemented in an engineered clinical theranostic platform. In vivo experiments were conducted to collect and analyze DRS spectra of tissues during laser lithotripsy. Illumination was performed via the endoscope, and detection was performed via the treatment fiber. Classification of urinary stones and soft tissues was performed using machine learning methods, i.e., Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA). The system demonstrated high diagnostic performance, with 93% sensitivity for soft tissue identification and 93% specificity for stone detection evaluated by the LDA method. This real-time differentiation effectively minimized unintended laser exposure to non-target tissues.

Copyright © Wiley Periodicals LLC. All rights reserved.

Source: Korneva, N., Budylin, G., Tseregorodtseva, P., et al. Optical Feedback for Safe Automatic Laser Lithotripsy: Tissue Sensor Implementation in a Clinical System. Lasers Surg. Med.. 2026; 58(1): 38-48. Published: January, 2026. DOI: 10.1002/lsm.70081.

A Case Series

[Posted 13/Jan/2026]

AUDIENCE: General Surgery, Dermmatology, Internal Medicine

KEY FINDINGS: While hypopigmentation is rare with PSL treatment, it can occur even with conservative low-fluence settings and adequate intervals between sessions. One possible mechanism is thermal beam- stacking, where slow hand movement during treatment may lead to repeated pulses on the same area. This can result in localised thermal accumulation, potentially causing subcellular disruption of melanosomes without overt melanocyte loss. These findings suggest the need for clinician vigilance in monitoring for hypopigmentation, as re-pigmentation may not be achievable. Larger, controlled studies are needed to clarify risk factors and guide safer practice.

BACKGROUND: Picosecond lasers (PSL) are increasingly used for treating melasma, with fewer adverse effects reported compared to Q-switched lasers (QSL). However, the incidence of hypopigmentation following PSL treatment remains unexplored in detail. This case series aims to explore outcomes of hypopigmentation following PSL therapy in patients with melasma, and explore potential contributing factors.

DETAILS: A retrospective chart review identified four patients with hypopigmentation following PSL treatment for melasma, including one referral from another clinic. Across the cohort, 796 patients underwent 3096 sessions between 2021 and 2025. Treatments used 755 and/or 1064-nm wavelengths at low fluences, with intervals of 4–12 weeks. Three in-clinic patients (0.38%, 95% CI 0.13%–1.10%) and one referral developed hypopigmentation. Changes occurred across both wavelengths and beam profiles. Histology demonstrated preserved melanocyte density with reduced melanin pigment and melanosome content. None of the cases showed meaningful re-pigmentation at 6-month follow-up. No cases of post-inflammatory hyperpigmentation (PIH) were observed.

Copyright © Wiley Periodicals LLC. All rights reserved

Source: Hang, X. and Lim, D. S. Hypopigmentation Following Picosecond Laser Treatment for Melasma: A Case Series. Lasers Surg. Med.. 2025; Published: December, 2025. DOI: 10.1002/lsm.70077.

[Posted 27/Oct/2025]

AUDIENCE: Infectious Disease, Microbiologists

KEY FINDINGS: Enhanced antibiotic performance observed in preclinical mouse models. Potential to improve treatment outcomes for multiple intracellular bacterial infections. Ongoing efforts include mechanism elucidation and patent development.

BACKGROUND: Antibiotic resistance has severely limited the effectiveness of conventional treatments against persistent bacterial infections. Some pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, and Salmonella enterica, can survive inside immune cells, remaining dormant and shielded from antibiotic action. The increasing prevalence of such infections underscores an urgent need for alternative approaches that do not rely solely on developing stronger antibiotics.

DETAILS: Researchers at the University of North Carolina (UNC) School of Medicine, led by Dr. Brian Conlon and Dr. Kuan-Yi Lu, identified a novel small molecule that modifies immune cell behavior to enhance antibiotic performance. Instead of directly targeting bacteria, the molecule reprograms the host's immune cells to activate dormant pathogens, rendering them more susceptible to antibiotic killing.

The team screened approximately 5,000 small molecules through the UNC Small Molecule Screening Core. They used luminescent reporter strains of S. aureus to identify compounds that triggered bacterial activation. The most promising compound was subsequently tested in mouse models, where it significantly improved antibiotic efficacy when administered alongside standard treatments.

In animal models, the selected molecule substantially improved pathogen clearance for S. aureus, M. tuberculosis, and S. enterica when used in combination with existing antibiotics. This finding supports a new therapeutic concept: targeting the host cell environment can potentiate antibiotic activity and overcome intracellular bacterial persistence. The discovery presents an innovative direction for combating infections that evade standard therapy.

Copyright © UNC School of Medicine. All rights reserved.

Source: Conlon, B. and Kuan-Yi, L. UNC Researchers Discover Method to Combat Antibiotic Treatment Failure. UNC Health Newsroom. 2025; Published: October 14, 2025.