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Genomic analysis and antimicrobial resistance of Vibrio cholerae isolated during Zambia’s 2023 cholera epidemic

Microb Genom. 2025 Dec;11(12). doi: 10.1099/mgen.0.001566.

ABSTRACT

Introduction. Cholera, caused by Vibrio cholerae, remains a priority public health concern, particularly in developing countries. The first cholera outbreak in Zambia was documented in the 1970s, with recurring epidemics reported since then. In 2023, a cholera outbreak affected Zambia, particularly in districts bordering Malawi, Mozambique and the Democratic Republic of Congo, with significant cases reported in these neighbouring countries. This study aims to analyse cholera cases and isolates obtained during the 2023 epidemic, focusing on geographical distribution, genetic relatedness of isolates and their antibiotic resistance profiles.Methods. Stool samples were collected from patients presenting with cholera-like symptoms across three provinces of Zambia. A total of 98 samples were cultured on thiosulphate citrate bile salts sucrose agar, resulting in 32 sequenced V. cholerae isolates. Whole-genome sequencing was performed using Oxford Nanopore Technology, and phylogenetic inference was also achieved by the analysis of SNPs. Phenotypic antimicrobial resistance testing was conducted following Clinical and Laboratory Standards Institute guidelines. The genomic data were analysed for virulence factors and antimicrobial resistance profiles.Results. Of the 98 stool samples tested, 38 confirmed cholera cases were identified. A subset of 32 confirmed V. cholerae isolates, predominantly from the Eastern Province of Zambia (n=21), was selected for whole-genome sequencing. Genomic analysis revealed that all isolates belonged to the seventh pandemic El Tor lineage and the O1 serogroup, with two distinct clades identified corresponding to the 10th (T10) and 15th (T15) transmission events. Geographical analysis indicated a predominance of Ogawa serotypes in Eastern Province and Inaba in Northern Province. The virulence gene analysis confirmed the presence of key cholera toxin genes (ctxA and ctxB) and intestinal colonization factors. All isolates carried genes or mutations predicted to confer resistance to multiple antibiotics, including decreased susceptibility to ciprofloxacin, recommended for the treatment of cholera by the World Health Organization.Conclusion. The findings highlight the critical need for enhanced surveillance and targeted interventions to mitigate cholera outbreaks in Zambia. The emergence of resistant V. cholerae strains necessitates innovative strategies, including improved water sanitation, vaccination efforts and novel therapeutic approaches to combat this enduring public health threat.

PMID:41329510 | DOI:10.1099/mgen.0.001566

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Continuous Glucose Monitoring in Insulin-Treated Older Adults With Diabetes and Alzheimer Disease and Related Dementias

JAMA Netw Open. 2025 Dec 1;8(12):e2541939. doi: 10.1001/jamanetworkopen.2025.41939.

ABSTRACT

IMPORTANCE: Cognitive impairment and glycemic control have a bidirectional association. Understanding the impact of continuous glucose monitoring (CGM) vs self-monitoring of blood glucose (SMBG) is important for treating older adults with Alzheimer disease and related dementias (ADRD) and diabetes that is treated with insulin.

OBJECTIVE: To compare the risks of glycemic outcomes and related adverse events between CGM users and prevalent SMBG users in insulin-treated older adults with ADRD and diabetes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, prevalent-new user cohort study utilized a nationwide, 15% random sample of Medicare claims data (Parts A, B, and D) from January 2016 to December 2020 to ensure balanced cohorts. Insulin-treated older adults (≥66 years) with ADRD and diabetes were included. Individuals in hospice care or with a professional CGM use were excluded. Analysis was carried out from August 2023 to December 2024.

EXPOSURE: Therapeutic CGM use vs prevalent SMBG use.

MAIN OUTCOMES AND MEASURES: Primary outcomes included hypoglycemia hospitalizations, hyperglycemia crisis, and all-cause mortality; falls and all-cause hospitalizations were secondary outcomes. Upper respiratory tract infections served as a negative control outcome. A 1:1 propensity score matching with a 0.25 caliper was carried out for confounding control. Cox proportional hazards models were used for outcome analysis.

RESULTS: In this cohort of 2022 insulin-treated older adults with diabetes and ADRD (1011 CGM users and 1011 SMBG users; mean [SD] age, 76.4 [6.7] years; 1133 female [56.0%]), CGM use was significantly associated with lower risk of all-cause hospitalization (hazard ratio [HR], 0.86; 95% CI, 0.76-0.96) and mortality (HR, 0.57; 95% CI, 0.48-0.67) compared with SMBG use. CGM use had lower point estimates for hypoglycemia hospitalization (HR, 0.66; 95% CI, 0.40-1.08) and falls (HR, 0.86; 95% CI, 0.68-1.08) and higher point estimates for hyperglycemia crisis (HR, 1.38; 95% CI, 0.99-1.94) vs SMBG use, but these findings were not significant. Exploratory subgroup analyses showed varied benefits. The negative control outcome showed no significant differences across analyses.

CONCLUSIONS AND RELEVANCE: In this cohort study of insulin-treated older adults with ADRD and diabetes, CGM use was associated with improved long-term clinical outcomes. Pragmatic (ie, evaluating the effectiveness of healthcare interventions in everyday settings) trials are needed to validate these findings and to assess the feasibility of CGM use in this population.

PMID:41329488 | DOI:10.1001/jamanetworkopen.2025.41939

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Trends in Hospital Resource Use for Children With Complex Chronic Conditions

JAMA Netw Open. 2025 Dec 1;8(12):e2544686. doi: 10.1001/jamanetworkopen.2025.44686.

ABSTRACT

IMPORTANCE: Despite a small prevalence, children with complex chronic conditions (CCCs) use substantial inpatient resources.

OBJECTIVE: To assess national trends in hospital discharges, bed days, and hospital charges for children with and without CCCs in the US from 2000 to 2022.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, repeated cross-sectional study used hospital discharge data from the Kids’ Inpatient Database (KID) from the years 2000, 2003, 2006, 2009, 2012, 2016, 2019, and 2022 for US children aged 0 to 18 years, excluding uncomplicated newborn discharges.

EXPOSURE: Presence of 0, 1, 2, or 3 or more CCCs.

MAIN OUTCOMES AND MEASURES: Trends in the hospital discharge rate per 100 000 children and percentage of total hospital discharges, bed days, and charges attributable to children with CCCs, identified with International Classification of Diseases, 9th Revision, Clinical Modification and International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Clinical Modification codes using Feudtner’s diagnosis code classification system, version 3. Survey weights were applied to estimate hospital discharges, bed days, and charges. Sociodemographic (eg, primary payer) and clinical (eg, technology dependence, mental health comorbidity) characteristics for each hospital discharge were also assessed.

RESULTS: Across all years, there were an estimated 26 342 497 hospital discharges, of which 54.1% (95% CI, 54.0%-54.2%) were among males and 55.4% (95% CI, 54.4%-55.8%) were for infants. From 2000 to 2022, the discharge rate per 100 000 US children increased by 24.3% (95% CI, 22.7%-26.3%), from 779 to 968, for children with 1 or more CCCs and decreased by 9.7% (95% CI, 9.4%-10.0%), from 3831 to 3459, for children with no CCCs. From 2000 to 2022, the percentage change in the hospital discharge rate varied by number of CCCs: a 3.8% (95% CI, 0.9%-6.0%) decrease was found for 1 CCC, a 60.9% (95% CI, 57.7%-65.5%) increase for 2 CCCs, and a 340.0% (95% CI, 332.6%-351.1%) increase for 3 or more CCCs. In 2000 and 2022, children with 1 or more CCCs accounted for 16.9% (95% CI, 15.7%-17.9%) and 21.9% (95% CI, 20.7%-22.9%) of hospital discharges, 32.0% (95% CI, 30.8%-33.1%) and 44.1% (95% CI, 42.6%-45.4%) of bed days, and 44.2% (95% CI, 42.6%-45.5%) and 59.5% (95% CI, 57.8%-60.9%) of hospital charges, respectively. From 2000 to 2022, the percentage of hospital discharges in children with 1 or more CCCs increased with gastroenterologic technology dependence (7.0% [95% CI, 6.0%-8.0%] to 14.4% [95% CI, 12.4%-16.4%]), neurodevelopmental or neurocognitive disorders (5.7% [95% CI, 4.8%-6.5%] to 13.5% [95% CI, 11.7%-15.2%]), and public insurance (40.9% [95% CI, 38.8%-42.9%] to 52.1% [95% CI, 50.2%-54.1%]).

CONCLUSIONS AND RELEVANCE: In this national, repeated cross-sectional study, the hospital discharge rate and the percentage of hospital resource use attributable to children with CCCs increased from 2000 to 2022, and these trends were mainly attributable to children with multiple CCCs. It is critical that health systems are equipped with the resources, staff, and payments to sustainably meet the increasing needs for inpatient care among children with CCCs.

PMID:41329487 | DOI:10.1001/jamanetworkopen.2025.44686

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Decision-Making and Downstream Outcomes of the Gabapentinoid-Diuretic Prescribing Cascade

JAMA Netw Open. 2025 Dec 1;8(12):e2545274. doi: 10.1001/jamanetworkopen.2025.45274.

ABSTRACT

IMPORTANCE: Prescribing cascades are an underrecognized driver of polypharmacy among older adults (aged ≥65 years). The clinical decision-making processes underlying cascades and their downstream consequences are poorly understood.

OBJECTIVE: To explore clinical reasoning leading to prescribing cascades and downstream outcomes (eg, falls, electrolyte abnormalities) via the exemplar gabapentinoid (gabapentin and pregabalin)-loop diuretic (LD) cascade.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study randomly selected medical records from a cohort of US veterans aged 66 years or older between January 1, 2013, and August 31, 2019, who potentially experienced the gabapentinoid-LD prescribing cascade. The medical record review and data analysis were performed between October 24, 2023, and July 22, 2025.

EXPOSURES: Initiation of gabapentinoid and LD.

MAIN OUTCOMES AND MEASURES: Abstractors evaluated clinical documentation in the 30 days prior to and 60 days after LD initiation to evaluate decision-making processes and potential downstream outcomes of the gabapentinoid-LD cascade. Secondary analyses examined whether a dementia diagnosis was associated with clinician decision-making and patient outcomes.

RESULTS: The analytic cohort comprised 120 patients (mean [SD] age, 73.9 [7.1] years; 116 male [96.7%]; 106 [88.3%] taking ≥5 long-term medications). Documentation of a differential diagnosis for edema was noted in 73 patients (60.8%), most commonly referencing congestive heart failure (n = 47 [39.2%]) and/or venous stasis (n = 16 [13.3%]). Gabapentinoids were rarely noted in the differential (n = 4 [3.3%]). The majority of clinicians documented the indication for LD (n = 116 [96.7%]), most commonly for lower-extremity edema (n = 104 [86.7%]), congestive heart failure (n = 16 [13.3%]), and/or dyspnea (n = 15 [12.5%]). In the 60 days following LD initiation, 28 patients (23.3%) experienced 37 events potentially attributable to LD initiation. The most common downstream events were worsening kidney function (n = 9 [7.5%]), orthostasis (n = 7 [5.8%]), electrolyte abnormalities (n = 6 [5.0%]), and falls (n = 5 [4.2%]). Six patients (5.0%) were evaluated in the emergency department and/or hospital for potential downstream events. Documentation of differential diagnoses, indications, actions taken regarding gabapentinoids, and downstream events generally did not vary between patients with and without dementia.

CONCLUSIONS AND RELEVANCE: This cohort study found that among older veterans who received LD following gabapentinoid initiation and experienced a potential gabapentinoid-LD prescribing cascade, clinicians almost never explicitly considered gabapentinoid adverse drug effects in their treatment of edema. These findings suggest that potential downstream harms of this overlooked prescribing cascade are common, underscoring the importance of addressing prescribing cascades in clinical practice.

PMID:41329486 | DOI:10.1001/jamanetworkopen.2025.45274

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Vitamin D Levels During Pregnancy and Dental Caries in Offspring

JAMA Netw Open. 2025 Dec 1;8(12):e2546166. doi: 10.1001/jamanetworkopen.2025.46166.

ABSTRACT

IMPORTANCE: Maternal vitamin D level during pregnancy has been repeatedly reported to be associated with early childhood caries (ECCs) in offspring, yet the conclusions remain inconsistent.

OBJECTIVE: To evaluate the association between maternal vitamin D status in different trimesters during pregnancy and offspring dental caries.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was based on the Zhoushan Pregnant Women Cohort, which enrolled pregnant women between August 2011 to May 2021, and followed up on their offspring until November 2022, at Zhoushan Maternal and Child Health Hospital in Zhoushan, Zhejiang Province, China. Data were analyzed from October 2024 to April 2025.

EXPOSURES: Maternal plasma 25-hydroxyvitamin D (25[OH]D) levels measured in the first, second, and third trimesters and vitamin D deficiency (VDD).

MAIN OUTCOMES AND MEASURES: The primary outcome was offspring ECCs. Secondary outcomes included the decayed, missing, or filled teeth (dmft, with lowercase term denoting primary, instead of permanent, dentition) index and caries rate (the ratio of dmft to number of erupted teeth).

RESULTS: The cohort included 4109 mother-offspring pairs (maternal median [IQR] age, 29.0 [27.0-32.0] years; offspring gestational age at birth, 39.0 [38.0-40.0] weeks; 2121 males [51.6%]), of whom 960 children had ECCs and 3149 did not. Higher maternal 25(OH)D levels were associated with reduced odds of ECCs in offspring (first trimester odds ratio [OR], 0.98 [95% CI, 0.97-0.99], false discovery rate [FDR]-adjusted P = .009; second trimester OR, 0.98 [95% CI, 0.97-0.99], FDR-adjusted P = .001; third trimester OR, 0.99 [95% CI, 0.98-1.00], FDR-adjusted P = .009), while Cox proportional hazards regression models showed protective benefits of 25(OH)D levels against ECC risk throughout all trimesters. Categorical analyses suggested elevated odds of ECCs in offspring of mothers with vitamin D insufficiency, VDD, or severe VDD compared with the vitamin D sufficiency group, although the statistical significance of some associations was attenuated after FDR correction. Moreover, higher maternal 25(OH)D levels (μg/mL) were associated with lower dmft scores (third trimester: β [SE] = -9.97 [3.97]; P = .01) and caries rate (third trimester: β [SE] = -50.87 [19.78]; P = .01). Generalized estimation equation models also confirmed the inverse associations.

CONCLUSIONS AND RELEVANCE: In this cohort study, maternal 25(OH)D levels throughout pregnancy were inversely associated with odds of offspring ECCs. These findings support the potential benefit of vitamin D supplementation before or during pregnancy in reducing the risk and severity of childhood dental caries.

PMID:41329485 | DOI:10.1001/jamanetworkopen.2025.46166

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Surgical Low-Value Care Between Fee-For-Service and Salaried Health Care Systems

JAMA Netw Open. 2025 Dec 1;8(12):e2546213. doi: 10.1001/jamanetworkopen.2025.46213.

ABSTRACT

IMPORTANCE: Low-value care has been recognized as a pernicious phenomenon that increases health care costs and contributes to suboptimal care delivery. Low-value surgery may be less likely in systems that used salaried reimbursement as opposed to fee-for-service.

OBJECTIVE: To explore the association of reimbursement model with low-value surgery among a battery of elective procedures.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used TRICARE health care claims to compare rates of low-value surgery over fiscal years 2016 to 2023. Participants included patients aged 10 years and older who underwent acromioplasty, partial knee meniscectomy, shoulder rotator cuff repair, wrist arthroscopy, or ankle arthroscopy. Data were analyzed from January to May 2025.

EXPOSURE: Direct vs private sector care.

MAIN OUTCOMES AND MEASURES: The primary outcome was the comparison of low-value care in patients in direct care vs private-sector care. An interaction between environment of care and year of surgery was retained in all models. Multivariable logistic regression analyses were used to adjust for case mix. Secondary analyses were limited to non-active-duty individuals to account for differences in low-value care for each surgical procedure.

RESULTS: A total of 304 908 procedures were included. The mean (SD) patient age was 47.2 (12.9) years, with 189 648 (62%) male patients. Partial meniscectomy was the most common surgical procedure (128 363 procedures [42%]), followed by acromioplasty (87 721 procedures [29%]). The percentage of low-value surgery in direct care was 20%, compared with 35% in the private-sector (χ22,304 908 = 90007.01; P < .001). After adjusting for case mix, the private sector demonstrated significantly greater odds of low-value surgery (odds ratio [OR], 1.41; 95% CI, 1.38-1.45). Low-value surgery was significantly lower in each respective sector for 2020 to 2023 compared with 2016 to 2019 (direct care: OR, 0.78; 95% CI, 0.73-0.83; private sector: OR, 0.93; 95% CI, 0.91-0.96).

CONCLUSIONS AND RELEVANCE: In this cohort study of 304 908 surgical procedures, direct care evinced a significantly lower likelihood of low-value surgery in both 2016 to 2019 and 2020 to 2023. These findings support the contention that changing clinician reimbursement models from fee-for-service to salaried is associated with lower rates of low-value care.

PMID:41329484 | DOI:10.1001/jamanetworkopen.2025.46213

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Evaluation of the effectiveness of Cambridge Visual Stimulator treatment in amblyopia patients: a retrospective study

Strabismus. 2025 Dec 2:1-8. doi: 10.1080/09273972.2025.2579178. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to evaluate the long-term efficacy of the Cambridge Visual Stimulator (CAM) in pediatric amblyopia, by comparing outcomes of standard occlusion therapy alone versus occlusion combined with CAM.

METHODS: In this retrospective cohort, 112 patients (112 eyes) aged ≤10 years with strabismic or anisometropic amblyopia were assigned to one of two groups. Group 1 (n = 64) received three hours/day of occlusion therapy; Group 2 (n = 48) received the same occlusion regimen plus a supervised 5-day CAM course (six rotating high-contrast spatial-frequency disks, 18 minutes daily). Best-corrected visual acuity was recorded in logMAR at baseline, 6 months, and 12 months. Within-group improvements were analyzed using the Wilcoxon signed-rank test, and between-group differences with the Mann – Whitney U test. P-value of <0.05 was considered statistically significant.

RESULTS: Both groups showed significant acuity gains at 6 and 12 months versus baseline (p < .001 for all comparisons). Numerically, Group 2 improved more (6 months: -0.137 ± 0.231 vs. -0.127 ± 0.196; 12 months: -0.192 ± 0.267 vs. -0.190 ± 0.225), but these differences did not reach significance (6 months p = .402; 12 months p = .883).

CONCLUSION: Occlusion therapy markedly enhances visual acuity in amblyopic children, whereas adjunctive CAM yields only limited additional benefit. Prospective, larger-scale trials are needed to determine whether specific subgroups – such as treatment-resistant cases – may derive clinically meaningful gains from CAM.

PMID:41329471 | DOI:10.1080/09273972.2025.2579178

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The effect of epinephrine-infused irrigation fluid on visual clarity in arthroscopic shoulder surgery: a meta-analysis

Eur J Orthop Surg Traumatol. 2025 Dec 2;36(1):33. doi: 10.1007/s00590-025-04605-w.

ABSTRACT

BACKGROUND: In shoulder arthroscopy, visual clarity is essential for safe and efficient procedures, yet intraoperative bleeding often compromises the surgical field. Several randomized studies have demonstrated that adding epinephrine to irrigation fluid significantly reduces bleeding and enhances visual clarity. This meta-analysis synthesizes findings from multiple studies to critically evaluate the overall efficacy and safety of epinephrine in improving intraoperative visualization during arthroscopic shoulder surgery.

METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and Google Scholar for studies published up to September 8, 2025. Eligible studies included randomized controlled trials and comparative observational studies evaluating the effect of epinephrine added to irrigation fluid during shoulder arthroscopy in adults. Primary outcomes included surgeon-rated visual clarity (scored on a 1-to-10 scale) and the incidence of increased pump pressure. Secondary outcomes included operative time, irrigation fluid volume used, and mean arterial pressure.

RESULTS: Six studies met the inclusion criteria, including 422 adult patients undergoing arthroscopic shoulder surgery. Epinephrine use was associated with significantly improved surgeon-reported visual clarity, with a mean difference of 2.32 (95% CI 0.32-4.32; p = 0.02) compared to controls. The epinephrine group also had a significantly lower likelihood of requiring increased pump pressure (risk ratio = 0.39; 95% CI 0.27-0.57; p < 0.001). While trends toward reduced operative time (MD = – 4.38 min; 95% CI: – 10.41 to 1.64; p = 0.15) and lower irrigation fluid volume (MD = – 0.83 L; 95% CI: – 2.04 to 0.37; p = 0.18) were observed, these differences were not statistically significant. No significant differences in mean arterial pressure were found between groups (p > 0.05).

CONCLUSION: In the studies reviewed, epinephrine in irrigation fluid during arthroscopic shoulder surgery significantly increases visual clarity. Based on surgical and patient-specific factors, this should be taken into consideration for arthroscopic shoulder procedures.

PMID:41329443 | DOI:10.1007/s00590-025-04605-w

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Carbon-ions, protons or photons for head and neck cancer radiotherapy-an in silico planning study

Phys Eng Sci Med. 2025 Dec 2. doi: 10.1007/s13246-025-01677-0. Online ahead of print.

ABSTRACT

To compare dose to the organ at risk (OAR) and target coverage of carbon-ion beam, protons, and photons for patients with head and neck cancer. Treatment plans for carbon-ion pencil beam scanning (C-PBS) (64 Gy (RBE) in 16 fractions), proton pencil beam scanning (P-PBS), and volumetric modulated arc therapy (VMAT) (70 Gy in 35 fractions for P-PBS and VMAT) were generated and compared using different dose constraints per treatment modality. Dose metrics (e.g. D95,V20) were analyzed. Statistical significance was assessed by the Wilcoxon signed-rank test. Also, we investigated howmany normal tissues were irradiated above the constraint after achieving the planning goals (pass rate) in the OARs. C-PBS outperformed P-PBS and VMAT in PTV coverage (p = 0.01 for both); however, P-PBS and VMAT did not differ substantially from each another (p = 0.35). C-PBS was superior in limiting the dose to the OAR. The pass rates for C-PBS, P-PBS, and VMAT were 94%, 81%, and 69%, respectively. C-PBS demonstrated superior performance compared to VMAT and P-PBS in terms of dose conformation to the target volume and normal tissue sparing, and achieved the highest pass rate in meeting dose constraints.

PMID:41329435 | DOI:10.1007/s13246-025-01677-0

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Short-term outcomes of robotic versus conventional unicompartmental knee arthroplasty: evidence from a national database

J Orthop Traumatol. 2025 Dec 2;26(1):74. doi: 10.1186/s10195-025-00896-1.

ABSTRACT

BACKGROUND: Robotic-assisted unicompartmental knee arthroplasty (UKA) has gained popularity for its potential to improve implant precision and reduce surgical errors. However, comparative evidence on short-term outcomes versus conventional UKA is lacking. Thus, the purpose of this study was to compare the short-term outcomes of robotic-assisted versus conventional UKA using a nationally representative database.

METHODS: The Nationwide Readmissions Database 2016-2020 was retrospectively examined to identify adult patients who received an elective UKA. After applying exclusion criteria and 1:2 propensity score matching (PSM), 8310 patients were included in the analysis. Outcomes included in-hospital complications, implant malposition or failure, perioperative fracture, length of hospital stay (LOS), hospital costs, and 30- and 90-day readmission rates. Multivariable regression analyses were performed to adjust for residual confounding factors.

RESULTS: Robotic-assisted UKA was associated with significantly lower complication rates compared with conventional UKA (3.7% versus 13.2%, p < 0.001). Specifically, robotic-assisted procedures had reduced risks of implant malposition or failure (odds ratio [OR] = 0.08; 95% confidence interval [CI]: 0.05-0.13; p < 0.001) and perioperative fracture (OR = 0.18; 95% CI 0.04-0.76; p = 0.020). No significant differences were observed in LOS, total hospital costs, or readmission rates at 30 and 90 days.

CONCLUSIONS: Robotic-assisted UKA is associated with improved short-term surgical safety, including fewer complications, particularly, reduced implant malposition and perioperative fractures. However, broader hospital metrics such as LOS, cost, and readmissions were comparable between the two approaches. Further prospective studies are needed to validate these findings and assess long-term outcomes and cost-effectiveness.

LEVEL OF EVIDENCE: Level III.

CLINICAL TRIAL REGISTRATION NUMBER: Not applicable.

PMID:41329432 | DOI:10.1186/s10195-025-00896-1