Category: Nevin Manimala

J Am Acad Orthop Surg. 2026 Mar 10. doi: 10.5435/JAAOS-D-25-00824. Online ahead of print.

ABSTRACT

BACKGROUND: Tandem spinal stenosis (TSS) is characterized by stenosis in two or more noncontiguous spinal regions. Surgical management may involve simultaneous decompression or staged procedures; however, no universally accepted decision-making algorithm exists.

METHODS: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Scopus, and EMBASE databases were searched for studies reporting outcomes of simultaneous and/or staged surgery for TSS. Fifteen studies were included in the qualitative review, and 12 were eligible for meta-analysis. Surgical strategies were compared based on postoperative functional outcomes.

RESULTS: A total of 1,006 interventions (604 staged and 402 simultaneous) were analyzed. Overall, significant postoperative improvement in Japanese Orthopaedic Association scores was observed (pooled SMD, 2.87; 95% CI, 1.88 to 3.86). Subgroup analysis demonstrated the greatest improvement with staged surgery using a cervical-first approach (SMD, 4.31; 95% CI, 3.87 to 4.76; I2 = 0%), followed by simultaneous surgery (SMD, 2.65; 95% CI, 1.76 to 3.53). Lumbar-first staged surgery showed smaller and statistically negligible improvement (SMD, 1.94; 95% CI, -1.69 to 5.56). Complication rates were higher in older patients and in those with longer operative times and greater estimated blood loss.

CONCLUSIONS: Surgical strategy for TSS should be individualized. In the presence of myelopathy, staged surgery prioritizing cervical decompression is recommended. In the absence of myelopathy, simultaneous decompression may be considered in patients who can tolerate longer operative times. We propose a treatment algorithm to guide surgical decision-making based on symptom predominance, presence of myelopathy, and patient comorbidities.

PMID:41802210 | DOI:10.5435/JAAOS-D-25-00824

Ocul Immunol Inflamm. 2026 Mar 9:1-7. doi: 10.1080/09273948.2026.2633445. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate retinal and choroidal microvascular alterations in sarcoidosis using optical coherence tomography angiography (OCTA) and assess their association with different clinical phenotypes and disease duration.

METHODS: This cross-sectional study included 76 patients with sarcoidosis divided into three subgroups: pulmonary (n = 33), pulmonary + ocular (n = 25), and pulmonary + extrapulmonary involvement (n = 18), along with 31 healthy controls. OCTA was used to quantify vessel density (VD) in the superficial (SCP) and deep capillary plexus (DCP), foveal avascular zone (FAZ) area, choriocapillaris flow, and radial peripapillary capillary (RPC) network. Statistical analyses included ANOVA, Tukey post hoc, and correlation tests.

RESULTS: No significant differences were observed between groups for SCP-VD, RPC-VD, FAZ area, or choriocapillaris flow. However, DCP-VD showed significant intergroup differences, particularly in foveal and perifoveal regions (p = 0.005 and p = 0.012). Post hoc analyses revealed that DCP-VD was significantly lower in sarcoidosis subgroups than in controls, even among patients without clinical ocular involvement. No significant correlation was found between disease duration and OCTA metrics, though weak negative trends were observed for perifoveal DCP-VD and foveal SCP-VD.

CONCLUSIONS: DCP-VD is selectively reduced in sarcoidosis, suggesting early subclinical microvascular compromise, particularly in extrapulmonary and ocular phenotypes. OCTA may serve as a valuable non-invasive tool for detecting subtle retinal microvascular changes before clinical signs appear. Further longitudinal studies are warranted to assess the prognostic implications of these findings.

PMID:41802207 | DOI:10.1080/09273948.2026.2633445

Prostate. 2026 Mar 9. doi: 10.1002/pros.70156. Online ahead of print.

ABSTRACT

BACKGROUND: Active surveillance (AS) is the preferred management approach for patients with low-risk prostate cancer (PC); yet whether younger patients with favorable-intermediate-risk (FIR) PC experience increased mortality-risk when electing AS remains unknown. We evaluated all-cause, PC-specific, and non-PC-specific mortality (ACM, PCSM, and non-PCSM) in younger patients with FIR PC managed with either AS/watchful-waiting (WW) or immediate definitive treatment, stratified by race.

METHODS: We conducted a retrospective cohort study using SEER data (2010-2020). Patients included were < 60 years-old with FIR PC. The primary outcome was ACM, secondary outcomes PCSM and non-PCSM. Multivariable Cox and Fine-Gray competing-risk regressions were used, adjusting for known prognostic factors. Interaction by race (White vs underrepresented minority [URM]) was explored. Statistical significance was set at p < 0.025 (Bonferroni-adjusted).

RESULTS: Among 3,832 patients, 127 died (3.31%), including 18 of the 127 deaths from PC (14.17%). Initial treatment with RP/RT did not significantly reduce ACM or non-PCSM compared to AS/WW in White (ACM AHR, 0.92; 95% CI, 0.44-1.94; non-PCSM AHR, 1.36; 95% CI, 0.53-3.46) or URM patients (ACM AHR, 0.68; 95% CI, 0.33-1.43; non-PCSM AHR, 1.04; 95% CI, 0.44-2.44). However, after adjustment for multiplicity RP/RT significantly reduced PCSM-risk compared to AS/WW in URM (AHR, 0.03; 95% CI, 0.00-0.48; p = 0.01), but not in White patients (AHR, 0.21; 95% CI, 0.05-0.88; p = 0.03) although the median follow-up was 6.5-months longer in URM patients undergoing AS/WW compared to RP/RT.

CONCLUSIONS: Early mortality-risks were similar and low in patients age < 60 years with FIR PC managed with AS/WW compared to RP/RT, irrespective of race.

PMID:41802205 | DOI:10.1002/pros.70156

Evolution. 2026 Mar 9:qpag037. doi: 10.1093/evolut/qpag037. Online ahead of print.

ABSTRACT

One of the most fundamental calculations needed in an examination of the effect of natural selection in a Mendelian population is to find the rate of change in continuous-time of the frequency of any allele under natural selection, and from this to find the number of generations needed for the frequency of an allele to change from one given value to another. In this paper we analyze the presently accepted self-contained continuous-time theory of allele frequency change for large populations caused only by natural selection, which assumes no mutation and no gene frequency changes due to random genetic drift in a monoecious diploid population. We claim that the present theory is incomplete, with severe restrictions on how the population size varies over time, and with no natural generations concept built in. In order to remedy this we propose a new self-contained theory, making throughout the same assumptions described above concerning mutation and random genetic drift, and also assuming a monoecious diploid population.

PMID:41802202 | DOI:10.1093/evolut/qpag037

J Am Acad Orthop Surg. 2026 Mar 10. doi: 10.5435/JAAOS-D-25-00569. Online ahead of print.

ABSTRACT

BACKGROUND: Periacetabular metastatic disease can cause notable morbidity, prompting potential surgical intervention. Open approaches, including the Harrington type reconstructive with a total hip replacement and cemented gap cup, have been the standard approach; however, these surgeries are invasive. Minimally invasive techniques, including screw fixation with cementation and potential ablation, aim to reduce morbidity. This study compares surgical and short-term postoperative outcomes between open reconstructive techniques and minimally invasive treatments in patients with periacetabular metastatic disease.

METHODS: Prospectively maintained institutional medical records were used to retrospectively identify patients who had undergone an open approach, who would be minimally invasive candidates, and patients who have undergone the minimally invasive procedure. Demographic, surgical data, and postoperative outcomes of patients with minimum 3-month follow-up were collected. Wilcoxon rank-sum test, chi-squared, and minimal clinically important difference (MCID) tests were used to determine statistical and clinical differences.

RESULTS: Seventeen open and 48 minimally invasive patients were identified. Minimally invasive patients had statistically significant lower rate of surgical blood loss, transfusion rates, surgical time, and length of stay (P < 0.05). Fourteen open and 32 minimally invasive patients had minimum 3-month follow-up. No notable difference was found in the need for secondary procedures, complications, death within 90 days, or Pain and Ambulatory Function Scores (P > 0.05). 57.1% of the open cohort and 43.8% of the minimally invasive cohort met the MCID threshold. Minimally invasive patients had statistically significant quicker return to adjuvant therapies (P < 0.05).

DISCUSSION: Our cohort study demonstrated that minimally invasive techniques reduced surgical morbidity while achieving similar short-term (3 month) postoperative outcomes and a faster return to potentially life-prolonging therapies. Larger patient sample will help determine patients at risk for failure of both approaches and the need for secondary procedures to further define patients who might benefit from the different techniques.

PMID:41802193 | DOI:10.5435/JAAOS-D-25-00569

Mol Carcinog. 2026 Mar 9. doi: 10.1002/mc.70106. Online ahead of print.

ABSTRACT

Oral administration of broccoli constituent sulforaphane (SFN) prevents prostate cancer development in preclinical mouse models. However, the mechanism(s) underlying prostate cancer prevention by SFN are not fully understood. In this study, we used a human relevant mouse model (Hi-Myc mice) to demonstrate restoration of immune surveillance by oral SFN administration. Treatment of Hi-Myc mice with SFN for 16 weeks resulted in about 1.33-fold increase in the number of prostate tumor-infiltrating CD8α + T cells (p = 0.02 by Student’s t-test). The number of CD4+ helper T cells was not affected by SFN treatment. The number of CD11c/MHCII+ dendritic cells was increased by about 57% upon SFN administration. On the other hand, the number of NKp46+ natural killer cells was not significantly affected by SFN treatment. Oral administration of SFN resulted in about 30% decrease in the number of Gr1/CD11b+ myeloid-derived suppressor cells in the prostate tumor when compared to control mice. Plasma levels of interleukin (IL)-1α, IL-1β, IL-4, IL-5, IL-10, and C-X-C motif chemokine ligand 2 (CXCL2 or MIP-2) were statistically significantly lower in SFN-treated mice when compared to control mice. Treatment of recurrent prostate cancer patients with 200 μmol/day of SFN-rich broccoli sprout extract for 20 weeks also caused a statistically significant decrease in plasma levels of IL-1β, IL-4, and IL-13. Cell proliferation inhibition by SFN in vitro was partially but significantly attenuated by IL-4 and IL-13 supplementation in 22Rv1 cells. These results indicate restoration of immune surveillance by oral SFN treatment in Hi-Myc mouse model.

PMID:41802185 | DOI:10.1002/mc.70106

J Occup Environ Med. 2026 Mar 6. doi: 10.1097/JOM.0000000000003694. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the global burden and trends of ischemic heart disease (IHD) attributable to non-optimal temperature among younger and older populations using Global Burden of Disease 2021 data.

METHODS: We estimated temperature-attributable IHD burden (high, low, non-optimal) from 1990-2021 using deaths, Disability-adjusted life years (DALYs), age-standardized rates, and joinpoint regression, stratified by age, sex, region, and Socio-demographic Index. Decomposition analysis examined demographic contributions.

RESULTS: From 1990-2021, age-standardized mortality and disability rates declined globally, yet absolute numbers of deaths and DALYs, especially in older adults. The burden from low temperatures was disproportionately higher in older adults, with extreme disparities in Central Asia. Sex differences shifted with age, and burdens were consistently higher in lower SDI regions.

CONCLUSIONS: Older adults bear a substantially greater IHD burden attributable to non-optimal temperature, highlighting the need for targeted prevention strategies.

PMID:41801250 | DOI:10.1097/JOM.0000000000003694

West Afr J Med. 2025 Aug 29;42(8):677-686.

ABSTRACT

BACKGROUND AND OBJECTIVES: This study aimed to assess the knowledge and perception of Nigerian paediatricians regarding paediatric sleep disorders and their management. It also assessed the state of their current practice with screening, evaluating and treating sleep disorders in children and the perceived barriers and facilitators to the provision of quality care for sleep disorders for Nigerian children.

METHODS: This descriptive cross-sectional study was conducted among 153 Paediatricians who practice in Nigeria and attended the Annual Scientific Meeting of the Paediatrics Association of Nigeria (PAN) held in January 2023 at Akure, Ondo state, Nigeria. We utilized a pilot-tested, semi-structured questionnaire adapted from the Paediatrics sleep survey questionnaire. Data was analysed with the IBM SPSS software, version 20.

RESULTS: The 153 respondents were from the six geopolitical zones in Nigeria. More than two-thirds (66.7%) had a poor knowledge score (<6). The majority of the respondents rated their confidence in diagnosing sleep disorders as fair (63.4%), while 22.2% rated it as poor. Almost all (98.7%) reported the lack of sleep laboratory in their centre of practice. Also, about two-thirds (68.0%) had no paediatric sleep clinic. The main barriers to the management of paediatric sleep disorders were lack of training (119; 77.3%) and lack of sleep laboratory (102; 66.7%). Having a sleep laboratory in the centre of practice was significantly associated with the knowledge of the paediatricians (p = 0.044).

CONCLUSION: There is a need for interventions to improve the knowledge of Nigerian paediatricians on sleep medicine and the provision of Paediatric sleep laboratory facilities in Nigeria.

PMID:41801239

JAMA Pediatr. 2026 Mar 9. doi: 10.1001/jamapediatrics.2026.0071. Online ahead of print.

ABSTRACT

IMPORTANCE: Whether maternal use of acetaminophen during pregnancy is associated with offspring’s neurodevelopment remains debated.

OBJECTIVE: To evaluate the associations of maternal prenatal prescriptions of acetaminophen with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs) among offspring.

DESIGN, SETTING, PARTICIPANTS: This cohort study analyzed 2 092 926 singleton births between 2004 and 2015 in Taiwan, with 1 231 819 having at least 1 sibling. Estimated hazard ratios (HRs) and 95% CIs were examined for offspring ADHD or ASDs according to prenatal acetaminophen prescriptions, adjusting for confounding factors.

EXPOSURE: Prescriptions of acetaminophen were extracted from the National Health Insurance Research Database (NHIRD). Acetaminophen use was defined as having at least 2 dispense records during pregnancy, and the total number of prescriptions and the estimated mean daily dispensed dose were examined.

MAIN OUTCOMES AND MEASURES: The primary outcome was ascertaining diagnoses of ADHD and ASDs from the NHIRD.

RESULTS: Of the 2 092 926 singleton births between 2004 and 2015, 48.3% (n = 1 012 159) were born to mothers with at least 2 acetaminophen prescriptions during pregnancy. In the full cohort ASD dataset (N = 2 092 926), 23 557 children (0.01%) had ASD, and in the full ADHD dataset (N = 2 079 935), 116 387 children (0.06%) had ADHD. In the full cohort, offspring ADHD and ASDs were associated with prenatal prescriptions to acetaminophen, with associations noted for higher frequencies of acetaminophen use or higher mean daily dispensed doses of acetaminophen. In sibling-matched analyses, the associations between prenatal exposures to acetaminophen and ADHD and ASDs among offspring were null. However, a positive association was observed when only the older sibling was exposed (HR, 1.33 [95% CI, 1.17-1.52] for ADHD; HR, 1.75 [95% CI, 1.29-2.36] for ASDs), and a negative association was observed when only the younger sibling was exposed (HR, 0.75 [95% CI, 0.67-0.84] for ADHD; HR, 0.74 [95% CI, 0.57-0.96] for ASDs). The divergence of associations persisted in the bidirectional analyses of higher frequencies of acetaminophen use or higher mean daily doses of acetaminophen.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study in Taiwan suggest that positive associations were observed between maternal prenatal acetaminophen prescriptions and offspring’s ADHD or ASDs in the full cohort but not in the sibling-matched analyses. A substantial divergence in associations in the sibling bidirectional analyses indicates unaddressed sources of bias and prevents firm conclusions from being drawn using the sibling design.

PMID:41801232 | DOI:10.1001/jamapediatrics.2026.0071

JAMA Netw Open. 2026 Mar 2;9(3):e2560058. doi: 10.1001/jamanetworkopen.2025.60058.

ABSTRACT

IMPORTANCE: Increased use of the emergency department (ED) creates strain on the single-payer public health care system in Canada.

OBJECTIVE: To evaluate trends in ED visits and hospital admission rates for urologic conditions in Ontario, Canada, and to determine trends and associated factors for wait times to see a urologist among patients presenting to the ED.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, retrospective cohort study used health administrative data from all EDs and acute care hospitals in Ontario for all adult patients presenting to the ED with a primary urological diagnosis between January 1, 2007, and December 31, 2022. Analyses were performed from January 2023 to April 2024.

MAIN OUTCOMES AND MEASURES: The main outcome was the rate of ED visits with new urologic diagnoses over time. Crude, age-standardized, and sex-standardized annual rates were estimated for index ED visits and hospital admissions. Wait times to see a urologist after ED visit were also determined.

RESULTS: A total of 2 192 213 unique visits to the ED with a main diagnosis of a urologic disorder were identified (mean [SD] patient age, 52.1 [21.2] years; 66.5% female). Of these, 1 732 356 visits represented a new urologic diagnosis (no visits in the prior 2 years). Age- and sex-standardized ED visit rates rose annually from 2007 (0.91 visits per 100 people) to 2015 (1.0 visits per 100 people) (rate ratio [RR], 1.10; 95% CI, 1.09-1.11), then decreased until 2020 (RR, 0.88; 95% CI, 0.87-0.88), before rising again until 2022 (RR, 0.91; 95% CI, 0.90-0.91). Among people seen in the ED with a urologic diagnosis, 10.0% were admitted to the hospital during the study period. The crude rate of admission rose annually (RR, 1.04; 95% CI, 1.03-1.05; P < .001), from 0.07 (95% CI, 0.07-0.08) admissions per 100 people in 2007 to 0.09 (95% CI, 0.09-0.09) in 2022. Patients with greater continuity of outpatient care had lower odds of being admitted. The mean (SD) wait time to see a urologist after an ED visit increased from 62.5 (80.3) days in 2007 to 84.8 (89.3) days in 2014. It subsequently decreased annually until 2022, to 71.1 (70.6) days. Increased comorbidity was associated with lower risk of outpatient urology visit.

CONCLUSIONS AND RELEVANCE: In this cohort study, the annual ED visit rates for new urologic diagnoses, hospital admissions, and wait times to see urologists significantly increased over the study period. These trends were associated with decreasing continuity of care. This increasing burden of acute urologic disease necessitates investment in health care.

PMID:41801205 | DOI:10.1001/jamanetworkopen.2025.60058