Nevin Manimala

J Thromb Haemost. 2023 Oct 20:S1538-7836(23)00779-1. doi: 10.1016/j.jtha.2023.10.011. Online ahead of print.

ABSTRACT

BACKGROUND: The safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known.

OBJECTIVE: To conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs. LMWH.

METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I² statistic. A total of 10 retrospective studies (n=1,638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup.

RESULTS: The pooled RR for ICH in patients receiving DOACs vs. those receiving LMWH was 0.65 (95% confidence interval [CI], 0.36-1.17; P = 0.15; I² = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = 0.003; I² = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = 0.80; I² = 0%). The overall risk of fatal ICH was not different between anticoagulants.

DISCUSSION: The risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.

PMID:37866517 | DOI:10.1016/j.jtha.2023.10.011

J ISAKOS. 2023 Oct 20:S2059-7754(23)00582-5. doi: 10.1016/j.jisako.2023.10.007. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effects of liposomal bupivacaine use for interscalene blocks on postoperative analgesia in total shoulder arthroplasty patients.

METHODS: De-identified total or reverse total shoulder arthroplasty patients between 2018 and 2021 were analyzed. Patients were grouped into single shot interscalene block with Liposomal Bupivacaine (LB) with plain bupivacaine, Other Block (OB) with other local anesthetics (mepivacaine, ropivacaine, or plain bupivacaine), or No Block (NB). The primary outcome was the proportion of patients with clinically tolerable pain scores (mean VAS <4) from 0 – 24 hours in each group. Secondary outcomes included averaged visual analog pain scores (VAS) and opioid consumption measured in morphine milligram equivalents (MMEs) from 0 – 24 hours. We also analyzed the proportion of patients with clinically tolerable pain, mean VAS, and opioid consumption from 0 – 72 hours in those patients with at least a 3-day hospital length of stay.

RESULTS: A total of 491 de-identified total shoulder arthroplasty patients, 285 liposomal bupivacaine group (LB), 178 other block group (OB), and 28 no block group (NB), were analyzed. The primary outcome showed a statistically significant different proportion of patients with clinically tolerable pain from 0 – 24 hours in the LB group (69%) vs. OB group (39%) vs. NB group (11%) (<0.001). Secondary outcomes included statistically significant differences in VAS (LB median = 3.35, OB median = 4.38, NB median = 5.25 (p <0.001, <0.001)) and total MME opioid consumption (LB median= 40, OB median=60, NB median=88 (p < 0.001, 0.001)) between groups from 0 – 24 hours. For patients who had hospital stays of at least 3 days, a significant association was found with having achieved clinically tolerable pain 0-72 hours and the LB group (51%) vs. OB group (21%) vs. NB group (11%) (P= 0.006). However, there was no statistical difference in mean VAS or opioid consumption between these groups.

CONCLUSION: A greater proportion of total shoulder arthroplasty patients that received liposomal bupivacaine in interscalene block have clinically tolerable pain scores from 0 to 24 hours, lower VAS, and lower MME consumption in patients following total shoulder arthroplasty.

LEVEL OF EVIDENCE: Level III – Clinical Study.

PMID:37866512 | DOI:10.1016/j.jisako.2023.10.007

Chem Biol Interact. 2023 Oct 20:110774. doi: 10.1016/j.cbi.2023.110774. Online ahead of print.

ABSTRACT

Reports on Chinese patent medicines preparations containing Epimedii Folium (EF) and Psoraleae Fructus (PF) resulting in idiosyncratic drug-induced liver injury (IDILI) have received widespread attention. Previous studies have shown that bavachin and epimedin B-two active ingredients derived from both EF and PF-are potential components associated with IDILI, but the underlying mechanism remains unclear. We evaluated bavachin and epimedin B-induced IDILI under TNF-α-mediated immunological stress conditions and generated liver lipid metabolism profiles using lipidomics and multivariate statistical analysis. We next applied transcriptomics to identify the differential gene expression on the transcription level. Our results showed that co-exposure to bavachin, epimedin B under immunological stress conditions resulted in obvious liver injury. The differential metabolites screened in our study were closely related to the immune homeostasis of the liver. Sixteen differentially expressed genes were found, Zc3h6 and R3hdml were upregulated, while Sumo2, Cd74, Banp, Oas3, Oas2, Gbp8, Slfn8, Gbp2b, Serpina3g, Zbtb40, H2-Ab1, Osgin1, Tgtp1 and Hspa1b were all downregulated. These differentially expressed genes were associated with biological processes concerning metabolic process and immune system process. Further integrative analysis indicated that bavachin combined with epimedin B affected genes that were not only related to immune system processes, but also to lipid metabolism. Ultimately, this led to an imbalance in the immune microenvironment in the liver and may have contributed to the observed liver injury.

PMID:37866487 | DOI:10.1016/j.cbi.2023.110774

J Am Acad Child Adolesc Psychiatry. 2023 Oct 18:S0890-8567(23)02136-6. doi: 10.1016/j.jaac.2023.10.004. Online ahead of print.

ABSTRACT

OBJECTIVE: Adolescence is a key developmental window that may determine long-term mental health. As schools may influence students’ mental health, we examined the association of school-level characteristics with students’ mental health over time.

METHOD: We analysed longitudinal data from a cluster randomised controlled trial on 8,376 students (55% female; aged 11-14 years at baseline) across 84 schools in the United Kingdom. Data collection started in the academic years 2016/2017 (Cohort 1) and 2017/2018 (Cohort 2), with follow-up at 1, 1.5, and 2 years. We explored students’ mental health (risk for depression (Center for Epidemiologic Studies-Depression Scale), social-emotional-behavioural difficulties (Strength and Difficulties Questionnaire)) and well-being (Warwick-Edinburgh Mental Well-Being Scale), and their relationship with student- and school-level characteristics, using multilevel regression models.

RESULTS: Mental health difficulties and poorer well-being increased over time, particularly in girls. Differences among schools represented a small but statistically significant proportion of variation (95% CI) in students’ mental health at each timepoint: depression: 1.7% (0.9%-2.5%) to 2.5% (1.6%-3.4%), social-emotional-behavioural difficulties: 1.9% (1.1%-2.7%) to 2.8% (2.1%-3.5%), and well-being: 1.8% (0.9%-2.7%) to 2.2% (1.4%-3.0%). Better student-rated school climate analysed as time-varying at the student- and school-level was associated with lower risk of depression (regression coefficient (95%CI) student-level: -4.25 (-4.48,-4.01), school-level: -4.28 (-5.81,-2.75)), fewer social-emotional-behavioural difficulties (student-level: -2.46 (-2.57,-2.35), school-level: -2.36 (-3.08,-1.63)), and higher well-being (student-level: 3.88 (3.70,4.05); school-level: 4.28 (3.17,5.38)), which was a stable relationship.

CONCLUSION: Student-rated school climate predicted mental health in early adolescence. Policy and system interventions that focus on school climate may promote students’ mental health.

PMID:37866473 | DOI:10.1016/j.jaac.2023.10.004

J Heart Lung Transplant. 2023 Oct 20:S1053-2498(23)02078-8. doi: 10.1016/j.healun.2023.10.014. Online ahead of print.

ABSTRACT

OBJECTIVE: The development of modern antiviral therapy for hepatitis C virus (HCV) has allowed for the transplantation of HCV nucleic acid amplification testing positive (NAT+) donor lungs with acceptable short-term outcomes. We sought to evaluate trends and mid-term outcomes of lung transplant recipients of HCV NAT+ donor allografts.

METHODS: All adults undergoing isolated lung transplantation in the United Network for Organ Sharing database from January 2016 to December 2022 were included in the study. Lung transplant recipients were stratified based on donor HCV status (HCV NAT+ vs NAT-). Propensity-score matching was used to adjust for differences between groups. Several outcomes, including acute rejection by one year, early (30-day and in-hospital) mortality and both 1- and 3-year survival were compared between matched groups.

RESULTS: A total of 16,725 patients underwent lung transplantation during the study period, with 489 (3%) receiving HCV NAT+ donor lungs. Regions 1 (18%), and 6/8 (both 0%) had the highest and lowest proportions, respectively, of HCV NAT+ donor transplants. Utilization of HCV NAT+ donors increased throughout the study period from 2 (0.1%) in 2016 to a peak of 117 (5%) in 2019. Donors who were HCV NAT+ were younger (34 vs 36 years, P<0.001), more often female (44% vs 39%, P<0.01) and more commonly died due to drug intoxication (56% vs 15%, P<0.001). Recipients of HCV NAT+ donor lungs were similar in age (62 vs 62 years, P=0.69) and female gender (43% vs 39%, P=0.15) but had lower lung allocation scores (38 vs 41, P<0.001) compared to others. Rates of acute rejection (13% vs 17%, P=0.09), early mortality (30-day: 2% vs 1%, P=0.59, in-hospital: 3% vs 4%, P=0.38) as well as 1- (90% vs 92%, P=0.29) and 3-year survival (69% vs 75%, P=0.13) were not significantly different between matched groups.

CONCLUSIONS: Lung transplant recipients of HCV NAT+ donor allografts experience similar rates of acute rejection, early mortality and 3-year survival compared to all other lung recipients. Increased use of HCV NAT+ donor allografts may help to expand the donor pool and alleviate donor shortages.

PMID:37866469 | DOI:10.1016/j.healun.2023.10.014

J Am Acad Dermatol. 2023 Oct 20:S0190-9622(23)03029-3. doi: 10.1016/j.jaad.2023.10.026. Online ahead of print.

ABSTRACT

BACKGROUND: Eblasakimab, an interleukin (IL)-13 receptor α1 antagonist, blocks IL-4 and IL-13 signaling through the type 2 receptor.

OBJECTIVE: The safety and efficacy of eblasakimab was evaluated in adults with moderate-to-severe atopic dermatitis (AD).

METHODS: In this phase 1b randomized, double-blinded study, 52 patients with moderate-to-severe AD received weekly subcutaneous injections of eblasakimab 200, 400, or 600 mg, or placebo for 8 weeks. Primary outcome was the incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included percentage change in the Eczema Area and Severity Index (EASI) from baseline; EASI improvement of at least 50%, 75%, or 90% from baseline; and percentage change in the peak-pruritus numeric rating scale score from baseline.

RESULTS: TEAEs were reported in 47% placebo and 71% eblasakimab patients; most were considered mild or moderate and did not lead to study discontinuation. At week 8 eblasakimab 600 mg showed statistically significant improvement in mean percentage change in EASI vs. placebo (-65% vs. -27%, P=0.014). Other key secondary physician- and patient-reported end points were met.

LIMITATIONS: Longer studies are required to confirm eblasakimab safety and efficacy in AD patients.

CONCLUSIONS: Treatment of adults with moderate-to-severe AD with eblasakimab was well-tolerated and associated with significant clinical improvements vs. placebo.

PMID:37866456 | DOI:10.1016/j.jaad.2023.10.026

Photodiagnosis Photodyn Ther. 2023 Oct 20:103855. doi: 10.1016/j.pdpdt.2023.103855. Online ahead of print.

ABSTRACT

AIM: To evaluate serum vitamin D levels in sub-types of retinal vascular occlusions and compare the levels in ischemic and non-ischemic presentations.

METHODS: This study included 50 patients of retinal vascular occlusions comprising central retinal vein occlusion, branch retinal vein occlusion, central retinal artery occlusion, branch retinal artery occlusion (study group) diagnosed on basis of clinical characteristics as well as investigations and an age and gender-matched healthy control group (control group). The study group was further classified into ischemic and non-ischemic subtypes and serum vitamin D levels were analysed and compared.

RESULTS: There were 50 patients of various sub-types of retinal vascular occlusions comprising 13 cases of CRVO, 30 cases of BRVO, 05 cases of CRAO, 02 cases of BRAO and 50 age and sex-matched controls. Mean BCVA and CMT in RVO patients was +1.12 log MAR, 346.72± 27.93µm while in control group was +0.37 log MAR, 236.22 ±3.71 µm which were statistically significant (p=0.004; p=0.002). The mean serum vitamin D value in study group was 18.39 ng/dl as compared to 32.31ng/dl in control group which was statistically significant (p=0.001). The difference in the baseline vitamin D value between the ischemic and non -ischemic sub groups among total vascular occlusion was found to be statistically significant (p= 0.010). However, baseline vitamin D levels difference among ischemic and non-ischemic cases in individual sub-types of vascular occlusion was statistically insignificant.

CONCLUSION: High prevalence of low serum vitamin D levels is seen in patients of retinal vascular occlusion spectrum diseases. Moreover, ischemic types of retinal vascular occlusion have significantly lower serum vitamin D levels as compared to non – ischemic despite having fewer no of patients in arterial occlusion sub-types. Therefore, vitamin D supplements may be considered as possible future targeted therapy in optimizing the severity of disease.

PMID:37866444 | DOI:10.1016/j.pdpdt.2023.103855

Photodiagnosis Photodyn Ther. 2023 Oct 20:103840. doi: 10.1016/j.pdpdt.2023.103840. Online ahead of print.

ABSTRACT

BACKGROUND: Photodynamic therapy (PDT) is a potential treatment for port-wine stains (PWS), but its effects on intraocular pressure (IOP) have not been reported. This study evaluated the efficacy of PDT for facial PWS and analyzed the changes in IOP before and after treatment.

METHODS: Data from 32 patients with facial PWS who underwent single PDT treatment at our department were collected. The patients were divided into three groups based on the location of the PWS. Group A (15 cases) involved the eyelid of the eye being measured; Group B (10 cases) was located near the eyes but did not involve the measured eyelid; and Group C (7 cases) was situated on the face but not near the eyes. IOP measurements were taken before and after treatment, and the efficacy and changes in IOP were analyzed.

RESULTS: The overall efficacy rates of single PDT were 84.37%, demonstrating superior efficacy for the pink type, age < 6 years, and skin lesions < 10 cm² (P < 0.05). The higher IOP was observed on the side with eyelid involvement of PWS (P < 0.001). The IOP of the affected side in Group A decreased by 2.13 ± 2.10 mmHg on average after treatment, which was statistically significant compared with the other two groups (P<0.05).

CONCLUSIONS: Eyelid involvement in PWS increases the risk of elevated IOP. Hemoporfin-mediated PDT can reduce the IOP in patients with PWS involving the eyelid within a safe range. PDT for facial PWS is considered to be safe and effective.

PMID:37866443 | DOI:10.1016/j.pdpdt.2023.103840

Lancet Child Adolesc Health. 2023 Oct 19:S2352-4642(23)00216-X. doi: 10.1016/S2352-4642(23)00216-X. Online ahead of print.

ABSTRACT

BACKGROUND: Paediatric health systems across high-income countries are facing avoidable adverse outcomes and increasing demands and costs. The aim of this study was to compare the effect of an enhanced usual care model with that of an integrated health-care model that offers local health clinics for general paediatric problems and early intervention and care for children and young people with tracer conditions.

METHODS: In this pragmatic two-arm cluster randomised controlled trial, we compared the Children and Young People’s Health Partnership (CYPHP) model of care versus enhanced usual care (EUC) among children registered at general practices in south London, UK. The CYPHP trial intervention was delivered between April 1, 2018, and June 30, 2021, and children younger than 16 years during the intervention period and registered at study practices on June 30, 2021, were included in the analysis. A restricted randomisation (1:1) following a computer-generated sequence was done by a masked independent statistician at the level of general practice cluster, stratified by borough (Lambeth or Southwark). Cluster allocation and data collection were masked, with unmasking of trial statisticians before analysis. The CYPHP model comprised all elements of EUC (electronic decision support, a primary care hotline, health checks, self-management support and health promotion, and resilience building and mental health first aid) plus local child health clinics delivered by paediatricians and general practitioners, and a nurse-led early intervention service for children with tracer conditions (asthma, eczema, and constipation). Primary outcomes were non-elective admissions (NELA; admissions coded as an emergency) among the whole trial population up to June 30, 2021, and paediatric quality of life (Pediatric Quality of Life Inventory [PedsQL]) among participants with tracer conditions at 6 months after recruitment. Secondary outcomes were primary and secondary care use, child mental health, parental wellbeing, standardised symptom scores for asthma, eczema, and constipation, health-care quality, and child absences from school and parent absences from work. The trial was registered on ClinicalTrials.gov, NCT03461848, and is complete.

FINDINGS: The trial was conducted between April 1, 2018, and Dec 31, 2021. In total, 23 general practice clusters, consisting of 70 practices with 97 970 registered children, were randomised to CYPHP (n=11) or EUC (n=12). We found no effect, at the population level, of CYPHP versus EUC on non-elective admissions during the intervention period (adjusted mean incidence rate ratio [IRR] 1·00 [95% CI 0·91 to 1·10], p=0·99). Among children with tracer conditions, we found no difference in paediatric quality of life (PedsQL score) at 6 months (adjusted mean difference -0·033 [95% CI -0·122 to 0·055], p=0·46). As a secondary outcome, among children with tracer conditions and requiring care, NELA rates at 12 months did not differ between the CYPHP and EUC groups (66·1 per 1000 person-years vs 75·3 per 1000 person-years; adjusted mean IRR 0·87 [0·61-1·22], p=0·42). In children requiring care, a statistically significant improvement was observed in eczema symptoms at 6 months from baseline in the CYPHP group versus the EUC group (adjusted mean difference -1·370 [-2·630 to -0·122], p=0·032). Quality of asthma care significantly improved among children in the CYPHP group compared with children in the EUC group. No significant improvement was seen for all other secondary outcomes.

INTERPRETATION: Although the CYPHP trial found a null effect for the primary outcomes, we found clinically important improvements in some secondary outcomes including care quality. Previous research has shown that large-scale system change requires time to observe a potential positive effect.

FUNDING: Guy’s and St Thomas Charity, the Lambeth and Southwark Clinical Commissioning Groups, and Evelina London Children’s Hospital.

PMID:37866369 | DOI:10.1016/S2352-4642(23)00216-X

Int Immunopharmacol. 2023 Oct 20;125(Pt A):111041. doi: 10.1016/j.intimp.2023.111041. Online ahead of print.

ABSTRACT

MAGEA family proteins are immunogenic and can produce corresponding autoantibodies, and we aim to evaluate the diagnostic value of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma (ESCC). Protein chip was used to detect the expression level of anti-MAGEA autoantibodies (IgG and IgM) in 20 mixed serum samples. Enzyme linked immunosorbent assay was adopted to determine the expression level of autoantibodies in 1019 serum samples (423 ESCC, 423 healthy control (HC), 173 benign esophageal disease (BED)), and stepwise logistic regression analysis was used for developing a diagnostic model. Eight anti-MAGEA autoantibodies were screened out based on the protein chip. The levels of 7 autoantibodies (MAGEA1-IgG, MAGEA3-IgG, MAGEA3-IgM, MAGEA4-IgG, MAGEA6-IgG, MAGEA10-IgG, MAGEA12-IgG) in ESCC were significantly higher than that in HC, and the levels of anti-MAGEA1 IgG, anti-MAGEA3-IgG, anti-MAGEA4-IgG, anti-MAGEA10-IgG and anti-MAGEA12-IgG autoantibodies in ESCC group were significantly higher than those in BED group. The area under curve (AUC), sensitivity and specificity of the logistic regression model (MAGEA1-IgG, MAGEA4-IgG, MAGEA6-IgG, MAGEA12-IgG) in the training set and the validation set were 0.725 and 0.698, 55.2% and 51.8%, 80.4% and 84.5%, respectively, in distinguishing ESCC and HC. The model also could distinguish between ESCC and BED, with the AUC of 0.743, sensitivity of 55.4% and specificity of 89.0%. The positive rate of the model combined with cytokeratin 19 fragment to diagnose ESCC reached 78.0%. The study identified anti-MAGEA autoantibodies with potential diagnostic value for ESCC, which may provide new promising for the detection of the disease.

PMID:37866309 | DOI:10.1016/j.intimp.2023.111041