Nevin Manimala

J Pediatr Surg. 2024 Oct 11;60(1):161994. doi: 10.1016/j.jpedsurg.2024.161994. Online ahead of print.

ABSTRACT

BACKGROUND/PURPOSE: The most frequent complication following hypospadias correction is fistula formation. Recently, fibrin glue has been employed as a 2nd layer covering the urethroplasty resulting in a reduction in the incidence of fistulas. Platelet-rich fibrin (PRF) is an autologous growth factor-rich source. Although the authors recommend the use of additional layers in hypospadias correction, there remains a controversy. In a trial to address this issue, our research was conducted to compare the accessibility of urethroplasty coverage using PRF to traditional local flaps, aiming to prevent fistula formation in hypospadias repair.

PATIENTS AND METHODS: This is a prospective single-blinded randomized controlled study that involved 60 hypospadias cases admitted to Mansoura University Children Hospital’s Pediatric Surgery department between March 2021 and March 2023. These 60 cases were randomly divided into 2 equal groups: (group A platelet-rich fibrin coverage membrane & group B local dartos flap as an additional layer). Both groups were compared regarding the rate of complications. All cases were evaluated regarding age at repair, type of hypospadias, urethral plate width, length of urethroplasty, and size of the 2nd layer. The blood loss and operative time were documented and post-operatively; the cases were assessed for the repair intactness, shape, and size of the neo-meatus, existence of any post-operative problems such as urethral fistula, urethral stricture, meatal stenosis, failure of the repair, or diverticulum. Statistical analysis was carried out following data collection.

RESULTS: The median length of the 2nd layer in group A was 20 mm (range 15-23 mm) and in group B was 22.5 mm (range 19.5-25 mm) and the difference between the two groups was statistically significant (p = 0.012∗), while its median width in group A was 10 mm (range 10-11 mm) and in group B was 15 mm (range 10-18 mm) and also there was statistically significant difference (p = 0.001∗). The mean operative time in group A was 95.73 ± 11.9 min and in group B was 102.33 ± 10.32 min and there was a statistically significant difference (P < 0.001). The length of hospital stay in group A was 5.47 ± 1.11 days and in group B was 5.47 ± 0.89 days. The urethral fistula was detected in 4 cases of group A (13.3%) and 3 cases of group B (10%). The failure of repair was similar, one case of each group (3.3%). The meatal stenosis was reported in only one case of group A (3.4%) and 7 cases of group B (24.1%) (P = 0.02∗) and the difference was statistically significant. There were no reports of urethral strictures among the cases in either group over the follow-up period (mean 9 months, range 5-17 months).

CONCLUSION: PRF patch may be employed as a coverage layer over the urethroplasty in repair of the distal hypospadias, especially in cases without accessible vascular flap with comparable outcome to traditional local flaps.

TYPE OF STUDY: A prospective single blinded randomized controlled trial (computer-generated numbers method).

LEVEL OF EVIDENCE: Level 2.

PMID:39461004 | DOI:10.1016/j.jpedsurg.2024.161994

J Med Econ. 2024 Oct 26:1-8. doi: 10.1080/13696998.2024.2422227. Online ahead of print.

ABSTRACT

OBJECTIVE: In the absence of head-to-head clinical trials, matching-adjusted indirect comparison (MAIC) was used to compare 2 Bruton tyrosine kinase inhibitors (BTKis) approved for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL). This analysis compares the efficacy and safety of acalabrutinib versus ibrutinib using a more mature dataset than a previously published MAIC.

METHODS: Individual patient data from 122 patients treated with acalabrutinib in a phase 2 study were weighted to match aggregate baseline characteristics of patients pooled from 3 separate trials of ibrutinib. Patients were matched on Eastern Cooperative Oncology Group performance status, simplified Mantle Cell Lymphoma International Prognostic Index, lactate dehydrogenase, prior lines of therapy, tumor burden, and blastoid histology. Outcomes assessed included progression-free survival (PFS), overall survival (OS), and adverse events.

RESULTS: After matching, differences in PFS between acalabrutinib (median 17.8 months) and ibrutinib (median 12.8 months) were not statistically significant (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.74-1.15; P = 0.48). Similarly, after matching, OS differences between acalabrutinib (median 36.5 months) and ibrutinib (median 27.9 months) did not reach statistical significance (HR, 0.87; 95% CI, 0.64-1.17; P = 0.35). Acalabrutinib was associated with an improved safety profile compared with ibrutinib, with statistically significantly lower rates of grade ≥3 atrial fibrillation and thrombocytopenia.

CONCLUSIONS: This comparison of 2 BTKis used in the treatment of R/R MCL showed that PFS and OS risk was not statistically different between the treatments; however, acalabrutinib had an improved safety profile compared with ibrutinib.

PMID:39461001 | DOI:10.1080/13696998.2024.2422227

Pak J Pharm Sci. 2024 Sep;37(5):1033-1041.

ABSTRACT

Phytomedicine is gaining acceptance as well preference in health care management for various diseases. Drug combinations are mostly used clinically for hyperlipidemia, as single-agent therapy is insufficient. Statins remain the cornerstone of hyperlipidemia. The objective of the present research is to manage hyperlipidemia with the least amount of medicine effective clinically, thereby limiting its side effects. Study was carried out with 140 registered hyperlipidemia patients, divided into two groups. Group-A received simvastatin 20mg oral daily & Group B received a combination of simvastatin and beta-valgaris capsules twice a day for 90 days. Pre and post treatment values were compared within the groups and between the groups. Group B shows statistically significant decrease (p<0.05) in serum total cholesterol, low density lipoprotein (LDL), triglycerides (TG) and CRP levels. Also significant improvement (p<0.05) was noted for high density lipoprotein (HDL) levels (20.1% to 57.4%) in group B after completion of study. On the basis of our study results, we can conclude that statins remained to be the mainstay treatment for patients with elevated cholesterol levels. However, the combination has a synergistic effect and reduces oxidative stress (OS) as well.

PMID:39460970

Pak J Pharm Sci. 2024 Sep;37(5):961-968.

ABSTRACT

Hospitalized post-operative cardiovascular disease (CVD) patients are often subject to polypharmacy, increasing the risk of potential drug-drug interactions (pDDIs). This observational study assessed 384 post-operative CVD patients for pDDIs using Micromedex Drug-Int® and Lexicomp Interact®. Prevalence, severity, onset and documentation of pDDIs were analyzed using SPSS 23.0, with logistic regression identifying factors associated with at least two major pDDIs or two pDDIs categorized as X, D, or C. Micromedex Drug-Int® revealed a median of 6.23 pDDIs per patient, with 98.7% of patients having ≥1 pDDIs. Of 2,389 pDDIs, 64.1% were major. Lexicomp Interact® data showed a median of 7.15 pDDIs per patient, with 99.2% of patients having ≥1 pDDIs. Class C interactions were the most frequent (62.1%), followed by Classes B, D and X. Additionally, the study identified unique pDDIs from Lexicomp, including Ipratropium-Orphenadrine and Furosemide-Levosulpiride, not listed in Micromedex. The findings highlight the high prevalence of pDDIs in this population, emphasizing the need for regular monitoring. Using pDDI screening tools, clinical pharmacists can be crucial in mitigating these risks, particularly in high-risk patients.

PMID:39460961

Bioinformatics. 2024 Oct 26:btae642. doi: 10.1093/bioinformatics/btae642. Online ahead of print.

ABSTRACT

SUMMARY: Introgression (the flow of genes between species) is a major force structuring the evolution of genomes, potentially providing raw material for adaptation. Here, we present a versatile Bayesian model selection approach for detecting and quantifying introgression, df0BF, that builds upon the recently published distance-based df statistic. Unlike df, df0BF accounts for the number of variant sites within a genomic region. The underlying model parameter of our df0BF method, here denoted as dfθ, accurately quantifies introgression, and the corresponding Bayes Factors (df0BF) enables weighing the strength of evidence for introgression. To ensure fast computation we use conjugate priors with no need for computationally demanding MCMC iterations. We compare our method with other approaches including df, fd, Dp, and Patterson’s D using a wide range of coalescent simulations. Furthermore, we showcase the applicability of df0BF and dfθ using whole-genome mosquito data. Finally, we integrate the new method into the powerful genomics R-package PopGenome.

AVAILABILITY: The presented methods are implemented within the R-package PopGenome (https://github.com/pievos101/PopGenome) and the simulation as the application results can be reproduced from the source code available from a dedicated GitHub repository (https://github.com/pievos101/Introgression-Simulation).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:39460951 | DOI:10.1093/bioinformatics/btae642

Bioinformatics. 2024 Oct 26:btae618. doi: 10.1093/bioinformatics/btae618. Online ahead of print.

ABSTRACT

MOTIVATION: The versatile binding properties of antibodies have made them an extremely important class of biotherapeutics. However, therapeutic antibody development is a complex, expensive and time-consuming task, with the final antibody needing to not only have strong and specific binding, but also be minimally impacted by developability issues. The success of transformer-based language models in protein sequence space and the availability of vast amounts of antibody sequences, has led to the development of many antibody-specific language models to help guide antibody design. Antibody diversity primarily arises from V(D)J recombination, mutations within the CDRs, and/or from a few non-germline mutations outside the CDRs. Consequently, a significant portion of the variable domain of all natural antibody sequences remains germline. This affects the pre-training of antibody-specific language models, where this facet of the sequence data introduces a prevailing bias towards germline residues. This poses a challenge, as mutations away from the germline are often vital for generating specific and potent binding to a target, meaning that language models need be able to suggest key mutations away from germline.

RESULTS: In this study, we explore the implications of the germline bias, examining its impact on both general-protein and antibody-specific language models. We develop and train a series of new antibody-specific language models optimised for predicting non-germline residues. We then compare our final model, AbLang-2, with current models and show how it suggests a diverse set of valid mutations with high cumulative probability.

AVAILABILITY AND IMPLEMENTATION: AbLang-2 is trained on both unpaired and paired data, and is freely available at https://github.com/oxpig/AbLang2.git.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Journal Name online.

PMID:39460949 | DOI:10.1093/bioinformatics/btae618

Semin Ophthalmol. 2024 Oct 26:1-6. doi: 10.1080/08820538.2024.2421475. Online ahead of print.

ABSTRACT

PURPOSE: To describe the presence of pupillary peaking and dysphotopsias in a sample of eyes following glaucoma drainage device (GDD) surgery.

METHODS: Cross-sectional analysis of 68 glaucoma patients with GDD, 45 patients with glaucoma and no GDD, and 50 control patients was conducted in a single academic center. Patients with an appropriate diagnosis that met the inclusion criteria were asked to enroll in the study. All patients received an 8-item dysphotopsia questionnaire and were age-matched. Photographs of pupils were taken to assess pupillary peaking. One-way analysis of variance (ANOVA) testing was performed for statistical analysis.

RESULTS: Of the 68 patients with GDD, 25 (36.76%) had pupillary abnormalities with peaking most commonly occurring in the direction of the tube entry superotemporally, and 50 (73.53%) had reported one or more dysphotopsias. In patients reporting one or more dysphotopsias, the rate of lines, crescents, ghost images, and shadows was significantly higher when compared to glaucoma patients without GDD and control patients (p < .01). This corresponded to a lower best-corrected visual acuity in the GDD group compared to the glaucoma and control groups (p < .001).

CONCLUSIONS: Over a third of glaucoma patients receiving GDD had pupillary abnormalities, and nearly 3 out of 4 patients with GDD reported one or more dysphotopsias when compared to glaucoma patients without GDD and an age-matched control group. Glaucoma specialists and patients should be aware of these complications when proceeding with GDD surgery.

PMID:39460927 | DOI:10.1080/08820538.2024.2421475

Am J Cardiovasc Drugs. 2024 Oct 26. doi: 10.1007/s40256-024-00689-7. Online ahead of print.

ABSTRACT

BACKGROUND: Colchicine has been shown to reduce adverse cardiovascular events (ACE) and stroke among patients with coronary artery disease. However, its efficacy with short- and long-term use and risk of stroke has not been well studied, with conflicting results to date.

OBJECTIVE: We sought to evaluate the efficacy of colchicine for the prevention of stroke and other cardiovascular outcomes and to evaluate the effect of short- and long-term use.

METHODS: We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until July 20th, 2024. Odds ratios (ORs) were pooled using a random-effect model, and a p value of < 0.05 was considered statistically significant.

RESULTS: A total of 16 RCTs with 24,967 patients were included (12,538 in colchicine group and 12,429 in the control group) in the analysis. Pooled analysis of primary outcomes showed that risk of incidence of stroke was comparable between colchicine and placebo groups (OR 0.78, 95% confidence interval [CI] 0.59-1.02, p = 0.07). Pooled analysis of secondary outcomes showed that colchicine significantly reduced the risk of incidence of ACE by 33% (OR 0.67, 95% CI 0.54-0.82, p < 0.001), and myocardial infarction by 21% (OR 0.79, 95% CI 0.65-0.95, p = 0.01) compared with placebo. However, the risk of all-cause mortality (OR 0.98, 95% CI 0.79-1.21, p = 0.83) and cardiovascular mortality (OR 0.78, 95% CI 0.56-1.08, p = 0.14) were comparable between both groups of patients.

CONCLUSION: Colchicine was associated with an overall reduction in the risk of incidence of ACE and MI; however, no such effect was observed with mortality and stroke.

PMID:39460903 | DOI:10.1007/s40256-024-00689-7

Ophthalmol Ther. 2024 Oct 26. doi: 10.1007/s40123-024-01054-2. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to evaluate intraretinal microvascular abnormalities (IRMA) in eyes with advanced nonproliferative diabetic retinopathy (NPDR) using multimodal approach in co-located areas focusing on central retina (up to 50°) and to look at possible correlations between IRMA and other structural changes, like ischemia and presence of microaneurysms.

METHODS: The RICHARD study (NCT05112445) included 60 eyes from 60 patients with type 2 diabetes with moderate-severe NPDR, diabetic retinopathy severity levels 43, 47, and 53 (DRSS). IRMA were defined as capillary tortuosity covering a minimum circular area of 300 µm (calculated to correspond to the Early Treatment Diabetic Retinopathy Study standard photo 8A) and were identified using multimodal imaging with distinct fields of view (FoV): color fundus photography (CFP) using a Topcon TRC-50DX camera (Topcon Medical Systems, Japan), Optos California ultra wide field fundus fluorescein angiography (UWF-FFA) (Optos plc, UK), and swept-source optical coherence tomography angiography (SS-OCTA) (PLEX® Elite 9000, ZEISS, USA). Different areas of the retina were examined: central macula (up to 20°) and posterior pole (between 20° and 50°).

RESULTS: Multimodal imaging was used to identify IRMA in co-located areas (FoV < 50°) including UWF-FFA, CFP, and SS-OCTA. In eyes with DRSS levels 47 and 53, IRMA were identified in both areas of the retina, while in eyes with DRSS level 43, IRMA were detected only outside of the central macula (FoV > 20°). Our results show that when evaluating the presence of IRMA (FoV < 50°), UWF-FFA detected 203 IRMA, SS-OCTA detected 133 IRMA, and CFP detected 104 IRMA. Our results also show that the presence of IRMA was positively associated with presence of microaneurysms.

CONCLUSIONS: Identification of IRMA in eyes with advanced NPDR is better achieved by UWF-FFA than CFP and SS-OCTA. A statistically significant correlation was found between the presence of IRMA and the increase in number of microaneurysms.

TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05112445.

PMID:39460896 | DOI:10.1007/s40123-024-01054-2

Aging Clin Exp Res. 2024 Oct 26;36(1):212. doi: 10.1007/s40520-024-02864-x.

ABSTRACT

BACKGROUND: Dynapenic abdominal obesity (DAO) may be associated with an increased risk of disability. However, to date, this has not been investigated in low- and middle-income countries (LMICs), while the mediators are largely unknown.

AIMS: Therefore, we aimed to investigate the association between DAO and activities of daily living (ADL) disability, and to identify potential mediators among older adults from six LMICs.

METHODS: Cross-sectional, nationally representative data from the WHO Study on global AGEing and adult health were analyzed. Data on 20,198 adults aged ≥ 60 years were analyzed [mean (SD) age 69.3 (13.1) years; 54.1% females]. Dynapenia was defined as handgrip strength of < 26 kg for men and < 16 kg for women. Abdominal obesity was defined as waist circumference of > 88 cm for women and > 102 cm for men. DAO was defined as having both dynapenia and abdominal obesity. Disability was defined as severe or extreme difficulty in conducting at least one of six types of ADL. Multivariable logistic regression and mediation analysis were conducted.

RESULTS: Compared to no dynapenia and no abdominal obesity, DAO was significantly associated with 2.08 (95%CI = 1.37-3.17) times higher odds for ADL disability Mediation analysis showed that diabetes (mediated percentage 4.7%), hypertension (7.2%), and angina (7.7%) were significant mediators in the association between DAO and ADL disability.

CONCLUSIONS: DAO was associated with increased odds for ADL disability among older adults from LMICs. Future longitudinal studies are warranted to assess temporal associations, and whether addressing or preventing DAO can impact on future occurrence of disability.

PMID:39460890 | DOI:10.1007/s40520-024-02864-x