Nevin Manimala

Cardiovasc Drugs Ther. 2025 Aug 26. doi: 10.1007/s10557-025-07764-4. Online ahead of print.

ABSTRACT

PURPOSE: Homozygous Familial Hypercholesterolemia (HoFH) is a rare and life-threatening genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and early-onset atherosclerotic cardiovascular disease. Lomitapide, a microsomal triglyceride transfer protein (MTP) inhibitor, decreases LDL-C independent of LDL receptor function, providing an alternative treatment in this population. We aimed to evaluate the efficacy and safety of lomitapide in patients with HoFH through a systematic review and meta-analysis of available clinical evidence.

METHODS: A comprehensive search was conducted in PubMed, Scopus, and Web of Science through March 2025. Observational studies and clinical trials reporting on lipid profile changes and safety outcomes in HoFH patients receiving lomitapide were included. Outcomes were pooled using random-effects models, and heterogeneity was assessed using the I² statistic.

RESULTS: Eight studies comprising both adult and pediatric patients (n = 209) were included. Lomitapide significantly reduced LDL-C levels by 49.27%, total cholesterol by 46.05%, and apolipoprotein B by 51.01%. Reductions were also observed in triglycerides, VLDL-C, and non-HDL-C. HDL-C remained relatively unchanged. Adverse events were mostly gastrointestinal, with a 14% discontinuation rate. The overall quality of studies ranged from fair to good.

CONCLUSIONS: Lomitapide demonstrates substantial efficacy in reducing LDL-C and other atherogenic lipids in HoFH patients, with an acceptable safety profile. These findings support its role as an adjunctive therapy in this population, though further randomized controlled trials are warranted to validate long-term safety and effectiveness.

PMID:40856940 | DOI:10.1007/s10557-025-07764-4

Mol Diagn Ther. 2025 Aug 26. doi: 10.1007/s40291-025-00812-7. Online ahead of print.

ABSTRACT

Cardiovascular aging is a complex biological process involving progressive cellular and molecular changes that impair heart and vascular function. This review evaluates both fundamental mechanisms and therapeutic strategies, focusing on how recent advances in pharmacology, gene therapy, and regenerative medicine can be translated into clinical practice to mitigate age-related cardiovascular decline. We conducted a comprehensive analysis of peer-reviewed studies from 2000 to 2023, examining molecular pathways of cardiovascular aging and their modulation through pharmacological, genetic, and lifestyle interventions. The review prioritized clinical trials, translational research, and meta-analyses to assess therapeutic efficacy and safety. Current evidence highlights the effectiveness of senolytic drugs such as dasatinib and quercetin in reducing age-related cardiovascular dysfunction, while rapamycin and metformin show promise in improving cardiac longevity through metabolic regulation. Gene therapies, including clustered regularly interspaced short palindromic repeats (CRISPR)-based interventions, demonstrate potential in preclinical models for cardiac regeneration. Stem cell therapies and nanotechnology-based drug delivery systems are emerging as innovative approaches to enhance tissue repair. In addition, lifestyle modifications such as Mediterranean diet adherence and exercise significantly improve vascular health in aging populations. However, challenges remain in drug delivery, patient-specific responses, and long-term safety of novel therapies. The integration of targeted pharmacological treatments, advanced regenerative techniques, and personalized lifestyle interventions represents a transformative approach to managing cardiovascular aging. Future research should focus on optimizing therapeutic combinations, refining delivery methods, and validating biomarkers for clinical monitoring. A multidisciplinary strategy combining these advances will be essential to improve cardiovascular outcomes in aging populations.

PMID:40856932 | DOI:10.1007/s40291-025-00812-7

Jpn J Ophthalmol. 2025 Aug 26. doi: 10.1007/s10384-025-01265-5. Online ahead of print.

ABSTRACT

PURPOSE: This study evaluated the efficacy and safety of initially implanted PreserFlo MicroShunt (PMS) in Japanese patients with exfoliation glaucoma (XFG). Using propensity score matching, intraocular pressure (IOP) control rates were compared between patients with XFG and primary open-angle glaucoma (POAG).

STUDY DESIGN: Retrospective observational study.

METHODS: This study reviewed 31 eyes of 31 patients with XFG who underwent initial PMS implantation with mitomycin C. IOP, medication scores, and corneal endothelial cell density (CECD) were assessed preoperatively and at up to 6 months postoperatively. Kaplan-Meier analysis was used to estimate the 6-month survival rate, defined as an IOP reduction of > 20% from baseline and an IOP < 15 mmHg. The incidences of needling, reoperation, and complications were also assessed. IOP control was compared between XFG and propensity-score-matched POAG patients using the log-rank test.

RESULTS: At 6 months, the mean IOP had decreased significantly, from 22.3 ± 6.6 to 14.7 ± 6.6 mmHg, and the medication score had declined from 4.5 to 1.4. CECD decreased from 2127 to 1902 cells/mm², although this was not statistically significant. The complete success rate (without any glaucoma medications or intervention) was 48%. Postoperative complications included anterior chamber hemorrhage and choroidal detachment. Needling was performed in nine eyes (29.0%), and additional surgery was performed in five eyes (16.1%). Compared to POAG patients (11.9 mmHg), XFG patients had higher postoperative IOP (14.8 mmHg) and higher medication scores (0.5 vs 1.4, p = 0.04) and a lower success rate (62.2% vs 41.7%).

CONCLUSIONS: PMS in Japanese patients with XFG resulted in a significant IOP reduction over 6 months, with a relatively favorable safety profile. However, its efficacy was slightly inferior to that in POAG, implying potential differences in PMS responsiveness between glaucoma subtypes.

PMID:40856918 | DOI:10.1007/s10384-025-01265-5

Am J Clin Dermatol. 2025 Aug 26. doi: 10.1007/s40257-025-00977-1. Online ahead of print.

ABSTRACT

BACKGROUND: Erythrodermic psoriasis (EP) is a severe and rare variant of psoriasis. Clinical features include scaling and erythema affecting more than 75% of body surface area, associated with systemic symptoms such as lymphadenopathy, arthralgia, fever, fatigue, dehydration, serum electrolyte disturbances, and tachycardia, making this condition a potentially life-threatening disease. Differential diagnosis can be challenging, encompasses atopic dermatitis, cutaneous adverse drug reaction, and advanced cutaneous lymphoma. Following a correct diagnostic framing, appropriate systemic treatment must be initiated. Unfortunately, there are no recent up-to-date guidelines and standardized treatment options for EP are still lacking.

OBJECTIVE: To review the current reported systemic treatment options for EP.

METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and based on a search in MEDLINE, PubMed, Scopus, and Cochrane Library for articles in English from first available publication to 9 November 2024.

RESULTS: In all, 145 studies were included in the review. Case reports and case series are the main available work, reporting heterogeneous outcomes and effectiveness with nonbiologic and biologic systemic agents. Among non-biologic systemic treatments, methotrexate and cyclosporin are the most widely reported as treatment for EP, showing clinical response in over 60% of cases, with cyclosporine offering a faster onset of action and being suitable for acute management. Available randomized controlled trials include patients with EP treated with etretinate, infliximab, certolizumab-pegol (CZP), Ixekizumab, guselkumab, risankizumab, and deucravacitinib. However, these trials were not specifically designed for erythrodermic psoriasis, and the sample size of EP patients included is limited, resulting in reduced statistical power and limiting the reliability of the findings. Among TNF-α inhibitors, infliximab is the most reported agent, with data on 103 patients. Certolizumab pegol (CZP) also showed promising results, with PASI 75 achieved in over 80% of patients at 52 weeks. A retrospective analysis comparing infliximab, adalimumab, etanercept, ustekinumab, and efalizumab found TNF-α inhibitors to be superior to other biologic classes. Regarding IL-17 inhibitors, secukinumab is the second most frequently studied biologic, with 93 patients reported. It demonstrated rapid efficacy, achieving PASI 75 in more than 80% of patients by week 8. A head-to-head comparison with ixekizumab showed comparable outcomes. Among IL-23 inhibitors, risankizumab led to PASI 90 in over 75% of patients at week 16, suggesting high efficacy despite more limited data.

CONCLUSIONS: Non-biologic systemic drugs appear to be a rational first-line therapy, with cyclosporine showing good results in managing the acute phase and methotrexate being effective in maintaining remission. In the case of contraindications or treatment failure of traditional systemic therapies, among biologic drugs, the rapidity of action, safety, and limited evidence of efficacy are in favor of IL-17 inhibitors and risankizumab. However, the findings we report are limited by the evidence available in current literature, which is characterized by low statistical power.

PMID:40856907 | DOI:10.1007/s40257-025-00977-1

Clin Implant Dent Relat Res. 2025 Aug;27(4):e70085. doi: 10.1111/cid.70085.

ABSTRACT

OBJECTIVES: The primary aim of this study was to compare the histomorphometric characteristics of two different cortico-cancellous collagenic porcine bone (CCPB) formulations combined with a stabilizing agent used for alveolar ridge preservation (ARP), and the secondary aim was to evaluate and compare clinical and aesthetic outcomes of dental implants placed in augmented sites.

MATERIALS AND METHODS: This was a prospective, cohort-comparative study conducted on patients requiring a tooth extraction followed by ARP and subsequent implant placement. Tooth extractions were performed trying to reduce the surgical trauma as much as possible, and then ARP was performed using two different formulations of CCPB combined with a thermogel in different ratios (50:50 hand-mixed and 80:20 pre-mixed). After 4 months of healing, implant placement was performed, and a bone biopsy was retrieved from the surgical site for histomorphometric analyses. Implants were rehabilitated 3 months following placement with screw-retained crowns, then patients were re-evaluated 1 year following prosthetic loading.

RESULTS: We report the clinical and histomorphometric outcomes of 20 patients divided into the two study groups (10 patients per group). ARP performed with a hand-mixed biomaterial in a 50:50 ratio had higher percentages of newly formed bone (36.15% vs. 27.18%) when compared to a pre-mixed biomaterial in an 80:20 ratio, even though the difference was not statistically significant (p = 0.064). Implants placed in ARP-treated sites showed a very low mean marginal bone loss at the 1-year follow-up in both experimental groups (0.06 ± 0.15 mm in the 50:50 group and 0.25 ± 0.35 mm in the 80:20 group) with no statistically significant differences (p = 0.42), as well as the aesthetic outcomes assessed through the pink aesthetic score.

CONCLUSIONS: Both biomaterials showed effective and favorable outcomes, and the histomorphometric differences observed in our sample did not have any impact on the final clinical and aesthetic outcomes.

PMID:40853738 | DOI:10.1111/cid.70085

Ophthalmic Plast Reconstr Surg. 2025 Aug 23. doi: 10.1097/IOP.0000000000003018. Online ahead of print.

ABSTRACT

PURPOSE: The vasculature within the lower eyelid fat pads in bilateral lower eyelid blepharoplasty (BLLB) surgery is not well described. Characterization of vasculature may help prevent excessive bleeding by describing the locations where pre-emptive cautery may be indicated. We hypothesize that during BLLB, vasculature is most often encountered within the nasal fat pads compared with the central and lateral fat pads.

METHODS: Retrospective chart review of patients who underwent BLLB by a single surgeon was performed. Patients were included if they underwent transconjunctival BLLB with documentation of the encountered intrafat vasculature (I-FV). I-FV was defined as the vessels coursing through the nasal, central, and lateral fat pads and excludes the fine vasculature in the surrounding fat pad shea th. If I-FV was present, it was recorded as “mild,” “moderate,” or “large.” If no vasculature was observed, “minimal” vasculature was documented.

RESULTS: A total of 222 lower eyelids of 111 patients were included. About 78% (173/222) of lower nasal fat pads contained I-FV, which was statistically higher than the 15% (33/222) of lateral (p < 0.001) and 5% (10/222) of central fat pads (p < 0.001). Symmetry in the presence or absence of I-FV between the left and right sides was found in 65% (72/111) of patients.

CONCLUSIONS: During BLLB, I-FV is most prevalent in the nasal fat pads than in the central or lateral fat pads. We recommend extra caution and potential pre-emptive cautery when manipulating the nasal fat pad to prevent bleeding. The pattern of vasculature encountered on the first operative site may provide insight into the contralateral side.

PMID:40853729 | DOI:10.1097/IOP.0000000000003018

Pacing Clin Electrophysiol. 2025 Aug 25. doi: 10.1111/pace.70033. Online ahead of print.

ABSTRACT

INTRODUCTION: Premature ventricular complexes (PVC) are a common phenomenon observed in both normal and pathological heart conditions. However, they do not always behave in the same way. Different PVCs present with varying QRS morphologies, mechanisms, and origin sites. These differences may imply distinct prognoses. To date, the impact of the three-dimensional distribution of PVCs across the heart on the prognosis of ICD recipients has not been adequately investigated.

MATERIAL AND METHODS: We conducted an ambidirectional cohort study. Patients underwent two twelve-lead ambulatory ECG recordings during follow-up. The spatial distribution of PVCs was analyzed using the algorithm proposed by Kuchar et al. The impact of this spatial distribution on clinical variables was assessed using mixed generalized models.

RESULTS: Fifty-five patients were enrolled, with a mean follow-up time of 41.12 ± 13.48 months. All patients underwent two 12-lead ambulatory ECG recordings. The median PVC count was 91.5. PVCs were classified according to the algorithm proposed by Kuchar et al. PVCs arising from exit sites located in the intermediate left ventricle were associated with a higher number of therapies (odds ratio [OR]: 4.78; 95% confidence interval [CI], 1.19-19.26; p = 0.028) and prolonged QRS duration. PVCs with exit sites located in the septal region were associated with higher NYHA functional classes (OR: 2.22 [95% CI: 1.08-4.44]; p = 0.030). No statistically significant interaction was found between PVC topography and gender, number of ATP episodes, ATP success rate, or number of shock episodes.

CONCLUSION: The spatial distribution of PVCs influenced the prognosis of ICD recipients.

PMID:40853721 | DOI:10.1111/pace.70033

J Law Med. 2025 Jul;32(2):294-297.

ABSTRACT

Risk assessment is an important component of many areas of the law, including criminal law. Forensic psychologists and psychiatrists are sometimes called upon to provide evidence of the risk of future criminal activity through identifying and measuring risk factors with the aid of tools that use scales based on statistical or actuarial risk prediction. At present, there is an emphasis on “structured professional judgment” which combines the use of risk assessment tools with clinical judgment. However, the development of risk assessment tools by private companies using algorithms that are not released to the public raises both ethical and legal issues that are highlighted in this column.

PMID:40853693

JAMA Netw Open. 2025 Aug 1;8(8):e2526148. doi: 10.1001/jamanetworkopen.2025.26148.

ABSTRACT

IMPORTANCE: Transcranial direct current stimulation (tDCS) is emerging as a home-based intervention for neuropsychiatric conditions and cognitive enhancement. However, its effectiveness is limited by interindividual variability, as fixed-dose protocols have failed to account for anatomic differences influencing current delivery to targeted regions and treatment outcome. While computational modeling supports individualized dosing to improve consistency, experimental validation remains limited.

OBJECTIVE: To compare the behavioral and neurophysiologic outcomes of fixed-dose vs individualized-dose tDCS.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study using a within-participant, double-masked, crossover design was conducted from January 1, to March 31, 2024, at the National Institute of Mental Health and Neurosciences in India. Adult participants (aged 21-35 years) received 3 sessions of tDCS (fixed-dose, individualized-dose, and sham stimulation) in counterbalanced order. Individualized doses were calculated using a custom-built simulation toolbox.

MAIN OUTCOMES AND MEASURES: Behavioral performance was measured using reaction time during a rapid naming task. Neurophysiologic effects were assessed using motor-evoked potentials (MEPs) recorded before and after stimulation. Linear mixed-effects models were used for the statistical analysis.

RESULTS: Sixteen right-hand-dominant, bilingual English-Dravidian speakers (mean [SD] age, 23.1 [3.9] years; 8 female [50%]) were included. Individualized-dose tDCS associated with significantly greater reaction time improvement over sham (estimated marginal mean [SD]: before, 753.0 [41.1] ms; after, 619.0 [41.1] ms; change [Δ] = 133.6 ms; SE, 10.2 ms; z score ratio, 13.09) compared with fixed-dose tDCS (before, 694.0 [41.1] ms; after, 680.0 [41.1] ms; Δ = 14.6 ms; SE, 10.1 ms; z score ratio, 1.45). Variability was lower with individualized-dose stimulation (coefficient of variation, -1.14 vs 0.39 fixed vs individualized dose, respectively). Sex-stratified analyses showed that women had improvements with both fixed (Δ = 58.0 ms; P = .003) and individualized (Δ = 113.8 ms; P < .001) stimulation, while men had improvement only with individualized tDCS (Δ = 153.4 ms; P < .001). Seven participants (5 men and 2 women) converted from nonresponders to responders with individualized dosing. For MEPs, individualized-dose tDCS showed greater poststimulation amplitude increases over sham (β [SE], 0.91 [0.23]), although fixed-dose tDCS poststimulation amplitude was smaller, but significant (β [SE], 0.56 [0.23]; P = .02) and showed a higher percentage change (β [SE], 144.26% [55.74%]; P = .01) and reduced variability (coefficient of variation, -0.79 vs 1.12 [fixed]).

CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study, dose-controlled tDCS was associated with consistent behavioral and neurophysiologic improvement, highlighting its translational importance in the treatment of neuropsychiatric disorders.

PMID:40853662 | DOI:10.1001/jamanetworkopen.2025.26148

JAMA Netw Open. 2025 Aug 1;8(8):e2526990. doi: 10.1001/jamanetworkopen.2025.26990.

ABSTRACT

IMPORTANCE: Cancer screening is a critical tool in cancer control, reducing cancer-specific mortality. However, it also has potential harms, including overdiagnosis and overtreatment. Measuring the effect of screening based on all-cause mortality is insensitive to both benefits and harms and requires substantially large sample sizes. Understanding the impact of screening on noncancer-related (off-target) mortality is essential for evaluating its overall benefit.

OBJECTIVE: To assess the association between cancer screening and off-target mortality by comparing mortality rates between screened and unscreened populations based on randomized clinical trials (RCTs).

DATA SOURCES: The analysis examined all RCTs included in a previously published (August 28, 2023) meta-analysis of cancer screening trials that included the end point of all-cause mortality in addition to targeted cancer mortality.

STUDY SELECTION: All RCTs included in the previous meta-analysis were included. The latest search in that meta analysis was conducted on October 12, 2022, with no language or publication date restrictions.

DATA EXTRACTION AND SYNTHESIS: The study followed relevant portions of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Two authors independently extracted data, and a third author verified those data. Off-target mortality was analyzed using rate ratios (RRs) and 95% CIs via a fixed-effects model. Heterogeneity was assessed using the I2 statistic.

MAIN OUTCOME AND MEASURES: The primary outcome was off-target mortality, defined as deaths with a cause that was not the targeted cancer.

RESULTS: A total of 17 RCTs (8 of colorectal, 3 prostate, 3 lung, 2 breast, and 1 multiple cancers) including 1 305 924 participants with 18 508 192 person-years of follow-up were included. Screening did not significantly increase off-target mortality (RR, 1.00; 95% CI, 1.00-1.01); the overall increase in off-target mortality was 0.2% (95% CI, -0.5% to 0.9%). There was no evidence of heterogeneity between trials (I2 = 0.00%; Cochran Q = 14.96, df = 18; P = .66). The trial-specific RRs ranged from 0.89 (95% CI, 0.69-1.15) to 1.09 (95% CI, 0.98-1.22), with all 95% CIs including 1. Targeted cancer deaths accounted for 2.6% to 33.1% of all deaths, depending on the cancer type.

CONCLUSIONS AND RELEVANCE: These findings show that randomization to cancer screening was not associated with more than a very small increase in noncancer-related mortality, with the 95% CI excluding an increase of greater than 1%. The findings emphasize the importance of evaluating targeted and off-target mortality separately rather than relying solely on all-cause mortality.

PMID:40853661 | DOI:10.1001/jamanetworkopen.2025.26990