Tag: nevin manimala

AIDS. 2024 Apr 16. doi: 10.1097/QAD.0000000000003908. Online ahead of print.

ABSTRACT

OBJECTIVES: Some drugs that augment cell-intrinsic defenses or modulate cell death/survival pathways have been reported to selectively kill cells infected with HIV or SIV, but comparative studies are lacking. We hypothesized that these drugs may differ in their ability to kill cells infected with intact and defective proviruses.

DESIGN: To investigate this hypothesis, drugs were tested ex vivo on Peripheral Blood Mononuclear Cells (PBMC) from nine ART-suppressed individuals.

METHODS: We tested drugs currently in clinical use or human trials, including auranofin (p53 modulator), interferon alpha2A, interferon gamma, acitretin (RIG-I inducer), GS-9620/vesatolimod (TLR7 agonist), nivolumab (PD-1 blocker), obatoclax (Bcl-2 inhibitor), birinapant (IAP inhibitor), bortezomib (proteasome inhibitor), and INK128/sapanisertib (mTOR[c]1/2 inhibitor). After six days of treatment, we measured cell counts/viabilities and quantified levels of total, intact, and defective HIV DNA by droplet digital PCR (Intact Proviral DNA Assay).

RESULTS: Obatoclax reduced intact HIV DNA (median = 27-30% of DMSO) but not defective or total HIV DNA. Other drugs showed no statistically significant effects.

CONCLUSIONS: Obatoclax and other Bcl-2 inhibitors deserve further study in combination therapies aimed at reducing the intact HIV reservoir in order to achieve a functional cure and/or reduce HIV-associated immune activation.

PMID:38626436 | DOI:10.1097/QAD.0000000000003908

Int J Surg. 2024 Apr 17. doi: 10.1097/JS9.0000000000001379. Online ahead of print.

ABSTRACT

BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients.

METHODS: Prospectively colleced data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analysed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×103 U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS.

RESULTS: The normal group (n=179 patients) and the normalization group (n=73 patients) had better OS and RFS than the non-normalization group (n=65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P<0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P=0.255; RFS, P=0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P=0.025; RFS, P=0.003).

CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

PMID:38626431 | DOI:10.1097/JS9.0000000000001379

Int J Surg. 2024 Apr 15. doi: 10.1097/JS9.0000000000001480. Online ahead of print.

ABSTRACT

BACKGROUND: Migraine affects approximately 14-15% of the global population, contributing to nearly 5% of the world’s health burden. When drug treatments prove ineffective for intractable migraines, highly specific surgical interventions emerge as potential solutions. We aimed to analyze surgical approaches for these refractory or intractable migraines through a systematic review and meta-analysis.

METHODS: We conducted a literature search across databases such as PubMed, Scopus, Web of Science, and Embase, focusing on studies related to migraines and surgical outcomes. We considered clinical trials or observational studies that included any surgical intervention for refractory or intractable migraines, emphasizing key outcomes such as reductions in migraine intensity, Migraine Disability Assessment scores (MIDAS), and 50% Migraine Headache Index (MHI) reduction rates. Statistical analyses were performed using R version 4.3.

RESULTS: Eleven studies were included in the systematic review. A meta-analysis of four studies involving overall 95 patients showed a significant reduction in mean migraine intensity scores using ONS (-2.27, 95% CI: -3.92 to -0.63, P=0.021). Three studies with 85 patients showed an average MIDAS score reduction of -52.3, though this was not statistically significant (95% CI: -136.85 to 32.19, P=0.116). Two additional studies corroborated these reductions in MIDAS scores. Nerve decompression surgery showed a substantial decrease in the average migraine intensity (from 8.31 down to 4.06). Median MIDAS score dropped from 57 to 20. Two studies indicated a success rate of 40% and 82%, respectively, in achieving a 50% reduction in the Migraine MHI through nerve decompression. Findings from two studies suggest that septorhinoplasty and sinus surgery effectively decrease migraine intensity scores.

CONCLUSION: The existing evidence emphasizes the potential advantages of surgical interventions as a promising approach to managing intractable or refractory migraines. However, robust and comprehensive research is crucial to refine and solidify the efficacy of these surgical methods, aiming for widespread benefits for patients, considering cost-effectiveness factors.

PMID:38626410 | DOI:10.1097/JS9.0000000000001480

Neurol Neuroimmunol Neuroinflamm. 2024 May;11(3):e200231. doi: 10.1212/NXI.0000000000200231. Epub 2024 Apr 16.

ABSTRACT

BACKGROUND AND OBJECTIVES: Real-life studies noted that the risk of disease activity in multiple sclerosis (MS) after switching to rituximab (RTX) or ocrelizumab (OCR) may be unequal depending on prior disease-modifying therapy (DMT), with a higher risk associated with fingolimod (FING).

METHODS: We performed a retrospective analysis of a structured prospective data collection including all consecutive patients with relapsing MS who were prescribed RTX/OCR in the MS center of Marseille. Cox proportional hazards models were applied to clinical and MRI outcomes.

RESULTS: We included 321 patients with a median (interquartile range [IQR]) follow-up of 3.5 years (1.5-5) after RTX/OCR initiation. At the first RTX/OCR infusion, the mean (SD) age of patients was 37 (10) years, and the median (IQR) disease duration was 8 years (3-15): 68 patients did not receive treatment before RTX/OCR and 108 switched from FING, 47 from low efficacy therapy, and 98 from natalizumab. For statistical analysis, the group “FING” was divided into “short-FING” and “long-FING” groups according to the median value of the group’s washout period (27 days). On Cox proportional hazards analysis, for only the “long-FING” group, the risk of relapse within the first 6 months of RTX/OCR was increased as compared with patients without previous DMT (hazard ratio [HR]: 8.78; 95% CI 1.72-44.86; p < 0.01). Previous DMT and washout period duration of FING had no effect on B-cell levels at 6 months. Beyond the first 6 months of RTX/OCR, age <40 years was associated with increased risk of relapse (HR: 3.93; 95% CI 1.30-11.89; p = 0.01), male sex with increased risk of new T2 lesions (HR: 2.26; 95% CI 1.08-4.74; p = 0.03), and EDSS ≥2 with increased risk of disability accumulation (HR: 3.01; 95% CI 1.34-6.74; p < 0.01). Previous DMT had no effect on the effectiveness of RTX/OCR beyond 6 months after initiation.

DISCUSSION: For patients switching from FING to RTX/OCR, the risk of disease reactivation within the first 6 months of treatment was increased as compared with patients with other DMT or no previous DMT only when the washout period exceeded 26 days. Neither FING nor other previous DMT reduced the effectiveness of RTX/OCR beyond the first 6 months of treatment.

PMID:38626360 | DOI:10.1212/NXI.0000000000200231

Environ Technol. 2024 Apr 16:1-15. doi: 10.1080/09593330.2024.2334292. Online ahead of print.

ABSTRACT

The use of mathematical and statistical models to investigate potential sources of pollutants that have been transported by air masses to a study site is important for establishing control and monitoring measures for air pollutants such as PM₁₀ and PM_2.5. During the study period, from 2018 to 2021, the concentrations of PM₁₀ and PM_2.5 recorded in Ribeirão Preto (SP, Brazil) were higher during spring and winter, with a tendency to increase the amplitude and its maximum values relative to daily averages. The source-receptor model, Potential Source Contribution Function (PSCF), was used to identify probable sources of these pollutants, and the regions known as Triângulo Mineiro and Intermediate Geographic Region of Juiz de Fora (MG, Brazil) were the main regions associated with high PSCF probability values (> 0.5) as sources of PM. These regions indicate that the possible sources of PM emissions are associated with industrial complexes and agriculture, especially coffee production.

PMID:38626330 | DOI:10.1080/09593330.2024.2334292

Int J Neurosci. 2024 Apr 16:1-9. doi: 10.1080/00207454.2024.2341908. Online ahead of print.

ABSTRACT

PURPOSE: The study aims to investigate the effect of prognostic nutritional index (PNI) on the outcome of patients with SAH undergone endovascular occlusion or surgical clipping.

METHODS: Clinical data of consecutive patients with SAH patients who were managed in the neurosurgical department of Kanuni Research and Training Hospital in Trabzon from January 2020 to June 2022 was analyzed. The primary endpoint was early mortality in one month. The prognostic role of PNI was investigated.

RESULTS: Of the 46 patients, 17 were male and 29 were female. The median age was 57.3 (33-89). the last status according to the PNI values of the patients was statistically significant (p = 0.023 < 0.=5). When the patients were divided into two groups according to Glasgow Coma Score as group 1 (the patient’s GCS was lower than 12) and Group 2 (GCS score whose GCS score was between 12-15, the non-parametric Mann-Whitney U test showed a statistical significant between this two group.

CONCLUSION: This study indicates that PNI was correlated with the outcome in patients with SAH. Preoperative impaired nutritional status based on PNI can be accepted as a predictor of affecting the outcome in aneurysmal SAH patients undergoing endovascular occlusion or surgical clipping.

PMID:38626294 | DOI:10.1080/00207454.2024.2341908

JMIR Mhealth Uhealth. 2024 Apr 16. doi: 10.2196/59587. Online ahead of print.

ABSTRACT

BACKGROUND: Wearable sensors are increasingly being explored in healthcare, including in cancer care, for their potential in continuously monitoring patients. Despite their growing adoption, significant challenges remain in the quality and consistency of data collected from wearable sensors. In particular, preprocessing pipelines to clean and standardize raw data have not been fully optimized.

OBJECTIVE: The aim of this study was to conduct a systematic review of preprocessing techniques employed on wearable sensor data to ensure their readiness for artificial intelligence/machine learning (“AI/ML-ready”) applications. Specifically, we sought to understand the landscape of current approaches applied in cleaning, normalizing, and transforming raw datasets into usable formats for subsequent AI/ML analysis.

METHODS: We systematically searched IEEE Xplore, PubMed, Embase (including Embase, Embase Classic, MEDLINE, PubMed-not-MEDLINE), and Scopus to identify potentially relevant studies for this review. The eligibility criteria included: (1) mHealth and wearable sensor studies in cancer; (2) written and published in English; (3) published between January 2018 and December 2023; (4) full text available rather than abstracts; (5) original studies published in peer-reviewed journals or appeared in conference proceedings. The Covidence app was used as a review resource for the screening stage. Statistical learning and image processing techniques were considered irrelevant.

RESULTS: In the initial phase, 2,147 papers were identified between January 2018-December 2023. After a thorough evaluation of these selected papers, we applied our predefined eligibility criteria, which resulted in a total of 20 papers. The following three categories for preprocessing techniques were identified: (1) Data Transformation, (2) Data Scaling, (3) and Data Cleaning.

CONCLUSIONS: While wearable sensors are gaining traction in cancer care, there remain challenges in the application of standard AI/ML techniques due to low quality of raw data captured and not applying appropriate preprocessing pipelines to enrich the data quality. As of now, AI/ML methodologies remain individually tailored to specific studies or types of data, and limit the generalizability of research findings. A general framework for those multiple types of databases has been proposed in this work. Our findings suggest a pressing need to develop and adopt uniform data quality and pre-processing workflows of wearable sensor data that can support the breadth of cancer research and its diverse patient populations.

PMID:38626290 | DOI:10.2196/59587

Aesthet Surg J. 2024 Apr 16:sjae089. doi: 10.1093/asj/sjae089. Online ahead of print.

ABSTRACT

BACKGROUND: Anxiety disorders, both with and without comorbid depression, are widespread globally. This study investigates the intersection of anxiety, depression, and self-reported Breast Implant Illness (BII) in women undergoing aesthetic breast surgery.

OBJECTIVES: The objective of our research is to enhance understanding about mental health history, psychotropic medication use, and its relation to BII symptoms.

METHODS: A cohort of 240 consecutive female patients undergoing elective breast surgery was studied. The study categorized patients into groups based on the presence of self-reported BII symptoms and the type of breast surgery performed. Mental health history, psychotropic medication use, and time spent in treatment for mental illness were scrutinized. Statistical analyses were conducted, including multiple regression analysis.

RESULTS: Results reveal that patients with self-reported BII symptoms often have a pre-existing anxiety/depression disorder treated medically before obtaining breast implants, and this disorder predicts the occurrence of BII symptoms. These patients tend to be diagnosed with anxiety and depression at a younger age, initiate medication therapy earlier, take more medications for their condition, and spend more time in therapy compared to others undergoing elective breast surgery.

CONCLUSIONS: Implications of this study highlight the need for comprehensive counseling between plastic surgeons and patients with self-reported BII symptoms. Understanding the role of anxiety/depression in the pathogenesis of self-reported BII is crucial, and collaboration with psychiatrists and other mental health professionals can ensure improved supportive care. The findings contribute to a better understanding of the psychological aspects surrounding breast implant surgery and self-reported BII and emphasize the importance of preoperative mental health assessments in appropriate patient selection for elective breast surgery.

PMID:38626277 | DOI:10.1093/asj/sjae089

Diabetes Care. 2024 Apr 16:dc232311. doi: 10.2337/dc23-2311. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate glucose metrics and identify potential predictors of the achievement of glycemic outcomes in children and adolescents during their first 12 months of MiniMed 780G use.

RESEARCH DESIGN AND METHODS: This multicenter, longitudinal, real-world study recruited 368 children and adolescents with type 1 diabetes (T1D) starting SmartGuard technology between June 2020 and June 2022. Ambulatory glucose profile data were collected during a 15-day run-in period (baseline), 2 weeks after automatic mode activation, and every 3 months. The influence of covariates on glycemic outcomes after 1 year of MiniMed 780G use was assessed.

RESULTS: After 15 days of automatic mode use, all glucose metrics improved compared with baseline (P < 0.001), except for time below range (P = 0.113) and coefficient of variation (P = 0.330). After 1 year, time in range (TIR) remained significantly higher than at baseline (75.3% vs. 62.8%, P < 0.001). The mean glycated hemoglobin (HbA1c) over the study duration was lower than the previous year (6.9 ± 0.6% vs. 7.4 ± 0.9%, P < 0.001). Time spent in tight range (70-140 mg/dL) was 51.1%, and the glycemia risk index was 27.6. Higher TIR levels were associated with a reduced number of automatic correction boluses (P < 0.001), fewer SmartGuard exits (P = 0.021), and longer time in automatic mode (P = 0.030). Individuals with baseline HbA1c >8% showed more relevant improvement in TIR levels (from 54.3 to 72.3%).

CONCLUSIONS: Our study highlights the sustained effectiveness of MiniMed 780G among youths with T1D. Findings suggest that even children and adolescents with low therapeutic engagement may benefit from SmartGuard technology.

PMID:38626260 | DOI:10.2337/dc23-2311

Eur Heart J Suppl. 2020 Dec 17;22(Suppl N):N81-N82. doi: 10.1093/eurheartj/suaa200. eCollection 2020 Dec.

ABSTRACT

AIMS: Strong epidemiologic evidence has highlighted the role of pollution, on top of adverse climate features, as a novel cardiovascular risk factor. However, mechanistic proof that reducing pollution may be beneficial to prevent atherothrombotic events is limited. We aimed at appraising the impact of temporary traffic bans in a large metropolitan area on the risk of acute coronary syndromes.

METHODS AND RESULTS: Aggregate and anonymized data from 15 tertiary cardiac care centers were obtained detailing pre-coronarivus disease 2019 (COVID-19) daily cases of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), including those treated with percutaneous coronary intervention (PCI). Data on pollutants and climate were sought for the same days. Mixed level regression was used to compare the week before vs. after the traffic ban (Fortnight analysis), the 3 days before vs. after (Weekly analysis) and the Sunday before vs. after (Sunday analysis). A total of 8 days of temporary traffic bans were included, occurring between 2017 and 2020, totaling 802 STEMI and 1196 NSTEMI in the Fortnight analysis, 382 STEMI and 585 in the Weekly analysis, and 148 STEMI and 210 NSTEMI in the Sunday analysis. Fortnight and Sunday analysis did not disclose a significant impact of traffic ban on STEMI or NSTEMI (all P > 0.05). Conversely, Weekly analysis showed non-significant changes for STEMI but a significant decrease in daily NSTEMI when comparing the 3 days before the traffic ban with the ban day (P = 0.043), as well as the 3 days before vs. the 3 days after the ban (P = 0.025). No statistically significant effect of traffic ban was found at Fortnight, Weekly or Sunday analyses for daily mean concentrations of benzene, carbon monoxide, nitric oxide, nitrogen dioxide, ozone, sulfur dioxide, particulate matter (PM) <2.5 µm or PM < 10 µm (all P > 0.05). However, minimum daily concentrations showed a significant reduction of ozone during the ban in comparison to the week preceding it (P = 0.034), nitric oxide during the ban in comparison to the 3 days preceding it (P = 0.046), and an increase in benzene during the ban in comparison to the Sunday before (P = 0.039).

CONCLUSION: Temporary traffic bans may favorably reduce coronary atherothrombotic events, and in particular NSTEMI, even if not globally and immediately impacting on environmental pollution. Further controlled studies are required to confirm and expand this hypothesis-generating results.

PMID:38626246 | PMC:PMC7799104 | DOI:10.1093/eurheartj/suaa200