Hepatotoxicity induced by isoniazid in patients with latent tuberculosis infection: a meta-analysis

Adverse drug reaction; Latent tuberculosis; Liver injuryReacción adversa a medicamentos; Tuberculosis latente; Lesión hepáticaReacció adversa a medicaments; Tuberculosi latent; Lesió hepàticaAim: The aim of the present study was to conduct a meta-analysis of the frequency of isoniazid-induced liver injury (INH-ILI) in patients receiving isoniazid (INH) preventative therapy (IPT). Background: The frequency of hepatotoxicity (drug-induced liver injury: DILI) of antituberculosis drugs has been studied, especially when INH, rifampin, and pyrazinamide are co-administered. However, little is known about the frequency of DILI in patients with latent tuberculosis infection (LTBI), where IPT is indicated. Methods: We searched PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews for studies reporting the frequency of INH-ILI in patients with IPT using one or more diagnostic indicators included in the criteria of the DILI Expert Working Group. Results: Thirty-five studies comprising a total of 22,193 participants were included. The overall average frequency of INH-ILI was 2.6% (95% CI, 1.7-3.7%). The mortality associated with INH-DILI was 0.02% (4/22193). Subgroup analysis revealed no significant differences in the frequency of INH-ILI in patients older or younger than 50 years, children, patients with HIV, candidates for liver, kidney, or lung transplant, or according to the type of study design. Conclusion: The frequency of INH-ILI in patients receiving IPT is low. Studies on INH-ILI are needed where the current DILI criteria are used

Evaluation of the Timed Up and Go test for screening vulnerability and frailty in older cancer patients

Introduction. The need for comprehensive geriatric assessment (CGA) in older adults with cancer is increasing, which makes it necessary to have a screening instrument to identify those who would benefit from this evaluation. This study aimed to investigate diagnostic performance of the Timed Up and Go test (TUG) for identifying vulnerable or frail older adults with cancer who might benefit from CGA.  Material and methods. This observational and retrospective study took place at the geriatric center of Almenara Hospital in Lima, Peru. We extracted CGA reports from electronic medical records of outpatients and inpatients aged 60 years and older with cancer, who were evaluated between November 2022 and July 2023. Patients were classified based on SIOG-2 (International Society of Geriatric Oncology) criteria as fit, vulnerable, or frail, based on scales including Activities of Daily Living (ADL), Instrumental ADL, Mini-Nutritional Assessment (MNA), Mini-Mental State Exam (MMSE), Geriatric Depression Scale, and Cumulative Illness Rating Scale-Geriatrics (CIRS-G). For the study, two groups were formed: fit patients and non-fit patients (vulnerable plus frail). We estimated sensitivity, specificity, and positive predictive values of the TUG test. The accuracy of the TUG test was analyzed using the area under the receiver operating characteristic curve (AUC).  Results. Among the 283 included patients, 154 were men (54.4%) and 129 women (45.6%), and the mean age was 76.8 ± 15.8 years. The most common neoplasms were colorectal (19.4%), stomach (15.2%), prostate (9.9%), and bile duct cancers (8.1%). The percentage of fit and non-fit patients was 21.9% and 78.1%, respectively. When the TUG test was equal to or greater than 15.5 seconds, sensitivity, specificity, positive predictive value, and AUC were 68.5% (95% CI 61.9–74.5), 88.5% (77.8–95.3), 95.6% (91.1–98.2), and 84.8% (0.80–0.90), respectively.  Conclusions. A TUG test result equal to or greater than 15.5 seconds demonstrated good screening properties for identifying older cancer patients who were vulnerable or frail and could benefit from CGA

Comprehensive geriatric assessment and clinical outcomes of frail older adults with diffuse large B-cell lymphoma: a metanalysis

Introduction. Comprehensive geriatric assessment (CGA) is used to personalize cancer treatments in frail older adults. However, its utility to guide treatments in frail older patients with diffuse large B-cell lymphoma (DLBCL) is not well known. We performed a meta-analysis of evidence published in this area.  Material and methods. We searched PubMed and Google Scholar for studies published between January 2000 and January 2023 that included patients aged ≥ 65 years with a diagnosis of DLBCL who underwent CGA before treatment (CGA-modulated studies) and who did not (non-CGA-modulated studies). We evaluated clinical outcomes in frail/unfit patients in terms of complete response (CR), incidence of grade ≥ 3 toxicity, and 2-year overall survival (OS) in both types of studies.  Results. Fifteen studies [8 CGA-modulated (n = 733, median age 76, 54% male, 52% frail/unfit) and 7 non-CGA-modulated (n = 2447, median age 76, 52% male, 32% frail/unfit)] were included. In the CGA-modulated studies, the CR proportion of frail/unfit patients was 34% (95% CI 23–46%) vs. 28% (95% CI 19–38%) in the non-CGA-modulated studies (p = 0.436). Grade 3–4 hematological toxicity in frail/unfit patients was 26% (95% CI 5–55%) vs. 36% (95% CI 13–63%) (p = 0.583), respectively. Two-year OS of frail/unfit patients was 52% (95% CI 38–66%) vs. 27% (95% CI 19–36%) (p = 0.003), respectively.  Conclusions. Although the proportion of frail/unfit patients was lower in non-CGA-modulated studies, CGA-modulated studies reported higher OS. CGA could be useful to guide the treatment plan in older patients with DLBCL. Randomized clinical trials with standardized CGA instruments are necessary to confirm these findings

Severity of SARS-COV-2 infection and angiotensin converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis

Background: The mechanism of entry of SARS-COV-2 into the human host cell is through the ACE2 receptor. During the pandemic, a hypothesis has been proposed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) could be risk factors for the development of severe SARS-COV-2 infection. The objective of the study was to conduct a meta-analysis of the association between ACEI or ARB use and SARS-COV-2 infection severity or mortality. Material and methods: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for observational studies published between December 2019 and August 4, 2020 Studies were included if they contained data on ACEI or ARB use and SARS-COV-2 infection severity or mortality. Effect statistics were pooled using random-effects models. The quality of included studies was assessed with the Newcastle–Ottawa Scale (NOS). Data on study design, study location, year of publication, number of participants, sex, age at baseline, outcome definition, exposure definition, effect estimates and 95% CIs were extracted. Results: Twenty-six studies (21 cohort studies and 5 case-control studies) were identified for inclusion, combining to a total sample of 361467 participants. Mean age was 61.48 (SD 8.26) years and 51.63 % were men. The mean NOS score of included studies was 7.85 (range: 7–9). Results suggested that ACEI or ARB use did not increase the risk of severe disease or mortality from SARS-COV-2 infection (OR = 0.88, 95% CI: 0.75–1.02, p > 0.05). Conclusions: At present, the evidence available does not support the hypothesis of increased SARS-COV-2 risk withACEI or ARB drugs

Metformin therapy and severity and mortality of SARS-CoV-2 infection: a meta-analysis

Background: It has been postulated that metformin could have anti-SARS-CoV-2 action. This raises the hypothesis that people who take metformin may have lower SARS-CoV-2 severity and/or mortality. Objective To conduct a meta-analysis of the association between the use of Metformin and risk of severity and mortality in SARS-CoV-2 infection. Data Sources We searched PubMed, EMBASE, Google scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv and Research Square) for studies published between December 2019 and January 2021. Data was extracted on study location, year of publication, design, number of participants, sex, age at baseline, body mass index, and exposure and outcome definition. Effect statistics were pooled using random effects models with 95% confidence intervals (CI). The quality of included studies was assessed with the Newcastle–Ottawa Scale (NOS). Results Thirty-two observational studies were included, combining to a total sample of 44306 participants. The mean NOS score of included studies was 7.9. Results suggested that metformin use was associated with a reduced risk of SARS-CoV-2 mortality (OR= 0.56, 95% CI: 0.46-0.68, p<0.001; 22 studies) but not to disease severity (OR=0.85, 95% CI: 0.71-1.02, p=0.077; 15 studies). In the subgroup analysis, metformin reduces the risk of mortality (OR = 0.69, 95% CI: 0.55-0.88; p=0.002) and severity (OR = 0.83, 95% CI: 0.70-0.97, p=0.023) in patients aged 70 and above. Conclusions The use of metformin was associated to lower risk of mortality from SARS-CoV-2 infection. This association does not imply causation and further research is required to clarify potential mechanisms

Estudio comparativo de RM perfusión en pacientes diagnosticados de hidrocefalia normotensiva con pacientes controles

Diversos estudis han demostrat que existeix una disminució en la irrigació de la substància blanca periventricular en pacients diagnosticats d'hidrocefàlia normotensiva quan es comparen amb subjectes normals. Amb l'objectiu de demostrar aquestes troballes, pacients afectes d'aquesta patología es van sotmetre a una RM cerebral morfológica, un estudi de dinàmica de fluxe de LCR i un estudi de perfusió. Amb aquestes exploracions es va demostrar un augment en l'índex d'Evans i una disminución dels valors de VSC (Volum Sanguini Cerebral) de la substància blanca periventricular als pacients casos enfront dels controls.Diversos estudios han demostrado que existe una disminución en la irrigación de la sustancia blanca periventricular en pacientes diagnosticados de hidrocefalia normotensiva cuando se comparan con sujetos normales. Con el objetivo de demostrar estos hallazgos, pacientes afectos de dicha patología se sometieron a una RM cerebral morfológica, un estudio de dinámica de flujo del LCR y un estudio de perfusión. Con estas exploraciones se demostró un aumento en el índice de Evans y una disminución de los valores de VSC (Volumen Sanguíneo Cerebral) de la sustancia blanca periventricular en los pacientes casos frente a los controles

Estudio comparativo de los valores de difusión por RM de las radiaciones ópticas en pacientes diagnosticados de síndrome clínico aislado con pacientes controles

Diversos estudis han demostrat que, en pacients amb esclerosi múltiple, existeixen alteracions als paràmetres de difusió mesurats amb Resonància Magnètica als tractes de substància blanca que es mostren aparentment normals en les seqüències convencionals. Amb l'objectiu de demostrar si aquestes alteracions apareixen precoçment en la fase de síndrome clínic aïllada, es van analitzar una sèrie d'estudis de Resonància Magnètica cerebral amb seqüències potenciades en difusió i tractografia de les radiacions òptiques, de pacients amb el diagnòstic de síndrome clínic aïllada i pacients controls, mesurant en tots ells els valors dels paràmetres principals de difusió: coeficient de difusió aparent y fracció d'anisotropia. Amb aquestes exploracions no es van demostrar alteracions als paràmetres de difusió en fases tan precoces de la malaltia als pacients casos davant els controls.Diversos estudios han demostrado que, en pacientes con esclerosis múltiple, existen alteraciones en los parámetros de difusión medidos por Resonancia Magnética en los tractos de sustancia blanca que se muestran aparentemente normales en las secuencias convencionales. Con el objetivo de comprobar si estas alteraciones aparecen precozmente en la fase de síndrome clínico aislado, se analizaron una serie de estudios de Resonancia Magnética cerebral con secuencias potenciadas en difusión y tractografía de las radiaciones ópticas, de pacientes con el diagnóstico de síndrome clínico aislado y pacientes controles, midiendo en las mismas los valores de los parámetros principales de difusión: coeficiente de difusión aparente y fracción de anisotropía. Con estas exploraciones no se demostraron alteraciones en los parámetros de difusión en fases tan precoces de la enfermedad en los pacientes casos frente a los controles

The relationship between the severity and mortality of SARS-CoV-2 infection and 25-hydroxyvitamin D concentration — a metaanalysis

Introduction: There is increasing scientific interest in the possible association between hypovitaminosis D and the risk of SARS-CoV-2 infection severity and/or mortality.  Objective: To conduct a metanalysis of the association between 25-hydroxyvitamin D (25(OH)D) concentration and SARS-CoV-2 infection severity or mortality.Material and methods: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for studies published between December 2019 and December 2020. Effect statistics were pooled using random effects models. The quality of included studies was assessed with the Newcastle–Ottawa Scale (NOS). Targeted outcomes: mortality and severity proportions in COVID-19 patients with 25(OH)D deficiency, defined as serum 25(OH)D < 50 nmol/L.  Results: In the 23 studies included (n = 2692), the mean age was 60.8 (SD ± 15.9) years and 53.8% were men. Results suggested that vitamin 25(OH)D deficiency was associated with increased risk of severe SARS-CoV-2 disease (RR 2.00; 95% CI 1.47–2.71, 17 studies) and mortality (RR 2.45; 95% CI 1.24–4.84, 13 studies). Only 7/23 studies reported C-reactive protein values, all of which were > 10 mg/L.Conclusions 25(OH)D deficiency seems associated with increased SARS-CoV-2 infection severity and mortality. However, findings do not imply causality, and randomized controlled trials are required, and new studies should be designed to determine if decreased 25(OH)D is an epiphenomenon or consequence of the inflammatory process associated with severe forms of SARS-CoV-2. Meanwhile, the concentration of 25(OH)D could be considered as a negative acute phase reactant and a poor prognosis in COVID-19 infection

Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis

Brown adipose tissue (BAT) thermogenesis affects energy balance, and thereby it has the potential to induce weight loss and to prevent obesity. Here, we document a macroautophagic/autophagic-dependent mechanism of peroxisome proliferator-activated receptor gamma (PPARG) activity regulation that induces brown adipose differentiation and thermogenesis and that is mediated by TP53INP2. Disruption of TP53INP2-dependent autophagy reduced brown adipogenesis in cultured cells. In vivo specific-tp53inp2 ablation in brown precursor cells or in adult mice decreased the expression of thermogenic and mature adipocyte genes in BAT. As a result, TP53INP2-deficient mice had reduced UCP1 content in BAT and impaired maximal thermogenic capacity, leading to lipid accumulation and to positive energy balance. Mechanistically, TP53INP2 stimulates PPARG activity and adipogenesis in brown adipose cells by promoting the autophagic degradation of NCOR1, a PPARG co-repressor. Moreover, the modulation of TP53INP2 expression in BAT and in human brown adipocytes suggests that this protein increases PPARG activity during metabolic activation of brown fat. In all, we have identified a novel molecular explanation for the contribution of autophagy to BAT energy metabolism that could facilitate the design of therapeutic strategies against obesity and its metabolic complications

Optic Nerve Topography in Multiple Sclerosis Diagnosis

To assess the added value of the optic nerve region (by using visual evoked potentials [VEPs]) to the current diagnostic criteria. From the Barcelona clinically isolated syndrome (CIS) cohort, patients with complete information to assess dissemination in space (DIS), the optic nerve region, and dissemination in time at baseline (n = 388) were selected. Modified DIS (modDIS) criteria were constructed by adding the optic nerve to the current DIS regions. The DIS and modDIS criteria were evaluated with univariable Cox proportional hazard regression analyses with the time to the second attack as the outcome. A subset of these patients who had at least 10 years of follow-up or a second attack occurring within 10 years (n = 151) were selected to assess the diagnostic performance. The analyses were also performed according to CIS topography (optic neuritis vs non-optic neuritis). The addition of the optic nerve as a fifth region improved the diagnostic performance by slightly increasing the accuracy (2017 DIS 75.5%, modDIS 78.1%) and the sensitivity (2017 DIS 79.2%, modDIS 82.3%) without lowering the specificity (2017 DIS 52.4%, modDIS 52.4%). When the analysis was conducted according to CIS topography, the modDIS criteria performed similarly in both optic neuritis and non-optic neuritis CIS. The addition of the optic nerve, assessed by VEP, as a fifth region in the current DIS criteria slightly improves the diagnostic performance because it increases sensitivity without losing specificity