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BACKGROUND: Graft-versus-host disease (GVHD) is a recognized complication among individuals undergoing bone marrow transplantation (BMT). There is a requirement for supplementary data regarding the in-patient outcomes of GVHD in individuals who have undergone BMT. Our analysis seeks to assess the healthcare burden and outcomes associated with GVHD in hospitalized patients who have undergone BMT. METHOD: In this retrospective study, we used data from the National Inpatient Sample (NIS) database spanning from 2016 to 2019. Utilizing ICD-10 codes, we distinguished hospitalizations related to BMT and grouped them into two categories: those with GVHD and those without GVHD. Our areas of focus included in-hospital mortality, length of stay, charges, and associations related to GVHD. Unadjusted odds ratios/coefficients were computed through univariable analysis, followed by adjusted odds ratios (aORs)/coefficients from multivariable analysis that considered potential confounding factors. RESULTS: From 2016 to 2019, data were collected from 13,999 hospitalizations with bone marrow transplants. Among them, 836 had GVHD cases. Patient characteristics showed slight differences in mean age and demographics between the two groups, with GVHD patients having a mean age of 51.61 years and higher percentages of males and whites. Analyzing outcomes, patients with GVHD experienced significantly longer hospital stays (41.4 days vs. 21.3 days) and higher total hospital charges ($824,058 vs. $335,765). Adjusting for confounding factors, GVHD posed a substantial risk. The aOR for mortality in GVHD hospitalizations was 7.20 (95% CI: 5.54-9.36, p < .001). The coefficient for the length of stay was 19.36 days (95% CI: 17.29-21.42, p < .001), and the coefficient for total hospital charges was $453,733 (95% CI: $396,577 to $510,889, p < .001) in GVHD cases. Furthermore, GVHD in patients was associated with elevated risks of various medical conditions. The aORs for sepsis, pneumonia, acute respiratory failure, intubation and mechanical ventilation, Clostridium difficile infection, and acute kidney injury (AKI) in GVHD patients were 2.79 (95% CI: 2.28-3.41, p < .001), 3.30 (95% CI: 2.57-4.24, p < .001), 5.10 (95% CI: 4.01-6.49, p < .001), 4.88 (95% CI: 3.75-6.34, p < .001), 1.45 (95% CI: 1.13-1.86, p = .003), and 3.57 (95% CI: 2.97-4.29, p < .001). CONCLUSION: GVHD in individuals undergoing BMT is linked to elevated mortality rates, prolonged hospitalization, and higher healthcare costs. Moreover, they face a significantly increased risk of developing complications, such as sepsis, pneumonia, acute respiratory failure, C. difficile infection, and AKI. These results underscore the critical need for vigilant monitoring and effective GVHD management to improve patient outcomes and reduce the complications associated with BMT. Nevertheless, further prospective studies are essential to obtain a more profound understanding and a comprehensive assessment of outcomes in these hospitalized patients.
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The efficacy and acceptability of various non-invasive brain stimulation (NIBS) interventions for autism spectrum disorder remain unclear. We carried out a systematic review for randomized controlled trials (RCTs) regarding NIBS for reducing autistic symptoms (INPLASY202370003). Sixteen articles (N = 709) met the inclusion criteria for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios with 95â¯% confidence intervals (CIs). Fourteen active NIBS interventions, including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation, and transcranial pulse stimulation were analyzed. Only anodal tDCS over the left dorsolateral prefrontal cortex paired with cathodal tDCS over an extracephalic location (atDCS_F3 + ctDCS_E) significantly improved autistic symptoms compared to sham controls (SMD = - 1.40, 95â¯%CIs = - 2.67 to - 0.14). None of the NIBS interventions markedly improved social-communication symptoms or restricted/repetitive behaviors in autistic participants. Moreover, no active NIBS interventions exhibited significant dropout rate differences compared to sham controls, and no serious adverse events were reported for any intervention.
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BACKGROUND: Resistance to chemotherapy is a major problem in the treatment of patients with triple-negative breast cancer (TNBC). Preclinical data suggest that TNBC is dependent on proteasomes; however, clinical observations indicate that the efficacy of proteasome inhibitors in TNBC may be limited, suggesting the need for combination therapies. METHODS: We compared bortezomib and carfilzomib and their combinations with nelfinavir and lopinavir in TNBC cell lines and primary cells with regard to their cytotoxic activity, functional proteasome inhibition, and induction of the unfolded protein response (UPR). Furthermore, we evaluated the involvement of sXBP1, ABCB1, and ABCG2 in the cytotoxic activity of drug combinations. RESULTS: Carfilzomib, via proteasome ß5 + ß2 inhibition, is more cytotoxic in TNBC than bortezomib, which inhibits ß5 + ß1 proteasome subunits. The cytotoxicity of carfilzomib was significantly potentiated by nelfinavir or lopinavir. Carfilzomib with lopinavir induced endoplasmic reticulum stress and pro-apoptotic UPR through the accumulation of excess proteasomal substrate protein in TNBC in vitro. Moreover, lopinavir increased the intracellular availability of carfilzomib by inhibiting carfilzomib export from cells that express high levels and activity of ABCB1, but not ABCG2. CONCLUSION: Proteasome inhibition by carfilzomib combined with nelfinavir/lopinavir represents a potential treatment option for TNBC, warranting further investigation.
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While high-dose therapy and autologous stem cell transplant (ASCT) remain integral to the primary treatment of newly diagnosed transplant-elble multiple myeloma (MM) patients, the challenge of disease progression persists. The primary objective of this meta-analysis is to evaluate the efficacy and safety of tandem ASCT compared to single ASCT. We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies comparing tandem ASCT with single ASCT in patients with newly diagnosed MM. We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials databases for studies published up to January 2024. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and treatment-related mortality (TRM). We used a random-effects model to calculate pooled hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs). Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa Scale. Twelve studies involving 5057 patients met the inclusion criteria. Tandem ASCT was associated with a significantly higher CRR compared to single ASCT (HR 1.33, 95% CI 1.03-1.71, I2 = 15%), but no significant differences were observed in PFS (HR 0.75, 95% CI 0.42-1.34, I2 = 14%), OS (HR 0.60, 95% CI 0.33-1.10, I2 = 27%), or the ORR (RR 0.80, 95% CI 0.59-1.08, I2 = 33%). However, tandem ASCT was associated with a significantly higher risk of TRM (RR 1.78, 95% CI 1.00-3.18, I2 = 0%). Tandem ASCT improves the CRR but does not provide significant benefits in terms of PFS, OS, or ORR compared to single ASCT in patients with newly diagnosed MM. Moreover, tandem ASCT is associated with a higher risk of TRM. The decision to pursue tandem ASCT should be made on an individual basis, carefully weighing the potential benefits and risks in light of each patient's unique clinical situation. Future research should focus on identifying patient subgroups most likely to benefit from tandem ASCT and exploring strategies to optimize the efficacy and safety of this approach in the context of novel agent-based therapies.
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In this study, we summarized the key findings and potential implications of association studies investigating the relationship between gut microbiota composition and risks for Diabetic nephropathy (DN). We used Mendelian randomization (MR) analysis to explore the relationship between gut microbiota and DN using two different publicly available DN databases. The results were also summarized using five mainstream MR analysis methods. We controlled for various possible biases in the results. The results showed that specific bacterial genera were associated with increased or decreased risk of DN. These associations can be attributed to a variety of factors, including metabolites produced by certain bacteria. Most of our findings are consistent with the existing research findings, but there are still some differences with the existing results. In addition, we also pointed out that some microbiota that may be associated with DN but remain unnoticed can bring new research directions. Our work made use of MR, a reliable technique for examining causal correlations using genetic data investigating potential processes, carrying out longitudinal studies, looking into intervention options, and using a multi-omics approach may be future research avenues. Further, our findings also point to a few unexplored possible study paths for DN in the future. These initiatives may improve our reconciliation of the internal relationships between the gut microbiota and DN and pave the way for more precise prevention and treatment methods. However, it is also critical to recognize any potential restrictions, such as those caused by sample size, population variety, and analytical techniques.
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Nefropatías Diabéticas , Microbioma Gastrointestinal , Análisis de la Aleatorización Mendeliana , Humanos , Microbioma Gastrointestinal/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/microbiología , Factores de RiesgoRESUMEN
INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.
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Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos por Estrés Postraumático , Estimulación Transcraneal de Corriente Directa , Estimulación Magnética Transcraneal , Humanos , Aceptación de la Atención de Salud , Trastornos por Estrés Postraumático/terapia , Estimulación Transcraneal de Corriente Directa/métodos , Estimulación Magnética Transcraneal/métodos , Resultado del Tratamiento , Estimulación del Nervio Vago/métodosRESUMEN
We report the case of a 42-year-old female diagnosed with acute promyelocytic leukemia (APL), who developed differentiation syndrome (DS) on day 14 during induction therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) with sudden-onset dyspnea, abdominal pain, tachycardia, and fever. Her laboratory findings were remarkable for acute kidney injury (AKI), worsening leukocytosis, thrombocytopenia, and lactic acidosis. She was also found to have flash pulmonary edema and a pericardial effusion. Despite immediate dexamethasone and methylprednisolone administration along with cessation of induction therapy, she continued to worsen and suffered a non-shockable cardiac arrest. Return of spontaneous circulation (ROSC) was achieved, but she was in profound shock requiring multiple vasopressors. The patient suffered repeat cardiac arrest later that day and passed away within 24 hours. DS is a potentially life-threatening complication in APL treatment, occurring in about 25% of APL patients and posing significant treatment challenges.
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Objective: Acute promyelocytic leukemia (APL) is associated with an elevated risk of developing disseminated intravascular coagulation (DIC). The purpose of this study was to assess the outcomes of hospitalizations related to DIC in APL and their impact on healthcare. Materials and Methods: This study entailed a cross-sectional and retrospective analysis of the US National Inpatient Sample database. We identified adults with APL and categorized them into groups of patients with and without DIC. Our focus areas included in-hospital mortality, length of stay, charges, and complications associated with DIC. Unadjusted odds ratios/coefficients were computed in univariate analysis, followed by adjusted odds ratios (aOR)/coefficients from multivariate analysis that accounted for confounding factors. Results: Our analysis revealed that APL patients with DIC had a substantially higher aOR for mortality (aOR: 6.68, 95% confidence interval [CI]: 4.76-9.37, p<0.001) and a prolonged length of stay (coefficient: 10.28 days, 95% CI: 8.48-12.09, p<0.001) accompanied by notably elevated total hospital charges (coefficient: $215,512 [95% CI: 177,368-253,656], p<0.001), thereby emphasizing the reality of extended medical care and economic burden. The presence of DIC was associated with increased odds of sepsis, vasopressor support, pneumonia, acute respiratory failure, intubation/mechanical ventilation, and acute kidney injury, reflecting heightened vulnerability to these complications. Patients with DIC demonstrated significantly higher odds ratios for major bleeding, intracranial hemorrhage, gastrointestinal bleeding, red blood cell transfusion, platelet transfusion, fresh frozen plasma transfusion, and cryoprecipitate transfusion, highlighting the pronounced hematological risks posed by DIC. Conclusion: This study has revealed the significant associations between DIC in APL and various outcomes, underscoring the clinical and economic implications of these conditions. The hematological risks further increase patients' vulnerability to bleeding events and the need for transfusions.
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Coagulación Intravascular Diseminada , Leucemia Promielocítica Aguda , Adulto , Humanos , Leucemia Promielocítica Aguda/complicaciones , Leucemia Promielocítica Aguda/epidemiología , Leucemia Promielocítica Aguda/terapia , Coagulación Intravascular Diseminada/epidemiología , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/terapia , Estudios Retrospectivos , Transfusión de Componentes Sanguíneos/efectos adversos , Estudios Transversales , Plasma , Hemorragia , Hospitales , Atención a la SaludRESUMEN
Detecting anti-PF4 antibodies remains the golden diagnostic method for heparin-induced thrombocytopenia (HIT) diagnosis with high sensitivity and specificity. Various lab tests detect anti-PF4 antibodies, including immunoassays and functional assays. Even with positive detection of the anti-PF4 antibody, several factors are involved in the result. The concept of anti-PF4 disorders was recently brought to light during the COVID pandemic since the development of vaccine-induced thrombotic thrombocytopenia (VITT) with the adenovirus-vectored-DNA vaccine during the pandemic. Circumstances that detect anti-PF4 antibodies are classified as anti-PF4 disorders, including VITT, autoimmune HIT and spontaneous HIT. Some studies showed a higher percentage of anti-PF4 antibody detection among the population infected by COVID-19 without heparin exposure and some supported the theory that the anti-PF4 antibodies were related to the disease severity. In this review article, we provide a brief review of anti-PF4 disorders and summarize the current studies of anti-PF4 antibodies and COVID-19 infection.
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BACKGROUND: To investigate the association of four insulin resistance (IR) indicators with hepatic steatosis and fibrosis in patients with metabolic syndrome (MetS), as well as to compare the diagnostic value of these indicators in identifying hepatic steatosis and fibrosis in individuals with MetS. METHODS: This cross-sectional study used the data from the National Health and Nutrition Examination Survey 2017-2018. IR indicators included homeostasis model assessment of IR (HOMA-IR), triglyceride/glucose (TyG) index, triglyceride glucose-waist-to-height ratio (TyG-WHtR), and metabolic score for IR (METS-IR). The main endpoints of this study were hepatic steatosis and hepatic fibrosis. Weighted univariate and multivariate logistic regression models were employed to evaluate the association between four IR indicators and both hepatic steatosis, hepatic fibrosis. The efficacy of various IR indicators in the detection of hepatic steatosis and hepatic fibrosis were assessed using receiver operating characteristics curve (ROC). RESULTS: A total of 876 participants with MetS were enrolled. Among the participants, hepatic steatosis was observed in 587 MetS individuals, while hepatic fibrosis was identified in 151 MetS individuals. In multivariate logistic regression model, HOMA-IR, TyG, TyG-WHtR, and METS-IR were related to the increased odd of hepatic steatosis. Additionally, HOMA-IR, TyG-WHtR, and METS-IR were associated with increased odd of hepatic fibrosis. According to the ROC analysis, the area under the curve (AUC) of the TyG-WHtR (AUC = 0.705, 95%CI: 0.668-0.743) was higher than HOMA-IR (AUC = 0.693, 95%CI: 0.656-0.730), TyG (AUC = 0.627, 95%CI: 0.587-0.666), and METS-IR (AUC = 0.685, 95%CI: 0.648-0.722) for identifying hepatic steatosis of MetS patients. Likewise, TyG-WHtR was also higher than HOMA-IR, TyG, and METS-IR for identifying hepatic fibrosis of MetS patients. CONCLUSION: HOMA-IR, TyG-WHtR, and METS-IR may be associated with the risk of hepatic steatosis and fibrosis among the U.S. adult population with MetS. In addition, TyG-WHtR may have a good predictive value for hepatic steatosis and hepatic fibrosis.
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Hígado Graso , Resistencia a la Insulina , Síndrome Metabólico , Adulto , Humanos , Síndrome Metabólico/complicaciones , Estudios Transversales , Encuestas Nutricionales , Cirrosis Hepática , Hígado Graso/complicaciones , Glucosa , TriglicéridosRESUMEN
Small extracellular vesicles (EVs) are signalling messengers that regulate inter-tissue communication through delivery of their molecular cargo. Here, we show that liver-derived EVs are acute regulators of whole-body glycaemic control in mice. Liver EV secretion into the circulation is increased in response to hyperglycaemia, resulting in increased glucose effectiveness and insulin secretion through direct inter-organ EV signalling to skeletal muscle and the pancreas, respectively. This acute blood glucose lowering effect occurs in healthy and obese mice with non-alcoholic fatty liver disease, despite marked remodelling of the liver-derived EV proteome in obese mice. The EV-mediated blood glucose lowering effects were recapitulated by administration of liver EVs derived from humans with or without progressive non-alcoholic fatty liver disease, suggesting broad functional conservation of liver EV signalling and potential therapeutic utility. Taken together, this work reveals a mechanism whereby liver EVs act on peripheral tissues via endocrine signalling to restore euglycaemia in the postprandial state.
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Vesículas Extracelulares , Enfermedad del Hígado Graso no Alcohólico , Humanos , Animales , Ratones , Control Glucémico , Glucemia , Ratones ObesosRESUMEN
Locally advanced esophageal cancer (LAEC) poses a significant and persistent challenge in terms of effective treatment. Traditionally, the primary strategy for managing LAEC has involved concurrent neoadjuvant chemoradiation followed by surgery. However, achieving a pathologic complete response (pCR) has proven to be inconsistent, and despite treatment, roughly half of patients experience locoregional recurrence or metastasis. Consequently, there has been a paradigm shift towards exploring the potential of immunotherapy in reshaping the landscape of LAEC management. Recent research has particularly focused on immune checkpoint inhibitors, investigating their application in both neoadjuvant and adjuvant settings. These inhibitors, designed to block specific proteins in immune cells, are meant to enhance the immune system's ability to target and combat cancer cells. Emerging evidence from these studies suggests the possibility of a mortality benefit, indicating that immunotherapy may contribute to improved overall survival rates for individuals grappling with esophageal cancer. This manuscript aims to meticulously review the existing literature surrounding neoadjuvant and adjuvant immunotherapy in the context of LAEC management. The intention is to thoroughly examine the methodologies and findings of relevant studies, providing a comprehensive synthesis of the current understanding of the impact of immunotherapy on esophageal cancer.
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BACKGROUND: Our study employs machine learning to predict serum valproic acid (VPA) concentrations, aiming to contribute to the development of non-invasive assays for therapeutic drug monitoring. METHODS: Medical records from 2002 to 2019 were obtained from the Taiwan Chang Gung Research Database. Using various machine learning algorithms, we developed predictive models to classify serum VPA concentrations into two categories (1-50 µg/ml or 51-100 µg/ml) and predicted the exact concentration value. The models were trained on 5142 samples and tested on 644 independent samples. Accuracy was the main metric used to evaluate model performance, with a tolerance of 20 µg/ml for continuous variables. Furthermore, we identified important features and developed simplified models with fewer features. RESULTS: The models achieved an average accuracy of 0.80-0.86 for binary outcomes and 0.72-0.88 for continuous outcome. Ten top features associated with higher serum VPA levels included higher VPA last and daily doses, bipolar disorder or schizophrenia spectrum disorder diagnoses, elevated levels of serum albumin, calcium, and creatinine, low platelet count, low percentage of segmented white blood cells, and low red cell distribution width-coefficient of variation. The simplified models had an average accuracy of 0.82-0.86 for binary outcome and 0.70-0.86 for continuous outcome. LIMITATIONS: The study's predictive model lacked external test data from outside the hospital for validation. CONCLUSIONS: Machine learning models have the potential to integrate real-world data and predict VPA concentrations, providing a promising tool for reducing the need for frequent monitoring of serum levels in clinical practice.
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Trastorno Bipolar , Ácido Valproico , Humanos , Ácido Valproico/uso terapéutico , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/tratamiento farmacológico , Registros Médicos , Algoritmos , Aprendizaje AutomáticoRESUMEN
Non-invasive brain stimulation (NIBS) is a promising treatment for bipolar depression. We systematically searched for randomized controlled trials on NIBS for treating bipolar depression (INPLASY No: 202340019). Eighteen articles (N = 617) were eligible for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios (ORs) with 95% confidence intervals (CIs). Anodal transcranial direct current stimulation over F3 plus cathodal transcranial direct current stimulation over F4 (a-tDCS-F3 +c-tDCS-F4; SMD = -1.18, 95%CIs = -1.66 to -0.69, N = 77), high-definition tDCS over F3 (HD-tDCS-F3; -1.17, -2.00 to -0.35, 25), high frequency deep transcranial magnetic stimulation (HF-dTMS; -0.81, -1.62 to -0.001, 25), and high frequency repetitive TMS over F3 plus low frequency repetitive TMS over F4 (HF-rTMS-F3 +LF-rTMS-F4; -0.77, -1.43 to -0.11, 38) significantly improved depressive symptoms compared to sham controls. Only a-tDCS-F3 +c-tDCS-F4 (OR = 4.53, 95%CIs = 1.51-13.65) and HF-rTMS-F3 +LF-rTMS-F4 (4.69, 1.02-21.56) showed higher response rates. No active NIBS interventions exhibited significant differences in dropout or side effect rates, compared with sham controls.
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Trastorno Bipolar , Estimulación Transcraneal de Corriente Directa , Humanos , Trastorno Bipolar/terapia , Trastorno Bipolar/etiología , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Estimulación Magnética Transcraneal , Encéfalo/fisiologíaRESUMEN
Methods: Twenty individuals in the chronic stage of stroke walked: (1) at their normal pace, (2) slower than normal, and (3) as fast as possible. Functional near-infrared spectroscopy was used to assess bilateral prefrontal, premotor, sensorimotor, and posterior parietal cortices during walking. Results: No significant differences in laterality were observed between walking speeds. The ipsilesional prefrontal cortex was overall more active than the contralesional prefrontal cortex. Premotor and posterior parietal cortex activity were larger during slow and fast walking compared to normal-paced walking with no differences between slow and fast walking. Greater increases in brain activation in the ipsilesional prefrontal cortex during fast compared to normal-paced walking related to greater gait speed modulation. Conclusions: Brain activation is not linearly related to gait speed. Ipsilesional prefrontal cortex, bilateral premotor, and bilateral posterior parietal cortices are important areas for gait speed modulation and could be an area of interest for neurostimulation.
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Corteza Motora , Humanos , Corteza Motora/fisiología , Caminata/fisiología , Lóbulo Parietal , Encéfalo , Corteza Prefrontal/fisiología , MarchaRESUMEN
Chimeric antigen receptor (CAR)-T cell therapies have been approved by FDA to treat relapsed or refractory hematological malignancies. However, the adverse effects of CAR-T cell therapies are complex and can be challenging to diagnose and treat. In this review, we summarize the major adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR T-cell associated HLH (carHLH), and discuss their pathophysiology, symptoms, grading, and diagnosis systems, as well as management. In a future outlook, we also provide an overview of measures and modifications to CAR-T cells that are currently being explored to limit toxicity.
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Neoplasias Hematológicas , Síndromes de Neurotoxicidad , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/genética , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/terapia , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/terapiaRESUMEN
Tau protein is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies, but its physiological function is in debate. Mostly explored in the brain, tau is also expressed in the pancreas. We further explored the mechanism of tau's involvement in the regulation of glucose-stimulated insulin secretion (GSIS) in islet ß-cells, and established a potential relationship between type 2 diabetes mellitus (T2DM) and AD. We demonstrate that pancreatic tau is crucial for insulin secretion regulation and glucose homeostasis. Tau levels were found to be elevated in ß-islet cells of patients with T2DM, and loss of tau enhanced insulin secretion in cell lines, drosophila, and mice. Pharmacological or genetic suppression of tau in the db/db diabetic mouse model normalized glucose levels by promoting insulin secretion and was recapitulated by pharmacological inhibition of microtubule assembly. Clinical studies further showed that serum tau protein was positively correlated with blood glucose levels in healthy controls, which was lost in AD. These findings present tau as a common therapeutic target between AD and T2DM.
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Enfermedad de Alzheimer , Diabetes Mellitus Tipo 2 , Humanos , Ratones , Animales , Insulina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Secreción de Insulina , Proteínas tau/metabolismo , Páncreas/metabolismo , Páncreas/patología , Glucosa/metabolismo , Enfermedad de Alzheimer/metabolismoRESUMEN
Purpose: To evaluate the dissemination and implementation impacts of a rehabilitation intervention. Methods: Systematic evaluation of data sources including academic publishing metrics, publications, and surveys was used to describe the dissemination and implementation impact of the graded repetitive arm supplementary program (GRASP). Three categories in the Payback Framework were evaluated: knowledge production and dissemination, benefits to future research and research use, and real-world uptake and implementation. Results: In the Knowledge production and dissemination category, seven publications, authored by the GRASP research team, were associated with the GRASP, and there were approximately 17,000 download counts of GRASP manuals from the website from 120 countries. In the Benefits to future research and research use category, 15 studies and 8 registered clinical trials, authored by researchers outside of the GRASP team, have used GRASP as an intervention. In the real-world uptake and implementation category, GRASP has informed recommendations in 2 clinical guidelines and 20 review papers, and had high implementation uptake (e.g., 35% [53/154] of UK therapists surveyed had used GRASP; 95% [649/681] who downloaded GRASP had used it). More than 75% of those who had used GRASP identified that GRASP provides more intensity in upper extremity rehabilitation, is evidence-based and easy to implement, and the equipment and manual are easy to obtain. Conclusion: The Payback Framework is useful to evaluate the dissemination and implementation impacts of a rehabilitation intervention. GRASP has been implemented extensively in clinical practice and community in a relatively short time since it has been developed.
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Dental X-ray images are important and useful for dentists to diagnose dental diseases. Utilizing deep learning in dental X-ray images can help dentists quickly and accurately identify common dental diseases such as periodontitis and dental caries. This paper applies image processing and deep learning technologies to dental X-ray images to propose a simultaneous recognition method for periodontitis and dental caries. The single-tooth X-ray image is detected by the YOLOv7 object detection technique and cropped from the periapical X-ray image. Then, it is processed through contrast-limited adaptive histogram equalization to enhance the local contrast, and bilateral filtering to eliminate noise while preserving the edge. The deep learning architecture for classification comprises a pre-trained EfficientNet-B0 and fully connected layers that output two labels by the sigmoid activation function for the classification task. The average precision of tooth detection using YOLOv7 is 97.1%. For the recognition of periodontitis, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve is 98.67%, and the AUC of the precision-recall (PR) curve is 98.38%. For the recognition of dental caries, the AUC of the ROC curve is 98.31%, and the AUC of the PR curve is 97.55%. Different from the conventional deep learning-based methods for a single disease such as periodontitis or dental caries, the proposed approach can provide the recognition of both periodontitis and dental caries simultaneously. This recognition method presents good performance in the identification of periodontitis and dental caries, thus facilitating dental diagnosis.
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BACKGROUND: The follow-up effect after acute repetitive transcranial magnetic stimulation (rTMS) for major depressive episodes remains unclear. Furthermore, the benefits of maintenance rTMS are poorly understood. AIM: To investigate the trajectory of changes in depressive symptoms after acute rTMS and effects of maintenance rTMS during this period. METHOD: This meta-analysis (PROSPERO: CRD42022374077) searched major databases up to October 1, 2022. Treatment outcome was depressive scores collected at least 3 months after the end of an acute rTMS course for depression. We extracted data at different time points after acute rTMS and categorized by whether maintenance rTMS was performed. A single-stage random-effects dose-response meta-analysis was undertaken to model the nonlinear relationships. Effect sizes were calculated as standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: 24 eligible studies comprising 911 total patients-225 of whom received maintenance rTMS-were included. Maintenance rTMS contributed to relative stability in patients' mood symptoms during the first 5 months (SMD [95% CI]: 3rd month, -0.10 [-0.30 to 0.10]; 5th month, 0.00 [-0.55 to 0.55]), with heterogeneity characterized as low to moderate. Further analysis revealed that maintenance rTMS performed monthly or more frequently provided sustained benefits for up to 6-12 months. Conversely, patients without maintenance rTMS had moderate to high heterogeneity, although the change in mean mood symptom scores during the 12-month follow-up was also minor (6th month, 0.03 [-0.51 to 0.56]; 12th month, 0.10 [-0.59 to 0.79]). CONCLUSION: Maintenance rTMS might keep patients' mood relatively stable for up to 5 months after acute rTMS. Monthly or more frequent maintenance rTMS offers greater benefits.