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BACKGROUND: Cardiovascular disease (CVD) remains the foremost cause of mortality globally. Taurine, an amino acid, holds promise for cardiovascular health through mechanisms such as calcium regulation, blood pressure reduction, and antioxidant and anti-inflammatory effects. Despite these potential benefits, previous studies have yielded inconsistent results. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the existing evidence on the quantitative effects of taurine on hemodynamic parameters and cardiac function grading, which are indicative of overall cardiovascular health and performance. METHODS: We conducted an electronic search across multiple databases, including Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, from their inception to January 2, 2024. Our analysis focused on key cardiovascular outcomes, such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) Functional Classification. Meta-regression was applied to explore dose-dependent relationships based on the total taurine dose administered during the treatment period. A subgroup analysis, stratified according to the baseline disease status of patients, was also conducted. RESULTS: The analysis included a pooled sample of 808 participants from 20 randomized controlled trials. Taurine demonstrated a significant reduction in HR (weighted mean difference [WMD] = -3.579 bpm, 95% confidence interval [CI] = -6.044 to -1.114, p = 0.004), SBP (WMD = -3.999 mm Hg, 95% CI = -7.293 to -0.706, p = 0.017), DBP (WMD: -1.435 mm Hg, 95% CI: -2.484 to -0.386, p = 0.007), NYHA (WMD: -0.403, 95% CI: -0.522 to -0.283, p < 0.001), and a significant increase in LVEF (WMD: 4.981%, 95% CI: 1.556 to 8.407, p = 0.004). Meta-regression indicated a dose-dependent reduction in HR (coefficient = -0.0150 per g, p = 0.333), SBP (coefficient = -0.0239 per g, p = 0.113), DBP (coefficient = -0.0089 per g, p = 0.110), and NYHA (coefficient = -0.0016 per g, p = 0.111), and a positive correlation with LVEF (coefficient = 0.0285 per g, p = 0.308). No significant adverse effects were observed compared to controls. In subgroup analysis, taurine significantly improved HR in heart failure patients and healthy individuals. Taurine significantly reduced SBP in healthy individuals, heart failure patients, and those with other diseases, while significantly lowered DBP in hypertensive patients It notably increased LVEF in heart failure patients and improved NYHA functional class in both heart failure patients and those with other diseases. CONCLUSIONS: Taurine showed noteworthy effects in preventing hypertension and enhancing cardiac function. Individuals prone to CVDs may find it advantageous to include taurine in their daily regimen.
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Presión Sanguínea , Enfermedades Cardiovasculares , Ensayos Clínicos Controlados Aleatorios como Asunto , Taurina , Taurina/farmacología , Taurina/administración & dosificación , Humanos , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Volumen Sistólico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Introduction: Revision hip and knee total joint arthroplasty (TJA) carries a high burden of postoperative complications, including surgical site infections (SSI), venous thromboembolism (VTE), reoperation, and readmission, which negatively affect postoperative outcomes and patient satisfaction. Socioeconomic area-level composite indices such as the area deprivation index (ADI) are increasingly important measures of social determinants of health (SDoH). This study aims to determine the potential association between ADI and SSI, VTE, reoperation, and readmission occurrence 90 days following revision TJA. Methods: 1047 consecutive revision TJA patients were retrospectively reviewed. Complications, including SSI, VTE, reoperation, and readmission, were combined into one dependent variable. ADI rankings were extracted using residential zip codes and categorized into quartiles. Univariate and multivariate logistic regressions were performed to analyze the association of ADI as an independent factor for complication following revision TJA. Results: Depression (p = 0.034) and high ASA score (p < 0.001) were associated with higher odds of a combined complication postoperatively on univariate logistic regression. ADI was not associated with the occurrence of any of the complications recorded following surgery (p = 0.092). ASA remained an independent risk factor for developing postoperative complications on multivariate analysis. Conclusion: An ASA score of 3 or higher was significantly associated with higher odds of developing postoperative complications. Our findings suggest that ADI alone may not be a sufficient tool for predicting postoperative outcomes following revision TJA, and other area-level indices should be further investigated as potential markers of social determinants of health.
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Crohn's disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.
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Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.
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Trichomonas tenax, an oral commensal parasite commonly found in the human mouth, is associated with periodontitis and poor oral hygiene. However, it has also been identified in the bronchoalveolar lavage fluid (BALF) of individuals with lung diseases. Notably, significant quantities of T. tenax have been isolated following bronchoscopy in cases of empyema and acute respiratory distress syndrome (ARDS). Furthermore, research has demonstrated its ability to induce inflammation in pulmonary epithelial cells. To comprehend the potential role of T. tenax in pneumonia, it is crucial to elucidate the relationship between the parasite and the disease. We investigated the clinical factors associated with T. tenax infection in patients with pneumonia. Employing nested polymerase chain reactions, we amplified nucleic acids from BALF and analyzed the relationships between T. tenax and various clinical factors. Our data revealed a significant association between T. tenax and bacterial infections, high pneumonia severity index (PSI) scores, nasogastric tube feeding, and pulmonary complications. Logistic regression analyses also showed strong associations between T. tenax and these clinical factors in pneumonia patients. These findings suggest that T. tenax infection in pneumonia is accompanied by bacterial infection and severe clinical manifestations.
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Background: Low-dose ketamine infusion has been demonstrated to exert antisuicidal effects on patients with treatment-resistant depression (TRD) and strong suicidal ideation. Although evidence suggests an association between hopelessness and suicidality, very few studies have investigated the antihopelessness effects of ketamine.Methods: This study included 84 patients with TRD and strong suicidal ideation. The diagnosis of depression was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria for major depressive disorder. They were randomly assigned to receive a single infusion of either 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. Hopelessness and suicidal symptoms were assessed at baseline, at 240 minutes postinfusion, and on Days 2, 3, 7, and 14 postinfusion. The assessments were performed using the self-report Beck Hopelessness Scale (BHS) and Positive and Negative Suicide Ideation Inventory (PANSI). The analysis focused on the positive and negative domains of the BHS and PANSI, respectively. The clinical trial was conducted between August 15, 2018, and November 30, 2021.Results: Statistical analyses performed using a generalized linear model revealed that the ketamine group had significantly higher PANSI-positive (P = .008) and lower PANSI-negative (P = .015) suicidal ideation scores on Day 2 postinfusion than did the midazolam group. At 240 minutes postinfusion, the ketamine group had significantly lower BHS-negative domain scores than did the midazolam group (P = .031). Notably, the observed ketamine-induced reduction in hopelessness at 240 minutes postinfusion was associated with its antisuicidal effect on Day 2 postinfusion.Discussion: A single infusion of low-dose ketamine resulted in a brief (â¼4 hours) yet significant reduction in hopelessness. Subjective antisuicidal effects of ketamine were noted on Day 2 postinfusion. Further studies are needed to elucidate the neuromechanisms underlying the antihopelessness and antisuicidal effects of ketamine.Trial Registration: UMIN Clinical Trials Registry identifiers: UMIN000033916 and UMIN000033760.
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Trastorno Depresivo Resistente al Tratamiento , Ketamina , Ideación Suicida , Humanos , Ketamina/administración & dosificación , Ketamina/farmacología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/psicología , Infusiones Intravenosas , Midazolam/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Esperanza , Escalas de Valoración PsiquiátricaRESUMEN
Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is also unclear. Two resting-state functional MRIs were collected in two clinical trials of 48 patients with TRD (clinical trial 1; 32 receiving ketamine, 16 receiving a normal saline placebo) and 48 patients with TRD and strong suicidal ideation (clinical trial 2; 24 receiving ketamine, 24 receiving midazolam), respectively. All participants underwent rs-fMRI before and 3 days after infusion. Seed-based functional connectivity (FC) was analyzed in the left/right thalamus. FCs between the bilateral thalamus and right middle frontal cortex (BA46) and between the left thalamus and left anterior paracingulate gyrus (BA8) increased among patients in the ketamine group in clinical trials 1 and 2, respectively. FCs between the right thalamus and bilateral frontal pole (BA9) and between the right thalamus and left rostral paracingulate gyrus (BA10) decreased among patients in the ketamine group in clinical trials 1 and 2, respectively. However, the associations between those FC changes and clinical symptom changes did not survive statistical significance after multiple comparison corrections. Whether ketamine-related changes in thalamocortical connectivity may be associated with ketamine's antidepressant and antisuicidal effects would need further investigation. Clinical trials registration: UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000016985 and UMIN000033916.
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Background: Discharge disposition and length of stay (LOS) are widely recognized markers of healthcare utilization patterns of total hip and knee joint arthroplasty (TJA). These markers are commonly associated with increased postoperative complications, patient dissatisfaction, and higher costs. Area deprivation index (ADI) has been validated as a composite metric of neighborhood-level disadvantage. This study aims to determine the potential association between ADI and discharge disposition or extended LOS following revision TJA. Methods: This study conducted a retrospective analysis of a consecutive series of revision hip and knee TJA patients from a single tertiary institution. Univariate and multivariate regression analysis was used to determine the association between ADI and discharge disposition or LOS, adjusting for patient demographics and comorbidities. Results: 1047 consecutive revision TJA patients were identified across 463 different neighborhoods. 193 (18.4 %) had an extended LOS, and 334 (31.9 %) were discharged to non-home facilities. Compared with Q1 (least deprived cohort), Q2 (odds ratio [OR] = 1.63; p = 0.030) and Q4 (most deprived cohort: OR = 2.04; p = 0.002) cohorts demonstrated higher odds of non-home discharge. Patients in the highest ADI quartile (most deprived cohort) were associated with increased odds of prolonged LOS following revision TJA compared to those in the lowest ADI quartile (OR = 2.63; p < 0.001). Conclusion: This study suggests that higher levels of neighborhood-level disadvantage may be associated with higher odds of non-home discharge and prolonged LOS following revision TJA. Development of interventions based on the area deprivation index may improve discharge planning and reduce unnecessary non-home discharges in patients living in areas of socioeconomic deprivation.
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INTRODUCTION: Lung cancer is one of the most prevalent malignancies worldwide. Substantial research has illuminated the intricate interplay between microorganisms and human health, revealing their role in disease regulation. Trichomonads is a flagellated protozoan in the human cavity and have been previously identified as a pathogen associated with pneumonia, contributing to tissue chronic inflammation and carcinogenesis. METHODS: Nested polymerase chain reaction methods were employed to scrutinize the prevalence of trichomonads in the bronchovesicular fluid of patients diagnosed with lung cancer. Subsequently, the influence of Trichomonas tenax invasion on lung cancer cells was elucidated through proliferation assays, migration assays, and transcription analysis. RESULTS: Bronchoalveolar fluid samples from lung cancer patients yielded positive nested PCR results for eight out of twenty-seven samples. Seven of these samples were identified as Trichomonas tenax, while one was identified as Tetratrichomonas spp. Our findings revealed a significant upregulation of pathways associated with carcinogenesis, including cellular proliferation, migration, and drug resistance, in response to T. tenax invasion. CONCLUSIONS: This study underscores the importance of recognizing the presence of trichomonads and the influence of T. tenax invasion on host responses to respiratory diseases. The identified pathways implicated in cancer development may pave the way for developing targeted treatment strategies for pulmonary diseases. These findings hold promise for informing and improving the precision of therapeutic interventions in the context of pulmonary ailments.
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Neoplasias Pulmonares , Tricomoniasis , Trichomonas , Humanos , Neoplasias Pulmonares/parasitología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Trichomonas/genética , Tricomoniasis/parasitología , Células Epiteliales/parasitología , Líquido del Lavado Bronquioalveolar/parasitología , Masculino , Movimiento Celular , Proliferación Celular , Femenino , Persona de Mediana Edad , Anciano , Pulmón/parasitología , Pulmón/patología , Reacción en Cadena de la PolimerasaRESUMEN
High levels of non-esterified fatty acids (NEFAs) during the transition period lead to increased oxidative stress and immunosuppression in cows. Feeding them a vitamin-E-supplemented diet reduces reactive oxygen species (ROS) levels in the blood and diminishes immunosuppression in the transition period. However, whether the restoration of immune cell function occurs through the direct action of vitamin E in cells is still a topic that requires further discussion. Therefore, in this experiment, we aimed to investigate the effect of NEFAs on peripheral blood leukocytes (PBLs) and whether vitamin E mitigates the impact of NEFAs. We employed three groups: (1) blank, (2) NEFA only, and (3) pre-culturing with vitamin E before NEFA treatment (VENEFA). In peripheral blood mononuclear cells (PBMCs), there were no differences in vitamin E content among the three groups. However, in the vitamin E pre-treatment group, the vitamin E levels of polymorphonuclear neutrophils (PMNs) were significantly higher than those in the other two groups. NEFA levels increased malondialdehyde (MDA) levels in PBMCs, but pre-treatment with vitamin E reduced accumulation of MDA levels. Regarding the expression of proinflammatory genes, NEFAs increased the expression of interleukin-1ß in PBMCs and colony-stimulating factor 2 in PMNs. Vitamin E pre-treatment restored the increase in interleukin-1ß levels caused by NEFAs in PBMCs. None of the groups affected the phagocytosis of PMNs. Few studies have confirmed that NEFAs cause oxidative stress in bovine PBLs. In summary, this study found that NEFAs induce oxidative stress in PBLs and alter the expression of inflammation-related genes; meanwhile, vitamin E can reduce some of the effects caused by NEFAs. This result may suggest that vitamin E can assist bovine PBLs in resisting the immune suppression caused by an NEB during the transition period.
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Importance: Antidepressant responses and the phenotype of treatment-resistant depression (TRD) are believed to have a genetic basis. Genetic susceptibility between the TRD phenotype and other psychiatric disorders has also been established in previous genetic studies, but population-based cohort studies have not yet provided evidence to support these outcomes. Objective: To estimate the TRD susceptibility and the susceptibility between TRD and other psychiatric disorders within families in a nationwide insurance cohort with extremely high coverage and comprehensive health care data. Design, Setting, and Participants: This cohort study assessed data from the Taiwan national health insurance database across entire population (N = 26â¯554â¯001) between January 2003 and December 2017. Data analysis was performed from August 2021 to April 2023. TRD was defined as having experienced at least 3 distinct antidepressant treatments in the current episode, each with adequate dose and duration, based on the prescribing records. Then, we identified the first-degree relatives of individuals with TRD (n = 34â¯467). A 1:4 comparison group (n = 137â¯868) of first-degree relatives of individuals without TRD was arranged for the comparison group, matched by birth year, sex, and kinship. Main Outcomes and Measures: Modified Poisson regression analyses were performed and adjusted relative risks (aRRs) and 95% CIs were calculated for the risk of TRD, the risk of other major psychiatric disorders, and different causes of mortality. Results: This study included 172â¯335 participants (88â¯330 male and 84â¯005 female; mean [SD] age at beginning of follow-up, 22.9 [18.1] years). First-degree relatives of individuals with TRD had lower incomes, more physical comorbidities, higher suicide mortality, and increased risk of developing TRD (aRR, 9.16; 95% CI, 7.21-11.63) and higher risk of other psychiatric disorders than matched control individuals, including schizophrenia (aRR, 2.36; 95% CI, 2.10-2.65), bipolar disorder (aRR, 3.74; 95% CI, 3.39-4.13), major depressive disorder (aRR, 3.65; 95% CI, 3.44-3.87), attention-deficit/hyperactivity disorders (aRR, 2.38; 95% CI, 2.20-2.58), autism spectrum disorder (aRR, 2.26; 95% CI, 1.86-2.74), anxiety disorder (aRR, 2.71; 95% CI, 2.59-2.84), and obsessive-compulsive disorder (aRR, 3.14; 95% CI, 2.70-3.66). Sensitivity and subgroup analyses validated the robustness of the findings. Conclusions and Relevance: To our knowledge, this study is the largest and perhaps first nationwide cohort study to demonstrate TRD phenotype transmission across families and coaggregation with other major psychiatric disorders. Patients with a family history of TRD had an increased risk of suicide mortality and tendency toward antidepressant resistance; therefore, more intensive treatments for depressive symptoms might be considered earlier, rather than antidepressant monotherapy.
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Trastorno Depresivo Resistente al Tratamiento , Predisposición Genética a la Enfermedad , Humanos , Masculino , Femenino , Trastorno Depresivo Resistente al Tratamiento/epidemiología , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Adulto , Taiwán/epidemiología , Persona de Mediana Edad , Adulto Joven , Adolescente , Familia/psicología , Estudios de Cohortes , Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genéticaRESUMEN
First-line treatment of multiple myeloma, a prevalent blood cancer lacking a cure, using anti-CD38 daratumumab antibody and lenalidomide is often inadequate due to relapse and severe side effects. To enhance drug safety and efficacy, an antibody-drug conjugate, TE-1146, comprising six lenalidomide drug molecules site-specifically conjugated to a reconfigured daratumumab to deliver cytotoxic lenalidomide to tumor cells is developed. TE-1146 is prepared using the HighDAR platform, which employs i) a maleimide-containing "multi-arm linker" to conjugate multiple drug molecules creating a drug bundle, and ii) a designed peptide with a Zn2+-binding cysteine at the C-termini of a reconfigured daratumumab for site-specific drug bundle conjugation. It is shown that TE-1146 remains intact and effectively enters CD38-expressing tumor cells, releasing lenalidomide, leading to enhanced cell-killing effects compared to lenalidomide/daratumumab alone or their combination. This reveals the remarkable potency of lenalidomide once internalized by myeloma cells. TE-1146 precisely delivers lenalidomide to target CD38-overexpressing tumor cells. In contrast, lenalidomide without daratumumab cannot easily enter cells, whereas daratumumab without lenalidomide relies on Fc-dependent effector functions to kill tumor cells.
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Anticuerpos Monoclonales , Inmunoconjugados , Lenalidomida , Mieloma Múltiple , Mieloma Múltiple/tratamiento farmacológico , Humanos , Inmunoconjugados/farmacología , Inmunoconjugados/química , Lenalidomida/farmacología , Lenalidomida/uso terapéutico , Anticuerpos Monoclonales/farmacología , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ratones , Animales , Modelos Animales de EnfermedadRESUMEN
INTRODUCTION: Although electrocardiographic changes have been previously reported in patients with acute pancreatitis, diffuse ST-segment elevation without occluded coronary arteries is rarely documented. PATIENT CONCERNS: A 45-year-old man presented to our emergency department due to persistent epigastric pain for 2 hours. However, ECG in the emergency department revealed regular sinus rhythm at 67 beats per minute, peaked T waves in lead V3-5, and upsloping ST-segment elevation in leads II, III, aVF, and V2-6. DIAGNOSIS: He was diagnosed with acute pancreatitis and presented with diffuse ST-segment elevation. INTERVENTIONS: Laboratory workup and computed tomography supported the diagnosis of acute gallstone pancreatitis and endoscopic retrograde cholangiopancreatography was performed. Coronary angiography showed patent coronary arteries finally. OUTCOMES: Endoscopic retrograde cholangiopancreatography and endoscopic papillo-sphincterotomy were performed, and the stone in the common bile duct was removed smoothly without immediate complication. Due to his relatively stable condition, he was discharged on day 7 of admission. CONCLUSION: We presented an uncommon case of acute pancreatitis demonstrating similar features of AMI. This reminds cardiologists and emergency physicians to make the judgment with more caution to avoid jumping to conclusions and providing inappropriate treatment.
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Colelitiasis , Infarto del Miocardio , Pancreatitis , Masculino , Humanos , Persona de Mediana Edad , Pancreatitis/diagnóstico , Pancreatitis/etiología , Infarto del Miocardio/diagnóstico , Enfermedad Aguda , Angiografía Coronaria , Arritmias Cardíacas , Electrocardiografía/métodosRESUMEN
IMPORTANCE: At the National Cheng Kung University Hospital, numerous cases of amoebic keratitis had been identified with concurrent bacterial infections. Among these bacterial coinfections, Pseudomonas aeruginosa accounted for 50% of the reported cases. However, the impact of pathogenic bacteria on amoeba-induced corneal damage remains unclear. In our study, we successfully demonstrated that P. aeruginosa accumulated on the Acanthamoeba castellanii surface and caused more severe corneal damage. We also indicated that the exposure of P. aeruginosa to amoeba-soluble antigens enhanced its adhesion ability, promoted biofilm formation, and led to more severe corneal cell damage. These findings significantly contributed to our understanding of the risk associated with P. aeruginosa coinfection in the progression of amoeba keratitis.
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Coinfección , Lesiones de la Cornea , Queratitis , Humanos , Pseudomonas aeruginosa , Coinfección/patología , Córnea , Queratitis/patología , Lesiones de la Cornea/patologíaRESUMEN
BACKGROUND: The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk. METHODS: A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis. RESULTS: In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%. CONCLUSIONS: This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.
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Enfermedad de Crohn , Fístula Rectal , Humanos , Adolescente , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Infliximab/uso terapéutico , Factor de Necrosis Tumoral alfa , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Recurrencia , Necrosis/complicaciones , Resultado del Tratamiento , Estudios Retrospectivos , Fístula Rectal/etiología , Fístula Rectal/complicacionesRESUMEN
Whether current suicide risk or a history of attempted suicide is related to the antidepressant effect of a low-dose ketamine infusion remains unclear. In total, 47 patients with treatment-resistant depression (TRD), including 32 with low current suicide risk and 15 with moderate or high current suicide risk, were randomized to groups receiving a low-dose ketamine infusion of either 0.2 or 0.5 mg/kg. Among the patients, 21 had a lifetime history of attempted suicide. Suicide risk was assessed based on the Suicidal scale of the Mini-International Neuropsychiatric Interview. The 17-item Hamilton Depression Rating Scale (HDRS) was used to measure depressive symptoms at baseline, at 40 and 240 min after infusion, and sequentially on Days 2-7 and 14 after ketamine infusion. Generalized estimating equation models indicated that the time effects of both 0.5 and 0.2 mg/kg ketamine infusions were significant during the study period. The models also indicated that current suicide risk (p = .037) but not lifetime history of attempted suicide (p = .184) was related to the trajectory of total HDRS scores. Patients with moderate-to-high current suicide risk benefited more from the low-dose ketamine infusion compared with those with the low current suicide risk. Patients with TRD having moderate or high current suicide risk may be prioritized to receive a low-dose ketamine infusion, which may aid suicide prevention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Ketamina , Humanos , Ketamina/uso terapéutico , Ketamina/farmacología , Intento de Suicidio , Depresión , Infusiones Intravenosas , Antidepresivos/uso terapéutico , Resultado del TratamientoRESUMEN
Preparing Cd3As2, which is a three-dimensional (3D) Dirac semimetal in certain crystal orientation, on Si is highly desirable as such a sample may well be fully compatible with existing Si CMOS technology. However, there is a dearth of such a study regarding Cd3As2films grown on Si showing the chiral anomaly. Here,for the first time, we report the novel preparation and fabrication technique of a Cd3As2(112) film on a Si (111) substrate with a ZnTe (111) buffer layer which explicitly shows the chiral anomaly with a nontrivial Berry's phase ofπ. Despite the Hall carrier density (n3D≈9.42×1017cm-3) of our Cd3As2film, which is almost beyond the limit for the portents of a 3D Dirac semimetal to emerge, we observe large linear magnetoresistance in a perpendicular magnetic field and negative magnetoresistance in a parallel magnetic field. These results clearly demonstrate the chiral magnetic effect and 3D Dirac semimetallic behavior in our silicon-based Cd3As2film. Our tailoring growth of Cd3As2on a conventional substrate such as Si keeps the sample quality, while also achieving a low carrier concentration.
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The role of melancholic features on the antisuicidal effect of 0.5 mg/kg ketamine infusion has remained unclear in patients with treatment-resistant depression (TRD) and strong suicidal ideation (SI). Whether ketamine diminishes suicidal ideation in patients with TRD-SI was also unknown. We enrolled 84 patients with TRD-SI, including 27 with melancholic features and 57 without, and then randomly administered a single infusion of 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. The clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) item 10, Columbia Suicide Severity Rating Scale-Ideation Severity Subscale (CSSRS-ISS), and self-reported Positive and Negative Suicide Ideation Inventory (PANSI) were used to assess suicidal symptoms from baseline to day 7. Generalized estimating equation models showed that only patients without melancholic features (MADRS item 10: infusion group effect, p = 0.017; CSSRS-ISS: infusion group × time effect, p = 0.008; PANSI-negative suicidal ideation: infusion group effect, p = 0.028) benefited from the antisuicidal effect of low-dose ketamine. The PANSI-positive ideation scores were higher in the ketamine group than in the midazolam group (p = 0.038) for patients with melancholic features. Additional studies are necessary to clarify the neuromechanisms underlying the ketamine-related positive effect against SI and antisuicidal effects among patients with TRD-SI. Additional studies are necessary to clarify the neuromechanisms underlying the ketamine-related positive effect against SI and antisuicidal effects among patients with TRD-SI.
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Depression and sleep disturbance are related closely with bidirectional relationship. The heterogenic diagnostic criteria of major depressive disorder composed by the myriad combination of symptoms including sleep disturbance. Insomnia is an identifiable risk factor for depression and the treatment of insomnia might be able to prevent subsequent major depressive episodes which draws psychiatrists' attention to the interface of psychiatry and sleep medicine field. It is important to identify occult sleep disturbance in patients with treatment-resistant depression to improve treatment outcome. New tools to objectively measure sleep at home environment represent a great march in clinical care and research modalities but need further validation before they can be applying widespread at sleep and depression intersection. Careful evaluation and measurement of the phenotype and nature of sleep disturbance will continue to advance understanding of the biological bases of psychiatric disorders and the connections with sleep.