A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal antibody, can result in targeted clearance of CD38-positive cells, including plasma cells. METHODS: We conducted a phase 1-2, open-label study to evaluate the safety and efficacy of CM313 in adult patients with ITP. CM313 was administered intravenously at a dose of 16 mg per kilogram of body weight every week for 8 weeks, followed by a 16-week follow-up period. The primary outcomes were adverse events and documentation of two or more consecutive platelet counts of at least 50×109 per liter within 8 weeks after the first dose of CM313. The status of peripheral-blood immune cells in patients and changes in the mononuclear phagocytic system in passive mouse models of ITP receiving anti-CD38 therapy were monitored. RESULTS: Of the 22 patients included in the study, 21 (95%) had two consecutive platelet counts of at least 50×109 per liter during the treatment period, with a median cumulative response duration of 23 weeks (interquartile range, 17 to 24). The median time to the first platelet count of at least 50×109 per liter was 1 week (range, 1 to 3). The most common adverse events that occurred during the study were infusion-related reaction (in 32% of the patients) and upper respiratory tract infection (in 32%). After CD38-targeted therapy, the percentage of CD56dimCD16+ natural killer cells, the expression of CD32b on monocytes in peripheral blood, and the number of macrophages in the spleen of the passive mouse models of ITP all decreased. CONCLUSIONS: In this study, anti-CD38 targeted therapy rapidly boosted platelet levels by inhibiting antibody-dependent cell-mediated cytotoxicity on platelets, maintained long-term efficacy by clearing plasma cells, and was associated with mainly low-grade toxic effects. (Funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences and others; ClinicalTrials.gov number, NCT05694767).

Proteomics landscape and machine learning prediction of long-term response to splenectomy in primary immune thrombocytopenia.

This study aimed to identify key proteomic analytes correlated with response to splenectomy in primary immune thrombocytopenia (ITP). Thirty-four patients were retrospectively collected in the training cohort and 26 were prospectively enrolled as validation cohort. Bone marrow biopsy samples of all participants were collected prior to the splenectomy. A total of 12 modules of proteins were identified by weighted gene co-expression network analysis (WGCNA) method in the developed cohort. The tan module positively correlated with megakaryocyte counts before splenectomy (r = 0.38, p = 0.027), and time to peak platelet level after splenectomy (r = 0.47, p = 0.005). The blue module significantly correlated with response to splenectomy (r = 0.37, p = 0.0031). KEGG pathways analysis found that the PI3K-Akt signalling pathway was predominantly enriched in the tan module, while ribosomal and spliceosome pathways were enriched in the blue module. Machine learning algorithm identified the optimal combination of biomarkers from the blue module in the training cohort, and importantly, cofilin-1 (CFL1) was independently confirmed in the validation cohort. The C-index of CFL1 was >0.7 in both cohorts. Our results highlight the use of bone marrow proteomics analysis for deriving key analytes that predict the response to splenectomy, warranting further exploration of plasma proteomics in this patient population.

Elucidating the Clinical Interpretation and Impact of a Positive Plasma Cell-Free DNA Metagenomics Test Result-A Single Center Retrospective Study.

BACKGROUND: The Karius Test (KT), a cell-free DNA metagenomic next-generation sequencing assay, has potential to improve diagnostic evaluation of infectious diseases. Published data describing clinical impact of positive KT results are limited. We attempt to elucidate the clinical interpretation and impact of positive KT results based on types and patterns of detected pathogens and patient characteristics. METHODS: All positive KT results from a single institution in 2022 were screened. Patients with results that met predefined categories were included for review by a panel of 3 infectious diseases physicians and one clinical microbiologist. Predefined categories included reports with fungal, parasitic, notable bacterial, notable viral pathogens, or polybacterial results (≥3 bacteria). Polybacterial results were further classified into patterns of microbiome detected. Clinical impact and its correlation with result or patient characteristics were explored. RESULTS: Ninety-two patients met the inclusion criteria, most were immunocompromised (73%). Positive KT results that met predefined categories had the following clinical impact: positive in 30.4%, negative in 2.2%, and none in 65.2%. Polybacterial results, especially interpreted as oral flora had lowest clinical impact (7.1% and 0.0%, respectively), while detection of parasites or notable bacterial pathogens had the highest clinical impact (100% and 77.8%, respectively). There was no correlation between patient characteristics and clinical impact. CONCLUSIONS: Among a cohort of largely immunocompromised patients, we were able to demonstrate clinical impact of specific KT result types and patterns but did not find correlation between patient characteristics and clinical impact. Our results should be confirmed in future larger cohorts.

Effects of proactive healthcare on pain, physical and activities of daily living functioning in vulnerable older adults with chronic pain: a pragmatic clinical trial with one- and two-year follow-up.

PURPOSE: To investigate the changes in pain, physical and activities of daily living (ADL) functioning in vulnerable older adults with chronic pain after proactive primary care intervention. METHODS: This study was embedded in a prospective, pragmatic, matched-control multicenter trial at 19 primary care practices in Sweden, with proactive medical and social care (Intervention Group, IG, n = 134) in comparison with usual care (Control Group, CG, n = 121). Patients with chronic pain, defined as pain experienced longer than 3 months, were included in this subgroup analysis. Data on pain aspects, physical and ADL functioning were collected in the questionnaires at baseline, one- and two-year follow-up (FU-1 and FU-2). Data on prescribed pain medications was collected by local health authorities. RESULTS: Mean age was 83.0 ± 4.7 years with almost equal representation of both genders. From baseline until FU-2, there were no significant within-group or between-group changes in pain intensity. Small adjustments of pain medication prescriptions were made in both groups. Compared to FU-1, the functional changes were more measurable at FU-2 as fewer participants had impaired physical functioning in IG (48.4%) in comparison to CG (62.6%, p = 0.027, Effect Size φ = 0.14). Higher scores of ADL-staircase (more dependent) were found in both groups (p < 0.01, Effect Size r = 0.24 in CG and r = 0.16 in IG). CONCLUSION: Vulnerable older adults with chronic pain seemed to remain physical and ADL functioning after proactive primary care intervention, but they may need tailored strategies of pain management to improve therapeutic effects. TRIAL REGISTRATION: ClinicalTrials.gov 170608, ID: NCT03180606.

Reproductive outcome after laparoscopic ovarian cystectomy using barbed sutures versus conventional smooth sutures: A retrospective cohort study.

OBJECTIVE: To investigate the effects of barbed and conventional sutures on reproductive outcomes and ovarian reserve after laparoscopic treatment for benign non-endometrioma ovarian cysts. METHODS: This retrospective study was conducted at an affiliated women's hospital between May 2017 and December 2019. Patients with benign non-endometriotic ovarian cysts undergoing laparoscopic cystectomy were included. RESULTS: Patients received barbed sutures (221 patients) or conventional smooth sutures (203 patients) intraoperatively. The two groups had comparable baseline characteristics. The surgical duration and ovarian suturing time were significantly shorter in the barbed suture group than in the conventional smooth suture group (P < 0.001 and P = 0.002, respectively). The rate of postoperative hemoglobin decline and serum anti-Müllerian hormone decline were similar between the two groups (P > 0.05). A total of 316 (74.53%) patients experienced at least one pregnancy postoperatively: 170 (76.92%) and 146 (71.92%) patients in the barbed suture and conventional smooth suture groups, respectively (χ2 = 1.395, P = 0.238). Multivariate Poisson regression demonstrated that barbed sutures had no significant effect on the overall postoperative pregnancy rate (adjusted incidence rate ratio, 1.10; 95% confidence interval, 0.93-1.36; P = 0.382). CONCLUSION: In patients with benign non-endometriotic ovarian cysts undergoing laparoscopic ovarian cystectomy, barbed sutures had a reproductive outcome similar to that of conventional smooth sutures while providing higher surgical efficiency without adverse effects on the postoperative ovarian reserve. Barbed sutures are probably a viable option to conventional smooth sutures.

Eating habits and the desire to eat healthier among patients with chronic pain: a registry-based study.

Healthcare professionals often meet pain patients with a poor nutritional status such as obesity, unhealthy dietary behaviors, and a suboptimal dietary intake. A poor nutritional status may play a significant role in the occurrence, development, and prognosis of chronic pain. This study investigated eating habits in a specialized pain rehabilitation center using data (N = 2152) from the Swedish quality registry for pain rehabilitation during the period 2016-2021. Patients answered a lifestyle questionnaire regarding their eating habits and desire to modify their lifestyle. The mean (SD) patient age was 46.1 (14.6) years, with 24.8% classified as obese. Suboptimal eating habits included irregular mealtimes (27.2%), weekly consumption of fast-food (20.3%) and nearly daily consumption of confectionery (33.3%). Approximately 20% (n = 426) reported a desire to eat healthier. Frequent confectionery intake (Odds ratio [OR] 1.23, 95% Confidence Interval (CI) 1.04-1.47) and fast-food consumption (OR 1.58, 95% CI 1.24-2.02) increased the likelihood to desire healthier eating. Younger patients (18-29 years), those classified as obese, and those with more extended spatial pain were more likely to express a desire to eat healthier. Eating habits should be addressed in pain management and interdisciplinary pain rehabilitation teams are encouraged to provide nutritional care tailored to the patient's needs.

Novel Sm3+-doped La3Ga5MO14 (M = Si or Ge) phosphors for indoor illumination: effects of M cations on photoluminescence.

A series of La3(1-x)Ga5MO14:xSm3+ (M = Si or Ge) orange-red phosphors with high color purity, low correlated color temperature, and good thermal stability were successfully synthesized via a high-temperature solid-phase technique. The phase structure and morphology of La3Ga5SiO14(LGSi):xSm3+ and La3Ga5GeO14(LGGe):xSm3+ were investigated. Sm3+-doped LGSi and LGGe phosphors emitted orange-red light under an excitation of 403 nm, and the optimal doping concentrations were 3 mol% and 2 mol% with excellent color purities of 98.46% and 98.25%, respectively. The concentration quenching mechanism of both the samples was dominated by dipole-dipole interaction, and the effect of Si4+ and Ge4+ on luminescence performance was discussed. The internal quantum efficiencies of LGSi:0.03Sm3+ and LGGe:0.02Sm3+ were calculated to be 27.14% and 56.07%, respectively. The CIE and CCT values indicated that the luminescence of the prepared phosphors was in the orange-red region. Additionally, a white light-emitting diode (w-LED) was fabricated with LGGe:0.02Sm3+ phosphors, which was capable of emitting bright and warm white light and exhibiting a high color rendering index (CRI) of 87.17 and an appropriate correlated color temperature (CCT) of 6108 K. These results indicated that the prepared phosphors with excellent luminescent performances have potential application in indoor illumination.

Intertemporal Decision-Making, Diabetes Self-Management, and Health Outcomes in Patients With Type 2 Diabetes.

PURPOSE: The purpose of this study was to identify the independent factors associated with intertemporal decision-making and to examine its relationship with diabetes self-management behaviors, glucose variability, and diabetes complications in patients with diabetes. METHODS: A cross-sectional study using convenience sampling (n = 368) was conducted in patients with type 2 diabetes (T2DM) between November 2021 and April 2023. Data were collected using self-reported questionnaires and retrieval of clinical information from medical records. Intertemporal decision-making was operationalized using delay discounting. The outcome variables included diabetes self-management behaviors, A1C, diabetic retinopathy, and carotid artery disease. Hierarchical regression and binary logistic regression models were used to explore the relationships among intertemporal decision-making, self-management, A1C, and carotid artery disease. RESULTS: The analyses showed that intertemporal decision-making was negatively associated with physical activity and carotid artery disease, in which individuals with lower delay discounting tended to have healthier physical activity; when the delay discounting rate increased 1 unit, the risk of the carotid artery disease increased by 39.8%. CONCLUSIONS: The study reveals that a lower delay discounting can promote healthier physical activity and decrease the incidence of carotid artery disease. These results offer new knowledge for researchers and clinicians to consider intertemporal decision-making in developing interventional programs to improve physical activity and reduce carotid artery complication in patients with T2DM when providing care.

Acquired hemophilia A: a single-center study of 165 patients.

Background: Acquired hemophilia A (AHA) is a rare hemorrhagic disorder caused by factor (F)VIII inhibitors. The diagnosis and management of AHA remains challenging because of its rarity and heterogeneity. Objectives: To analyze the characteristics of AHA to enhance our understanding of this disease and identify effective treatment strategies. To analyze the characteristics of AHA to enhance our understanding of this disease and identify effective treatment strategies. Methods: Clinical features of 165 patients with AHA from a single center between July 1997 and December 2021 were retrospectively analyzed. Results: The median age of patients at diagnosis was 45 years. The median time to diagnosis was 30 days. All 165 patients experienced bleeding, with a median bleeding score (BS) of 4 (range, 2-12). Hemostatic therapy was administered to 129 (78.2%) patients. Bleeding control was achieved in 80.0% of patients who received prothrombin complex concentrate and in 92.3% of patients who were treated with recombinant activated FVII. Of the 163 patients who received immunosuppressive therapy, 80 (49.1%) received rituximab-based therapy with a 93.3% complete remission (CR) rate, 50 (30.7%) received steroids plus cyclophosphamide with an 85.0% CR rate, and 22 (13.5%) received steroids alone with an 82.4% CR rate. Six cases relapsed after a median duration of 330 days. Immunosuppressive therapy-related adverse events were reported in 17 patients. Seven deaths were recorded. FVIII inhibitor titer of ≥15 BU/mL and BS of ≥6 were identified as significantly poor prognostic factors for CR. Conclusion: Immunosuppressive therapies yield remarkably high response rates, with a CR rate exceeding 80%; notably, the regimen containing rituximab exhibits a CR rate of approximately 90%. FVIII inhibitor titer of ≥5 BU/mL and BS of ≥6 were poor predictors of CR in patients with AHA.

Combined pretreatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicts survival and prognosis in patients with non-metastatic nasopharyngeal carcinoma: a retrospective study.

The clinical significance of the combination of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily.

Multi-omics differences in the bone marrow between essential thrombocythemia and prefibrotic primary myelofibrosis.

Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms. These conditions share overlapping clinical presentations; however, their prognoses differ significantly. Current morphological diagnostic methods lack reliability in subtype differentiation, underlining the need for improved diagnostics. The aim of this study was to investigate the multi-omics alterations in bone marrow biopsies of patients with ET and pre-PMF to improve our understanding of the nuanced diagnostic characteristics of both diseases. We performed proteomic analysis with 4D direct data-independent acquisition and microbiome analysis with 2bRAD-M sequencing technology to identify differential protein and microbe levels between untreated patients with ET and pre-PMF. Laboratory and multi-omics differences were observed between ET and pre-PMF, encompassing diverse pathways, such as lipid metabolism and immune response. The pre-PMF group showed an increased neutrophil-to-lymphocyte ratio and decreased high-density lipoprotein and cholesterol levels. Protein analysis revealed significantly higher CXCR2, CXCR4, and MX1 levels in pre-PMF, while APOC3, APOA4, FABP4, C5, and CFB levels were elevated in ET, with diagnostic accuracy indicated by AUC values ranging from 0.786 to 0.881. Microbiome assessment identified increased levels of Mycobacterium, Xanthobacter, and L1I39 in pre-PMF, whereas Sphingomonas, Brevibacillus, and Pseudomonas_E were significantly decreased, with AUCs for these genera ranging from 0.833 to 0.929. Our study provides preliminary insights into the proteomic and microbiome variations in the bone marrow of patients with ET and pre-PMF, identifying specific proteins and bacterial genera that warrant further investigation as potential diagnostic indicators. These observations contribute to our evolving understanding of the multi-omics variations and possible mechanisms underlying ET and pre-PMF.

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia: a prospective, single arm, phase I trial.

Patients with refractory immune thrombocytopenia (ITP) frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing therapies. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) present a promising alternative, capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune disorders. This prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory ITP. The research design included administering UC-MSCs at escalating doses of 0.5 × 106 cells/kg, 1.0 × 106 cells/kg, and 2.0 × 106 cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase, followed by a dose of 2.0 × 106 cells/kg weekly for the dose-expansion phase. Adverse events, platelet counts, and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up period. Ultimately, 12 (with an addition of three patients in the 2.0 × 106 cells/kg group due to dose-limiting toxicity) and six patients were enrolled in the dose-escalation and dose-expansion phase, respectively. Thirteen patients (13/18, 72.2%) experienced one or more treatment emergent adverse events. Serious adverse events occurred in four patients (4/18, 22.2%), including gastrointestinal hemorrhage (2/4), profuse menstruation (1/4), and acute myocardial infarction (1/4). The response rates were 41.7% in the dose-escalation phase (5/12, two received 1.0 × 106 cells/kg per week, and three received 2.0 × 106 cells/kg per week) and 50.0% (3/6) in the dose-expansion phase. The overall response rate was 44.4% (8/18) among all enrolled patients. To sum up, UC-MSCs are effective and well tolerated in treating refractory ITP (ClinicalTrials.gov ID: NCT04014166).

The scientific system of human core balance in sports / O sistema científico do equilíbrio do core humano nos esportes / El sistema científico del equilibrio del core humano en los deportes

ABSTRACT Introduction: The human brain controls the body's balance, actinh on the muscle tissues of the body and thus controlling the balance of its center of gravity. Objective: To analyze 6 indicators that affect the brain's ability to control the body's balance and to verify the important muscle areas of the human body and prove that strength training can help improve the body's balance ability. Methods: This article selected young university students with the same physical fitness as sample and analyzed the factors that affect the body's strength and balance using statistical models. Results: Strength training can effectively improve the body›s balance when standing. Conclusion: Training the brain to control the body is mainly to exercise strength, stability, balance, and other abilities of human muscle tissue. Using this kind of exercise method can effectively improve the stability of the human body. Targeted training can also enhance the brain's ability to control the balance of the body. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: O cérebro humano controla o equilíbrio do corpo, agindo sobre seus tecidos musculares e, assim, controlando o equilíbrio de seu centro de gravidade. Objetivo: Analisar seis indicadores que afetam a capacidade do cérebro de controlar o equilíbrio do corpo, avaliar áreas musculares relevantes do corpo humano, e provar que atividade física voltada à força pode melhorar o equilíbrio do corpo. Métodos: Esse artigo selecionou como amostra jovens estudantes universitários com preparo físico similar, e analisou quais fatores afetam de maneira relevante a força e o equilíbrio do corpo por meio de modelos estatísticos. Resultados: Treinamentos de força podem efetivamente melhorar o equilíbrio do corpo quando de pé. Conclusão: Treinar o cérebro para controlar o corpo significa, principalmente, treinar a força, a estabilidade, o equilíbrio, e outras capacidades dos tecidos musculares humanos. O uso dessa metodologia de atividade física pode efetivamente aprimorar a estabilidade do corpo humano. O treinamento direcionado também pode melhorar a capacidade do cérebro de controlar o equilíbrio do corpo. Nível de evidência II; Estudos terapêuticos - investigação do resultado de tratamentos.

RESUMEN Introducción: El cerebro humano controla el equilibrio del cuerpo, actuando sobre sus tejidos musculares y, así, controlando el equilibrio de su centro de gravedad. Objetivo: Analizar seis indicadores que afectan la capacidad del cerebro de controlar el equilibrio del cuerpo, evaluar áreas musculares relevantes del cuerpo humano y probar qué actividad física centrada en la fuerza puede mejorar el equilibrio del cuerpo. Métodos: Este artículo seleccionó como muestra jóvenes estudiantes universitarios con preparación física similar y analizó cuáles factores afectan de manera relevante la fuerza y el equilibrio del cuerpo por medio de modelos estadísticos. Resultados: Entrenamientos de fuerza pueden efectivamente mejorar el equilibrio del cuerpo al estar de pie. Conclusión: Entrenar el cerebro para controlar el cuerpo significa, principalmente, entrenar la fuerza, la estabilidad, el equilibrio y otras capacidades de los tejidos musculares humanos. El uso de esta metodología de actividad física puede, efectivamente, mejorar la estabilidad del cuerpo humano. El entrenamiento dirigido también puede optimizar la capacidad del cerebro de controlar el equilibrio del cuerpo. Nivel de evidencia II; Estudios terapéuticos - investigación del resultado de tratamientos.