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High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit. RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study (\"rapid arm\") received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study (\"standard arm\") followed standard clinic procedures (three to five additional clinic visits over 2-4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition from care after ART initiation between the groups among those who initiated within 90 d. Three hundred and seventy-seven patients were enrolled in the study between May 8, 2013 and August 29, 2014 (median CD4 count 210 cells/mm3). In the rapid arm, 119/187 patients (64%) initiated treatment and were virally suppressed at 10 mo, compared to 96/190 (51%) in the standard arm (relative risk [RR] 1.26 [1.05-1.50]). In the rapid arm 182/187 (97%) initiated ART ≤90 d, compared to 136/190 (72%) in the standard arm (RR 1.36, 95% confidence interval [CI], 1.24-1.49). Among 318 patients who did initiate ART within 90 d, the hazard of attrition within the first 10 mo did not differ between the treatment arms (hazard ratio [HR] 1.06; 95% CI 0.61-1.84). The study was limited by the small number of sites and small sample size, and the generalizability of the results to other settings and to non-research conditions is uncertain. Offering single-visit ART initiation to adult patients in South Africa increased uptake of ART by 36% and viral suppression by 26%. This intervention should be considered for adoption in the public sector in Africa. ClinicalTrials.gov NCT01710397, and South African National Clinical Trials Register DOH-27-0213-4177.

Background Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use. Methods In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR. Results Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors ( P  < 0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI: − 31.81- -18.64, P  < 0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P  < 0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90–0.98) vs. 0.80 (95% CI: 0.73–0.87); 0.93 (95%CI:0.90–0.96) vs. 0.86 (95%CI:0.82–0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. 35 (10.03%) patients were intubated. In the intubated patients, initial and peak D-Dimer and NLR were much higher than non-intubated patients ( P  < 0.001). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR in prognosticate of intubation was 0.73 mg/L, 12.75 mg/L,7.28 and 27.55. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00–1.07, P  = 0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01–1.04, P  < 0.001) were prognostic factors for COVID-19 patients’ death. Conclusions To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19.

Background The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis. Methods A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected. Results On admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4 + T cells, CD8 + T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4 + T cells, CD8 + T cells and NK cells. Conclusions A sustained decrease in lymphocyte subsets, especially CD4 + T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.

Background Established prognostic factors for treatment response to cyclin-dependent kinases 4 and 6 inhibitors are currently lacking. We aimed to investigate the relationship of pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) to abemaciclib outcomes. Patients and Methods This was a post hoc analysis of data from MONARCH 2, a phase III study of abemaciclib or placebo plus fulvestrant in hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer that progressed on endocrine therapy. Patients were divided into high and low categories based on baseline NLR (cutoff: 2.5) and ALC (cutoff: 1.5 × 109/L). The association of baseline NLR and ALC with progression-free survival (PFS) and overall survival (OS) was explored using Cox models and Kaplan-Meier estimates. Tumor response and safety were also examined. Results NLR and ALC data were available for 645 patients (abemaciclib: N = 426; placebo: N = 219). Low-baseline NLR or high-baseline ALC was consistently associated with positive PFS and OS trends; low-baseline NLR subgroups also showed trends for better response. The abemaciclib treatment effect against placebo was observed regardless of baseline NLR or ALC. Univariate analyses showed baseline NLR and ALC were prognostic of PFS and OS. Baseline NLR remained significant in the multivariate model (P < .0001). No unexpected differences in safety were observed by baseline NLR or ALC. Conclusion Baseline NLR was independently prognostic of PFS and OS. Low-baseline NLR was associated with numerically better efficacy outcomes, but the benefit of adding abemaciclib to fulvestrant was similar irrespective of baseline NLR status. This post hoc analysis of data from MONARCH 2 focused on the relationship of pretreatment neutrophil-to-lymphocyte ratio and absolute lymphocyte count to abemaciclib outcomes.

B cells secrete antibodies and mediate the humoral immune response, making them extremely important in protective immunity against SARS-CoV-2, which caused the coronavirus disease 2019 (COVID-19) pandemic. In this review, we summarize the positive function and pathological response of B cells in SARS-CoV-2 infection and re-infection. Then, we structure the immunity responses that B cells mediated in peripheral tissues. Furthermore, we discuss the role of B cells during vaccination including the effectiveness of antibodies and memory B cells, viral evolution mechanisms, and future vaccine development. This review might help medical workers and researchers to have a better understanding of the interaction between B cells and SARS-CoV-2 and broaden their vision for future investigations.

Bacteraemia is a common cause of increased morbidity and mortality in critically ill patients, but its early diagnosis and identification are complicated. The neutrophil-lymphocyte count ratio (NLCR) has been suggested as a useful indicator for the diagnosis of bacteraemia. We performed this meta-analysis to investigate the diagnostic accuracy of the NLCR for bacteraemia. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for this meta-analysis. We calculated individual and pooled sensitivities and specificities. I2 statistics and Cochran's Q test were used to evaluate heterogeneity, and the cause of heterogeneity was explored with sensitivity analyses. In total, 8 of 1086 eligible articles were included in the present meta-analysis. The pooled analyses revealed that the diagnostic accuracy of the NLCR in terms of its bacteraemia sensitivity was 0.723 [95% CI: 0.660, 0.777], and its specificity was 0.596 [95% CI: 0.556, 0.634]. The area under the summary receiver operating characteristic curve was 0.69 [95% CI 0.65–0.73]. The NLCR is an easy-to-collect marker for bacteraemia. However, the NLCR is inadequate, and only a combination of multiple biomarkers will improve its diagnostic accuracy for bacteraemia.

We explored the relationship between platelet count to lymphocyte count ratio (PLR), monocyte count to lymphocyte count ratio (MLR), lactate dehydrogenase to albumin ratio (LAR), and long-term survival in patients with breast cancer. We retrospectively analyzed the clinical and follow-up data of 134 patients with breast cancer. The receiver operating characteristic curve (ROC curve) was used to distinguish between the low and high ratio groups. The chi-square test or Fisher's exact test was used to calculate the differences among the investigation factors. The Kaplan-Meier method was used to draw the survival curves. Log rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. A P value of <0.05 was considered statistically significant. The median follow-up time was 45 months. The PFS rates in the low group (LAR≤3.4066) at 18 months, 24 months, and 36 months were 100%, 100%, and 97.6%, and those in the high group (LAR > 3.4066) were 97.7%, 94.3%, and 87.3%, respectively. LAR was associated with Age (P=0.002) and BMI (body mass index) (P=0.002). Univariate analysis showed that Tumor size (P=0.027), Node positivity (P<0.001), TNM (tumor-node-metastasis) stage (P<0.001), PLR (P=0.034), MLR (P=0.038), and LAR (P=0.035) were significantly associated with PFS (progression-free survival) in breast cancer patients. Multivariate analysis showed that Node positivity (P<0.001) and LAR (P=0.035) were associated with PFS, while PLR and MLR were not independent prognostic indicators. Preoperative high LAR will be an independent predictor of prognosis in patients with breast cancer.

Background The impact of human immunodeficiency virus (HIV) low-level viremia (LLV) on CD4 + T lymphocyte (CD4) cell count recovery during antiretroviral therapy (ART) remains unknown in China. This study aimed to investigate the association between LLV and CD4 count recovery among adults on ART in Southwest China. Methods A longitudinal cohort study of persons living with HIV (PLHIV) were conducted in Dehong Prefecture, Southwest China. Incidence of CD4 count recovery (CD4 cell count ≥ 500 cells/µl) was calculated for each follow-up year and characteristics of LLV (VL between 50 and 999 copies/ml) were described. Group-based trajectory model (GBTM) was used to identify and characterize the trajectories of CD4 cell count and VL during follow up. Longitudinal associations between LLV and CD4 count recovery were examined using a generalized estimating equation (GEE) with LLV as a time-updated variable. Results The study included a total of 7,485 PLHIV who received ART between 2008 and 2021 in Dehong. The median follow-up duration was 8.5 years. At baseline, the participants had a median age of 36 years, with males accounting for 60.5%. The median CD4 cell count at baseline was 268 cells/µl. Results of GBTM demonstrated that 730 patients (9.8%) experience LLV trajectories and 2,125 patients (28.4%) reached CD4 count recovery during follow-up. Compared to participants with the trajectory of VL < 50 copies/ml, the probability of CD4 count recovery were lower among participants with the trajectories of LLV 50–199 copies/ml (adjusted odds ratio [aOR] 0.69, 95% confidence interval [CI] 0.63–0.76) and LLV 200–999 copies/ml (aOR 0.51, 95% CI 0.45–0.59), Conclusion Sustained LLV is associated with poorer CD4 recovery among HIV patients who are receiving ART. Interventions to ensure that PLHIV maintain durably undetectable VL during treatment should be prioritized to achieve immune recovery.

Background Since the HIV epidemic in the 1980s, CMV retinitis has been mainly reported in this context. CMV retinitis in persons living with HIV is usually observed when CD4 + cells are below 50 cells/mm3. This study aims to describe the immune markers of non-HIV-related CMV retinitis as well as to describe its clinical manifestations and outcomes. Methods Retrospective chart review of consecutive patients with CMV retinitis not related to HIV seen at the uveitis clinic of Jules Gonin Eye Hospital between 2000 and 2023. We reported the clinical manifestations and outcomes of the patients. We additionally assessed immune markers during CMV retinitis (leukocyte, lymphocyte, CD4 + cell and CD8 + cell counts as well as immunoglobulin levels). Results Fifteen patients (22 eyes) were included. Underlying disease was hematologic malignancy in 9 patients, solid organ transplant in 3 patients, rheumatic disease in 2 patients and thymoma in one patient. The median time between the onset of underlying disease and the diagnosis of retinitis was 4.8 years. Lymphopenia was observed in 8/15 patients (mild = 3, moderate = 4, severe = 1), and low CD4 counts were observed in 9/12 patients, with less than 100 cells/mm3 in 4 patients. Hypogammaglobulinemia was detected in 7/11 patients. Retinitis was bilateral in 7/15 patients, and severe visual loss was frequent (5/19 eyes). Disease recurrence was seen in 7/13 patients at a median time of 6 months after initial diagnosis. No differences in immune markers were observed in patients with vs. without recurrence. Conclusion CMV retinitis is a rare disorder that can affect patients suffering any kind of immunodeficiency. It is associated with a high visual morbidity despite adequate treatment. CD4 + cell counts are usually higher than those in HIV patients, but B-cell dysfunction is common.

Symptoms of COVID-19 vary in severity and presentation. When admitting patients to the hospital, it is desirable to isolate patients with COVID-19 from those without the disease. However, reliably identifying patients with COVID-19 in the emergency department before hospital admission is often limited by the speed and availability of testing. Previous studies determined a low lymphocyte count is commonly found in patients with COVID-19. We sought to explore the sensitivity of absolute lymphocyte count in patients presenting to the emergency department requiring subsequent hospitalization who were found to have COVID-19. A retrospective chart review was performed on 312 patients with laboratory-confirmed COVID-19 who were admitted to the hospital from the emergency department. The absolute lymphocyte count for these patients was used to calculate sensitivities at various cut-off values. The relationships between absolute lymphocyte count and variables, including age, sex, need for intubation, and mortality, were also explored. Cut-off values for absolute lymphocyte count ranged from 1.1 K/uL to 2.0 K/uL, with sensitivities of 72% and 94%, respectively. Additionally, lower mean absolute lymphocyte counts were identified in males, patients who required intubation, and patients who died. Knowing the sensitivity of absolute lymphocyte count in patients with COVID-19 may help identify patients who are unlikely to have the disease. Additionally, absolute lymphocyte count can be used as a marker of disease severity in patients with COVID-19. •Absolute lymphocyte count may help identify patients who are unlikely to have COVID-19.•Lymphopenia can be used as a marker of disease severity in patients with COVID-19.•Lymphopenia may serve as a prognostic indicator in patients with COVID-19.•Absolute lymphocyte count may help cohort patients who are unlikely to have COVID-19.