The Effects of LIT and MLR-Bf on Immune Biomarkers and Pregnancy Outcomes in Women With Previous Early Recurrent Miscarriage: A Retrospective Study

Background: Immunological failure during pregnancy is considered one of the etiologies of recurrent miscarriage (RM). The decreased production of mixed lymphocyte reaction-blocking factors (MLR-Bf) may play a major role in this condition. Lymphocyte immunotherapy (LIT), which induces the production of MLR-Bf, has been used in treating RM patients since 1984. However, the effectiveness of LIT is currently being heatedly debated. In addition to that, possible changes to the maternal immune system upon induced MLR-Bf production by LIT remains unclear.Objectives: To explore the possible impacts that MLR-Bf may have on the expression of immune biomarkers and pregnancy outcomes, and deduce whether the prevention of miscarriages is possible with LIT or MLR-Bf in RM patients.Materials and Methods: Women with previous early RM (eRM) were enrolled in this retrospective study after they got pregnant again. LIT was implemented before pregnancy and during the first trimester. MLR-Bf and immune biomarkers were checked as the clinical routine. Patients were followed up until 12 gestational weeks. Levels of immune biomarkers and successful pregnancy rates were compared between MLR-Bf− group and MLR-Bf+ group stratified by LIT. Independent associations between LIT, or MLR-Bf, and miscarriage were estimated. All data management and analysis were conducted using SPSS 20.0.Results: A total of 1,038 patients, 497 MLR-Bf− (49 cases accepted LIT), and 541 MLR-Bf+(463 cases induced by LIT) were included in the study. Percentage of lymphocytes, the ratio of CD4+ T cells/lymphocytes, and levels of some rheumatoid biomarkers (anti-U1-nRNP, anti-SAA-52kd, and anti-CENOP B) were statistically higher in MLR-Bf+ group than in MLR-Bf− group among women without LIT. With LIT treatment the successful pregnancy rate was statistically higher in MLR-Bf+ group than in MLR-Bf− group (66.7% vs. 51.0%, P = 0.028) among women with LIT. Meanwhile, LIT was estimated to have an independent negative association with miscarriage.Conclusion: Upon LIT treament levels of immune biomarkers were different in women with and without MLR-Bf when stratified by whether they received LIT. Not MLR-Bf, but LIT, has an independent protective effect on miscarriage.

Determinants of immunological recovery following HAART among severely immunosuppressed patients at enrolment to care in Northern Ethiopia: a retrospective study

ObjectiveThis study aimed to identify determinants of immunological recovery following highly active antiretroviral therapy (HAART) among severely immunosuppressed patients at enrolment to care in Northern Ethiopia.MethodsA retrospective study.SettingThe study was done in Tigray Region, Northern Ethiopia.ParticipantsThe study was done among severely immunosuppressed (<200 CD4 cells/mm3) individuals at initial enrolment to care and whose samples were sent for viral load determination from April 2015 to March 2019 in Tigray Health Research Institute.Main outcomesThe main outcome variable was immunological recovery, modelled using binary logistic regression.ResultsAmong the 9687 patients with severe immunosuppression at enrolment, 2746 (28.35%, 95% CI 27.45% to 29.26%) had immunological recovery following HAART for at least 6 months. Male gender (adjusted OR (AOR)=0.50, p<0.001), age 20–34 years old (AOR=0.33, p<0.001), age ≥50 years old (AOR=0.26, p<0.001), WHO clinical stage III (OR=0.68, p=0.036) and viral non-suppression (AOR=0.38, p<0.001) were strong predictors of immunological failure.ConclusionsImmunological recovery following HAART was low among severely immunosuppressed individuals at enrolment to care. Gender, age, WHO stage III and viral non-suppression were determinants of immunological recovery. Male patients, adolescents and virally non-suppressed patients should be identified as groups at higher risk for immunological failure. Therefore, greater support and intensive counselling should be prioritised among adolescents, men and virally non-suppressed patients for better immunological recovery.

Improving the UNAIDS 90-90-90 Treatment Targets: Solutions Suggested from a Qualitative Study of HIV Patients, Community Advocates, Health Workers and Program Managers in Jimma, Southwest Ethiopia

Ethiopia’s performance toward the UNAIDS 90-90-90 targets is low. The present study explored interventions to improve delayed HIV care presentation (first 90), poor retention (second 90) and clinical and immunological failure (third 90). We employed a qualitative approach using in-depth interviews with 10 HIV patients, nine health workers, 11 community advocates and five HIV program managers. Ethical approvals were obtained from Australia and Ethiopia. The following were suggested solutions to improve HIV care and treatment to meet the three 90s: (i) strengthening existing programs including collaboration with religious leaders; (ii) implementing new programs such as self-HIV testing, house-to-house HIV testing, community antiretroviral therapy (ART) distribution and teach-test-treat-link strategy; (iii) decentralizing and integrating services such as ART in health post and in private clinics, and integrating HIV care services with mental illness and other non-communicable diseases; and (iv) filling gaps in legislation in issues related with HIV status disclosure and traditional healing practices. In conclusion, the study suggested important solutions for improving delayed HIV care presentation, attrition, and clinical and immunological failure. A program such as the teach-test-treat-link strategy was found to be a cross-cutting intervention to enhance the three 90s. We recommend further nationwide research before implementing the interventions.

Impact of Lymphocyte and Neutrophil Counts on Mortality Risk in Severe Community-Acquired Pneumonia with or without Septic Shock

Background: Community-acquired pneumonia (CAP) is a frequent cause of death worldwide. As recently described, CAP shows different biological endotypes. Improving characterization of these endotypes is needed to optimize individualized treatment of this disease. The potential value of the leukogram to assist prognosis in severe CAP has not been previously addressed. Methods: A cohort of 710 patients with CAP admitted to the intensive care units (ICUs) at Hospital of Mataró and Parc Taulí Hospital of Sabadell was retrospectively analyzed. Patients were split in those with septic shock (n = 304) and those with no septic shock (n = 406). A single blood sample was drawn from all the patients at the time of admission to the emergency room. ICU mortality was the main outcome. Results: Multivariate analysis demonstrated that lymphopenia <675 cells/mm3 or <501 cells/mm3 translated into 2.32- and 3.76-fold risk of mortality in patients with or without septic shock, respectively. In turn, neutrophil counts were associated with prognosis just in the group of patients with septic shock, where neutrophils <8850 cells/mm3 translated into 3.6-fold risk of mortality. Conclusion: lymphopenia is a preserved risk factor for mortality across the different clinical presentations of severe CAP (sCAP), while failing to expand circulating neutrophils counts beyond the upper limit of normality represents an incremental immunological failure observed just in those patients with the most severe form of CAP, septic shock.