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This study delves into the intricate landscape of SARS-CoV-2 vaccine response in immunodeficient patients, focusing on the dynamics of both humoral and cell-mediated immunity. The cohort includes patients with common variable immunodeficiency (CVI), agammaglobulinemia (XLA), and combined immunodeficiency (CI). The findings reveal varying degrees of antibody production, with XLA patients exhibiting no measurable response but displaying a robust T-cell-mediated response. The study emphasizes the importance of considering both arms of the immune system in assessing vaccine immunogenicity, particularly in the context of immunodeficiency. The results challenge conventional measures of vaccine efficacy only based on antibody titers, highlighting the need for a more comprehensive understanding of the immune response in this vulnerable population. This research contributes valuable insights to guide clinical decisions regarding vaccination strategies, booster doses, and overall protection in immunodeficient individuals.

Multiple myeloma (MM) is a hematologic malignancy with a multistep evolutionary pattern, in which the pro-inflammatory and immunosuppressive microenvironment and genomic instability drive tumor evolution. MM microenvironment is rich in iron, released by pro-inflammatory cells from ferritin macromolecules, which contributes to ROS production and cellular damage. In this study, we showed that ferritin increases from indolent to active gammopathies and that patients with low serum ferritin had longer first line PFS (42.6 vs. 20.7 months and, p = 0.047, respectively) and OS (NR vs. 75.1 months and p = 0.029, respectively). Moreover, ferritin levels correlated with systemic inflammation markers and with the presence of a specific bone marrow cell microenvironment (including increased MM cell infiltration). Finally, we verified by bioinformatic approaches in large transcriptomic and single cell datasets that a gene expression signature associated with ferritin biosynthesis correlated with worse outcome, MM cell proliferation, and specific immune cell profiles. Overall, we provide evidence of the role of ferritin as a predictive/prognostic factor in MM, setting the stage for future translational studies investigating ferritin and iron chelation as new targets for improving MM patient outcome.

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by a multistep evolutionary pathway, with an initial phase called monoclonal gammopathy of undetermined significance (MGUS), potentially evolving into the symptomatic disease, often preceded by an intermediate phase called "smoldering" MM (sMM). From a biological point of view, genomic alterations (translocations/deletions/mutations) are already present at the MGUS phase, thus rendering their role in disease evolution questionable. On the other hand, we currently know that changes in the bone marrow microenvironment (TME) could play a key role in MM evolution through a progressive shift towards a pro-inflammatory and immunosuppressive shape, which may drive cancer progression as well as clonal plasma cells migration, proliferation, survival, and drug resistance. Along this line, the major advancement in MM patients' survival has been achieved by the introduction of microenvironment-oriented drugs (including immunomodulatory drugs and monoclonal antibodies). In this review, we summarized the role of the different components of the TME in MM evolution from MGUS as well as potential novel therapeutic targets/opportunities.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has changed our lives. The scientific community has been investigating re-purposed treatments to prevent disease progression in coronavirus disease (COVID-19) patients., Objective: To determine whether ivermectin treatment can prevent hospitalization in individuals with early COVID-19., Design, Setting and Participants: A randomized, double-blind, placebo-controlled study was conducted in non-hospitalized individuals with COVID-19 in Corrientes, Argentina. Patients with SARS-CoV-2 positive nasal swabs were contacted within 48 h by telephone to invite them to participate. The trial randomized 501 patients between August 19th 2020 and February 22nd 2021., Intervention: Patients were randomized to ivermectin (N = 250) or placebo (N = 251) arms in a staggered dose, according to the patient's weight, for 2 days., Main Outcomes and Measures: The efficacy of ivermectin to prevent hospitalizations was evaluated as primary outcome. We evaluated secondary outcomes in relationship to safety and other efficacy end points., Results: The mean age was 42 years (SD ± 15.5) and the median time since symptom onset to the inclusion was 4 days [interquartile range 3-6]. The primary outcome of hospitalization was met in 14/250 (5.6%) individuals in ivermectin group and 21/251 (8.4%) in placebo group (odds ratio 0.65; 95% confidence interval, 0.32-1.31; p = 0.227). Time to hospitalization was not statistically different between groups. The mean time from study enrollment to invasive mechanical ventilatory support (MVS) was 5.25 days (SD ± 1.71) in ivermectin group and 10 days (SD ± 2) in placebo group, (p = 0.019). There were no statistically significant differences in the other secondary outcomes including polymerase chain reaction test negativity and safety outcomes., Limitations: Low percentage of hospitalization events, dose of ivermectin and not including only high-risk population., Conclusion: Ivermectin had no significant effect on preventing hospitalization of patients with COVID-19. Patients who received ivermectin required invasive MVS earlier in their treatment. No significant differences were observed in any of the other secondary outcomes., Trial Registration: ClinicalTrials.gov NCT04529525 .

Background: Evaluating severity of illness of patients with prolonged mechanical ventilation (PMV) is important to adopt the best appropriate care management for each individual. Yet, no severity-of-illness scoring system has been specifically designed for this type of patients. The aim of this study was to develop and validate a new instrument, the Multi-INdependence Dimensions (MIND) questionnaire designed to comprehensively measure the severity of illness of patients under PMV., Methods: The validation of the MIND questionnaire was performed during a longitudinal observational study conducted with PMV subjects in weaning facilities in three countries (Argentina, Colombia and Germany). The questionnaire validity was tested in 3 stages: 1) Specification of components, with description of item responses, inter-item and Cronbach alpha correlations; 2) Creation of the composite scores; 3) Measurement properties determination including test-retest reliability after 30 days, clinical validity (Medical Research Council (MRC) muscle strength score, Sepsis-related Organ Failure Assessment (SOFA), Glasgow Coma Scale (GCS), Dependence Nursing Scale and EuroQol-5 Dimension evaluated at inclusion), and ability to detect change., Results: A total of 128 subjects participated in the validation study. Eleven component scores and four composite scores were created. MIND scores significantly correlated with MRC muscle strength, SOFA, DNS, GCS and EQ-5D, supporting the validity of the new scores. Intraclass Correlation Coefficient greater than 0.82 were observed for all composite scores, indicating good test-retest reliability. MIND scores were able to detect improvement in subject severity of illness., Conclusion: The MIND questionnaire is a valid and reliable instrument for measuring comprehensively the multiple dimensions characterizing the severity of illness of PMV patients., Trial Registration: NCT02255058 .

Insufficient cough strength has a major role in extubation and decannulation outcomes. Cough capacity can be easily evaluated by measuring flows during coughing. Values vary depending on whether cough flows are measured through the mouth or through a tracheostomy or endotracheal tube. It is important to standardize these measurements and start using them routinely in the extubation and decannulation processes. Values of cough peak flow >160 L/min measured at the mouth or a value of cough PEF >60 L/min measured at the endotracheal tube suggest successful decannulation or extubation., (Copyright © 2014 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

A one-day point prevalence study to investigate the patterns of antibiotic use was undertaken in 43 latin American (LA) intensive care units. Of 510 patients admitted, 231 received antibiotic treatment on the day of the study (45%); in 125 cases (54%) due to nosocomial-acquired infections. The most frequent infection reported was nosocomial pneumonia (43%). Only in 122 patients (53%) were cultures performed before starting antibiotic treatment. 33% of the isolated microorganisms were enterobacteriaceae (40% extended-spectrum beta-lactamase-producing), 23% methicillin-resistant Staphylococcus aureus and 17% carbapenems-resistant non-fermentative Gram-negatives. The antibiotics most frequently prescribed were carbapenems (99/231, 43%); alone (60/99, 60%) or in combination with vancomycin (39/99, 40%). "Restricted" antibiotics (carbapenems, vancomycin, piperacillin-tazobactam, broad-spectrum cephalosporins, tigecycline, polymixins and linezolid) were most frequently indicated in severely ill patients (APACHE II score at admission >15, p=0.0007 and, SOFA score at the beginning of the antibiotic treatment >3, p=0.0000). Only 36% of antibiotic treatments were cultured-directed.Our findings help explain the high rates of multidrug-resistant pathogens in LA settings (i.e. ESBL-producing Gram-negatives) and the severity of the registered patients illnesses.

The aim of our study is to evaluate the extent and distribution of grey matter demyelinating lesions in multiple sclerosis (MS), addressing also neuronal loss and synaptic loss. Whole coronal sections of 6 MS brains and 6 control brains were selected. Immunohistochemistry was performed for myelin basic protein, neurofilaments, synaptophysin, ubiquitin, and activated caspase-3. Neuronal density and optical density of synaptophysin staining were estimated in cortical lesions and compared with those observed in corresponding areas of normal (i.e. nondemyelinated) cortex in the same section. Demyelinating lesions were observed in the cerebral cortex, in the thalamus, basal ganglia, and in the hippocampus. The percentage of demyelinated cortex was remarkable in 2 cases of secondary progressive MS (48% and 25.5%, respectively). Neuronal density was significantly reduced in cortical lesions (18-23% reduction), if compared with adjacent normal cortex, in the 2 cases showing the higher extent of cortical demyelination; in the same cases, very rare apoptotic neurons expressing caspase-3 were observed in cortical lesions and not in adjacent normal cortex. No significant decrease in optical density of synaptophysin staining was observed in cortical lesions. Grey matter demyelination and neuronal loss could contribute to disability and cognitive dysfunctions in MS.