A New Registry for Genetic Diagnosis of Inborn Errors of Immunity within the Military Health System

Genotypic definition of monogenic inborn errors of immunity (IEIs) continues to accelerate with broader access to next generation sequencing, underscoring this aggregated group of disorders as a major health burden impacting both civilian and military populations. At an estimated prevalence of 1 in 1200 individuals, IEIs affect ~8,000 patients within the Military Health System (MHS). Despite access to targeted gene/exome panels at military treatment facilities, most affected patients never receive a definitive genetic diagnosis that would significantly improve clinical care. To address this gap, we established the first registry of IEI patients within the MHS with the goal of identifying known and novel pathogenic genetic defects to increase diagnosis rates and enhance clinical care. Using the registry, a research protocol was opened in July 2022. Since July we have enrolled 75 IEI patients encompassing a breadth of phenotypes including severe and recurrent infections, bone marrow failure, autoimmunity/autoinflammation, atopic disease, and malignancy. Enrolled patients provide blood and bone marrow samples for whole genome, ultra-deep targeted panel and comprehensive transcriptome sequencing, plus cryopreservation of peripheral blood mononuclear cells for future functional studies. We are also implementing and developing analytical methods for identifying and interrogating non-coding and structural variants. Suspected pathogenic variants are adjudicated by a clinical molecular geneticist using state-of-the-art analysis pipelines. These analyses subsequently inform in vitro experiments to validate causative mutations using cell reporter systems and primary patient cells. Clinical variant validation and return of genetic results are planned with genetic counseling provided. As a proof of principle, this integrated genetic evaluation pipeline revealed a novel, candidate TLR7 nonsense variant in two adolescent brothers who both endured critical COVID-19 pneumonia, requiring mechanical ventilation and extracorporeal membrane oxygenation. Our protocol is therefore poised to greatly enrich clinical genetics resources available in the MHS for IEI patients, contributing to better diagnosis rates, informed family counseling, and targeted treatments that collectively improve the health and readiness of the military community. Moreover, our efforts should yield new mechanistic insights on immune pathogenesis for a broad variety of known and novel IEIs.Copyright © 2023 Elsevier Inc.

SARS-CoV-2 seroprevalence in workers from a Colombian University Hospital.

BACKGROUND: Antibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection. AIMS: To describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia. METHODS: In this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT-PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT-PCR/antigen test (<3 months, 3-6 months, >6 months). RESULTS: We included 1021 workers (80% women, median age 34 years (interquartile range 28-42), 73% medical personnel, 23% with previous positive RT-PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6-37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT-PCR/antigen test, the seroprevalence was 90% (<3 months), 82% (3-6 months) and 48% (>6 months). In participants with a previous negative RT-PCR/antigen test, the seroprevalence was 17% (<3 months), 21% (3-6 months) and 29% (>6 months). CONCLUSIONS: High IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT-PCR/antigen status and time elapsed since the diagnostic test.

Learning in Project-Based Engineering Education: A Bibliometric Analysis

The events caused by the COVID-19 pandemic forced educators to transition to a fully online education system. Therefore, the implementation of project-based learning (PBL) in education is not an easy task. However, since PBL offers students many learning benefits, the aim of this paper is to conduct a bibliometric analysis to measure the performance of using PBL in engineering courses. Two computer tools have been used to carry out the analysis: a) Scopus as a performance analysis tool and b) SciMAT to carry out the bibliometric analysis of content from scientific maps. The results show that the topic with the highest performance for the period 2000-2015 corresponds to the topic of engineering educators, with a h-index of 19, 157 linked articles and, 4815 citations. However, the transition to digital teaching is shown in the period 2016-2021, where e-learning systems represent a cross-cutting theme in the field of research. Therefore, the close relationship of the PBL methodology with engineering educators and the transition to virtual education is shown. However, it requires the integration of e-learning platforms. This is closely related to the driving topics shown in the strategic map for the 2016-2021 period, such as: ensuring the quality of teamwork;properly monitor learning experiences;enhance the focus on engineering design;and work on planning the design of the curriculum, to involve all the activities and evaluations of the educational goals. © 2022 Latin American and Caribbean Consortium of Engineering Institutions. All rights reserved.

An Analysis on Hybrid Brain Storm Optimisation Algorithms

Optimisation can be described as the process of finding optimal values for the variables of a given problem in order to minimise or maximise one or more objective function(s). Brain storm optimisation (BSO) algorithm is relatively new swarm intelligence algorithm that mimics the brainstorming process in which a group of people solves a problem together. The aim of this paper is to present hybrid BSO algorithm solutions in general, and particularly: (i) a hybrid BSO for improving the performances of the original BSO algorithm;(ii) a hybrid BSO for the flexible job-shop scheduling problem;and (iii) a feature selection by a hybrid BSO algorithm for the COVID-19 classification. The hybrid BSO algorithm overcomes the lack of exploitation in the original BSO algorithm, and simultaneously, the obtained better results prove their efficiency and robustness. © 2022, Springer Nature Switzerland AG.

Small business community needs assessment: A case during the pandemic situation

The study is aimed at assessing small businesses during a pandemic situation. Specifically, this research delved into the business condition, characteristics in common, difficulties encountered, and improvement measures. It utilized the descriptive type of research using a qualitative approach. It covered six small businesses at Klong 15, Ongkharak, Nakhon Nayok, Thailand The safety measures and restrictions imposed by the government had greatly affected small businesses. They were found to be family-owned or home-based, with distinct product or service offerings, the same marketing activities, and local customers. They have difficulties with the narrow product or service offerings, limited marketing activities, and sustaining their operations. A contingency plan is recommended for the new normal situation.

HP36: Diaphragm impairment in patients with COVID-19: A case-control study

Objective: Physicians have observed ventilation disorders in patients with COVID-19. The possible impairment of the diaphragm could be related to the systemic inflammatory response that typifies this infection. We aimed to assess the diaphragmatic function in patients with severe COVID-19. Methods: We recruited patients admitted with pneumonia and positive PCR for SARS-CoV-2, differentiating two groups according to their respiratory symptoms. The cases group consisted of 9 inpatients with moderate-severe dyspnea, pain with diaphragmatic origin or hiccup. The control group consisted of 10 inpatients who suffered from mild dyspnea. We performed phrenic nerve electroneurogram and diaphragmatic ultrasound to assess the diaphragmatic function. Results: We observed differences in the amplitude of evoked potentials, being 25.92% (SEM:7.22) in the cases group vs 19.81% (SEM:5.27) in the control group (p = 0.711). The right diaphragm thickness mean was 46.67% (SEM:8.86) in the cases group vs 62.15% (SEM:5.58) in the control group (p = 0.432), the left diaphragm thickness mean was 57.89% (SEM:15.36) in the cases group vs 73.34% (SEM:6.74) in the control group (p = 0.730), the right expiratory fraction mean was 0.53 (SEM:0.11) in the cases group vs 0.59 (SEM:0.05) in the control group (p = 0.674), and the left expiratory fraction mean was 0.58 (SEM:0.15) in the cases group vs 0.73 (SEM:0.07) in the control group (p = 0.195). Conclusion: Although diaphragmatic dysfunction is difficult to detect, our combined functional and morphological approach with electroneurograms and ultrasounds could improve diagnostic sensitivity. We suggest that diaphragmatic dysfunction could play a relevant role in respiratory failure in patients with COVID-19. [ FROM AUTHOR] Copyright of Clinical Neurophysiology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

Assistance pressure in oncohaematological dispensation area during the covid pandemic

Background and importance During the pandemic caused by the SARS-CoV-2 virus, many pathologies have not been diagnosed and/or treated in hospitals because most of the material and human resources have been allocated to the diagnosis and treatment of COVID-19 as well as to preventing the spread of the virus. In the case of oncological and haematological patients, the first analyses show that a significant number of Spanish patients have had delays in starting their treatments and interruptions, according to the Spanish Society of Medical Oncology (SEOM). Aim and objectives The objective was to analyse the evolution of the care activity provided to oncohaematological patients with hospital dispensation of oral chemotherapy in the pharmacy service of a Spanish hospital during the SARS-CoV-2 pandemic. Material and methods A retrospective descriptive study was carried out. It included all patients who attended the oncohaematological dispensation area of the pharmacy service between March and June 2020. Results were compared with the same period in the previous year (2019). Results The total number of dispensations during the 4 months of the study was 2182 patients in 2019 and 2155 in 2020, so the total reduction in the number of patients was not significant (1.24% lower). However, during April and May, coinciding with the critical point of the quarantine period, the largest differences occurred: 11.6% and 18.4%, respectively, with a total of 545/482 and 615/503 patients. During April and May, initiation of treatments decreased by 33.33% and 39.47% compared with the same months in the previous year, and treatment continuations showed a reduction of 9.7% and 16.9%. These results confirm the data published by the SEOM regarding the delay in the initiation and discontinuation in certain patients. Delays in initial care and diagnosis are especially worrisome because of the consequences they can have on the evolution and prognosis of patients. Conclusion and relevance The results showed a reduction of almost 40% in the initiation of treatments during the main months of quarantine in Spain. The delay in starting treatment highlights the risk. Telematic visits and the possibility of electronic drug prescription have partially controlled this attention deficit.

Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19: A proposal for a multi-centric prospective trial.

BACKGROUND: COVID-19 is a highly contagious viral infection with high morbidity that is draining health resources. The biggest complication is pneumonia, which has a serious inflammatory component, with no standardized treatment. Low-dose radiation therapy (LD-RT) is non-invasive and has anti-inflammatory effects that can interfere with the inflammatory cascade, thus reducing the severity of associated cytokine release and might be useful in the treatment of respiratory complications caused by COVID-19. STUDY DESIGN AND METHODS: This multicentric prospective clinical trial seeks to evaluate the efficacy of bilateral lung LD-RT therapy as a treatment for interstitial pneumonia in patients with COVID-19 for improving respiratory function.This prospective study will have 2 phases: I) an exploratory phase enrolling 10 patients, which will assess the feasibility and efficacy of low-dose lung irradiation, evaluated according to an increase in the PaO2/FiO2 ratio of at least 20% at 48-72 h with respect to the pre-irradiation value. If a minimum efficiency of 30% of the patients is not achieved, the study will not be continued. II) Non-randomized comparative phase in two groups: a control group, which will only receive pharmacological treatment, and an experimental arm with pharmacological treatment and LD-RT. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm. The primary end-point will be the efficacy of LD-RT in patients with COVID-19 pneumonia according to an improvement in PaO2/FiO2. Secondary objectives will include the safety of bilateral lung LD-RT, an improvement in the radiology image, overall mortality rates at 15 and 30 days after irradiation and characterizing anti-inflammatory mechanisms of LD-RT by measuring the level of expression of adhesion molecules, anti-inflammatory cytokines and oxidative stress mediators.Trial registration: ClinicalTrial.gov NCT-04380818 https://clinicaltrials.gov/ct2/show/NCT04380818?term=RADIOTHERAPY&cond=COVID&draw=2&rank=4.

Pregnancy outcomes among women with and without COVID-19 in a national level III hospital in Peru

Objective: To compare pregnancy outcomes among women with and without COVID-19 infection attended in a national level III hospital in Peru. Method: Observational, retrospective and comparative study. RT-PCR positive pregnant women participated in a 1:1 ratio with negative RT-PCR, and 1:2 with pregnant women of 2019. Maternal and perinatal information was collected. Fisher’s exact test was used with a significance level of 0.05 and prevalence ratios (PR) with their confidence interval of 95% (CI95%). Results: 51 pregnant women with positive RT-PCR, 51 with negative RT-PCR and 102 pregnant women in 2019 participated. RT-PCR test were associated to preterm delivery (p < 0.05). The PR for preterm delivery in women with positive RT-PCR compared to pregnant women in 2019 was 3.14 (CI95%: 1.29-7.64);and compared to women with negative RT-PCR was 4.0 (CI95%: 1.13-14.17). Conclusions: The study’s findings suggest the existence of an association between maternal COVID-19 and preterm birth. However, more studies are required to analyze the role of maternal factors. © 2021 Sociedad Chilena de Obstetricia y Ginecología.