Risk Of Severe Infection Research Articles

Management and documentation of pneumonia – a comparison of patients consulting primary care and emergency care

Patients may attend either primary or emergency care without referral in Sweden. Guidelines recommend a severity assessment, including assessment of vital signs, to be performed for all patients presenting with suspected pneumonia. Objective To compare management and documentation of vital signs, symptoms and infection severity in pneumonia patients seeking primary care and emergency care without referral. Design Medical record review of vital signs, examination findings and severity of pneumonia. Setting Primary and emergency care. Subjects Two hundred and forty patients diagnosed with pneumonia. Main outcome measures Vital signs, examination findings and severity of pneumonia. Assessments of pneumonia severity according to the reviewers, the traffic light score and CRB-65. Results Respiratory rate, blood pressure, heart rate and oxygen saturation were less often documented in primary care (p < .001). Chest X-ray was performed in 5% of primary care patients vs. 88% of emergency care patients (p < .01). Primary care patients had longer symptom duration, higher oxygen saturation and lower respiratory rate. In total, the reviewers assessed 63% of all pneumonias as mild and 9% as severe. The traffic light scoring model identified 11 patients (9%) in primary care and 53 patients (44%) in emergency care at high risk of severe infection. Conclusions Vital signs were documented less often in primary care than in emergency care. Patients in primary care appear to have a less severe pneumonia, indicating attendance to the correct care level. The traffic light scoring model identified more patients at risk of severe infection than CRB-65, where the parameters were documented to a limited extent.

Antigenic drift and immunity gap explain reduction in protective responses against influenza A(H1N1)pdm09 and A(H3N2) viruses during the COVID-19 pandemic: a cross-sectional study of human sera collected in 2019, 2021, 2022, and 2023

BackgroundNon-pharmaceutical interventions implemented during the COVID-19 pandemic resulted in a marked reduction in influenza infections globally. The absence of influenza has raised concerns of waning immunity, and potentially more severe influenza seasons after the pandemic.MethodsTo evaluate immunity towards influenza post-COVID-19 pandemic we have assessed influenza A epidemics in Norway from October 2016 to June 2023 and measured antibodies against circulating strains of influenza A(H1N1)pdm09 and A(H3N2) in different age groups by hemagglutination inhibition (HAI) assays in a total of 3364 serum samples collected in 2019, 2021, 2022 and 2023.ResultsInfluenza epidemics in Norway from October 2016 until June 2023 were predominately influenza As, with a mixture of A(H1N1)pdm09 and A(H3N2) subtype predominance. We did not observe higher numbers of infections during the influenza epidemics following the COVID-19 pandemic than in pre-COVID-19 seasons. Frequencies of protective HAI titers against A(H1N1)pdm09 and A(H3N2) viruses were reduced in sera collected in 2021 and 2022, compared to sera collected in 2019. The reduction could, however, largely be explained by antigenic drift of new virus strains, as protective HAI titers remained stable against the same strain from one season to the next. However, we observed the development of an immunity gap in the youngest children during the pandemic which resulted in a prominent reduction in HAI titers against A(H1N1)pdm09 in 2021 and 2022. The immunity gap was partially closed in sera collected in 2023 following the A(H1N1)pdm09-dominated influenza seasons of 2022/2023. During the 2022/2023 epidemic, drift variants of A(H1N1)pdm09 belonging to the 5a.2a.1 clade emerged, and pre-season HAI titers were significantly lower against this clade compared to the ancestral 5a.2 clade.ConclusionThe observed reduction in protective antibodies against A(H1N1)pdm09 and A(H3N2) viruses post COVID-19 is best explained by antigenic drift of emerging viruses, and not waning of antibody responses in the general population. However, the absence of influenza during the pandemic resulted in an immunity gap in the youngest children. While this immunity gap was partially closed following the 2022/2023 influenza season, children with elevated risk of severe infection should be prioritized for vaccination.

Incidence of hypogammaglobulinaemia in children with steroid-dependent/frequently relapsing nephrotic syndrome treated with rituximab and its association with severe infections

Objective: To investigate the incidence and influencing factors of hypogammaglobulinemia (HGG) in children with steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) treated with rituximab (RTX), and its relationship with the risk of severe infections. Methods: The clinical data of children with SDNS/FRNS treated with RTX at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University from December 2020 to January 2023 were retrospectively analyzed. RTX treatment was performed using a B-cell-guided regimen (a single dose of 375 mg/m2, a maximum of 500 mg/dose, and an additional one dose when reassessment of peripheral blood CD19+B cells≥1%). Patients were divided into HGG and non-HGG groups according to the presence or absence of HGG during the follow-up period. A multivariate logistic regression model was used to analyze the influencing factors of HGG, and the predictive value of each influencing factor on HGG was assessed by plotting the receiver operating characteristic (ROC) curve. Results: A total of 59 SDNS/FRNS children (48 males and 11 females) were included, and aged [M (Q1, Q3)] 9.4 (6.5, 12.2) years at the time of the first RTX treatment, with a median application of 3 (2, 4) doses of RTX. During the follow-up period of 15.5 (9.9, 22.8) months, the HGG was present in 16 (27.1%) children, of which seven persisted for more than 1 year. Compared with non-HGG group, HGG group had a shorter duration of the disease [3.3 (2.1, 3.6) vs 4.6 (2.4, 8.0) years, P=0.030], younger age at the time of the first RTX treatment [6.2 (5.6, 7.4) vs 11.3 (8.8, 13.3) years, P<0.001], and lower serum IgG levels [5.9 (4.9, 6.4) vs 7.5 (6.1, 8.2) g/L, P<0.001]. Multivariate logistic regression analysis showed that young age at the time of the first RTX treatment (OR=0.52, 95%CI: 0.35-0.78, P=0.002) was an influencing factor of HGG. The area under the curve (AUC) for age at first RTX treatment to predict HGG was 0.887 (95%CI: 0.778-0.955, P<0.001), with an optimal cut-off value of 8.3 years. During the follow-up period, six children (10.2%) developed severe infectious, and there was no statistically significant difference in the incidence of serious infections between the HGG and non-HGG groups [12.5% (2/16) vs 9.3% (4/43), P=1.000]. Conclusions: HGG is frequent in children with SDNS/FRNS treated with RTX, and nearly half of HGG persists for more than 1 year. The possibility of HGG is greater in those≤8.3 years at the first RTX treatment, but HGG does not increase the risk of severe infections in children.

Unveiling the impact of COVID-19 on diabetics: vaccination status and infection rates in a North Indian state-insights from a primary healthcare centre-based non-communicable disease registry

Background: Patients with diabetes are at an increased risk of severe infection and mortality due to COVID-19. Absence of effective pharmacological treatments, vaccination remains one of the most effective means of controlling the pandemic. Our study aims to investigate the prevalence of COVID-19 infection among patients with diabetes mellitus and assess the coverage of COVID-19 vaccination among these patients. Methods: The patients were identified from a primary healthcare centre (PHC) based non-communicable disease (NCD) registry at PHC Najafgarh, New Delhi. A total of 480 patients were included in this study. The data was retrieved from NCD registry and vaccination status was confirmed from their vaccination certificates. Results: In our study 91.3% (438) of diabetic patients had received the first dose of COVID-19 vaccine and the coverage for second dose and third dose among these same patients are 84.6% and 27.3% respectively. Conclusions: Only a quarter of all the patients have received precautionary dose (3rd dose), and almost a tenth of all the patients have not even received a single dose of COVID-19 vaccine, the patients should be counselled and encouraged for vaccination. Also, it is recommended to take COVID-19 vaccination into consideration while taking the medical history of diabetics.

Late-onset and long-lasting neutropenias in the young: A new entity anticipating immune-dysregulation disorders.

This study identifies a new chronic form of immune neutropenia in the young with or without detectable indirect anti-neutrophil antibodies, characterized by mild/moderate neutropenia low risk of severe infection (14%), tendency to develop autoimmune phenomena over the course of the disease (cumulative incidence of 58.6% after 20 years of disease duration), leukopenia, progressive reduction of absolute lymphocyte count and a T- and B-cell profile similar to autoimmune disorders like Sjogren syndrome, rheumatoid arthritis, and systemic lupus erythematosus (increased HLADR+ and CD3 + TCRγδ cells, reduced T regulatory cells, increased double-negative B and a tendency to reduced B memory cells). In a minority of patients, P/LP variants related to primary immuno-regulatory disorders were found. This new form may fit the group of "Likely acquired neutropenia," a provisional category included in the recent International Guidelines on Diagnosis and Management of Neutropenia of EHA and EUNET INNOCHRON ACTION 18233. The early recognition of this form of neutropenia would help clinicians to delineate better specific monitoring plans, genetic counseling, and potentially targeted therapies.

Clinical Risk and Outpatient Therapy Utilization for COVID-19 in the Medicare Population

Multiple therapies are available for outpatient treatment of COVID-19 that are highly effective at preventing hospitalization and mortality. Although racial and socioeconomic disparities in use of these therapies have been documented, limited evidence exists on what factors explain differences in use and the potential public health relevance of these differences. To assess COVID-19 outpatient treatment utilization in the Medicare population and simulate the potential outcome of allocating treatment according to patient risk for severe COVID-19. This cross-sectional study included patients enrolled in Medicare in 2022 across the US, identified with 100% Medicare fee-for-service claims. The primary outcome was any COVID-19 outpatient therapy utilization. Secondary outcomes included COVID-19 testing, ambulatory visits, and hospitalization. Differences in outcomes were estimated based on patient demographics, treatment contraindications, and a composite risk score for mortality after COVID-19 based on demographics and comorbidities. A simulation of reallocating COVID-19 treatment, particularly with nirmatrelvir, to those at high risk of severe disease was performed, and the potential COVID-19 hospitalizations and mortality outcomes were assessed. In 2022, 6.0% of 20 026 910 beneficiaries received outpatient COVID-19 treatment, 40.5% of which had no associated COVID-19 diagnosis within 10 days. Patients with higher risk for severe disease received less outpatient treatment, such as 6.4% of those aged 65 to 69 years compared with 4.9% of those 90 years and older (adjusted odds ratio [aOR], 0.64 [95% CI, 0.62-0.65]) and 6.4% of White patients compared with 3.0% of Black patients (aOR, 0.56 [95% CI, 0.54-0.58]). In the highest COVID-19 severity risk quintile, 2.6% were hospitalized for COVID-19 and 4.9% received outpatient treatment, compared with 0.2% and 7.5% in the lowest quintile. These patterns were similar among patients with a documented COVID-19 diagnosis, those with no claims for vaccination, and patients who are insured with Medicare Advantage. Differences were not explained by variable COVID-19 testing, ambulatory visits, or treatment contraindications. Reallocation of 2022 outpatient COVID-19 treatment, particularly with nirmatrelvir, based on risk for severe COVID-19 would have averted 16 503 COVID-19 deaths (16.3%) in the sample. In this cross-sectional study, outpatient COVID-19 treatment was disproportionately accessed by beneficiaries at lower risk for severe infection, undermining its potential public health benefit. Undertreatment was not driven by lack of clinical access or treatment contraindications.

Dynamics of torque teno virus load in kidney transplant recipients with indication biopsy and therapeutic modifications of immunosuppression.

Following kidney transplantation, lifelong immunosuppressive therapy is essential to prevent graft rejection. On the downside, immunosuppression increases the risk of severe infections, a major cause of death among kidney transplant recipients (KTRs). To improve post-transplant outcomes, adequate immunosuppressive therapy is therefore a challenging but vital aspect of clinical practice. Torque teno virus load (TTVL) was shown to reflect immune competence in KTRs, with low TTVL linked to an elevated risk for rejections and high TTVL associated with infections in the first year post-transplantation. Yet, little is known about the dynamics of TTVL after the first year following transplantation and how TTVL changes with respect to short-term modifications in immunosuppressive therapy. Therefore, we quantified TTVL in 106 KTRs with 108 clinically indicated biopsies, including 65 biopsies performed >12 months post-transplantation, and correlated TTVL to histopathology. In addition, TTVL was quantified at 7, 30, and 90 days post-biopsy to evaluate how TTVL was affected by changes in immunosuppression resulting from interventions based on histopathological reporting. TTVL was highest in patients biopsied between 1 and 12 months post-transplantation (N = 23, median 2.98 × 107 c/mL) compared with those biopsied within 30 days (N = 20, median 7.35 × 103 c/mL) and > 1 year post-transplantation (N = 65, median 1.41 × 104 c/mL; p < 0.001 for both). Patients with BK virus-associated nephropathy (BKVAN) had significantly higher TTVL than patients with rejection (p < 0.01) or other pathologies (p < 0.001). When converted from mycophenolic acid to a mTOR inhibitor following the diagnosis of BKVAN, TTVL decreased significantly between biopsy and 30 and 90 days post-biopsy (p < 0.01 for both). In KTR with high-dose corticosteroid pulse therapy for rejection, TTVL increased significantly between biopsy and 30 and 90 days post-biopsy (p < 0.05 and p < 0.01, respectively). Of note, no significant changes were seen in TTVL within 7 days of changes in immunosuppressive therapy. Additionally, TTVL varied considerably with time since transplantation and among individuals, with a significant influence of age and BMI on TTVL (p < 0.05 for all). In conclusion, our findings indicate that TTVL reflects changes in immunosuppressive therapy, even in the later stages of post-transplantation. To guide immunosuppressive therapy based on TTVL, one should consider inter- and intraindividual variations, as well as potential confounding factors.

The COVID-19 infection in liver transplant recipients: A Cohort Study

The immunosuppressed state of liver transplant recipients makes them vulnerable to infections after surgery. These infections are directly correlated with the net state of immunosuppression. Higher levels of immunosuppression mean a higher risk of infection, with rates of infection typically highest in the early post-transplant period. Coronavirus disease 2019 (COVID‐19) vaccines have shown efficacy in generating specific immune responses. This study aims to describe the COVID-19 infection before and after vaccination in liver recipients. This was a cohort study including 77 liver transplant recipients with laboratory radiological confirmed COVID-19. COVID-19 infection was present before vaccination in 30 patients. The most frequent COVID-19 clinical presentations before vaccination were cough in 32 patients and myalgia in 21 patients; 27 cases had oxygen depletion and required supplemental oxygen. Of the 30 COVID-19 patients, 4 patients re-experienced the disease about three months after complete vaccination. 33 liver transplant patients had not experienced COVID-19 before vaccination, of which 32 patients received vaccination. In conclusion, liver transplant patients infected with SARS-CoV-2 are at greater risk of severe infection and death compared with immunocompetent individuals. Thus, COVID-19 vaccination for all liver recipients is of paramount importance.

Risk factors for hypogammaglobulinemia and association with relapse and severe infections in ANCA-associated vasculitis: A cohort study.

B-cell depletion induced by rituximab (RTX) in ANCA-associated vasculitis (AAV) is a risk factor for hypogammaglobulinemia. Aggregating data on gammaglobulin levels kinetics during RTX and its association with the risk of relapse and severe infection is of interest. Gammaglobulin levels were collected before induction therapy and during RTX maintenance therapy. We used different definitions of gammaglobulin decline: 1/gammaglobulin levels <6g/L after induction; 2/>25% decline in gammaglobulin levels between induction and maintenance, and 3/both. Our primary objective was the impact of gammaglobulin decline on the risk of relapse and severe infections. We included 98 patients. Patients with gammaglobulin level <6g/L after induction and gammaglobulin decline >25% were older (OR 3.9; 95%CI 1.1-16.1), had more frequently baseline gammaglobulin levels <10g/L (OR 6.0; 95%CI 1.7-25.8) and received more frequent pulses of methylprednisolone at induction (OR 4.6; 95%CI 1.3-18.5). Severe infection-free survival was significantly poorer in patients with both gammaglobulin <6g/L and gammaglobulin decline >25% (adjusted HR 2.3; 95%CI 1.0-5.1) and in those who received pulses of methylprednisolone (HR 5.6; 95%CI 2.3-13.4). Gammaglobulin decline was in contrast not associated with the risk of relapse. Older age, low gammaglobulin levels and pulses of methylprednisolone at induction increase the likelihood of gammaglobulin decline after induction therapy. Such decline was associated with an increased risk of severe infections but not lower risk of vasculitis relapse. Pulses of methylprednisolone at induction had an independent negative impact on gammaglobulin levels and the risk of severe infections.

Risk of severe infection associated with immunoglobulin deficiency under rituximab therapy in immune-mediated inflammatory disease

ObjectivesWe evaluated the risk of severe infection in patients with immune-mediated inflammatory disease (IMID) treated with RTX and with Ig deficiency.MethodsThis was an observational, retrospective single-centre study of patients undergoing...

Sea urchin nanostructured nickel cobaltite modified carbon cloth integrated wearable patches for the on-site detection of the immunosuppressant drug mycophenolate mofetil.

Mycophenolate mofetil (MpM) is a medication used to prevent the rejection of transplanted organs, particularly in kidney, heart, and liver transplant surgeries. It is extremely important to be conscious that MpM can raise the risk of severe infections and some cancers if it exceeds the recommended dose while lower doses will result in organ rejections. So, it is essential to monitor the dosage of MpM in real time in the micromolar range. In this work, we have synthesized 3-aminopropyltriethoxysilane (APTES) functionalized nickel cobaltite (NiCo2O4) and this amino functionalization was chosen to enhance the stability and electrochemical activity of NiCo2O4. The enhanced activity of NiCo2O4 was used for developing an electrochemical sensor for the detection of MpM. APTES functionalized NiCo2O4 was coated on carbon cloth and used as the working electrode. Surface functionalization with APTES on NiCo2O4 was aimed at augmenting the adsorption/interaction of MpM due to its binding properties. The developed sensor showed a very low detection limit of 1.23 nM with linear ranges of 10-100 nM and 1-100 μM and its practical applicability was examined using artificial samples of blood serum and cerebrospinal fluid, validating its potential application in real-life scenarios.

Preventive Care Practices: A Retrospective Database Study of Influenza and Pneumococcal Vaccination Among Adults with Diabetes

Background: Diabetes mellitus is a prevalent chronic disease that significantly increases the risk of complications from infections such as influenza and pneumococcal disease. Despite established recommendations for vaccination, coverage rates among adults with diabetes remain suboptimal. This study aims to analyze trends in influenza and pneumococcal vaccination rates among adults with diabetes using the United States Diabetes Surveillance System (USDSS) database. Methods: This retrospective database study utilized data from the USDSS from 2000 to 2022, which provides comprehensive nationwide data on diabetes care. The study population included adults aged 18 and above with a documented diagnosis of diabetes. Data were extracted on demographic variables (age, sex, race/ethnicity), clinical characteristics (type of diabetes, duration of diabetes, comorbid conditions), and vaccination records. Descriptive statistics summarized demographic and clinical characteristics, while temporal trends in vaccination rates were analyzed using graphical representations. Results: Over the past two decades, influenza vaccination rates among adults with diabetes increased from 41.4% in 2000 to 56.7% in 2019, reflecting improved awareness and healthcare practices, though slightly dipping to 54.2% in 2022. In contrast, pneumococcal vaccination rates showed more variability, starting at 29.3% in 2000, peaking at 39.4% in 2018, and declining to 30.2% in 2022, indicating challenges in maintaining high coverage. Influenza vaccination rates showed an overall increasing trend across all demographic groups: rates among Hispanic individuals increased from 32.1% in 2000 to 55.4% in 2022, non-Hispanic Whites from 43.4% to 52.7%, and non-Hispanic Blacks from 39.2% to 44.5%. Pneumococcal vaccination rates also increased but displayed more variability; Hispanic rates peaked at 33.3% in 2016, non-Hispanic Whites at 45.6% in 2019, and non-Hispanic Blacks at 41.7% in 2017. Higher educational attainment was consistently associated with higher vaccination rates for both vaccines. Conclusions: This study highlights significant improvements in influenza and pneumococcal vaccination rates among adults with diabetes over the past two decades. However, disparities remain, particularly among racial and educational groups. Targeted strategies are necessary to address these disparities and enhance vaccination coverage, ultimately reducing the risk of severe infections in this vulnerable population.

Escherichia coli: Epidemiology, Impact, Antimicrobial Resistance and Prevention: A review

Public health aims to protect and improve community health by preventing and controlling infectious diseases. This includes surveillance, policy development, health education, immunization, research, and collaboration. Escherichia coli (E. coli) is a bacterium found in the intestines of humans and animals, with harmless and pathogenic strains causing serious illnesses. Pathogenic E. coli, like Shiga toxin-producing E. coli (STEC), can lead to severe food poisoning and outbreaks, making it a major public health concern. E. coli is transmitted through contaminated food, water, and direct contact with infected animals or individuals. It can survive in various environments and acquire antibiotic resistance. Vulnerable populations, such as children, elderly, and immunocompromised individuals, are at higher risk of severe infections. Studies in Egypt show high resistance rates to commonly used antibiotics in both clinical and food samples.E. coli isolates from various sources in Egypt and Tunisia demonstrated high resistance to commonly used antibiotics, limiting treatment options and posing a public health risk. E. coli isolates from patient urine in Nigeria showed high resistance to most antibiotics tested except newer drugs, indicating misuse of antibiotics in healthcare. The typical symptoms of infection include diarrhea, abdominal pain, symptoms of urinary tract infection and fever. The most serious complication is hemolytic uremic syndrome (HUS), which can cause acute kidney failure and be life-threatening, especially in young children and elders. Long-term consequences of infection and HUS can include chronic kidney disease and neurological impairment. The present review article summarizes the current knowledge, highlights the challenges and gaps and provides recommendations and solutions.

Tissue Oxygenation in Individuals with Spinal Cord Injury: A Pilot Study.

Pressure injuries (PI) are debilitating tissue lesions characterised by slow healing and a high risk of severe infection. These injuries result from continued tissue hypoxia, or low tissue oxygen saturation (StO2), which is a consequence of impaired blood circulation caused by continued pressure against tissue. PI result in significant suffering and a substantial financial burden. Therefore, we aim to develop an effective preventive measure. Persons with spinal cord injury (SCI) are at a high risk for PI due to their impaired mobility and lack of sensation to alert them to danger. The aim was to test the feasibility of an alert system based on StO2 monitoring in persons with SCI using a novel textile-based near-infrared spectroscopy (NIRS) sensor.Sensors consisted of two emission and two detection points, each point comprising eight fibres each with three light-coupling bends. Textile integration of fibres was achieved by stitching on a mass-production stitching machine. Emission fibres were connected to LEDs of 740 nm and 810 nm. Detection fibres were connected to avalanche photodiodes. Sensors were attached to the skin in the high-PI-risk buttocks area covering the bony prominences of the ischial tuberosity. StO2 was measured in three healthy subjects and two subjects with SCI during repeated sitting and pressure recovery phases.Our experiments showed decreases in StO2 in both groups during sitting phases: during low-pressure sitting phases, StO2 decreased on average -0.32%/min in the healthy subjects and at -1.24%/min in the SCI subjects. During high-pressure sitting, these rates increased to -1.16%/min for the healthy subjects and -2.16%/min for the SCI subjects. During recovery phases, StO2 returned towards normal values, but did not always reach the initial baseline. No discomfort or skin irritation was observed.These first measurements show physiologically reasonable StO2 values and demonstrate sufficient comfort while sitting on a sensor with no skin irritation or other adverse effects of sitting on the sensor for over 30 min. The nurses involved were satisfied with the easy-of-use, materials used, and patient safety demonstrated during the study. These results show that it is feasible to develop an alert system for PI prevention using a safe, wearable, textile-based NIRS sensor.

Генетические предикторы выживаемости и развития MACE в остром периоде инфекции, вызванной SARS-COV-2, у пациентов высокого кардиоваскулярного риска

Introduction. Despite the fact that the SARS-CoV-2 virus is highly contagious, the clinical manifestations of the disease caused by it can have significant differences: from a low-symptom course to extremely severe forms with the development of a fatal outcome. It is obvious that the observed polymorphism of the development of infection caused by SARS-CoV-2 is due, among other things, to genetic factors. These include single-nucleotide polymorphisms of genes involved in the stages of the pathogenesis of infection: from the penetration of the virus into target cells, the expression of its RNA to the response of the host organism. The study of genetic predictors that cause changes in susceptibility to the SARS-CoV-2 virus and differences in the severity of infection will help to better understand the pathogenesis of this disease and give an idea of promising areas of therapy and prevention. Aim. To study the relationship of genetic biomarkers with the severity of infection caused by SARS-CoV-2, cardiovascular complications and the risk of death in the early period of the disease. Design. A single-center retrospective study. Materials and methods. The study included 164 patients (90 men, 74 women) with infection caused by SARS-CoV-2. All patients were classified as high and very high cardiovascular risk. Concomitant somatic pathology: arterial hypertension in 164 (100%), coronary heart disease in 80 (48.9%), alimentary obesity in 100 (61%), prediabetes in 52 (31.74%), chronic kidney disease in 34 (20.7%) patients. At the first stage of the study, the relationship of genetic biomarkers with the severity of the disease was evaluated, at the second — with cardiovascular complications, and at the third — with the onset of death. Results. In the group of patients with severe disease, variant DD of ACE Alu I/D gene polymorphism, rs4646994 (p = 0.004), variant GG of IL-10 polymorphism 1082 G/A, rs1800896 (p = 0.043), allele *11 HLA-DRB1 (p = 0.015) were significantly more common. The genetic predictors of the development of cardiovascular complications were the genotype DD of the ACE gene (rs4646994) (p = 0.038), the allele *3 HLA-DRB1 (p = 0.041), the allele *13 HLA-DRB1 (p = 0.047) was less common. When searching for a correlation between the selected genetic biomarkers and mortality, only a negative contribution of the ACE Alu I/D polymorphism variant DD, rs4646994 (p = 0.015) was revealed. The survival analysis showed that in the DD variant of the ACE Alu polymorphism I/D, rs4646994, the median survival rate is lower than in the II variant (13 (9–15) days and 21 (12–n/o) days, respectively (p = 0.03)), and lower than in the ID (31 variant (14–n/ o) day (p &lt; 0.0001)). The survival rate of patients with the heterozygous variant of the polymorphism MTRR –66 A/G, rs1801394 was 11.5 (9–16) days, with variant AA — 7 (3–n/o), and with variant GG — 6 (4–14), p = 0.013. With the *16 HLA DRB1 allele, survival was only 5.5 (2–n/o) days versus 22 (17–n/o) days in patients without it, p = 0.04. Conclusion. Predictors of an increased risk of severe infection caused by SARS-CoV-2 include the DD variant of the ACE Alu I/D gene polymorphism, rs4646994, the GG variant of the IL-10 1082 G/A gene polymorphism, rs1800896 and the *11 HLA-DRB1 allele. The negative effect of the DD variant of the polymorphism of the ACE Alu I/D gene, rs4646994, the *3 HLA-DRB1 allele and the protective effect of the *13 HLA-DRB1 allele have been proven in relation to the overall risk of major cardiovascular complications. The carriage of the *16 HLA-DRB1 allele and the DD variant of the ACE Alu I/D gene polymorphism, rs4646994, correlate with an increased risk of early hospital mortality in patients. At the same time, the heterozygous variant of the MTRR –66 A/G polymorphism, rs1801394, is a protective biomarker and is associated with better survival. Key words: COVID-19, SARS-CoV-2 virus, mortality, cardiovascular complications, cardiovascular risk, genetic biomarkers

Risk of Severe COVID-19 and Protective Effectiveness of Vaccination Among Solid Organ Transplant Recipients.

Solid organ transplant recipients (SOTRs) are at higher risk for severe infection. However, the risk for severe COVID-19 and vaccine effectiveness among SOTRs remain unclear. This retrospective study used a nationwide health care claims database and COVID-19 registry from the Republic of Korea (2020 to 2022). Adult SOTRs diagnosed with COVID-19 were matched with up to 4 non-SOTR COVID-19 patients by propensity score. Severe COVID-19 was defined as treatment with high-flow nasal cannulae, mechanical ventilation, or extracorporeal membrane oxygenation. Among 6783 SOTRs with COVID-19, severe COVID-19 was reported with the highest rate in lung transplant recipients (13.16%), followed by the heart (6.30%), kidney (3.90%), and liver (2.40%). SOTRs had a higher risk of severe COVID-19 compared to non-SOTRs, and lung transplant recipients showed the highest risk (adjusted odds ratio, 18.14; 95% confidence interval [CI], 8.53-38.58). Vaccine effectiveness against severe disease among SOTRs was 47% (95% CI, 18%-65%), 64% (95% CI, 49%-75%), and 64% (95% CI, 29%-81%) for 2, 3, and 4 doses, respectively. SOTRs are at significantly higher risk for severe COVID-19 compared to non-SOTRs. Vaccination is effective in preventing the progression to severe COVID-19. Efforts should be made to improve vaccine uptake among SOTRs, while additional protective measures should be developed.

Development of a nomogram prognostic model for early Grade ≥ 3 infection in newly diagnosed multiple myeloma based on immunoparesis

BackgroundInfection, a significant cause of death in multiple myeloma (MM) patients, is a common complication and is closely associated with immunoparesis. There exists no clear definition of early infection, so early infection is defined in this paper as the occurrence within 3 months after diagnosis, considering the high incidence of infections within 3 months after diagnosis. This study established a new nomogram model based on immunoparesis to identify MM patients with high-risk early infection. Methods: A retrospective collection of 430 NDMM patients from June 2013 to June 2022 was conducted, and the patients were further divided into a training cohort and a validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) was used to select the best variables that can be used to establish a new nomogram prediction model. Validation was performed in the validation and entire cohorts. Results: After diagnosis, 67.7 % of the patients suffered from severe infection within 1 year, and 59.5 % experienced the first severe infection within 3 months. Variables associated with an increased risk of severe infection in the first 3 months included: BMPC, D-dimer, serum β2 microglobulin, immunoparesis, albumin, and eGFR. The nomogram based on the above six factors achieved a good C-index of 0.754, 0.73, and 0.731 in predicting early infection in the training cohort, validation cohort, and entire cohort, respectively. Finally, the time-dependent receiver operating characteristic (ROC) curve and decision curve analysis (DCA) of the nomogram showed that the model provided superior diagnostic capacity and clinical net benefit. Conclusion: In this study, we established a nomogram model to predict early grade ≥ 3 infection in NDMM patients. This model can assist clinicians in identifying NDMM patients with high-risk infections and improve their prognosis through early intervention.

A Toxoplasma gondii putative amino acid transporter localizes to the plant-like vacuolar compartment and controls parasite extracellular survival and stage differentiation.

Toxoplasma gondii is a protozoan parasite that infects a broad spectrum of hosts and can colonize many organs and cell types. The ability to reside within a wide range of different niches requires substantial adaptability to diverse microenvironments. Very little is known about how this parasite senses various milieus and adapts its metabolism to survive, replicate during the acute stage, and then differentiate to the chronic stage. T. gondii possesses a lysosome-like organelle known as the plant-like vacuolar compartment (PLVAC), which serves various functions, including digestion, ion storage and homeostasis, endocytosis, and autophagy. Lysosomes are critical for maintaining cellular health and function by degrading waste materials and recycling components. To supply the cell with the essential building blocks and energy sources required for the maintenance of its functions and structures, the digested solutes generated within the lysosome are transported into the cytosol by proteins embedded in the lysosomal membrane. Currently, a limited number of PLVAC transporters have been characterized, with TgCRT being the sole potential transporter of amino acids and small peptides identified thus far. To bridge this knowledge gap, we used lysosomal amino acid transporters from other organisms as queries to search the T. gondii proteome. This led to the identification of four potential amino acid transporters, which we have designated as TgAAT1-4. Assessing their expression and sub-cellular localization, we found that one of them, TgAAT1, localized to the PLVAC and is necessary for normal parasite extracellular survival and bradyzoite differentiation. Moreover, we present preliminary data showing the possible involvement of TgAAT1 in the PLVAC transport of arginine.IMPORTANCEToxoplasma gondii is a highly successful parasite infecting a broad range of warm-blooded organisms, including about one-third of all humans. Although Toxoplasma infections rarely result in symptomatic disease in individuals with a healthy immune system, the incredibly high number of persons infected, along with the risk of severe infection in immunocompromised patients and the potential link of chronic infection to mental disorders, makes this infection a significant public health concern. As a result, there is a pressing need for new treatment approaches that are both effective and well tolerated. The limitations in understanding how Toxoplasma gondii manages its metabolism to adapt to changing environments and triggers its transformation into bradyzoites have hindered the discovery of vulnerabilities in its metabolic pathways or nutrient acquisition mechanisms to identify new therapeutic targets. In this work, we have shown that the lysosome-like organelle plant-like vacuolar compartment (PLVAC), acting through the putative arginine transporter TgAAT1, plays a pivotal role in regulating the parasite's extracellular survival and differentiation into bradyzoites.

Rancangan video animasi edukasi kesiapsiagaan bencana non alam COVID-19 bagi ibu hamil. Uji validitas dan reliabilitas instrumen

Background: COVID-19 is transmitted through air transmission. Prevention of transmission of the COVID-19 virus in pregnant women will certainly reduce complications in pregnant women and the fetus. An educational animated video design can help increase pregnant women's understanding of preventing the transmission of COVID-19. The Coronavirus disease 2019 or COVID-19 in pregnant women will increase the risk of severe infection and pregnancy complications such as preterm labour. Pregnancy will cause physiological changes and maternal immunity, so pregnant women are in a high-risk group for COVID-19 infection. Prevention of COVID-19 virus transmission in pregnant women needs to be done to prevent complications in pregnant women and fetuses. Research objectives: The design of educational animated videos can help increase the understanding of pregnant women in preventing COVID-19 transmission and to test the validity and reliability of instruments.Method: Developing an educational video animation for non-natural disaster preparedness is carried out in several stages, namely making scenarios, storyboards, sketches, choosing colors, coloring, layering and combining them into animated videos. Then, the animated video was validated by a team of experts from the Langsa City Health Office. The content of this video is about preventing COVID-19 transmission in pregnant women. The animated video was tested on 20 respondents in June 2021 in Karang Anyar village, Langsa City. Furthermore, the instrument was tested for validity and reliability on 20 respondents in July 2021 in Paya Bujok Tunong Village, Langsa City.Results: Are 10 components assessed from educational animated videos, and the majority are very good ≥65%. The results of the validity and reliability tests show that the questionnaire is suitable for use in the condition of pregnant women when facing COVID-19 (p &gt; 0,05). However, one invalid statement item was found. The reliability test results show that all variables have an alpha value above 0,378.Conclusion: Respondents can use and distribute animated videos and research instruments.

Gender Differential In Symptoms, Morbidity, And Case Fatality Rate In The COVID-19 Pandemic In India

Background: The COVID-19 epidemic has taken a considerable toll worldwide and has harmed both male and female health. Statistics revealed that fewer females were directly affected than males; however, the latter may be more affected by the consequences. Some studies at the global level have suggested gender as the key determining factor in COVID-19, but there is a lack of such studies in developing countries like India. In light of the situation, this study has analyzed the gender-wise pattern of symptoms, morbidity, multimorbidity, and mortality due to COVID-19 in Karnataka, India. Methods: We used patient-level raw data from COVID19-India application programming interface (API) from 09th March to 05th September 2020. We have used descriptive statistics such as frequency, percentage distribution, and latent class analysis (LCA) to carry out this analysis. Findings: The study comprised 78,983 COVID-19 patients who were 63.6% males and 36.4 % females. Out of the total patients, 10.1% were reported as deceased, of which 68.4% were males and 31.6% were females. We found that all three symptoms (cough, breathlessness, and fever) were higher among males than females in the case of disease symptoms. Males had a higher risk of severe infection and mortality in general. In comparison, females suffered from comorbidities like diabetes and hypertension were at higher risk of mortality due to COVID-19 than their male counterparts. The latent class analysis also revealed that females had a more significant proportion of two or more symptoms, whereas males had more than two comorbidities. Interpretation: Given the differences in lethality between the two genders, we believe that our study has found the root causes of the gender differentials in the COVID-19 pandemic. Furthermore, our research mapped gender differences in various aspects of COVID-19, which will help policymakers find suitable interventions to reduce the burden.