Disease Severity Research Articles

Real-world effectiveness of the heterologous SOBERANA-02 and SOBERANA-Plus vaccine scheme in 2–11 years-old children during the SARS-CoV-2 Omicron wave in Cuba: a longitudinal case-population study

Increased pediatric COVID-19 occurrence due to the SARS-CoV-2 Omicron variant has raised concerns about the effectiveness of existing vaccines. The protection provided by the SOBERANA-02-Plus vaccination scheme against this variant has not yet been studied. We aimed to evaluate the scheme's effectiveness against symptomatic Omicron infection and severe disease in children. In September 2021, Cuba implemented a mass pediatric immunization with the heterologous SOBERANA-02-Plus scheme: 2 doses of conjugated SOBERANA-02 followed by a heterologous SOBERANA-Plus dose. By December, before the Omicron outbreak, 95.4% of 2-18 years-old had been fully immunized. During the entire Omicron wave, we conducted a nationwide longitudinal post-vaccination case-population study to evaluate the real-world effectiveness of the SOBERANA-02-Plus scheme against symptomatic infection and severe disease in children without previous SARS-CoV-2 infection. The identification of COVID-19 cases relied on surveillance through first line services, which refer clinical suspects to pediatric hospitals where they are diagnosed based on a positive RT-PCR test. We defined the Incidence Rate ratio (IRR) as IRvaccinated age group/IRunvaccinated 1-year-old and calculated vaccine effectiveness as VE= (1-IRR)∗100%. 24 months of age being the 'eligible for vaccination' cut-off, we used a regression discontinuity approach to estimate effectiveness by contrasting incidence in all unvaccinated 1-year-old versus vaccinated 2-years-old. Estimates in the vaccinated 3-11 years-old are reported from a descriptive perspective. We included 1,098,817 fully vaccinated 2-11 years-old and 98,342 not vaccinated 1-year-old children. During the 24-week Omicron wave, there were 7003/26,241,176 person-weeks symptomatic COVID-19 infections in the vaccinated group (38.2 per 105 person-weeks in 2-years-old and 25.5 per 105 person-weeks in 3-11 years-old) against 3577/2,312,273 (154.7 per 105 person-weeks) in the unvaccinated group. The observed overall vaccine effectiveness against symptomatic infection was 75.3% (95% CI, 73.5-77.0%) in 2-years-old children, and 83.5% (95% CI, 82.8-84.2%) in 3-11 years-old. It was somewhat lower during Omicron BA.1 then during Omicron BA.2 variant circulation, which took place 1-3 and 4-6 months after the end of the vaccination campaign. The effectiveness against severe symptomatic disease was 100.0% (95% CI not estimated) and 94.6% (95% CI, 82.0-98.6%) in the respective age groups. No child death from COVID-19 was observed. Immunization of 2-11 years-old with the SOBERANA-02-Plus scheme provided strong protection against symptomatic and severe disease caused by the Omicron variant, which was sustained during the six months post-vaccination follow-up. Our results contrast with the observations in previous real-world vaccine effectiveness studies in children, which might be explained by the type of immunity a conjugated protein-based vaccine induces and the vaccination strategy used. National Fund for Science and Technology (FONCI-CITMA-Cuba).

The effect of supplementation with vitamins A, B, C, D, and E on disease severity and inflammatory responses in patients with COVID-19: A randomized clinical trial

The effect of supplementation with vitamins A, B, C, D, and E on disease severity and inflammatory responses in patients with COVID-19: A randomized clinical trial

Assessment of chronic rhinosinusitis with nasal polyps: Development of the Nasal Polyp Patient Assessment Scoring Sheet tool.

Chronic rhinosinusitis (CRS) is a heterogeneous disorder with a wide range of validated subjective and objective assessment tools to assess disease severity. However, a comprehensive and easy-to-use tool that integrates these measures for determining disease severity and response to treatment is still obscure. The objective of this study was to develop a standardized assessment tool that facilitates diagnosis, uniform patient monitoring, and comparison of treatment outcomes between different centers both in routine clinical practice and in research. To develop this tool, published literature on assessment tools was searched on various databases. A panel of 12 steering committee members conducted an advisory board meeting to review the findings. Specific outcome measures to be included in a comprehensive assessment tool and follow-up sheet were then collated following consensus approval from the panel. The tool was further validated for content and revised with expert recommendations to arrive at the finalized Nasal Polyp Patient Assessment Scoring Sheet (N-PASS) tool. The N-PASS tool was developed by integrating the subjective and objective measures for CRS assessment. Based on expert opinions, N-PASS was revised to be used as an easy-to-use guidance tool that captures patient-reported and physician-assessed components for comprehensively assessing disease status and response to treatment. The N-PASS tool can be used to aid in the diagnosis and management of CRS cases with nasal polyps. The tool would also aid in improved monitoring of patients and pave the way for an international disease registry. Oxford Level 3.

Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study

Invasive pneumococcal disease due to serotype 3 (S3-IPD) is associated with high mortality rates and long-term adverse effects. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the Spanish paediatric immunisation programme has not led to a decrease in the adult S3-IPD. We aimed to analyse the incidence, clinical characteristics and genomics of S3-IPD in adults in Spain. Adult IPD episodes hospitalized in a Southern Barcelona hospital were prospectively collected (1994-2020). For genomic comparison, S3-IPD isolates from six Spanish hospitals (2008-2020) and historical isolates (1989-1993) were analysed by WGS (Illumina and/or MinION). From 1994 to 2020, 270 S3-IPD episodes were detected. When comparing pre-PCV (1994-2001) and late-PCV13 (2016-2020) periods, only modest changes in S3-IPD were observed (from 1.58 to 1.28 episodes per 100,000 inhabitants year). In this period, the incidence of the two main lineages shifted from 0.38 to 0.67 (CC180-GPSC12) and from 1.18 to 0.55 (CC260-GPSC83). The overall 30-day mortality remained high (24.1%), though a decrease was observed between the pre-PCV (32.4%; 95.0% CI, 22.0-45.0) and the late-PCV13 period (16.7%; 95.0% CI, 7.5-32.0) (p=0.06). At the same time, comorbidities increased from 77.3% (95.0% CI, 65.0-86.0) to 85.7% (95.0% CI, 71.0-94.0) (p=0.69). There were no differences in clinical characteristics or 30-day mortality between the two S3 lineages. Although both lineages were genetically homogeneous, the CC180-GPSC12 lineage presented a higher SNP density, a more open pan-genome, and a major presence of prophages and mobile genetic elements carrying resistance genes. Adult S3-IPD remained stable in our area over the study period despite PCV13 introduction in children. However, a clonal shift was observed. The decrease in mortality rates and the increase in comorbidities suggest a change in clinical management and overall population characteristics. The low genetic variability and absence of clinical differences between lineages highlight the role of the S3 capsule in the disease severity. This study has been funded by Instituto de Salud Carlos III (ISCIII) "PI18/00339", "PI21/01000", "INT22/00096", "FI22/00279", CIBER "CIBERES-CB06/06/0037", "CIBERINFEC-CB21/13/00009" and MSD grant "IISP 60168".

MUC5AC: A potential biomarker of severity in pediatric patients infected with influenza.

Numerous factors can increase the risk of severe influenza; however, a majority of severe cases occur in previously healthy children. Identification of high-risk children is important for targeted preventive interventions and prompt treatment. The aim of this study was to evaluate MUC5AC as a biomarker for influenza disease severity in children. For this, aprospective cohort study was conducted in 2019. Children hospitalized with acute respiratory infection (ARI) with confirmed positive influenza infection were enrolled. Influenza cases were identified by reverse transcriptase-polymerase chain reaction. Life-threatening disease (LTD) was defined by the need for intensive care and ventilatory support. MUC5AC, epidemiologic, and clinical risk factors were assessed. Three hundred and forty-two patients were hospitalized with ARI, of which 49 (14%) had confirmed influenza infection and 6 (12%) of them developed LTD. MUC5AC levels were higher in those patients with mild diseasecompared to cases with poorer outcomes. Our results show that the severity of influenza infection in children is significantly associated with low levels of MUC5AC. These findings suggest its potential as a suitable biomarker for predicting disease severity.

Clinical Characteristics of 427 Unvaccinated Chinese Adult Patients with Maintenance Hemodialysis Infected with the SARS-CoV-2 Omicron Variant: A Retrospective Study

Background: Maintenance hemodialysis (MHD) patients constitute a distinctive population characterized by unique traits, such as hemodialysis-related immune disturbances, and increased vulnerability to infections, heart failure, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite considerable research on MHD patients with coronavirus disease 2019 (COVID-19), there is limited information available on the clinical characteristics and outcomes of unvaccinated adult MHD patients infected with the SARS-CoV-2 Omicron variant. Methods: A retrospective investigation was conducted in a cohort of 427 unvaccinated MHD patients diagnosed with SARS-CoV-2 Omicron infection. The clinical symptoms, laboratory results, and treatment regimens were comprehensively examined. Multivariate regression identified independent risk factors for disease severity, and two-month follow-up assessments were conducted. Results: The cohort exhibited a spectrum of disease severity, with 37.5% classified as mild, 35.3% as common, 22.5% as severe, and 4.7% as critical. Serum C-reactive protein level, procalcitonin level, and bicarbonate concentration are related to the severity of the disease. Tailored treatment strategies—including nutritional support, hemodialysis management, anti-bacterial interventions, and more—were implemented. There was a 5.6% mortality rate, with a higher prevalence of deaths in the critical subtype. Independent risk factors for disease severity included fever, age, cycle threshold values (Ct values) of ORF1ab gene, and arterial oxygen partial pressure. Follow-up assessments revealed a median duration of 11 days for the negative nucleic acid of SARS-CoV-2. Twelve patients presented a second positive ORF1ab gene during follow-up but remained asymptomatic. Conclusion: These findings suggest the intricate clinical characteristics and outcomes of MHD patients with the SARS-CoV-2 Omicron infection. Tailored treatment strategies, continuous surveillance, and understanding prognostic factors are imperative for managing this high-risk population. Further research is warranted to validate these findings.

Homozygosity of a Founder Variant c.1508dupC in DOK7 Causes Congenital Myasthenia With Variable Severity.

Description of 15 patients with the same variant in DOK7 causing congenital myasthenic syndrome (CMS). Nine adult and 6 pediatric patients were studied with molecular genetic and clinical investigations. All patients were identified with the c.1508dupC variant in DOK7, of whom 13 were homozygous and 2 patients compound heterozygous. Only 2 patients had limb girdle phenotype, while all adult patients also had ptosis, ophthalmoplegia, facial weakness, as well as inspiratory stridor. Pediatric patients had severe respiratory insufficiency and feeding difficulties at birth. The disease severity in our patients varied extensively from ventilator or wheelchair dependence to mild facial weakness, ptosis, and ophthalmoparesis. Most of the patients had normal transmission in conventional 3 Hz stimulation electrophysiologic studies, making the diagnosis of CMS challenging. Our cohort of adult and pediatric patients expands the phenotype of DOK7 CMS and shows the importance of correct and early diagnosis.

Điều tra bệnh hại sau thu hoạch trên giống chuối Tiêu hồng (Musa acuminata) và chuối Nam Mỹ (Musa paradisiaca) ở Việt Nam

The survey implemented in the 2021 winter season on the Tieu hong banana cultivar (Musa acuminata) grown in Phu Tho and Hung Yen provinces showed that the most severe diseases were fruit rot and fruit spot with infection rates of 79.1% and 75.5%, respectively. Peel cracking and end rot (cigar rot) were also recorded at less than 5.0%. Fruit spot was the main disease that affected the South-American banana cultivar (Musa paradisiaca) during the 2022 spring-summer season in Gia Lai province. Of the 24 fungal and 37 bacterial strains isolated from the disease samples collected during the investigation and tested for their pathogenicity via artificial infection on healthy bananas, only 17 fungal strains showed the ability of lesion formation of which 4 strains caused typical symptoms of the fruit rot disease. There was not a single bacterial strain ascertained as phytopathogen indicating that fungi were the primary agents of post-harvest diseases on bananas. These four fungal strains were taxonomically characterized based on their morphology (colony and spore), comparative analysis of the ITS sequences of the 18S rDNA gene, and were then identified as Corynespora torulosa B2B, Microdochium colombiense B6, Fusarium circinatum B13F, and Aspergillus niger GL2.1. The ITS sequences of these strains were deposited to GenBank under the accession numbers OP855524, OP855525, OP855526, and OP855527, respectively.

Characteristics of neutralizing antibody titers of the SARS-CoV-2 vaccine in maintenance hemodialysis patients.

Hemodialysis patients have high COVID-19 severity and mortality rates. For this high-risk group of hemodialysis patients with SARS-CoV-2 infection, early SARS-CoV-2 vaccination is recommended to prevent infection and severe disease. Thus far, few reports have evaluated COVID-19 antibody titers in hemodialysis patients. In this study, we investigated the time course of antibody titers acquired by vaccination in patients on dialysis. The anti-SARS-CoV-2 spike protein S1 IgG (anti-SP-IgG) antibody titers were compared between 33 outpatient maintenance hemodialysis patients and 32 age- and sex-matched healthy subjects. Antibody tests were performed at five time points: 6 months after the 2nd vaccination, immediately before the 3rd vaccination (8 months after the 2nd vaccination), and 2 weeks, 1 month, and 3 months after the 3rd vaccination. The dialysis patient group had significantly lower values of anti-SP-IgG antibody titers than the control group 6 months after the 2nd vaccination (433.7 ± 36.24 vs. 650.2 (427.2 - 759.4) (AU/mL), p = 0.006) and immediately before the 3rd vaccination (219.3 (129.4 - 423.4) vs. 443.3 (267.1 - 600.4) (AU/mL), p = 0.034), but no significant differences were observed after the 3rd vaccination (19,000.0 (11,000.0 - 3,6000.0) vs. 23,500.0 (20,250.0 - 29,000.0) (AU/mL), p = 0.538). This study confirmed that patients undergoing hemodialysis were proven to have acquired sufficient antibody titers after the vaccination.

Handheld echocardiography for the screening and diagnosis of rheumatic heart disease: a systematic review to inform WHO guidelines

Early detection and diagnosis of acute rheumatic fever and rheumatic heart disease are key to preventing progression, and echocardiography has an important diagnostic role. Standard echocardiography might not be feasible in high-prevalence regions due to its high cost, complexity, and time requirement. Handheld echocardiography might be an easy-to-use, low-cost alternative, but its performance in screening for and diagnosing acute rheumatic fever and rheumatic heart disease needs further investigation. In this systematic review and meta-analysis, we searched Embase, MEDLINE, LILACS, and Conference Proceedings Citation Index-Science up to Feb 9, 2024, for studies on the screening and diagnosis of acute rheumatic fever and rheumatic heart disease using handheld echocardiography (index test) or standard echocardiography or auscultation (reference tests) in high-prevalence areas. We included all studies with useable data in which the diagnostic performance of the index test was assessed against a reference test. Data on test accuracy in diagnosing rheumatic heart disease, acute rheumatic fever, or carditis with acute rheumatic fever (primary outcomes) were extracted from published articles or calculated, with authors contacted as necessary. Quality of evidence was appraised using GRADE and QUADAS-2 criteria. We summarised diagnostic accuracy statistics (including sensitivity and specificity) and estimated 95% CIs using a bivariate random-effects model (or univariate random-effects models for analyses including three or fewer studies). Area under the curve (AUC) was calculated from summary receiver operating characteristic curves. Heterogeneity was assessed by visual inspection of plots. This study was registered with PROSPERO (CRD42022344081). Out of 4868 records we identified 11 studies, and two additional reports, comprising 15 578 unique participants. Pooled data showed that handheld echocardiography had high sensitivity (0·87 [95% CI 0·76-0·93]), specificity (0·98 [0·71-1·00]), and overall high accuracy (AUC 0·94 [0·84-1·00]) for diagnosing rheumatic heart disease when compared with standard echocardiography (two studies; moderate certainty of evidence), with better performance for diagnosing definite compared with borderline rheumatic heart disease. High sensitivity (0·79 [0·73-0·84]), specificity (0·85 [0·80-0·89]), and overall accuracy (AUC 0·90 [0·85-0·94]) for screening rheumatic heart disease was observed when pooling data of handheld echocardiography versus standard echocardiography (seven studies; high certainty of evidence). Most studies had a low risk of bias overall. Some heterogeneity was observed for sensitivity and specificity across studies, possibly driven by differences in the prevalence and severity of rheumatic heart disease, and level of training or expertise of non-expert operators. Handheld echocardiography has a high accuracy and diagnostic performance when compared with standard echocardiography for diagnosing and screening of rheumatic heart disease in high-prevalence areas. World Health Organization. For the Chinese, French, Italian, Persian, Portuguese, Spanish and Urdu translations of the abstract see Supplementary Materials section.

Validity of the Triglyceride-Glucose Indices for Predicting the Severity of Coronary Artery Disease in Patients With Nondiabetic Chronic Coronary Syndrome.

The triglyceride-glucose (TyG) index was shown to be an independent predictor of coronary artery disease (CAD) progression and prognosis. However, whether the TyG index can predict the severity of CAD in nondiabetic patients with chronic coronary syndrome remains unclear. A total of 118 individuals who underwent elective coronary angiography were classified into group A (59 with coronary lesions) and group B (59 with normal coronary arteries; as a control group) after coronary angiography and laboratory tests for fasting and the postprandial (PP) TyG index. The complexity of CAD was determined by the Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score >22 indicated moderate-high risk), and patients diagnosed with diabetes or prediabetes were excluded. The TyG index was not related to the SYNTAX score in groups A and B; however, in the CAD group with an low-density lipoprotein (LDL) concentration <70 mg/dL (group A1), a fasting TyG index ≥8.25 and a PP TyG index ≥11 could predict moderate-high SYNTAX risk score; in addition, the odds ratio (OR) was 4.3× higher and the relative risk (RR) was 1.8× greater (OR = 4.3, RR = 1.8, 95% confidence interval = 1.4-13.5, P < 0.05) for individuals with a higher fasting TyG index ≥8.25 to have a moderate-high SYNTAX risk score. Individuals with a higher PP TyG index ≥11 had OR of 2.6× higher and a RR of 1.4× greater to have moderate-high SYNTAX risk score. Both fasting and PP TyG levels were associated with greater coronary anatomical complexity (SYNTAX score >22) in nondiabetic chronic coronary patients with LDL <70 mg/dL. Fasting and the PP TyG indices can serve as noninvasive predictors of CAD complexity in nondiabetic patients with LDL <70 mg/dL and could change the management and therapeutic approaches.

Prediction of Parkinson’s Disease using Handwriting Analysis and Voice Dataset- A Review

Parkinson's disease is a common neurological movement illness that impairs motor coordination. Parkinson’s disease (PD) symptoms and severity, however, differ from person to person. By extracting insights, trends, and possibilities from the data, data research can be utilized to uncover solutions to problems in medical research by utilizing data, machine learning algorithms, and cutting-edge technology. Among the less evident early signs of Parkinson's disease are tremors, muscle stiffness, imbalance problems, and difficulty walking. There is currently no test to detect the illness early on, when symptoms might not be evident. However, handwriting and hand- drawn subjects in humans have been linked to PD. In addition to being a useful tool for PD prediction, speech smearing functions as an early warning system. In order to control symptoms and maybe halt the disease's progression, early detection makes it possible to organize treatments and intervene promptly. For those with Parkinson's disease, early application of certain therapies and medications can extend survival and enhance quality of life.

Herbs Used for the Management of Hypertension: A Systematic Review

Background: Hypertension is characterized by persistent high blood pressure and has emerged as a critical risk factor for severe cardiovascular diseases. Although several drugs have been designated to reduce blood pressure, these drugs can potentially cause side effects for patients. Therefore, medicinal plants are used to complement conventional drugs to treat various ailments. Methods: This study reviews the anti-hypertensive potential of herbs and plants and their mechanism of action in reducing blood pressure at their evaluated effective doses. Databases such as PubMed, Scopus, Science Direct, and Google Scholar were used to search articles from January 2016 to Sept 2022. The key search terms included “hypertension”, “lowers blood pressure”, “anti-hypertensive”, and “plants”. These generated 807 documents and using the PRISMA guidelines, thirty plants were identified for this review. Research studies with similar plant parts extracted from similar solvents, more than one dose, and animal models with a positive control were considered in this review. Studies that did not show significant blood pressure reduction were excluded. Results: Based on this criterion, the mechanism of actions of these plants was thematically grouped into three categories, namely 1) antioxidant, 2) angiotensin-converting enzyme (ACE) inhibition, and 3) calcium influx in vascular smooth muscle. The effective doses, plant parts used, and traditional medicine usage are presented in this review. Conclusion: Further research is highly recommended to identify the active compounds and to potentially develop them into anti-hypertensive drugs as well as to establish the safe doses and standardization of these plant extracts. This review is partially funded by grants from the Ministry of Higher Education.

Findings from the 2019 nationally representative oral health survey for adults in Singapore.

The aim of this study was to present key findings from the 2019 national adult oral health survey in Singapore (NAOHS). A multi-stage stratified sampling method was used to recruit participants for a representative national adult oral health survey. A total of 12 212 households were randomly selected from the National Database on Dwellings in Singapore. Within each household eligible persons aged ≥65 years were automatically invited to participate while a Kish selection method was used to invite those between 21 and 64 years old. The survey comprised a face-to-face interview questionnaire and a clinical examination which recorded details of tooth loss, DMFT, DMFS and prevalence of periodontal disease according to the CPITN and the US CDC-AAP classifications. Weighted analysis was performed to adjust for oversampling, non-response and post-stratification. Multivariate regression with backward stepwise selection was carried out to identify predictors of chronic periodontal disease and untreated dental caries. Six hundred and sixty-three participants completed both the questionnaires and the clinical examination. The prevalence of edentulousness was 2.7%. Of participants, 34.8% presented with untreated dental caries with a higher proportion found in those who were aged ≥60 years, of Malay ethnicity, living in 1-2-room public housing and who only visited the dentist when there was a problem. Mean DMFS and DMFT indices were 24.7 and 7.9 respectively. Based on the CDC-AAP classification, the prevalence of moderate-severe chronic periodontitis was 56.9% and increased with age, with a higher proportion in males. Participants with untreated dental caries were more likely to have moderate or severe periodontal disease. Survey findings showed high prevalence of dental caries and periodontal disease, at 34.8% and 77.6% respectively. A clear socio-economic gradient in the distribution of tooth loss, untreated dental caries and moderate-to-severe periodontitis was observed.

Association between the stress-hyperglycemia ratio and all-cause mortality in community-dwelling populations: An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014.

Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.

Syndromes coronaires aigus au cours du diabète : étude comparative entre patients diabétiques et non diabétiques en milieu urbain sénégalais

IntroductionDiabetes Mellitus is a strong cardiovascular risk factor in which acute coronary syndromes (ACS) are thought to have a particular feature. We aimed to determine the characteristics of acute coronary syndromes in diabetics compared with non-diabetics patients. Patients and methodsWe carried out a prospective, descriptive and analytical study comparing diabetic and non-diabetic patients admitted for acute coronary syndrome to the cardiology department of Idrissa Pouye general hospital over a period of one year by studying socio-demographic, clinical, paraclinical, therapeutic and evolutionary parameters. We performed a multivariable logistic regression analysis to identify factors associated with chest pain and triple vessels disease. ResultsOur study included 139 patients, 61 with diabetes (44%) and 78 without diabetes (56%). Among diabetics, there was a predominance of women (p = 0.0001) in contrast to non-diabetics. The mean age was 62.7 ± 10.8 years in diabetics and 56.9 ± 13.5 years in non-diabetics (p = 0.006). Chest pain was found in 88.5% of diabetics and 97.4% of non-diabetics (p = 0.03). The mean HbA1c in diabetics was 9.4 ± 3.3%. ST elevation acute coronary syndrome was predominant in both groups. The mean GRACE score was 147 ± 29 in diabetics and 132 ± 28 in non-diabetics (p = 0.003). In multivariable analysis, only diabetes was associated with triple vessels disease (aOR (IC à 95%): 2,60 (1.29–6.83); p = 0.042). A total of 31% of diabetics and 43% of nondiabetics undergoes cardiac revascularization. There was no difference between the two groups in terms of complications. The mortality was 6.6% and 3.8% respectively among diabetics and non-diabetics (p = 0.49). ConclusionAccording to our study, diabetes is frequently encountered during acute coronary syndromes. It also shows that diabetics are more likely to be female and older, with more atypical symptoms and more severe coronary disease.

Microglial SIX2 suppresses lipopolysaccharide (LPS)-induced neuroinflammation by up-regulating FXYD2 expression

Parkinson’s disease (PD) is a severe neurodegenerative disease associated with the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Although its pathogenesis remains unclear, microglia-mediated neuroinflammation significantly contributes to the development of PD. Here we showed that the sine oculis homeobox (SIX) homologue family transcription factors SIX2 exerted significant effects on neuroinflammation. The SIX2 protein, which is silenced during development, was reactivated in lipopolysaccharide (LPS)-treated microglia. The reactivated SIX2 in microglia mitigated the LPS induced inflammatory effects, and then reduced the toxic effect of conditioned media (CM) of microglia on co-cultured MES23.5 DA cells. Using the LPS-stimulated Cx3cr1-CreERT2 mouse model, we also demonstrated that the highly-expressed SIX2 in microglia obviously attenuated neuroinflammation and protected the DA neurons in SN. Further RNA-Seq analysis on the inflammatory activated microglia revealed that the SIX2 exerted these effects via up-regulating the FXYD domain containing ion transport regulator 2 (FXYD2). Taken together, our study demonstrated that SIX2 was an endogenous anti-inflammatory factor in microglia, and it exerted anti-neuroinflammatory effects by regulating the expression of FXYD2, which provides new ideas for anti-neuroinflammation in PD.

Non-obese lipedema patients show a distinctly altered quantitative sensory testing profile with high diagnostic potential.

Lipedema is a widespread severe chronic disease affecting mostly women. Characterized by painful bilateral fat accumulation in extremities sparing hands and feet, objective measurement-based diagnosis is currently missing. We tested for characteristic psychometric and/or sensory alterations including pain and for their potential for medical routine diagnosis. Pain psychometry was assessed using the German Pain Questionnaire. Sensory sensitivity toward painful and nonpainful stimuli was characterized in non-obese lipedema patients and matched controls using the validated quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain. Lipedema patients showed no overt psychometric abnormalities. Pain was reported as somatic rather than psychosomatic aversive. All QST measurements were normal, but the z-score of pressure pain thresholds (PPT) was twofold reduced and the z-score of vibration detection thresholds (VDT) was two and a half times increased. Both thresholds were selectively altered at the affected thigh but not the unaffected hand. Receiver operating characteristic analysis of the combination of PPT and VDT of thigh vs hand into a PVTH score (PPT, VDT, thigh, hand-score) shows high sensitivity and specificity, categorizing correctly 95.8% of the participants as lipedema patients or healthy controls. Bayesian inference analysis corroborated the diagnostic potential of such a combined PVTH score. We propose to assess PPT and VDT at the painful thigh and the pain-free hand. Combination in a PVTH score may allow a convenient lipedema diagnosis early during disease development.

Low Prevalence of Adequate Single-segment Great Saphenous Vein in Patients With Severe Peripheral Arterial Disease

Low Prevalence of Adequate Single-segment Great Saphenous Vein in Patients With Severe Peripheral Arterial Disease

Antiviral Compounds to Address Influenza Pandemics: An Update from 2016-2022.

In recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention of chemists is continuously focused on the synthesis of new antiviral drugs able to interact with the different molecular targets involved in the virus replication cycle. To date, different classes of influenza viruses inhibitors able to target neuraminidase enzyme, hemagglutinin protein, Matrix-2 (M2) protein ion channel, nucleoprotein or RNA-dependent RNA polymerase have been synthesized using several synthetic strategies comprising the chemical modification of currently used drugs. The best results, in terms of inhibitory activity, are in the nanomolar range and have been obtained from the chemical modification of clinically used drugs such as Peramivir, Zanamivir, Oseltamir, Rimantadine, as well as sialylated molecules, and hydroxypyridinone derivatives. The aim of this review is to report, covering the period 2016-2022, the most recent routes related to the synthesis of effective influenza virus inhibitors.