Evaluation of aortic elasticity properties in mucopolysaccharidosis patients; effect of enzyme replacement therapy (ERT) on aortic stiffness.

OBJECTIVES: We aimed to cardiologically evaluate the consequences of glycosaminoglycan (GAG) accumulation in the large vessels of patients with mucopolysaccharidosis (MPS). METHODS: The left ventricular wall thickness, left ventricular mass (LVmass) were evaluated and aortic annulus diameter (AA), aortic sinus valsalva diameter (SV), sinotubular junction diameter (STJ), systolic aortic diameter (ADs), diastolic aortic diameter (ADd) body indices were obtained by dividing by the surface area. Aortic distensibility and stiffness index were obtained using aortic strain. Ejection fraction, mitral E and A velocities, mitral early diastolic tissue velocity (e'), E/A ratio, and E/e' ratio were evaluated. RESULTS: The LVED-i, LVmass-i, AA-i, SV-i, STJ-i, ADs-i, and ADd-i values were significantly higher in the MPS group. While the E and e' velocities and E/A ratio were significantly low in the MPS group, the A velocity and E/e' ratio were significantly high. While the stiffness index, SBP, and PP values were significantly higher in the MPS group, the aortic strain and distensibility were significantly lower. There was a correlation between the stiffness index and the aortic strain, distensibility, SBP, PP, and ventricular function. Cardiac function, aortic diameter, and aortic elasticity characteristics were similar between patients with MPS who received ERT and those who did not. CONCLUSIONS: In the MPS group, aortic elasticity properties were impaired, and aortic stiffness increased. ERT has positive effects on cardiac function, aortic diameter, and aortic stiffness in MPS patients. An increased LVmass-i and impaired ventricular geometric structure in patients with MPS may be associated with increased aortic stiffness.

The evaluation of inherited metabolic diseases presenting with rhabdomyolysis from Turkey: Single center experience.

Aim: It was aimed to identify markers that would indicate which cases presenting with rhabdomyolysis are more likely to be associated with inherited metabolic diseases. Methods: We analyzed 327 children who applied to our Hospital Pediatric Nutrition and Metabolic Diseases Clinic with rhabdomyolysis. The diagnosis of rhabdomyolysis was made by measuring the serum creatinine kinase level in cases presenting with muscle pain, weakness and dark urine. Results: Metabolic disease was detected in 29 (16/13, M/F) patients from 26 different families. 298 patients (165/133, M/F) had normal metabolic work-up. We detected glutaric aciduria type 2 in 13 patients (44,6%), glycogen storage disease type 5 in three patients (10,3%), MCAD deficiency in three patients(10,3%), mitochondrial disease in three patients (10,3%), glycogen storage disease type 9 in one patient (3,5%), VLCAD deficiency in one patient (3,5%), LCHAD deficiency in one patient (3,5%), CPT2 deficiency in one patient(3,5%), Tango2 deficiency in one patient (3,5%), lipin-1 deficiency in one patient (3,5%) and primary carnitine deficiency in one patient (3,5%). Conclusion: In our study, consanguineous marriage, developmental delay, and intellectual disability were found more frequently in patients with metabolic disease. In addition, CK levels above 2610 U/L was found to be significantly correlated with metabolic disease.

Early empiric antibiotic use in COVID-19 patients: results from the international VIRUS registry.

OBJECTIVES: COVID-19 escalated inappropriate antibiotic use. We determined the distribution of pathogens causing community-acquired co-infections, the rate, and factors associated with early empiric antibiotic (EEAB) treatment among hospitalized COVID-19 patients. METHODS: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry including 68,428 patients from 28 countries enrolled between January 2020 and October 2021 were screened. After exclusions, 7830 patients were included in the analysis. Azithromycin and/or other antibiotic treatment given within the first 3 days of hospitalization was investigated. Univariate and multivariate analyses were performed to determine factors associated with EEAB use. RESULTS: The majority (6214, 79.4%) of patients received EEAB, with azithromycin combination being the most frequent (3146, 40.2%). As the pandemic advanced, the proportion of patients receiving EEAB regressed from 84.4% (786/931) in January-March 2020 to 65.2% (30/46) in April-June 2021 (P < 0.001). Beta-lactams, especially ceftriaxone was the most commonly used antibiotic. Staphylococcus aureus was the most commonly isolated pathogen. Multivariate analysis showed geographical location and pandemic timeline as the strongest independent predictors of EEAB use. CONCLUSIONS: EEAB administration decreased as pandemic advanced, which may be the result of intensified antimicrobial stewardship efforts. Our study provides worldwide goals for antimicrobial stewardship programs in the post-COVID-19 era.

The importance of skeletal x-ray screening for dysostosis multiplex in the early diagnosis of mucopolysaccharidosis.

PURPOSE: Our aim is the early detection of mucopolysaccharidosis (MPS) by examining the radiographs taken for reasons other than a metabolic disease, such as infection, trauma, and short stature. METHODS: The radiographs of children who applied to outpatient and emergency clinics in our hospital between 01/01/2022 and 31/12/2022 were examined by a pediatric radiologist retrospectively without knowledge of patient information. The MPS enzyme panel and urine glycosaminoglycan analysis were performed in patients having dysostosis multiplex on radiographs. In cases with MPS detected by enzyme and urine analysis, the definitive diagnosis was confirmed by genetic analysis. RESULTS: Skeletal radiographs of 15.104 cases admitted to our hospital were examined (11,270 chest x-ray, 314 lumbosacral spine x-ray, 2970 hand x-ray, 253 pelvis x-ray, 162 skull x-ray, and 135 complete skeletal surveys). In 67 children, dysostosis multiplex was observed in the skeletal X-ray. Among them, seven newly diagnosed MPS cases were detected. Three cases were diagnosed with MPS type 4A, two with MPS type 6, one with MPS type 2 and one with MPS type 3B. Age at diagnosis was 46.2 ± 30.6 months (range; 20-111 months). There was a history of consanguinity in 6 (85.7%) cases. CONCLUSION: Radiographs can provide clues for diagnosing MPS before the clinical findings become prominent in children admitted to the hospital for other complaints. Therefore, X-ray screening can be performed on children in endemic regions of MPS to search for dysostosis multiplex.

Factors Associated with 28-day Critical Illness Development During the First Wave of COVID-19.

Objective: This study aimed to define the predictors of critical illness development within 28 days postadmission during the first wave of the COVID-19 pandemic. Materials and Methods: We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020. Results: The most common presenting symptoms were cough, dyspnea, and fatigue. Critical illness developed in 45 (9.4%; 95% CI=7.0%-12.4%) patients. In the multivariable analysis, age (hazard ratio (HR)=1.05, p<0.001), number of comorbidities (HR=1.33, p=0.02), procalcitonin ≥0.25 µg/L (HR=2.12, p=0.03) and lactate dehydrogenase (LDH) ≥350 U/L (HR=2.04, p=0.03) were independently associated with critical illness development. The World Health Organization (WHO) ordinal scale for clinical improvement on admission was the strongest predictor of critical illness (HR=4.15, p<0.001). The patients hospitalized at the end of the study period had a much better prognosis compared to the patients hospitalized at the beginning (HR=0.14; p=0.02). The C-index of the model was 0.92. Conclusion: Age, comorbidity number, the WHO scale, LDH, and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seemed to be decreasing as the first wave of the pandemic advanced. Graphic Abstract: Graphic Abstract.

Comparison of 28-Day Mortality Between Hospital- and Community-Acquired Influenza Patients.

Objective: This study aimed to compare 28-day mortality between patients have hospital-acquired influenza (HAI) and those have community-acquired influenza (CAI) during the 2017-2019 influenza seasons in a tertiary care center in Istanbul, Türkiye. Materials and Methods: This retrospective cohort included all hospitalized patients who had confirmed influenza infection and were over 17 years old. HAI was defined as a case of influenza that tested negative in a PCR test or had no signs of influenza on admission but with a positive test result at any point after 72 hours of admission. CAI was defined as a case of influenza diagnosed within 72 hours of admission or before admission. The primary outcome was 28-day mortality after diagnosis. Biological sex, admission to the intensive care unit (ICU), presence of chronic obstructive pulmonary disease, cardiovascular and immunosuppressive comorbidities, influenza subtype, and other variables identified with univariate analyses (p<0.25) were entered into logistic regression analysis. Results: During the study period, 92 (46%) of 201 hospitalized patients who tested positive for influenza were identified as HAI, and the rest (109) were identified as CAI. Univariate analysis showed no differences between survivors and non-survivors in patient characteristics, except non-survivors were more likely to have an ICU admission. The multivariable logistic regression analysis results showed that HAI was associated with 5.6-fold increased odds of mortality (95% confidence interval [CI]=1.6-19.3; p=0.006), after adjustment for age, gender, comorbidity, and ICU admission. Conclusion: The results of this study revealed that patients who had HAI were more likely to die within 28 days compared to those who had CAI after controlling for key confounders. The high rate of HAI underscores the critical importance of robust infection control measures for hospital-acquired viral infections. Additional research and targeted interventions are necessary to improve the HAI prognosis.