Early Risk Stratification for Natural Disease Course in Fabry Patients Using Plasma Globotriaosylsphingosine Levels.

BACKGROUND: Fabry disease is a very heterogeneous X-linked lysosomal storage disease. Disease manifestations in the kidneys, heart, and brain vary greatly, even between patients of the same sex and with the same disease classification (classical or nonclassical). A biomarker with a strong association with the development of disease manifestations is needed to determine the need for Fabry-specific treatment and appropriate frequency of follow-up because clinical manifestations of the disorder may take decennia to develop. METHODS: We investigated the levels of plasma lysoGb3 levels over time and its association with disease manifestations and disease course in 237 untreated patients with Fabry disease (median age 42 years, 38% male) using linear mixed-effect models. RESULTS: LysoGb3 levels are stable over time in plasma of untreated patients with Fabry disease. Higher levels of lysoGb3 were associated with steeper decline in eGFR ( P = 0.05) and a faster increase in albuminuria (measured as the urinary albumin-to-creatinine ratio, P < 0.001), left ventricular mass (measured on echocardiography, P < 0.001), left atrial volume index ( P = 0.003), and Fazekas score ( P = 0.003). In addition, regardless of age, higher lysoGb3 levels were associated with higher relative wall thickness ( P < 0.001) and unfavorable functional markers on echocardiography, including septal mitral annular early diastolic velocity (e', P < 0.001) and the ratio of early transmitral velocity (E) to e' (E/e', P = 0.001). CONCLUSIONS: In an individual patient with Fabry disease, the plasma lysoGb3 level reached a specific level in early childhood which, in the absence of Fabry-specific treatment, remained stable throughout life. The level of lysoGb3 in untreated patients was associated with nearly all Fabry-specific disease manifestations, regardless of the sex of the patient.

Frequency and Risk Factors of Hypophosphatemia in Patients Admitted to Emergency Intensive Care Unit in Zagazig University Hospitals.

Background: Inorganic phosphate is a major electrolyte that participates in many functional and integral processes in the human body. Low Pi levels may lead to multiple organ dysfunction. It is estimated to occur in 40-80% of intensive care unit (ICU) patients. However, it may be ignored during the initial evaluation in ICU. Materials and methods: This prospective cross-sectional study included 500 adult ICU cases in two groups; a group with normal Pi levels and a group with hypophosphatemia. All admitted patients were subjected to full history taking, and clinical, laboratory, and radiological evaluation. Collected data were coded, processed, and analyzed using statistical package for social sciences (SPSS) software. Results: Among 500 adult ICU patients; 56.8% had normal phosphate levels while the remaining 43.2% had low phosphate levels. Patients in the hypophosphatemia group were associated with a significantly higher Acute Physiological and Chronic Health Evaluation (APACHE II) score, a longer hospital and ICU stay, a higher incidence of mechanical ventilation use with a longer duration on it, and a significantly higher mortality rate. Conclusion: Risk factors for hypophosphatemia include a higher APACHE II score, longer stay in the hospital and ICU, a higher ratio of mechanical ventilation, and a higher mortality rate. How to cite this article: El-Sayed Bsar AEM, El-Wakiel SAR, El-Harrisi MAH, Elshafei ASH. Frequency and Risk Factors of Hypophosphatemia in Patients Admitted to Emergency Intensive Care Unit in Zagazig University Hospitals. Indian J Crit Care Med 2023;27(4):277-282.

Serotyping and Antibiotic Susceptibility of Invasive Streptococcus agalactiae in Egyptian Patients with or without Diabetes Mellitus.

Streptococcus agalactiae serotype distribution and its antibiotic susceptibility affect disease prevention strategies, but the serotype distribution varies among patient groups. The objectives of this study were to establish the group B Streptococcus (GBS) serotype distribution in patients from Egypt and to assess antibiotic sensitivity of invasive GBS isolates. A total of 490 patients participated in this multicenter study; 160 had urinary tract infection, 115 complained of diabetic foot ulcers, 125 men had genital tract infections, and 30 women females had genital tract infections. Others had bronchopneumonia, otitis media, synovitis, or meningitis. Serotyping of the isolated GBS was performed at the CDC in the United States. Antibiotic sensitivity patterns were determined using the disk diffusion method. In men, the most common serotypes were II, III, and V, whereas types Ia, II, III, and V were isolated from women. Macrolides (erythromycin) resistance occurred in 4.1% of the isolates; 10.2% were resistant to both clindamycin and inducible resistance of macrolides, lincomycin, and streptogramin; 17.3% were resistant to quinolones; and 95.9% were resistant to tetracyclines. GBS primarily infected the urinary tract, skin, soft tissue, and genital tract in both genders. Isolates were sensitive to beta-lactam drugs, vancomycin, and linezolid; 14.0% were resistant to macrolides with or without clindamycin. Only 6.0% of the strains were sensitive to tetracyclines. Although GBS causes invasive infections in Egyptian adults, it rarely causes neonatal meningitis or sepsis. Future studies should determine whether GBS isolates are transmitted sexually, by performing a follow-up study of the partner of the infected patient.

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/ lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in Nacetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/ lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in Nacetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.