Biallelic mutations in FLG, TGM1, and STS genes segregated with different types of ichthyoses in eight families of Pakistani origin.

BACKGROUND: Congenital ichthyosis is a diverse group of keratinization disorders associated with generalized scaling of skin of varying severity. The non-syndromic forms of congenital ichthyosis are further grouped into common ichthyosis (ichthyosis vulgaris and X-linked ichthyosis), autosomal recessive congenital ichthyosis, and keratopathic ichthyosis. OBJECTIVE: To identify sequence variants involved in different forms of hereditary ichthyoses. METHODS: We studied eight families with different types of ichthyosis including four families with autosomal recessive congenital ichthyosis and four families with common ichthyosis. Whole exome sequencing and PCR based genotyping was carried out to find out the molecular basis of disease. RESULTS: In one family, a novel duplication sequence variant NM_002016.2:c.2767dupT; NP_002007.1:p.Ser923PhefsTer2 was identified in FLG gene; in four families a previously reported nonsense sequence variant NM_000359.3:c.232C>T; NP_002007.1:p.Arg78Ter was identified in TGM1 gene, while, in three families of X-linked recessive ichthyosis, the whole STS gene (NM_001320752.2; NP_001307681.2) regions were deleted. STUDY LIMITATION: Gene expression studies have not been performed that would have strengthened the findings of computational analysis. CONCLUSION: This study highlights the significance of the c.232C>T variant in the TGM1 gene as a possible founder mutation, complete STS gene deletion as reported previously in Pakistani population, while novel sequence variant in the FLG gene expands the spectrum of variations in this gene. These findings may be used for genetic counseling of the studied families.

Maturation and Patency Rates in Basilic Transposition Arteriovenous Fistula Under Regional Versus General Anesthesia: A Single-Center, Retrospective, Observational Study.

Background Basilic transposition arteriovenous fistula (BT AVF) is a viable option for dialysis-dependent patients, which can be performed under either general or regional anesthesia. Regional anesthesia is reported to cause vascular dilatation during the perioperative period, leading to improved fistula success. Regional anesthesia is also considered safe as compared to general anesthesia in terms of hemodynamic stability. Limited and conflicting data are available comparing regional versus general anesthesia in terms of fistula maturation and patency. We aimed to compare the maturation, one-year patency rates, and complication rates in patients undergoing single-stage BT AVF in regional versus general anesthesia. Methods This retrospective observational study was conducted on patients undergoing single-stage BT AVF from January 2016 to December 2019. Patients were divided into regional (RA) vs. general anesthesia (GA) groups and compared in terms of maturation, one-year patency, and perioperative complication rates. Results Out of 152 patients, 110 (72.37%) were in GA while 42 (27.63%) were in the RA group. Elderly, female, diabetic, ischemic heart disease, and American Society of Anesthesiologists (ASA) class IV patients were more in the RA group. Other comorbid and vascular access-related factors were comparable between the groups. A trend toward higher maturation rates (97.6% vs. 92.1%) and one-year patency rates (62.5% vs. 56.6%) was observed in the RA vs. GA group, however, the difference did not attain statistical significance, p=0.359 and p=0.327, respectively. The rate of access abandonment was higher in the GA group (43.4% vs. 37.5%). The most prevalent cause of abandonment was death in the RA group while it was access failure in the GA group. Overall complication rates were comparable between both groups (20.2 % vs. 17.5%, p=0.816). Conclusion Regional anesthesia is a useful technique with potentially improved maturation and patency rates. Nevertheless, an assumed benefit of regional anesthesia in terms of anesthesia-related complications was not observed.

Bacterial Sepsis Pathogens and Resistance Patterns in a South Asian Tertiary Care Hospital.

Objective The aim of this study was to determine common microorganisms causing septicemia and their antimicrobial sensitivities in patients admitted to a tertiary care hospital. Methods A cross-sectional study was conducted using clinical criteria to diagnose patients as having septicemia where blood for culture and sensitivity (CS) was sent to the laboratory of a tertiary care hospital, Rehman Medical Institute, (Peshawar), Pakistan, during 2019. All patients diagnosed with septicemia regardless of age and gender were included in the study. The blood CS report was collected after 7-14 days of inoculation. Data were recorded on structured performa and analyzed using SPSS Version 20 (IBM Corp.). Results A total of 176 patients, with a mean age of 2.92±1.32 years, fulfilled the criteria for sepsis with a mean age of 2.92±1.32 years. Among them, 61.9% were male and 38.1% were female. Among common bacterial isolates, Staphylococcus aureus was found in 37.5% of samples followed by skin contaminants (18.2%), methicillin-resistant Staphylococcus aureus (MRSA) (14.8%), and Escherichia coli in (11.4% cases). None of the antibiotics had susceptibility of more than 60%. Susceptibility to piperacillin/tazobactam and ampicillin/sulbactam was found in 21.5% and 14.6% of the samples, respectively, while in cephalosporins, cefoxitin's susceptibility was 28.5%, whereas both ceftriaxone and cephazolin were equally effective in 19.4% cases. Furthermore, 38.9% of the samples were susceptible to ciprofloxacin and 24.3% to levofloxacin. The susceptibilities of amikacin and gentamicin in aminoglycosides were 56.3% and 47.2%, respectively, while that of imipenem and meropenem were 59.7% and 22.9%, respectively. Lastly, clindamycin had an efficacy in 42.4% of samples. Conclusion The susceptibility of bacterial isolates in septicemia to common antibiotics was low, thus risking therapeutic failure in septic patients. Widespread resistance may be due to the excessive use along with over-the-counter availability of antibiotics, which therefore requires regulation as it is an alarming situation.