Cardiovascular defects in a mouse model of HOXA1 syndrome

Congenital heart disease is one of the most common human birth defects, yet many genes and pathways regulating heart development remain unknown. A recent study in humans revealed that mutations in a single Hox gene, HOXA1 (Athabascan Brainstem Dysgenesis Syndrome, Bosley-Salih-Alorainy Syndrome), can cause severe cardiovascular malformations, some of which are lethal without surgical intervention. Since the discovery of the human syndromes, there have been no reports of any Hox mouse mutants with cardiac defects, hampering studies to explore the developmental causes of the human disease. In this study, we identify severe cardiovascular malformations in a Hox mouse model, which mimic the congenital heart defects in HOXA1 syndrome patients. Hoxa1 null mice show defects such as interrupted aortic arch, aberrant subclavian artery and Tetralogy of Fallot, demonstrating that Hoxa1 is required for patterning of the great arteries and outflow tract of the heart. We show that during early embryogenesis, Hoxa1 is expressed in precursors of cardiac neural crest cells (NCCs), which populate the heart. We further demonstrate that Hoxa1 acts upstream of several genes, important for neural crest specification. Thus, our data allow us to suggest a model in which Hoxa1 regulates heart development through its influence on cardiac NCCs, providing insight into the mechanisms underlying the human disease.     

Immunological Study of IFN-γ, ICAM-4, and Vitamin D3 Markers among Gastrointestinal Tumor Patients in Babylon Province,Iraq

Objective: The current study was conducted to investigate the roles of ICAM-4, IFN-γ, and vitamin D3 markers among benign and malignant gastrointestinal stromal tumors (GISTs). Methodology: Eighty-eight participants, admitted to the Babylon GIT Center, Merjan Medical City, Iraq from April to December 2020, were recruited for the study. Blood samples were collected from the participants, who were divided into four groups: malignant GIT tumor (N = 42), benign GIT tumor (N = 29), irritable bowel disease as a positive control (N = 10), and healthy individuals as a negative control (N = 7). Serum ICAM-4, IFN-γ, and vitamin D3 levels were determined using the blood samples. Results: The younger males were more affected by malignant GIT tumors at a mean age of 53.39 years than benign GIT tumors, IBD, and healthy individuals. There is also an increase in ICAM-4, IFN-γ, and a decrease in vitamin D3 levels compared to healthy individuals. The vitamin D3 level decreased progressively with age and rose in ICAM-4 with a decrease in vitamin D3 level in patients, increasing the probability of infection with GIT tumor. ICAM-4 levels may grow and increase as interferon levels rise. Conclusion: The younger males are more prone to malignant GIT and the serum levels of ICAM-4, vitamin D3, and IFN-γ are high in malignant patients compared with benign GIT tumors and lower than the control.     

Seroepidemiology of Hepatitis B virus infection in Saudi children 8 years after a mass hepatitis B vaccination programme

OBJECTIVES: On October 1 1989, a programme was begun in Saudi Arabia in which the HBV vaccine was added as the 'seventh' primary immunogen of the Extended Programme of Immunization (EPI). In 1990, another programme was launched by the Ministry of Health to vaccinate all school children. Eight years after this mass vaccination programme, the efficacy of HBV vaccine was evaluated in a community-based study. METHODS: A community-based study was carried out in Saudi children in urban and rural areas, covering all the regions of Saudi Arabia. After informed consent, blood samples were obtained and tested for HBV markers. RESULTS: Among 4791 vaccinated Saudi children aged 1-12 years, only 15 were found to be HbsAg-positive (0.31%). HbsAg-positivity was 0.16% in children vaccinated at birth compared with 0.7% in those vaccinated at school entry. The overall HbsAg carrier rate dropped from 6.7% in 1989 to 0.3% in 1997 (P<0.00001). Similarly, there was a significant reduction in the prevalence of anti-HBc from 4.2% in 1989 to 0.46% in 1997 (P<0.00001). The overall seroconversion rate to HB vaccine among 4087 Saudi children up to 12 years of age was about 77%. Seroconversion rate in those vaccinated at birth was 77% compared with 71% in those vaccinated at school entry. After 8 years of receiving the third vaccine dose, close to 65% of the children had an anti-HBs titre of more than 10 IU/l compared with about 28% who had an anti-HBs titre of more than 100 IU/l after the same period. CONCLUSION: The result of this study demonstrates the tremendous impact of the mass HB vaccination programme on the seroepidemiology of HBV infection in Saudi Arabia. The ultimate goal of preventing HBV-related chronic liver disease and hepatocellular carcinoma in Saudi Arabia is foreseeable in the near future.     

MXene/Ag2CrO4 Nanocomposite as Supercapacitors Electrode

MXene/Ag₂CrO₄ nanocomposite was synthesized effectively by means of superficial low-cost co-precipitation technique in order to inspect its capacitive storage potential for supercapacitors. MXene was etched from MAX powder and Ag₂CrO₄ spinel was synthesized by an easy sol-gel scheme. X-Ray diffraction (XRD) revealed an addition in inter-planar spacing from 4.7 Å to 6.2 Å while Ag₂CrO₄ nanoparticles diffused in form of clusters over MXene layers that had been explored by scanning electron microscopy (SEM). Energy dispersive X-Ray (EDX) demonstrated the elemental analysis. Raman spectroscopy opens the gap between bonding structure of as-synthesized nanocomposite. From photoluminence (PL) spectra the energy band gap value 3.86 eV was estimated. Electrode properties were characterized by applying electrochemical observations such as cyclic voltammetry along with electrochemical impedance spectroscopy (EIS) for understanding redox mechanism and electron transfer rate constant K_app. Additionally, this novel work will be an assessment to analyze the capacitive behavior of electrode in different electrolytes such as in acidic of 0.1 M H₂SO₄ has specific capacitance C_sp = 525 F/g at 10 mVs⁻¹ and much low value in basic of 1 M KOH electrolyte. This paper reflects the novel synthesis and applications of MXene/Ag₂CrO₄ nanocomposite electrode fabrication in energy storage devices such as supercapacitors.     

The prognostic value of the lactate/albumin ratio for predicting mortality in septic patients presenting to the emergency department: a prospective study

ObjectivesLactate/albumin (L/A) ratio is a biomarker in sepsis that has been shown to outperform lactate. This prospective study aims to validate the superior prognostic value of the L/A ratio to lactate in sepsis and septic shock.MethodsProspective cohort conducted from September 2018 till February 2021 on adult patients presenting to the Emergency Department (ED) at a tertiary care centre with sepsis or septic shock. The primary outcome was the prognostic value of the L/A ratio compared to lactate with regards to mortality.ResultsA total of 939 septic patients were included throughout the study period. A total of 236 patients developed septic shock. The AUC value of the L/A ratio in septic patients was 0.65 (95% CI 0.61–0.70) and was higher than that of lactate alone 0.60 (95% CI 0.55–0.64) with a p < .0001. The optimal L/A ratio cut-off threshold that separated survivors from non-survivors was found to be 0.115 for all septic patients. The AUC of the L/A ratio was significantly higher for patients with a lactate ≥2 mmol/L: 0.69 (95% CI 0.64–0.74) versus 0.60 (95% CI 0.54–0.66) with a p < .0001 as well as for patients with an albumin level less than 30 g/L (AUC = 0.69 95% CI= 0.62–0.75 vs AUC= 0.66 95% CI= 0.59–0.73, p = .04). Among septic shock patients there was no statically significant difference in the AUC value of the L/A ratio compared to lactate (0.53 95% CI 0.45–0.61 vs 0.50 95% CI 0.43–0.58 respectively with a p-value = .11).ConclusionsThe L/A ratio is a better predictor of in-patient mortality than lactate in sepsis patients. This superiority was not found in the septic shock subgroup. Our results encourage the use of the ratio early in the ED as a superior prognostic tool in sepsis patients.

Key messages

1. We aimed to assess the prognostic usefulness of the Lactate/Albumin ratio compared to lactate alone in septic and septic shock patients.
2. The L/A ratio proved to be a better predictor of in-patient mortality than lactate alone in sepsis patients. This pattern also applies across various subgroups in our study (malignancy, diabetics, age above 65, lactate level less than 2 mmol/L, albumin less than 30 g/L). Our results favour the use of the L/A ratio over lactate alone in patients with sepsis and the previously mentioned subgroups.
3. Our results do not favour the use of the ratio instead of lactate in septic shock patients as there was no statistically significant difference between the AUCs of the ratio and lactate alone.

     

Efficacy of platelet‐rich plasma plus fractional carbon dioxide laser in treating posttraumatic scars

The management of posttraumatic scars is a great challenge. Autologous platelet‐rich plasma (APRP) and fractional carbon dioxide (CO2) laser can be applied as innovative treatments for posttraumatic scars. The aim of this study was to evaluate the efficacy, safety and complications of fractional CO2 laser exposure plus APRP injection in treating traumatic scars versus CO2 laser applied as a monotherapy. Twenty participants were treated 3 times at a 4‐week interval with a follow‐up visit. The scars were divided into an upper and lower half‐treated with fractional CO2 laser exposure plus APRP injection and CO2 laser alone, respectively. The scar was evaluated using the Vancouver scar scale (VSS), along with patient satisfaction. Twenty patients completed the 3 month treatment course. The mean VSS score improved significantly from 7.0 ± 3.97 to 3.25 ± 1.55 and 6.75 ± 1.77 to 3.85 ± 1.59 with fractional CO2 laser exposure plus APRP injection and CO2 laser exposure, respectively (p < .001). However, CO2 laser plus APRP was significantly superior to CO2 laser alone (p = .001), with fewer adverse effects. Our study shows that combined treatment with CO2 laser exposure plus APRP injection is safer and more effective for posttraumatic scar management than CO2 laser exposure alone.     

Behavior and Outcomes of Pregnancy Associated Breast Cancer

Introduction: Pregnancy Associated Breast cancer (PABC) is associated with poor prognosis and a decreased overallsurvival. A retrospective review was conducted to review the experience and outcome in a tertiary care hospital, and tocompare those seen in a matched group for year of diagnosis. Materials and Methods: This is a retrospective reviewof a prospectively collected breast cancer registry. The study was conducted in a tertiary care hospital in Riyadh, SaudiArabia from January to Decamber 2014 . Female patients with PABC were identified and matched with similar cohortof non-pregnant breast cancer patients that were diagnosed between 2001-2010. Clinical data including age, tumorbiology, clinical stage, follow up and outcomes (disease free survival, DFS) were analyzed and compared between thetwo groups using SAS 9.3 and R-2.14.1 Results: A total of 110 patients in Group 1 and 114 patients in Group II wereanalyzed. In both groups, the patient age ranged was between 20 to 45 years; the median follow up was 34 months inPABC and 54 months in non-pregnant cohort. PABC were statistically more likely to be triple negative (p value-0.05) anddiagnosed at advanced stage (stage 3 and 4) (p value-0.02). There was no difference in the occurrence of Her-2 positivedisease. In pregnant patients there was a 5-year survival rate of 65% compared to non-pregnant cohort of 82% with pvalue of 0.002 and DFS was also 47.5% versus 65.4% with a p value .002 which is statistically significant. Conclusion:Pregnancy associated breast cancer (PABC) is diagnosed at a more advanced stage and tends to be triple negative andthey are associated with a worse DFS and overall survival. Early detection during pregnancy may improve outcome.     

Accuracy of routinely collected comorbidity data in patients undergoing colectomy: a retrospective study

Objectives

This paper aimed to determine the baseline accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of routinely collected comorbidity data in patients undergoing any types of colectomy.

Methods

All patients aged >18 who underwent right hemicolectomy, left hemicolectomy, sigmoid colectomy, subtotal colectomy, or total colectomy between 1 January 2015 and 1 November 2016 were identified. The following comorbidities were considered: hypertension, ischemic heart disease (IHD), diabetes, asthma, chronic obstructive pulmonary disease (COPD), cerebrovascular disease (CVD), chronic kidney disease (CKD), and hypercholesterolemia. The comorbidity data from clinical notes were compared with corresponding data in hospital episode statistics (HES) database in order to calculate accuracy, sensitivity, specificity, PPV, and NPV of HES codes for comorbidities. In order to assess the agreement between clinical notes and HES data, we also calculated Cohen’s kappa index value as a more robust measure of agreement.

Results

Overall, 267 patients comprising 2136 comorbidity codes were included. Overall, HES codes for comorbidities in patients undergoing colectomy had substandard accuracy 94% (kappa 0.542), sensitivity (39%), and NPV (89%). The HES codes were 100% specific with PPV of 100%. The results were consistent when individual comorbidities were analyzed separately.

Conclusions

Our results demonstrated that HES comorbidity codes in patients undergoing colectomy are specific with good positive predictive value; however, they have substandard accuracy, sensitivity, and negative predictive value. Better documentation of comorbidities in admission clerking proforma may help to improve the quality of source documents for coders, which in turn may improve the accuracy of coding.