Mortality and associated risk factors of COVID-19 infection in dialysis patients in Qatar: A nationwide cohort study.

CONTEXT: Patients on maintenance dialysis are more susceptible to COVID-19 and its severe form. We studied the mortality and associated risks of COVID-19 infection in dialysis patients in the state of Qatar. METHODS: This was an observational, analytical, retrospective, nationwide study. We included all adult patients on maintenance dialysis therapy who tested positive for COVID-19 (PCR assay of the nasopharyngeal swab) during the period from February 1, 2020, to July 19, 2020. Our primary outcome was to study the mortality of COVID-19 in dialysis patients in Qatar and risk factors associated with it. Our secondary objectives were to study incidence and severity of COVID-19 in dialysis patients and comparing outcomes between hemodialysis and peritoneal dialysis patients. Patient demographics and clinical features were collected from a national electronic medical record. Univariate Cox regression analysis was performed to evaluate potential risk factors for mortality in our cohort. RESULTS: 76 out of 1064 dialysis patients were diagnosed with COVID-19 (age 56±13.6, 56 hemodialysis and 20 peritoneal dialysis, 56 males). During the study period, 7.1% of all dialysis patients contracted COVID-19. Male dialysis patients had double the incidence of COVID-19 than females (9% versus 4.5% respectively; p<0.01). The most common symptoms on presentation were fever (57.9%), cough (56.6%), and shortness of breath (25%). Pneumonia was diagnosed in 72% of dialysis patients with COVID-19. High severity manifested as 25% of patients requiring admission to the intensive care unit, 18.4% had ARDS, 17.1% required mechanical ventilation, and 14.5% required inotropes. The mean length of hospital stay was 19.2 ± -12 days. Mortality due to COVID-19 among our dialysis cohort was 15%. Univariate Cox regression analysis for risk factors associated with COVID-19-related death in dialysis patients showed significant increases in risks with age (OR 1.077, CI 95%(1.018-1.139), p = 0.01), CHF and COPD (both same OR 8.974, CI 95% (1.039-77.5), p = 0.046), history of DVT (OR 5.762, CI 95% (1.227-27.057), p = 0.026), Atrial fibrillation (OR 7.285, CI 95%(2.029-26.150), p = 0.002), hypoxia (OR: 16.6; CI 95%(3.574-77.715), p = <0.001), ICU admission (HR30.8, CI 95% (3.9-241.2), p = 0.001), Mechanical ventilation (HR 50.07 CI 95% (6.4-391.2)), p<0.001) and using inotropes(HR 19.17, CI 95% (11.57-718.5), p<0.001). In a multivariate analysis, only ICU admission was found to be significantly associated with death [OR = 32.8 (3.5-305.4), p = 0.002)]. CONCLUSION: This is the first study to be conducted at a national level in Qatar exploring COVID-19 in a dialysis population. Dialysis patients had a high incidence of COVID-19 infection and related mortality compared to previous reports of the general population in the state of Qatar (7.1% versus 4% and 15% versus 0.15% respectively). We also observed a strong association between death related to COVID-19 infection in dialysis patients and admission to ICU.

Targeting proapoptotic protein BAD inhibits survival and self-renewal of cancer stem cells.

Emerging evidence suggests that the resistance of cancer stem cells (CSC) to many conventional therapies is one of the major limiting factors of cancer therapy efficacy. Identification of mechanisms responsible for survival and self-renewal of CSC will help design new therapeutic strategies that target and eliminate both differentiated cancer cells and CSC. Here we demonstrated the potential role of proapoptotic protein BAD in the biology of CSC in melanoma, prostate and breast cancers. We enriched CD44(+)/CD24(-) cells (CSC) by tumorosphere formation and purified this population by FACS. Both spheres and CSC exhibited increased potential for proliferation, migration, invasion, sphere formation, anchorage-independent growth, as well as upregulation of several stem cell-associated markers. We showed that the phosphorylation of BAD is essential for the survival of CSC. Conversely, ectopic expression of a phosphorylation-deficient mutant BAD induced apoptosis in CSC. This effect was enhanced by treatment with a BH3-mimetic, ABT-737. Both pharmacological agents that inhibit survival kinases and growth factors that are involved in drug resistance delivered their respective cytotoxic and protective effects by modulating the BAD phosphorylation in CSC. Furthermore, the frequency and self-renewal capacity of CSC was significantly reduced by knocking down the BAD expression. Consistent with our in vitro results, significant phosphorylation of BAD was found in CD44(+) CSC of 83% breast tumor specimens. In addition, we also identified a positive correlation between BAD expression and disease stage in prostate cancer, suggesting a role of BAD in tumor advancement. Our studies unveil the role of BAD in the survival and self-renewal of CSC and propose BAD not only as an attractive target for cancer therapy but also as a marker of tumor progression.

Exploring the intrinsic polar [4+2(+)] cycloaddition reactivity of gaseous carbosulfonium and carboxonium ions.

Gas-phase reactions of model carbosulfonium ions (CH(3)-S(+)=CH(2;) CH(3)CH(2)-S(+)=CH(2) and Ph-S(+)=CH(2)) and an O-analogue carboxonium ion (CH(3)-O(+)=CH(2)) with acyclic (isoprene, 1,3-butadiene, methyl vinyl ketone) and cyclic (1,3-cyclohexadiene, thiophene, furan) conjugated dienes were systematically investigated by pentaquadrupole mass spectrometry. As corroborated by B3LYP/6-311 G(d,p) calculations, the carbosulfonium ions first react at large extents with the dienes forming adducts via simple addition. The nascent adducts, depending on their stability and internal energy, react further via two competitive channels: (1) in reactions with acyclic dienes via cyclization that yields formally [4+2(+)] cycloadducts, or (2) in reactions with the cyclic dienes via dissociation by HSR loss that yields methylenation (net CH(+) transfer) products. In great contrast to its S-analogues, CH(3)-O(+)=CH(2) (as well as C(2)H(5)-O(+)=CH(2) and Ph-O(+)=CH(2) in reactions with isoprene) forms little or no adduct and proton transfer is the dominant reaction channel. Isomerization to more acidic protonated aldehydes in the course of reaction seems to be the most plausible cause of the contrasting reactivity of carboxonium ions. The CH(2)=CH-O(+)=CH(2) ion forms an abundant [4+2(+)] cycloadduct with isoprene, but similar to the behavior of such α,ß-unsaturated carboxonium ions in solution, seems to occur across the C=C bond.

Corporeal body grafting using buccal mucosa for posterior hypospadias with severe curvature.

PURPOSE: Severe penile curvature correction by corporeal body grafting has been successfully performed using various grafts and biomaterials. We present our initial experience with buccal mucosa as a free corporeal graft to correct severe penile curvature as part of a multistage approach to posterior hypospadias repair. MATERIALS AND METHODS: A total of 12 children with a mean age of 6.2 years (range 4 to 8) with posterior hypospadias and severe ventral chordee (greater than 45 degrees) necessitating ventral grafting underwent correction using buccal mucosa. Preoperative androgen supplement was given when penile and glanular size was significantly small for age. Buccal mucosa was harvested from the inner side of the cheek or the lower lip. The harvested graft was defatted, fashioned and fixed to the ventral corporeal defect. The pre-grafting penile angle, immediate post-grafting angle and penile angle at 6 months were assessed. RESULTS: All children had penoscrotal or perineal hypospadias, 4 had partial androgen insensitivity syndrome and 1 underwent multiple previous failed repairs. Androgen was given preoperatively in 3 children. After chordee release and urethral plate transection the penile angle was between 45 and 80 degrees. Mean graft length and width was 2.5 and 1.6 cm, respectively. All children had a straight penis at the end of the procedure and none required additive dorsal plication. At the last followup at 12 months all children had a straight penis except 2 with mild curvature (less than 10 degrees). No complications were noted with this technique. CONCLUSIONS: Preliminary results of the novel use of buccal mucosa as a corporeal graft for severe chordee appear satisfactory. Longer term followup is needed to further document these data.

An investigation of chlorophenol proton affinities and their influence on the biological activity of microorganisms.

The proton affinities of 15 chlorophenols are calculated by ab initio methods. Straight correlation between proton affinities and changes in the electronic structure is observed. The proton affinities decrease linearly with the electronic density gain on the chlorine atoms, as the liberation of the proton increases. To confirm the importance of the proton affinities on the toxicity of chlorophenols, calorimetric responses of these molecules and related ones where the acid proton is changed to a methyl group (anisol and its chlorinated derivatives) were used to verify their effects on Chromobacterium violaceum. The results confirmed that the chlorophenols are more toxic than the respective chloroanisols and suggest that high proton affinities are associated with low toxic activity. The toxicity of the chlorophenols can be associated with the respiratory mechanism in some microorganisms.

Flow microcalorimetric studies of phenol and its chlorinated derivatives and a theoretical evaluation of their possible inhibition mode on Chromobacterium violaceum respiration.

The general belief that chemical structure determines the biological effect of drugs has led to several techniques to establish structure-activity relationships (SAR) that is useful in the development of more active compounds. Predicting toxic effects based on SAR, one can obtain toxicological data with a low cost-benefit ratio. Chlorophenols that represent a class of toxic agents frequently used in industrial processes are not satisfactorily described in the literature in relation to their toxicity. The main objective of this work is to relate the microbial activities of phenol, anisole and their chlorinated derivatives on Chromobacterium violaceum respiration with their physicochemical properties. Anisole and its chlorinated derivatives were used to evaluate the influence of phenol acidity on biological activity. The calculations were carried out at the semi-empirical AM1 and ab initio DFT levels employing the basis sets CEP-31G, CEP-31+Ge CEP-31G** that were parameterized using the continuum-solvation model COSMO for solvent contribution. Both empirical and theoretical properties were evaluated by chemometric analyses (hierarchical cluster analysis (HCA) and principal component analysis (PCA)), to correlate the physicochemical properties of the phenol, anisole and their chlorinated derivatives with their biological activities. The results obtained for the current work indicate that the biological activities of these compounds increase as the n-octanol/water (logP) partition coefficients, ionization energies (IP), melting points (mp) and dissociation constants increase and the solvent effects (SE), enthalpies of formation (DeltafH degrees ) and proton affinities (PA) decrease.

Seroepidemiology of hepatitis B virus markers among hospital health care workers. Analysis of certain potential risk factors.

OBJECTIVES: To determine, the prevalence of hepatitis B virus markers among hospital health care workers, to determine the influence of some risk factors on such prevalence and to outline the specific policies to tackle such problems among hospital health care workers. METHODS: Hepatitis B virus markers including hepatitis B surface antigen, anti-hepatitis B surface antigen and anti-hepatitis B core antigen were determined from sera samples collected from 459 hospital health care workers at different hospital departments. The prevalence of hepatitis B virus among these employees was correlated by a variety of risk factors such as gender, age, blood transfusion, and needle-stick and sharps injuries, and previous history of jaundice using logistic regression analyses. RESULTS: Of the hospital health care workers studied 143 (31%) of employees showed evidence of previous hepatitis B virus infection, including 17 (4%) carriers. The highest incidence was among those who were working at infectious diseases departments where 22 (43%) employees were found to be seropositive, followed by 26 (41%) employees from surgical departments. The risk factors, which were found to influence seropositivity, include age over 40 years old, needle-stick and sharps injuries and previous blood transfusion. Other factors such as gender, and previous history of jaundice were statistically insignificant. CONCLUSION: The hepatitis B virus infection was high among the hospital health care workers studied. This was influenced by certain potential occupational risk factors. As there is emerging evidence that vaccination among health care workers was infective. Specific measures should be implemented to reduce such risk. These may include strict policies on sharps and considering any blood or other body fluids being a potential risk. Education, clinical advice and health insurance should be available for health care workers who are at a higher risk of contracting hepatitis B virus infection.

Nissen fundoplication for gastro-esophageal reflux in repaired tracheo-esophageal fistula.

One hundred and fifty three patients had repair of tracheo-oesophageal fistula in a 15 year period of observation. Of these 55 had associated gastro-oesophageal reflux and of these 12 (8%) underwent a Nissen fundoplication. All patients manifested significant failure to thrive but weight-gain was documented in all patients following their fundoplication. Twenty five percent of patients demonstrated recurrent reflux in this study and emphasises the difficulty of treating gastro-oesophageal reflux in repaired tracheo-oesophageal fistula patients. Careful selection is important.