Sepsis in end-stage renal disease patients: are they at an increased risk of mortality?

ObjectivesThis study aims to examine the outcome of end-stage renal disease (ESRD) patients admitted with sepsis to the intensive care unit (ICU).DesignSingle centre, retrospective cohort studySettingThe study was conducted in the Intensive Care Department of King Abdulaziz Medical City, Riyadh, Saudi Arabia.ParticipantsData were extracted from a prospectively collected ICU database from 2002 to 2017. Patients were considered to have sepsis based on the sepsis-3 definition and were stratified into 2 groups based on the presence or absence of ESRD.Primary and secondary outcomesThe primary outcome of the study was in-hospital mortality. Secondary outcomes included ICU mortality, ICU and hospital lengths of stay, and mechanical ventilation duration.ResultsA total of 8803 patients were admitted to the ICU with sepsis during the study period. 730 (8.3%) patients had ESRD. 49.04% of ESRD patients with sepsis died within their hospital stay vs. 31.78% of non-ESRD patients. ESRD septic patients had 1.44 greater odds of dying within their hospital stay as compared to septic non-ESRD patients (OR 1.44, 95% CI 1.03–1.53). Finally, the predictors of hospital mortality in septic ESRD patients were found to be mechanical ventilation (OR 3.36; 95% CI 2.27–5.00), a history of chronic liver disease (OR 2.26; 95% CI 1.26–4.07), and use of vasopressors (OR 1.74; 95% CI 1.19–2.54). Among patients with ESRD, hospital mortality was higher in subgroups of patients with chronic cardiac (OR 1.86 (1.36–2.53) vs. 1.19 (0.96–1.47)) and chronic respiratory illnesses (OR 2.20 (1.52–3.20) vs. 1.21 (0.99–1.48)).ConclusionESRD patients admitted to the intensive care unit with sepsis are at greater odds of mortality compared to patients with non-ESRD. This risk is particularly increased if these patients have a concomitant history of chronic cardiac and respiratory illnesses.

Key Messages

• Sepsis and bacterial infections are very common in ESRD patients and following cardiovascular disease; sepsis is the second leading cause of death in patients with ESRD.
• This study aims to examine the outcome of patients with end-stage renal disease (ESRD) patients admitted with sepsis to the intensive care unit (ICU).
• The results of this study have shown that end-stage renal disease is associated with greater odds of ICU and hospital mortality among septic patients admitted to an intensive care unit.
• ESRD patients were also more likely to be started on vasopressors and mechanical ventilation.

     

Echogenic intracardiac focus on second trimester ultrasound: prevalence and significance in a Middle Eastern population

Objective: The association between echogenic intracardiac focus (EIF) and trisomy 21 is well established, with a recognized ethnic variation. Our study aimed to determine the prevalence of EIF in a Middle Eastern population and to examine its association with trisomy 21 and other adverse pregnancy outcomes.

Methods: Retrospective case-control study of second-trimester obstetric sonograms (16–28 weeks) performed at a tertiary care center over a 5-year period. Cases with EIF were retrieved, and a matched control group with no EIF was identified. The incidence of trisomy 21 and other adverse pregnancy outcomes was compared.

Results: A total of 9270 obstetric sonograms were examined, with an EIF prevalence of 2.5% (95% CI: 2.2–2.8%). Of patients with available outcome data, EIF was not associated with trisomy 21 (0/163 versus 1/163; p value = 1.00). Additionally, EIF was not associated with trisomy 18, trisomy 13, small for gestational age, preterm birth, fetal demise, cesarean delivery, operative vaginal delivery, or admission to the neonatal intensive care unit.

Conclusion: In a contemporary Middle Eastern population, EIF is a rare occurrence. As an isolated finding, it is not associated with aneuploidy or other adverse pregnancy outcomes. EIF appears to be incidental with no impact on clinical practice.     

Polystyrene/Montmorillonite Nanocomposites Prepared by In Situ Intercalative Polymerization: Influence of the Surfactant Type

Summary: Na‐montmorillonite (MMT) with a cation exchange capacity (CEC) of 90 meq/100 g was converted to MMT‐CTAB and MMT‐CPC by the intercalation of cetyltrimethylammonium bromide (CTAB) and cetylpyridinium chloride (CPC), respectively. The intercalation of CPC onto the basal space of the montmorillonite expanded the basal space from 12.19 to 21.47 Å, whereas in the case of CTAB, the spacing was only expanded to 19.35 Å. The MMT‐CPC and MMT‐CTAB forms were subsequently used as hosts for the preparation of polystyrene nanocomposites via intercalative free‐radical polymerization of styrene. Different structures were obtained by varying the preparation conditions; the exfoliated and intercalated nanocomposites were characterized by X‐ray diffraction (XRD), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), and differential scanning calorimeter (DSC). The produced nanocomposites exhibited improved thermal stability in comparison with that of pure polystyrene above 400 °C especially in the case of the nanocomposites based on the MMT‐CPC, in which intercalation exists. A glass transition temperature (T_g) could not be detected for the prepared nanocomposites using DSC; this was assumed to result from the restricted molecular motion of the polymer chains.

XRD pattern of PS nanocomposites prepared by intercalative polymerization.     

No evidence for an association between variants at the gamma-amino-n-butyric acid type A receptor beta2 locus and schizophrenia

The alpha1/beta2/gamma2-containing heteropentamer is the most abundant gamma-amino-n-butyric acid type A receptor subtype in mammalian brains and the corresponding genes, the GABRA1, GABRB2, and GABRG2 genes, are located in chromosomal region 5q34 that several genome wide scans have implicated as a susceptibility region for schizophrenia. Given this positional and functional evidence, Lo et al. (Mol Psychiatry 2004; 9: 603-608) performed systematic linkage disequilibrium mapping of the GABAAR gene cluster on 5q34 in 130 schizophrenic patients and 170 controls, all of Chinese Han origin. In the single locus and haplotype analyses, single nucleotide polymorphisms in the GABRB2 gene showed highly significant association. The estimated effect caused by GABRB2 varied between odds ratios of 2.27 and 5.12. In order to re-examine their findings, we analyzed the most significantly associated single nucleotide polymorphism in the GABRB2 gene in a sample of 367 patients with schizophrenia and 360 controls, all of German descent. Our sample had a sufficient power to detect the effects described. Neither single marker nor haplotype analysis revealed a significant association with the disease status. Thus, our results do not support the hypothesis that genetic variation at the GABRB2 locus plays a major role in schizophrenic patients of European descent and that such variation would explain the previously observed linkage findings at this chromosomal region.     

Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases

The present study was undertaken to investigate the expression of prostate-specific membrane antigen (PSMA) in normal breast tissues, in cancerous breast tissues and in distant metastases from patients with breast cancer. Immunohistochemical analysis was performed to determine PSMA expression and angiogenic activity using anti-PSMA mAb and anti-CD31 mAb respectively. Immunofluorescence staining was applied to confirm the exact co-localization of PSMA and CD31. We observed different patterns of PSMA expression between normal and cancerous tissues. Normal breast tissues showed PSMA expression only in normal glandular cells. However, primary breast tumors and distant metastases showed PSMA expression in tumor cells and in tumor-associated neovasculature. PSMA score group status in primary breast tumors was significantly associated with histologic type and tumor grade (p?=?0.026 and p?=?0.004 respectively). Distant metastases showed higher PSMA expression in tumor-associated neovasculature comparing with primary tumors. Moreover, brain tumor-associated neovasculture had significantly higher expression of PSMA comparing with bone tumor-associated neovasculture. The localized binding of PSMA mAb to the neovasculature endothelium was confirmed with the double Immunofluorescence staining. ⁶⁸Ga-PSAM imaging of a patient with metastatic breast cancer showed strong tracer uptake in all known skeletal metastases. To the best of our knowledge, this study is the second one that has assessed PSMA expression in a large number of breast cancer patients. Our findings showed that PSMA is particularly expressed in tumor-associated neovasculature of breast tumors and its distant metastases, thus enhancing the evidence on the potential usefulness of PSMA as a therapeutic vascular target.     

QRICH1 variants in Ververi‐Brady syndrome—delineation of the genotypic and phenotypic spectrum

Ververi‐Brady syndrome (VBS, # 617982) is a rare developmental disorder, and loss‐of‐function variants in QRICH1 were implicated in its etiology. Furthermore, a recognizable phenotype was proposed comprising delayed speech, learning difficulties and dysmorphic signs. Here, we present four unrelated individuals with one known nonsense variant (c.1954C > T; p.[Arg652*]) and three novel de novo QRICH1 variants, respectively. These included two frameshift mutations (c.832_833del; p.(Ser278Leufs*25), c.1812_1813delTG; p.(Glu605Glyfs*25)) and interestingly one missense mutation (c.2207G > A; p.[Ser736Asn]), expanding the mutational spectrum. Enlargement of the cohort by these four individuals contributes to the delineation of the VBS phenotype and suggests expressive speech delay, moderate motor delay, learning difficulties/mild ID, mild microcephaly, short stature and notable social behavior deficits as clinical hallmarks. In addition, one patient presented with nephroblastoma. The possible involvement of QRICH1 in pediatric cancer assumes careful surveillance a key priority for outcome of these patients. Further research and enlargement of cohorts are warranted to learn about the genetic architecture and the phenotypic spectrum in more detail.     

IL-1β acutely increases pulmonary SP and permeability without associated changes in airway resistance and ventilation in anesthetized rats

Bronchopulmonary C-fibers (PCFs), when activated, promote substance P (SP) release, increase microvascular leak, and produce bronchoconstriction and apnea. IL-1β administered systemically or locally into the pulmonary parenchyma stimulates PCFs. Thus, we tested whether right atrial bolus injection or aerosol inhalation of IL-1β, to mainly stimulate PCFs, would acutely affect pulmonary SP level and vascular permeability, airway resistance (R_L), and ventilation in anesthetized rats. Our results showed that 30 min after IL-1β injection (2–6 μg kg⁻¹), SP levels and Evans blue extravasation in bronchoalveolar lavage fluid were markedly increased and these responses were eliminated or largely reduced in neonatal capsaicin-treated rats. In contrast, neither injection nor inhalation of IL-1β (5–15 μg ml⁻¹) significantly altered R_L and ventilation. Additionally, the capsaicin-evoked (4 μg kg⁻¹, i.v.) apneic response was unaffected by IL-1β treatment. Our data suggest that IL-1β, as administered in this study, can acutely increase pulmonary SP and vascular permeability, likely via stimulating PCFs, with little impact on R_L and ventilation.     

Bi-allelic loss of function variants in SLC30A5 as cause of perinatal lethal cardiomyopathy

Perinatal mortality is a heavy burden for both affected parents and physicians. However, the underlying genetic causes have not been sufficiently investigated and most cases remain without diagnosis. This impedes appropriate counseling or therapy. We describe four affected children of two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. In the four patients, we found the following homozygous loss of function (LoF) variants in SLC30A5 NM_022902.4:c.832_836del p.(Ile278Phefs*33) and NM_022902.4:c.1981_1982del p.(His661Tyrfs*10). Knockout of SLC30A5 has previously been shown a cardiac phenotype in mouse models and no homozygous LoF variants in SLC30A5 are currently described in gnomAD. Taken together, we present SLC30A5 as a new gene for a severe and perinatally lethal form of cardiomyopathy.Subject terms: Cardiovascular diseases, Development, Medical genetics, Medical genomics     

Role of exposure to air pollutants in the development of type 1 diabetes before and after 5 yr of age

Abstract: Objective: To assess the role of ambient air pollutants in type 1 diabetes in children. Design and methods: Prediagnosis exposure to five air pollutants was studied in two subgroups with onset of type 1 diabetes before and after 5 yr of age, and two matched subgroups of healthy children. Zip codes and dates of residence from birth to diagnosis were used to obtain geographic‐ and time‐specific air concentrations of SO₂, NO₂, ozone (O₃), SO₄, and particulate matter < 10 µm in diameter (PM₁₀). Prediagnosis time‐adjusted pollutant exposure levels were created by summing up zip code‐specific pollution data and dividing by months of exposure from birth to diagnosis. Two‐tailed t‐test and logistic regression were used to evaluate relative effects and test data between cases and controls. Results: Prediagnosis average O₃ exposure was significantly higher in children with type 1 diabetes than in healthy controls. Prediagnosis PM₁₀ exposure was significantly higher in children diagnosed before 5 yr of age, when compared with healthy controls. SO₂ exposure was significantly higher in children with later‐onset diabetes compared with those with early‐onset diabetes (EOD). NO₂, SO₂ and SO₄ exposure was significantly lower in children diagnosed after 5 yr of age, when compared with healthy controls. O₃, NO₂, SO₄ and PM₁₀ levels did not significantly differ between the two diabetic subgroups. Conclusion: Increased ozone exposure may be a contributory factor to the increased incidence of type 1 diabetes. PM₁₀ may be a specific contributory factor to the development of type 1 diabetes before 5 yr of age.