ABSTRACT Cystic kidney diseases (CyKD) are a diverse group of disorders affecting more than 1 in 1000 individuals. Over 120 genes are implicated, primarily encoding components of the primary cilium, transcription factors, and morphogens. Prognosis varies greatly by molecular diagnosis. Causal variants are not identified in 10%–60% of individuals due to our limited understanding of CyKD. To elucidate the molecular landscape of CyKD, we queried the CAG Biobank using the ICD10 codes N28.1, Q61.1, Q61.11, Q61.19, Q61.2, Q61.3, and Q61.8 to identify individuals with CyKD. One hundred eight individuals met clinical criteria for CyKD and underwent proband‐only exome sequencing. Causal variants were identified in 86/108 (80%) individuals. The most common molecular diagnoses were PKD1 ‐related autosomal dominant polycystic kidney disease (32/108; 30%) and autosomal recessive polycystic kidney disease (21/108; 19%). Other common molecular diagnoses were ciliopathy syndromes (7/108; 6.5%) and Tuberous Sclerosis (6/108; 5.6%). Seven individuals had variants in genes not previously associated with CyKD (7/108; 6.5%). Candidate genes were identified in five individuals (5/108; 4.5%). Discordance between molecular and clinical diagnosis was present in two individuals. We demonstrate a high molecular diagnosis rate in individuals with CyKD that can result in diagnostic reclassification, supporting a role for genetic testing in CyKD.
Introduce a novel protocol to prevent clotting and citrate accumulation (CA) from blood product transfusion (BPT) during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in children.We prospectively compared fresh frozen plasma (FFP) and platelet transfusions between the two BPT protocols, direct transfusion protocol (DTP) and partial replacement of citrate transfusion protocol (PRCTP), in terms of the risks of clotting, citric accumulation (CA), and hypocalcemia. For DTP, blood products were directly transfused without any adjustment to the original RCA-CRRT regimen. For PRCTP, the blood products were infused into the CRRT circulation near the sodium citrate infusion point, and the dosage of 4% sodium citrate was reduced depending on the dosage of sodium citrate in the blood products. Basic information and clinical data were recorded for all children. Heart rate, blood pressure, ionized calcium (iCa) and various pressure parameters were recorded before, during and after BPT, as well as coagulation indicators, electrolytes, and blood cell counts before and after BPT.Twenty-six children received 44 PRCTPs and 15 children received 20 DTPs. The two groups had similar in vitro ionized calcium (iCa) concentrations (PRCTP: 0.33 ± 0.06 mmol/L, DTP: 0.31 ± 0.04 mmol/L), total filter lifespan (PRCTP: 49.33 ± 18.58, DTP: 50.65 ± 13.57 h), and filter lifespan after BPT (PRCTP: 25.31 ± 13.87, DTP: 23.39 ± 11.34 h). There was no visible filter clotting during BPT in any of the two groups. The two groups had no significant differences in arterial pressure, venous pressure, and transmembrane pressure before, during, or after BPT. Neither treatment led to significant decreases in WBC, RBC, or hemoglobin. The platelet transfusion group and the FFP group each had no significant decrease in platelets, and no significant increases in PT, APTT, and D-dimer. The most clinically significant changes were in the DTP group, in which the ratio of total calcium to ionized calcium (T/iCa) increased from 2.06 ± 0.19 to 2.52 ± 0.35, the percentage of patients with T/iCa above 2.5 increased from 5.0% to 45%, and the level of in vivo iCa increased from 1.02 ± 0.11 to 1.06 ± 0.09 mmol/L (all p < 0.05). Changes in these three indicators were not significant in the PRCTP group.Neither protocol was associated with filter clotting during RCA-CRRT. However, PRCTP was superior to DTP because it did not increase the risk of CA and hypocalcemia.
Vitamin D insufficiency correlates with mortality risk among patients with chronic kidney disease (CKD). The survival benefits of active vitamin D treatment have been assessed in patients with CKD not requiring dialysis and in patients with end stage renal disease (ESRD) requiring dialysis.MEDLINE, Embase, the Cochrance Library, and article reference lists were searched for relevant observational trials. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS) checklist. Pooled effects were calculated as hazard ratios (HR) using random-effects models.Twenty studies (11 prospective cohorts, 6 historical cohorts and 3 retrospective cohorts) were included in the meta-analysis., Participants receiving vitamin D had lower mortality compared to those with no treatment (adjusted case mixed baseline model: HR, 0.74; 95% confidence interval [95% CI], 0.67-0.82; P <0.001; time-dependent Cox model: HR, 0.71; 95% CI, 0.57-0.89; P <0.001). Participants that received calcitriol (HR, 0.63; 95% CI, 0.50-0.79; P <0.001) and paricalcitol (HR, 0.43 95% CI, 0.29-0.63; P <0.001) had a lower cardiovascular mortality. Patients receiving paricalcitol had a survival advantage over those that received calcitriol (HR, 0.95; 95% CI, 0.91-0.99; P <0.001).Vitamin D treatment was associated with decreased risk of all-cause and cardiovascular mortality in patients with CKD not requiring dialysis and patients with end stage renal disease (ESRD) requiring dialysis. There was a slight difference in survival depending on the type of vitamin D analogue. Well-designed randomized controlled trials are necessary to assess the survival benefits of vitamin D.
To study the risk factors of ventilator-associated pneumonia (VAP) in intensive care unit (ICU), in order to offer basic epidemiological data for the prevention of VAP in ICU.A prospective cohort study on VAP was carried out in intubated or tracheotomied patients in ICU of Fudan University Zhongshan Hospital from Dec.1999 to Feb. 2001. Single factor analysis and muti-variable logistic regression analysis were adopted to identify the possible risk factors of VAP.(1) Ninety-eight patients were enrolled in this study, of which 52 were diagnosed as having VAP. The incidence of VAP was 53.1%. The incidence of VAP was 32.4 cases per 1000 intubation days. (2) Single factor analysis showed that history of chronic obstructive pulmonary emphysema, use of H2-receptor blocker, the days of antibiotic use, the types of antibiotics, enteral feeding, APACHEII scores, the duration of mechanic ventilation, pH of gastric juice, hypoalbuminemia, tracheotomy, reintubation, colonization of gram negative bacilli in oropharynx, and conscious disturbance were related to the occurrence of VAP. (3) Multi-variable logistic analysis showed statistical significance in combination of over two types of antibiotics (OR = 7.59, 95% CI 4.31 - 38.29), reintubation (OR = 4.73, 95% CI 2.33 - 11.67), APACHE II scores over 15 (OR = 2.02, 95% CI 1.59 - 26.74), pH of gastric juice over 4 (OR = 1.23, 95% CI 1.02 - 1.54) and prolongation of mechanic ventilation (OR = 1.15, 95% CI 1.01 - 3.75).Various factors contributed to VAP in ICU. Further clinical trials are needed for evidence of the above-mentioned possible risk factors.
Abstract Secondary infection in septic patients has received widespread attention, although clinical data are still lacking. The present study was performed on 476 patients with septic shock. Time trends for mortality were analyzed using Spearman’s rank correlation test. Risk factors for secondary infection were investigated by binary logistic regression. The extended Cox model with time-varying covariates and hazard ratios (HR) was performed to determine the impact of secondary infection on mortality. Differences in hospital length of stay (LOS) between patients with and without secondary infection were calculated using a multistate model. Thirty-nine percent of septic shock patients who survived the early phase of the disease developed secondary infection. There was a statistically significant increased odds ratio for secondary infection in older patients and patients with a longer LOS in the intensive care unit (ICU), a higher Sequential Organ Failure Assessment (SOFA) score, and endotracheal intubation. Secondary infection significantly reduced the rate of discharge (HR 5.607; CI 95 3.612–8.704; P < 0.001) and was associated with an increased hospital LOS of 5.46 days. The present findings represent a direct description of secondary infection in septic shock patients and highlight the influence of this condition on septic shock outcomes.
Objective The objective of this article was to study the association of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) with bone mineral density (BMD). Methods Spine BMD was evaluated in a subset of 2028 participants from the Multiethnic Study of Atherosclerosis cohort who were NSAID users (including aspirin) and underwent both lumbar and thoracic imaging. Multiethnic Study of Atherosclerosis is a prospective cohort study that includes 4 ethnic groups (white, Asian, African American, and Hispanic). Trabecular BMD was evaluated by quantitative computed tomography based on cardiac computed tomography images, which were obtained during coronary calcium scans. The analyses were cross sectional using baseline examination data for exposure and outcomes. Results After adjustment for potential confounders including age, sex, race, and traditional cardiovascular risk factors, a small association between trabecular BMD and baseline use of COX-2–selective NSAID was observed. COX-2–selective NSAID use was associated with 7.4 mg/cm 3 (95% confidence interval [CI], 1.6–13.3; P = 0. 013) higher trabecular BMD in thoracic spine and 10.6 mg/cm 3 higher at lumbar spine (95% CI, 5.1–16.1; P < 0.001). Among regular aspirin users, there was no association between drug use and trabecular BMD. Considering all spine fractures together, the prevalence ratio of fractures among aspirin users was 1.0 (95% CI, 0.6–1.6) and 1.1 (95% CI, 0.5–2.3) among COX-2–selective NSAID users. Conclusions Regular use of aspirin has no significant association with trabecular BMD in either the thoracic or lumbar spine and no association with fracture prevalence. COX-2–selective NSAIDs may have modest positive association with BMD, but the mechanisms were not assessed and the observational study design makes residual confounding a possible alternate explanation. Potential pathological mechanisms warrant further longitudinal exploration.
A cationic near IR cyanine was used as a chromic probe and its binding reaction with nucleic acids was studied. In the medium of pH 6.0, the near IR cyanine showd a decrease in absorption at its maximal absorption peak (771nm) on binding to nucleic acids, and a new absorption peak appeared at 640 nm. Based on the fact, a novel near IR spectrophotometric method for the determination of nucleic acids was developed. The calibration graphs are linear over the range 60~2 000 ng/mL for Salmon Sperm DNA, 100~2 000 ng/mL for Yeast RNA, respectively. The detection limits is 30 ng/mLfor Salmon Sperm DNA, 50 ng/mL for Yeast RNA, respectively.
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