During the coronavirus disease 2019 (COVID-19) epidemic, many countries have instituted population-wide measures for social distancing. The requirement of patients on dialysis for regular treatment ...in settings typically not conducive to social distancing may increase their vulnerability to COVID-19.
Over a 6-week period, we recorded new COVID-19 infections and outcomes for all adult patients receiving dialysis in a large dialysis center. Rapidly introduced control measures included a two-stage routine screening process at dialysis entry (temperature and symptom check, with possible cases segregated within the unit and tested for SARS-CoV-2), isolated dialysis in a separate unit for patients with infection, and universal precautions that included masks for dialysis nursing staff.
Of 1530 patients (median age 66 years; 58.2% men) receiving dialysis, 300 (19.6%) developed COVID-19 infection, creating a large demand for isolated outpatient dialysis and inpatient beds. An analysis that included 1219 patients attending satellite dialysis clinics found that older age was a risk factor for infection. COVID-19 infection was substantially more likely to occur among patients on in-center dialysis compared with those dialyzing at home. We observed clustering in specific units and on specific shifts, with possible implications for aspects of service design, and high rates of nursing staff illness. A predictive epidemic model estimated a reproduction number of 2.2; cumulative cases deviated favorably from the model from the fourth week, suggesting that the implemented measures controlled transmission.
The COVID-19 epidemic affected a large proportion of patients at this dialysis center, creating service pressures exacerbated by nursing staff illness. Details of the control strategy and characteristics of this epidemic may be useful for dialysis providers and other institutions providing patient care.
Home dialysis therapies Corbett, Richard W
Clinical medicine (London, England),
20/May , Letnik:
23, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Home dialysis therapies offer a significant benefit to patients in respect of quality of life and autonomy, as compared with in-centre haemodialysis. There is significant unwarranted variation across ...the world in the availability of both peritoneal dialysis (PD) and home haemodialysis, which has led in the UK to a recommendation of a minimum 20% prevalent rate of dialysis patients at home. Key advances in PD have included changes in the approach to prescribing PD and the use of assisted dialysis. Peritonitis remains a significant complication which may present to general physicians and needs prompt recognition and treatment. The development of novel small dialysis machines has led to a resurgence of interest in home haemodialysis.
Delivering Person-Centered Peritoneal Dialysis Corbett, Richard W; Beckwith, Hannah; Lucisano, Gaetano ...
Clinical journal of the American Society of Nephrology,
03/2024, Letnik:
19, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Peritoneal dialysis (PD) enables people to have a home-based therapy, permitting greater autonomy for individuals along with enhanced treatment satisfaction compared with in-center dialysis care. The ...burden of treatment on PD, however, remains considerable and underpins the need for person-centered care. This reflects the need to address the patient as a person with needs and preferences beyond just the medical perspective. Shared decision making is central to the recent International Society for Peritoneal Dialysis recommendations for prescribing PD, balancing the potential benefits of PD on patient well-being with the burden associated with treatment. This review considers the role of high-quality goal-directed prescribing, incremental dialysis, and remote patient monitoring in reducing the burden of dialysis, including an approach to implementing incremental PD. Although patient-related outcomes are important in assessing the response to treatment and, particularly life participation, the corollary of dialysis burden, there are no clear routes to the clinical implementation of patient-related outcome measures. Delivering person-centered care is dependent on treating people both as individuals and as equal partners in their care.
We have developed a supportive two-exchange assisted continuous ambulatory peritoneal dialysis (asCAPD) programme for the older frail person who cannot do autonomous PD and do not want or are ...considered to be too high risk for haemodialysis (HD). Evaluation of the programme was determined by data collected retrospectively from patient records. Primary outcome was comparison of symptoms at start of dialysis and 3 months following dialysis start. Secondary outcomes were survival and peritonitis rate. Over a 4-year period (2016–2020), 49 patients with mean age 79.6 years (range 47–90) enrolled in the programme with eGFR 7.7 ± 2.6 ml/min (mean ± SD) at dialysis start. Forty-one patients had been on asCAPD for >3 months. There was an improvement in all symptoms at 3 months compared to baseline: anorexia (46% to 15%), fatigue (46% to 15%), shortness of breath (27% to 2%) and oedema (51% to 32%). One-year survival was 55%. Peritonitis rate was 0.52 episodes per patient year. The novel supportive two-exchange asCAPD programme shows potential improvement of symptoms after 3 months and may provide an acceptable dialysis modality for the frail co-morbid person with established kidney failure. More detailed study and evaluation are needed.
JAGuaR is an alignment protocol for RNA-seq reads that uses an extended reference to increase alignment sensitivity. It uses BWA to align reads to the genome and reference transcript models ...(including annotated exon-exon junctions) specifically allowing for the possibility of a single read spanning multiple exons. Reads aligned to the transcript models are then re-mapped on to genomic coordinates, transforming alignments that span multiple exons into large-gapped alignments on the genome. While JAGuaR does not detect novel junctions, we demonstrate how JAGuaR generates fast and accurate transcriptome alignments, which allows for both sensitive and specific SNV calling.
Next generation RNA-sequencing (RNA-seq) is a flexible approach that can be applied to a range of applications including global quantification of transcript expression, the characterization of RNA ...structure such as splicing patterns and profiling of expressed mutations. Many RNA-seq protocols require up to microgram levels of total RNA input amounts to generate high quality data, and thus remain impractical for the limited starting material amounts typically obtained from rare cell populations, such as those from early developmental stages or from laser micro-dissected clinical samples. Here, we present an assessment of the contemporary ribosomal RNA depletion-based protocols, and identify those that are suitable for inputs as low as 1-10 ng of intact total RNA and 100-500 ng of partially degraded RNA from formalin-fixed paraffin-embedded tissues.
Severe COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism ...in patients who died of severe COVID-19.
In this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients.
The median age at death of our cohort of ten patients was 73 years (IQR 52–79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight 89% of nine patients), heart (five 56%), and kidney (four 44%). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two 22% of nine patients), adrenal micro-infarction (three 33%), pericarditis (two 22%), disseminated mucormycosis (one 10% of ten patients), aortic dissection (one 11% of nine patients), and marantic endocarditis (one 11%). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of active viral replication outside the respiratory tract in three of five patients.
Our series supports clinical data showing that the four dominant interrelated pathological processes in severe COVID-19 are diffuse alveolar damage, thrombosis, haemophagocytosis, and immune cell depletion. Additionally, we report here several novel autopsy findings including pancreatitis, pericarditis, adrenal micro-infarction, secondary disseminated mucormycosis, and brain microglial activation, which require additional investigation to understand their role in COVID-19.
Imperial Biomedical Research Centre, Wellcome Trust, Biotechnology and Biological Sciences Research Council.
Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the ...spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, and an additional 7.1% had focal deletions), MYCN (1.7%, causing a recurrent p.Pro44Leu alteration) and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1 and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies that rely on frequently altered oncogenic drivers.
Follicular lymphoma (FL) and the GCB subtype of diffuse large B-cell lymphoma (DLBCL) derive from germinal center B cells. Targeted resequencing studies have revealed mutations in various genes ...encoding proteins in the NF-κB pathway that contribute to the activated B-cell (ABC) DLBCL subtype, but thus far few GCB-specific mutations have been identified. Here we report recurrent somatic mutations affecting the polycomb-group oncogene EZH2, which encodes a histone methyltransferase responsible for trimethylating Lys27 of histone H3 (H3K27). After the recent discovery of mutations in KDM6A (UTX), which encodes the histone H3K27me3 demethylase UTX, in several cancer types, EZH2 is the second histone methyltransferase gene found to be mutated in cancer. These mutations, which result in the replacement of a single tyrosine in the SET domain of the EZH2 protein (Tyr641), occur in 21.7% of GCB DLBCLs and 7.2% of FLs and are absent from ABC DLBCLs. Our data are consistent with the notion that EZH2 proteins with mutant Tyr641 have reduced enzymatic activity in vitro.
Patients receiving hemodialysis are at high risk from coronavirus disease 2019 (COVID-19) and demonstrate impaired immune responses to vaccines. There have been several descriptions of their ...immunologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, but few studies have described the clinical efficacy of vaccination in patients on hemodialysis.
In a multicenter observational study of the London hemodialysis population undergoing surveillance PCR testing during the period of vaccine rollout with BNT162b2 and AZD1222, all of those positive for SARS-CoV-2 were identified. Clinical outcomes were analyzed according to predictor variables, including vaccination status, using a mixed effects logistic regression model. Risk of infection was analyzed in a subgroup of the base population using a Cox proportional hazards model with vaccination status as a time-varying covariate.
SARS-CoV-2 infection was identified in 1323 patients of different ethnicities (Asian/other, 30%; Black, 38%; and White, 32%), including 1047 (79%) unvaccinated, 86 (7%) after first-dose vaccination, and 190 (14%) after second-dose vaccination. The majority of patients had a mild course; however, 515 (39%) were hospitalized, and 172 (13%) died. Older age, diabetes, and immune suppression were associated with greater illness severity. In regression models adjusted for age, comorbidity, and time period, prior two-dose vaccination was associated with a 75% (95% confidence interval, 56 to 86) lower risk of admission and 88% (95% confidence interval, 70 to 95) fewer deaths compared with unvaccinated patients. No loss of protection was seen in patients over 65 years or with increasing time since vaccination, and no difference was seen between vaccine types.
These data demonstrate a substantially lower risk of severe COVID-19 after vaccination in patients on dialysis who become infected with SARS-CoV-2.
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