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.
Follow the life of a celebrated guru, from hardscrabble boy to self-made man In Ringside Stories, real estate guru Dick Corbett reveals the secrets to his success in business and in life, tracking ...the rough-and-ready life of a man who won't accept failure as an outcome. Setbacks large and small are taken as lessons for the future, and one small success leads to another, larger one until the dream achieved is grander than any restless youth could have imagined. In Corbett's long and remarkably successful career, his commitment to economic development and growth management have been stunningly reflected in the more than one billion dollars of complex real estate ventures he's financed, developed, and constructed-including International Plaza, a three million square foot mixed-use retail, office, and hotel development at Tampa's International Airport. Corbett's work has generated thousands of permanent jobs, hundreds of new commercial sales entities, office space, adjunct hotels, and restaurants-all producing hundreds of millions of dollars annually for the regional economy. Richard A. Corbett's story begins with an alcoholic mother, an absentee father, and a search for self that resulted in boxing titles, street smarts, wilderness survival skills, degrees from Notre Dame and Harvard, a spot on the Kennedy presidential campaign, and later a place at Robert Kennedy's side when he died. This book documents the events that built this remarkable life, with lessons learned and wisdom gained. Mine the insight of a recognized real estate investing guru Learn how delicate relationships contributed to Corbett's success See the Kennedy family from the inner circle's perspective Discover how sheer ambition built Tampa's International Plaza Life is precious-everyone gets exactly one. Few can say they've truly lived, but Corbett's experiences mark him as a man who has been there, done that. Ringside Stories is the story of how wisdom found a truly self-made man.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Abstract
Tissues used in pathology laboratories are typically stored in the form of formalin-fixed, paraffin-embedded (FFPE) samples. One important consideration in repurposing FFPE material for next ...generation sequencing (NGS) analysis is the sequencing artifacts that can arise from the significant damage to nucleic acids due to treatment with formalin, storage at room temperature and extraction. One such class of artifacts consists of chimeric reads that appear to be derived from non-contiguous portions of the genome. Here, we show that a major proportion of such chimeric reads align to both the 'Watson' and 'Crick' strands of the reference genome. We refer to these as strand-split artifact reads (SSARs). This study provides a conceptual framework for the mechanistic basis of the genesis of SSARs and other chimeric artifacts along with supporting experimental evidence, which have led to approaches to reduce the levels of such artifacts. We demonstrate that one of these approaches, involving S1 nuclease-mediated removal of single-stranded fragments and overhangs, also reduces sequence bias, base error rates, and false positive detection of copy number and single nucleotide variants. Finally, we describe an analytical approach for quantifying SSARs from NGS data.
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.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
PDF
