Non-crystalline light chain proximal tubulopathy, a morphologically protean entity.

BACKGROUND: Light chain proximal tubulopathy (LCPT) is a rare form of paraprotein-related disease, occurring in two main histopathological forms: crystalline and non-crystalline. The clinicopathological features, treatment strategies and outcomes, especially of the non-crystalline form, are not well described. METHODS: We conducted a single-centre retrospective case series of 12 LCPT patients, 5 crystalline and 7 non-crystalline, between 2005 and 2021. RESULTS: The median age was 69.5 years (range 47-80). Ten patients presented with CKD and significant proteinuria (median estimated glomerular filtration rate of 43.5 ml/min/1.73 m2; urine protein:creatinine ratio 328 mg/mmol). Only six patients had known haematological disease at the time of renal biopsy. Multiple myeloma (MM) was diagnosed in seven patients cases and monoclonal gammopathy of renal significance (MGRS) in five patients. A clone was detected in all cases combining serum/urine electrophoresis and free light chain (LC) assays. Crystalline and non-crystalline variants had similar clinical presentations. For the non-crystalline variant, a diagnosis was reached based on a combination of CKD without another cause, haematological workup, LC restriction on immunofluorescence and abnormalities on electron microscopy (EM). Nine of 12 patients received clone-directed treatment. Patients who achieved haematological response (including all non-crystalline LCPT) had improved renal outcomes over a median follow-up of 79 months. CONCLUSIONS: The non-crystalline variant may go unrecognised because of its subtle histopathological features and requires EM to distinguish it from 'excessive LC resorption without tubular injury'. Clone-directed treatment with good haematological response improves renal outcomes in both variants but limited data exist in MGRS. Multicentre prospective studies are needed to better define the clinicopathological characteristics associated with poor outcomes and optimize treatment strategies in patients with MGRS.

Advanced heart failure in adult congenital heart disease: the role of renal dysfunction in management and outcomes.

AIMS: Previous studies in adult congenital heart disease (CHD) have demonstrated a link between renal dysfunction and mortality. However, the prognostic significance of renal dysfunction in CHD and decompensated heart failure (HF) remains unclear. We sought to assess the association between renal dysfunction and outcomes in adults with CHD presenting to our centre with acute HF between 2010 and 2021. METHODS AND RESULTS: This retrospective analysis focused on the association between renal dysfunction, pre-existing and on admission, and outcomes during and after the index hospitalization. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. Cox regression analysis was used to identify the predictors of death post-discharge. In total, 176 HF admissions were included (mean age 47.7 ± 14.5 years, 43.2% females). One-half of patients had a CHD of great complexity, 22.2% had a systemic right ventricle, and 18.8% had Eisenmenger syndrome. Chronic kidney disease was present in one-quarter of patients. The median length of intravenous diuretic therapy was 7 (4-12) days, with a maximum dose of 120 (80-160) mg furosemide equivalents/day, and 15.3% required inotropic support. The in-hospital mortality rate was 4.5%. The 1- and 5-year survival rates free of transplant or ventricular assist device (VAD) post-discharge were 75.4% [95% confidence interval (CI): 69.2-82.3%] and 43.3% (95% CI: 36-52%), respectively. On multivariable Cox analysis, CKD was the strongest predictor of mortality or transplantation/VAD. Highly complex CHD and inpatient requirement of inotropes also remained predictive of an adverse outcome. CONCLUSION: Adult patients with CHD admitted with acute HF are a high-risk cohort. CKD is common and triples the risk of death/transplantation/VAD. An expert multidisciplinary approach is essential for optimizing outcomes.

Renal dysfunction was associated with more advanced disease, higher diuretic doses, and a longer hospital inpatient stay. Chronic kidney disease was common and tripled the risk of death, transplantation, or ventricular assist device. Renal dysfunction in adults with congenital heart disease and heart failure should prompt intensified monitoring, optimization of medical therapy, and collaborative management with renal physicians.

Paediatric major incident triage: A Delphi process to determine clinicians' attitudes and beliefs within the United Kingdom and Ireland.

AIM: Triage is key to effective management of major incidents, yet there is scarce evidence surrounding the optimal method of paediatric major incident triage (MIT). This study aimed to derive consensus on key components of paediatric MIT among healthcare professionals responsible for triage during paediatric major incidents. METHODS: Two-round online Delphi consensus study delivered July 2021-October 2021, including participants from pre-hospital and hospital specialities responsible for triage during paediatric major incidents. A 5-point Likert scale was used to determine consensus, set a priori at 70%. RESULTS: 111 clinicians completed both rounds; 13 of 17 statements reached consensus. Positive consensus was reached on rescue breaths in mechanisms associated with hypoxia or asphyxiation, mobility assessment as a crude discriminator and use of adult physiology for older children. Whilst positive consensus was reached on the benefits of a single MIT tool across all adult and paediatric age ranges, there was negative consensus in relation to clinical implementation. CONCLUSIONS: This Delphi study has established consensus among a large group of clinicians involved in the management of major incidents on several key elements of paediatric major incident triage. Further work is required to develop a triage tool that can be implemented based on emerging and ongoing research and which is acceptable to clinicians.

Retrospective observational study of neonatal attendances to a children's emergency department.

AIM: Attendances to emergency departments (EDs) in the UK are increasing, particularly for younger children. Community services are under increasing pressure and parents may preferentially bring their babies to the ED, even for non-urgent problems. This study aimed to characterise the presenting features, management and disposition of neonatal attendances to a children's ED (CED). METHODS: Retrospective observational review of neonatal attendances (≤28 days) to the CED at Bristol Royal Hospital for Children (BRHC) from 01/01/2016 to 31/12/2016. Further information was obtained from investigation results and discharge summaries. Data abstracted included sex, age, referral method, presenting complaint, diagnosis, investigations and treatments. RESULTS: Neonatal attendances increased from 655 to 1,205 from 2008 to 2016. The most common presenting complaints were breathing difficulty (18.1%) and vomiting (8.3%). The most common diagnoses were 'no significant medical problem' (41.9%) and bronchiolitis (10.5%). Half of neonatal attendances to the CED had no investigations performed and most (77.7%) needed advice or observation only. CONCLUSION: Many neonates presenting to the CED were well and discharged with observation only. This suggests potential for improving community management and in supporting new parents. Drivers of health policy should consider developing enhanced models of out of hospital care which are acceptable to clinicians and families.

Risk of COVID-19 Disease, Dialysis Unit Attributes, and Infection Control Strategy among London In-Center Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Patients receiving in-center hemodialysis treatment face unique challenges during the coronavirus disease 2019 (COVID-19) pandemic, specifically the need to attend for treatment that prevents self-isolation. Dialysis unit attributes and isolation strategies that might reduce dialysis center COVID-19 infection rates have not been previously examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We explored the role of variables, including community disease burden, dialysis unit attributes (size and layout), and infection control strategies, on rates of COVID-19 among patients receiving in-center hemodialysis in London, United Kingdom, between March 2, 2020 and May 31, 2020. The two outcomes were defined as (1) a positive test for infection or admission with suspected COVID-19 and (2) admission to the hospital with suspected infection. Associations were examined using a discrete time multilevel time-to-event analysis. RESULTS: Data on 5755 patients dialyzing in 51 units were analyzed; 990 (17%) tested positive and 465 (8%) were admitted with suspected COVID-19 between March 2 and May 31, 2020. Outcomes were associated with age, diabetes, local community COVID-19 rates, and dialysis unit size. A greater number of available side rooms and the introduction of mask policies for asymptomatic patients were inversely associated with outcomes. No association was seen with sex, ethnicity, or deprivation indices, nor with any of the different isolation strategies. CONCLUSIONS: Rates of COVID-19 in the in-center hemodialysis population relate to individual factors, underlying community transmission, unit size, and layout.

Epidemiology of COVID-19 in an Urban Dialysis Center.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Central Venous Stenosis, Access Outcome and Survival in Patients undergoing Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: Central venous catheters have traditionally provided access for urgent hemodialysis, but are also sometimes advocated as an option for older or more comorbid patients. Adverse effects of this type of dialysis access include central venous stenosis, for which the risk factors and consequences are incompletely understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted two studies within the same population cohort, comprising all patients starting hemodialysis in a single center from January 2006 to December 2013. First, patients were retrospectively analyzed for the presence of central venous stenosis; their access outcomes are described and survival compared with matched controls drawn from the same population. Second, a subset of patients with a history of catheter access within this cohort was analyzed to determine risk factors for central venous stenosis. RESULTS: Among 2811 patients, central venous stenosis was diagnosed in 120 (4.3%), at a median dialysis vintage of 2.9 (interquartile range, 1.8-4.6) years. Compared with matched controls, patients with central venous stenosis had similar survival (median 5.1 versus 5.2 years; P=0.54). Among a subset of 500 patients, all with a history of catheter use, 34 (6.8%) developed central venous stenosis, at a rate of 2.2 per 100 patient-years. The incidence of central venous stenosis was higher with larger number of previous catheters (relative risk [RR], 2.2; 95% confidence interval [95% CI]. 1.6 to 2.9), pacemaker insertion (RR, 3.9; 95% CI, 1.7 to 8.9), and was lower with older age (RR, 0.7 per decade; 95% CI, 0.6 to 0.8). In a Cox proportional hazards model, the catheter number, pacemaker, and younger age at dialysis initiation were all significant independent risk factors for central venous stenosis. CONCLUSIONS: Central venous stenosis occurred in a minority of patients on hemodialysis, and was associated with compromised future access, but unchanged survival. Among patients with a history of catheter use, risk related to both the number of catheters and the total catheter duration, although nondialysis factors such as pacemakers were also important. Central venous stenosis risk was lower in older patients, supporting the selective use of tunneled catheters in this group.

Childhood meningitis in the conjugate vaccine era: a prospective cohort study.

Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16 years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis-13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3 months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3 months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay.