Case mix, outcome and activity for patients admitted to intensive care units requiring chronic renal dialysis: a secondary analysis of the ICNARC Case Mix Programme Database

INTRODUCTION: This report describes the case mix, outcome and activity for admissions to intensive care units (ICUs) of patients who require prior chronic renal dialysis for end-stage renal failure (ESRF), and investigates the effect of case mix factors on outcome. METHODS: This was a secondary analysis of a high-quality clinical database, namely the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, which includes 276,731 admissions to 170 adult ICUs across England, Wales and Northern Ireland from 1995 to 2004. RESULTS: During the eight year study period, 1.3% (n = 3,420) of all patients admitted to ICU were receiving chronic renal dialysis before ICU admission. This represents an estimated ICU utilization of six admissions (32 bed-days) per 100 dialysis patient-years. The ESRF group was younger (mean age 57.3 years versus 59.5 years) and more likely to be male (60.2% versus 57.9%) than those without ESRF. Acute Physiology and Chronic Health Evaluation II score and Acute Physiology Score revealed greater severity of illness on admission in patients with ESRF (mean 24.7 versus 16.6 and 17.2 versus 12.6, respectively). Length of stay in ICU was comparable between groups (median 1.9 days versus 1.8 days) and ICU mortality was only slightly elevated in the ESRF group (26.3% versus 20.8%). However, the ESRF group had protracted overall hospital stay (median 25 days versus 17 days), and increased hospital mortality (45.3% versus 31.2%) and ICU readmission (9.0% vs. 4.7%). Multiple logistic regression analysis adjusted for case mix identified the increased hospital mortality to be associated with increasing age, emergency surgery and nonsurgical cases, cardiopulmonary resuscitation before ICU admission and extremes of physiological norms. The adjusted odds ratio for ultimate hospital mortality associated with chronic renal dialysis was 1.24 (95% confidence interval 1.13 to 1.37). CONCLUSION: Patients with ESRF admitted to UK ICUs are more likely to be male and younger, with a medical cause of admission, and to have greater severity of illness than the non-ESRF population. Outcomes on the ICU were comparable between the two groups, but those patients with ESRF had greater readmission rates, prolonged post-ICU hospital stay and increased post-ICU hospital mortality. This study is by far the largest comparative outcome analysis to date in patients with ESRF admitted to the ICU. It may help to inform clinical decision-making and resource requirements for this patient population

Case mix, outcome and activity for patients admitted to intensive care units requiring chronic renal dialysis: a secondary analysis of the ICNARC Case Mix Programme Database

INTRODUCTION: This report describes the case mix, outcome and activity for admissions to intensive care units (ICUs) of patients who require prior chronic renal dialysis for end-stage renal failure (ESRF), and investigates the effect of case mix factors on outcome. METHODS: This was a secondary analysis of a high-quality clinical database, namely the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, which includes 276,731 admissions to 170 adult ICUs across England, Wales and Northern Ireland from 1995 to 2004. RESULTS: During the eight year study period, 1.3% (n = 3,420) of all patients admitted to ICU were receiving chronic renal dialysis before ICU admission. This represents an estimated ICU utilization of six admissions (32 bed-days) per 100 dialysis patient-years. The ESRF group was younger (mean age 57.3 years versus 59.5 years) and more likely to be male (60.2% versus 57.9%) than those without ESRF. Acute Physiology and Chronic Health Evaluation II score and Acute Physiology Score revealed greater severity of illness on admission in patients with ESRF (mean 24.7 versus 16.6 and 17.2 versus 12.6, respectively). Length of stay in ICU was comparable between groups (median 1.9 days versus 1.8 days) and ICU mortality was only slightly elevated in the ESRF group (26.3% versus 20.8%). However, the ESRF group had protracted overall hospital stay (median 25 days versus 17 days), and increased hospital mortality (45.3% versus 31.2%) and ICU readmission (9.0% vs. 4.7%). Multiple logistic regression analysis adjusted for case mix identified the increased hospital mortality to be associated with increasing age, emergency surgery and nonsurgical cases, cardiopulmonary resuscitation before ICU admission and extremes of physiological norms. The adjusted odds ratio for ultimate hospital mortality associated with chronic renal dialysis was 1.24 (95% confidence interval 1.13 to 1.37). CONCLUSION: Patients with ESRF admitted to UK ICUs are more likely to be male and younger, with a medical cause of admission, and to have greater severity of illness than the non-ESRF population. Outcomes on the ICU were comparable between the two groups, but those patients with ESRF had greater readmission rates, prolonged post-ICU hospital stay and increased post-ICU hospital mortality. This study is by far the largest comparative outcome analysis to date in patients with ESRF admitted to the ICU. It may help to inform clinical decision-making and resource requirements for this patient population

Generalized Farey trees, transfer Operators and phase transitions

We consider a family of Markov maps on the unit interval, interpolating between the tent map and the Farey map. The latter map is not uniformly expanding. Each map being composed of two fractional linear transformations, the family generalizes many particular properties which for the case of the Farey map have been successfully exploited in number theory. We analyze the dynamics through the spectral analysis of generalized transfer operators. Application of the thermodynamic formalism to the family reveals first and second order phase transitions and unusual properties like positivity of the interaction function.Comment: 39 pages, 10 figure

Ventricular noncompaction in a female patient with nephropathic cystinosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report an unusual and interesting case of a 24-year-old woman with nephropathic cystinosis in association with concomitant isolated noncompaction of the left ventricle. Left ventricular noncompaction usually presents with reduced exercise tolerance as a consequence of ventricular dysfunction, the result of embolus or with palpitations and syncope due to arrhythmia. There is no specific treatment directed at isolated noncompaction. Treatment is focused on the cause of presentation, with medication aimed at improving ventricular dysfunction, as well as treating and preventing thrombosis and arrhythmia.</p> <p>Case presentation</p> <p>Our patient presented with an episode of decompensated heart failure. Trans-thoracic echocardiography demonstrated excessive trabeculation with inter-trabecular recesses in the left ventricle typical of noncompaction of the left ventricle. The patient's admission was complicated by a cardiac arrest precipitated by ventricular tachycardia for which she subsequently underwent implantation of an automatic implantable cardioverter defibrillator.</p> <p>Conclusion</p> <p>This is, as far as we know, the first case report of the co-existence of nephropathic cystinosis and isolated noncompaction of the left ventricle. It highlights the importance of being vigilant to the diagnosis of left ventricular noncompaction.</p

Long-Term Transplantation Outcomes in Patients With Primary Hyperoxaluria Type 1 Included in the European Hyperoxaluria Consortium (OxalEurope) Registry

INTRODUCTION: In primary hyperoxaluria type 1 (PH1), oxalate overproduction frequently causes kidney stones, nephrocalcinosis, and kidney failure. As PH1 is caused by a congenital liver enzyme defect, combined liver–kidney transplantation (CLKT) has been recommended in patients with kidney failure. Nevertheless, systematic analyses on long-term transplantation outcomes are scarce. The merits of a sequential over combined procedure regarding kidney graft survival remain unclear as is the place of isolated kidney transplantation (KT) for patients with vitamin B6-responsive genotypes. METHODS: We used the OxalEurope registry for retrospective analyses of patients with PH1 who underwent transplantation. Analyses of crude Kaplan–Meier survival curves and adjusted relative hazards from the Cox proportional hazards model were performed. RESULTS: A total of 267 patients with PH1 underwent transplantation between 1978 and 2019. Data of 244 patients (159 CLKTs, 48 isolated KTs, 37 sequential liver–KTs [SLKTs]) were eligible for comparative analyses. Comparing CLKTs with isolated KTs, adjusted mortality was similar in patients with B6-unresponsive genotypes but lower after isolated KT in patients with B6-responsive genotypes (adjusted hazard ratio 0.07, 95% CI: 0.01–0.75, P = 0.028). CLKT yielded higher adjusted event-free survival and death-censored kidney graft survival in patients with B6-unresponsive genotypes (P = 0.025, P < 0.001) but not in patients with B6-responsive genotypes (P = 0.145, P = 0.421). Outcomes for 159 combined procedures versus 37 sequential procedures were comparable. There were 12 patients who underwent pre-emptive liver transplantation (PLT) with poor outcomes. CONCLUSION: The CLKT or SLKT remains the preferred transplantation modality in patients with PH1 with B6-unresponsive genotypes, but isolated KT could be an alternative approach in patients with B6-responsive genotypes

Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection

Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains. IMPORTANCE Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans

Determinants of Kidney Failure in Primary Hyperoxaluria Type 1:Findings of the European Hyperoxaluria Consortium

INTRODUCTION: Primary hyperoxaluria type 1 (PH1) has a highly heterogeneous disease course. Apart from the c.508G&gt;A (p.Gly170Arg) AGXT variant, which imparts a relatively favorable outcome, little is known about determinants of kidney failure. Identifying these is crucial for disease management, especially in this era of new therapies. METHODS: In this retrospective study of 932 patients with PH1 included in the OxalEurope registry, we analyzed genotype-phenotype correlations as well as the impact of nephrocalcinosis, urolithiasis, and urinary oxalate and glycolate excretion on the development of kidney failure, using survival and mixed model analyses.RESULTS: The risk of developing kidney failure was the highest for 175 vitamin-B6 unresponsive ("null") homozygotes and lowest for 155 patients with c.508G&gt;A and c.454T&gt;A (p.Phe152Ile) variants, with a median age of onset of kidney failure of 7.8 and 31.8 years, respectively. Fifty patients with c.731T&gt;C (p.Ile244Thr) homozygote variants had better kidney survival than null homozygotes ( P = 0.003). Poor outcomes were found in patients with other potentially vitamin B6-responsive variants. Nephrocalcinosis increased the risk of kidney failure significantly (hazard ratio [HR] 3.17 [2.03-4.94], P &lt; 0.001). Urinary oxalate and glycolate measurements were available in 620 and 579 twenty-four-hour urine collections from 117 and 87 patients, respectively. Urinary oxalate excretion, unlike glycolate, was higher in patients who subsequently developed kidney failure ( P = 0.034). However, the 41% intraindividual variation of urinary oxalate resulted in wide confidence intervals. CONCLUSION: In conclusion, homozygosity for AGXT null variants and nephrocalcinosis were the strongest determinants for kidney failure in PH1. </p

Bats host major mammalian paramyxoviruses

The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle disease-, respiratory syncytial virus and metapneumoviruses. Here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). Major discoveries include evidence of an origin of Hendra- and Nipah virus in Africa, identification of a bat virus conspecific with the human mumps virus, detection of close relatives of respiratory syncytial virus, mouse pneumonia- and canine distemper virus in bats, as well as direct evidence of Sendai virus in rodents. Phylogenetic reconstruction of host associations suggests a predominance of host switches from bats to other mammals and birds. Hypothesis tests in a maximum likelihood framework permit the phylogenetic placement of bats as tentative hosts at ancestral nodes to both the major Paramyxoviridae subfamilies (Paramyxovirinae and Pneumovirinae). Future attempts to predict the emergence of novel paramyxoviruses in humans and livestock will have to rely fundamentally on these data