Virus-host interactions predictor (VHIP): Machine learning approach to resolve microbial virus-host interaction networks.

Viruses of microbes are ubiquitous biological entities that reprogram their hosts' metabolisms during infection in order to produce viral progeny, impacting the ecology and evolution of microbiomes with broad implications for human and environmental health. Advances in genome sequencing have led to the discovery of millions of novel viruses and an appreciation for the great diversity of viruses on Earth. Yet, with knowledge of only "who is there?" we fall short in our ability to infer the impacts of viruses on microbes at population, community, and ecosystem-scales. To do this, we need a more explicit understanding "who do they infect?" Here, we developed a novel machine learning model (ML), Virus-Host Interaction Predictor (VHIP), to predict virus-host interactions (infection/non-infection) from input virus and host genomes. This ML model was trained and tested on a high-value manually curated set of 8849 virus-host pairs and their corresponding sequence data. The resulting dataset, 'Virus Host Range network' (VHRnet), is core to VHIP functionality. Each data point that underlies the VHIP training and testing represents a lab-tested virus-host pair in VHRnet, from which meaningful signals of viral adaptation to host were computed from genomic sequences. VHIP departs from existing virus-host prediction models in its ability to predict multiple interactions rather than predicting a single most likely host or host clade. As a result, VHIP is able to infer the complexity of virus-host networks in natural systems. VHIP has an 87.8% accuracy rate at predicting interactions between virus-host pairs at the species level and can be applied to novel viral and host population genomes reconstructed from metagenomic datasets.

Hypertension and cardiovascular risk factors in hemodialyzed diabetic patients.

In a retrospective study, the cause of death and the cardiovascular risk conferred by hypertension and other risk factors were analyzed in 200 diabetic and 200 nondiabetic patients who were matched for age, sex, year of admission, and center of treatment. Total and cardiovascular mortality were considerably higher in diabetics, cardiovascular mortality being 4.8 times higher in patients with type I and 3.0 times higher in those with type II diabetes compared to matched controls. Cardiovascular mortality progressively increased with age and had not improved in recent years. In both types I and II diabetes, the rate (58%) and proportion (38%) of deaths from cardiovascular causes were significantly higher in diabetics than in matched controls. Myocardial infarction (13%) and stroke (7%) accounted only for a minority of cardiovascular mortality, the majority (80%) being due to "sudden death of unknown cause." Autopsy was carried out in 33% of patients with sudden death. A documented history of long-standing hypertension increased cardiovascular death in diabetic more than in nondiabetic patients. Diabetic retinopathy (an index of microangiopathy) and absence of peripheral pulses, amputation, or history of myocardial infarction, stroke, or transient ischemic attacks (as evidence of macroangiopathy) caused surprisingly little increase in relative risk for cardiovascular death. In diabetics but not in nondiabetics, cardiomegaly, particularly in association with electrocardiographic abnormalities, was a strong predictor of cardiovascular death.

Controlled trial of a Y-set dialysis delivery system to prevent peritonitis in patients receiving continuous ambulatory peritoneal dialysis.

Peritonitis rates were compared in patients receiving continuous ambulatory peritoneal dialysis (CAPD) via either a Y-set dialysate delivery system or a standard system. Forty patients in each arm of the trial were matched for age (range 20-67 years, mean 49 years), and remained in the study for similar periods (range 3-36 months, mean 14.1 months). The observation time was 564 patient-months for each arm of the trial. There were 22 episodes of peritonitis in nine out of 40 patients using the Y-set and 57 episodes in 21 out of 40 patients using the standard system (P = 0.005 Wilcoxon signed rank test for episodes, P = 0.02 McNemar's chi 2 test for patients). Peritonitis rates were one episode per 25 patient-months in the Y-set group, and one episode per 9.7 patient-months in the standard group. In the Y-set group there were significantly fewer episodes caused by coagulase-negative staphylococci and Acinetobacter spp. There was no difference in the rate of episodes caused by Staphylococcus aureus, streptococci, enterococci, corynebacteria, enterobacteria or pseudomonads. There was no difference in the incidence of catheter exit wound infections. The Y-set dialysis delivery system is effective in reducing peritonitis rates in CAPD patients caused by organisms derived from the commensal skin flora, principally coagulase-negative staphylococci, but does not reduce peritonitis caused by other organisms.

Infective complications associated with the use of the Quinton 'Permcath' for long-term central vascular access in haemodialysis.

The major complication of central venous catheterization for immediate access for haemodialysis is infection. The Quinton Permcath is a tunnelled, double lumen, flexible silastic catheter with a Dacron cuff, and is claimed to be associated with a low rate of infection. In a two-year study we have monitored all complications including catheter-associated infection related to this device in haemodialysis patients while following a simple aseptic programme for the care of the catheter exit wound. Thirty four Permcaths were inserted in 30 patients for a mean duration of 6.2 months (SD +/- 5.7; range 2 days to 23 months). Catheter use amounted to a total of 197 months. Of twenty-seven catheter wound infections, 6 (22%) were caused by Staphylococcus aureus, and 15 (56%) by coagulase-negative staphylococci or corynebacteria. These occurred in 19 patients, giving an exit site infection rate of one episode per 7.4 catheter months. Catheter-associated septicaemia occurred in three patients (two S. aureus, one S. epidermidis), at a rate of one episode per 66 months. It was possible to correlate three episodes of infection with breakdown in aseptic care. This study confirms the low rate of infection associated with the use of the Permcath, and we conclude that the design of the device and aseptic care of the catheter and its wound contribute to this.

Contribution of toxic nephropathies to end-stage renal failure in Europe: a report from the EDTA-ERA registry.

In countries which reported to the registry of the European Dialysis and Transplant Association (EDTA)-European Renal Association, 2.4% of 147 092 treated patients were recognized as having analgesic nephropathy (AN) as the cause of end-stage renal failure (ESRF) on 31 December 1986. A small number of patients had other specific drug nephropathies, but these do not yet make an important contribution to ESRF treatment programmes. It is possible that more patients have ESRF due to AN, and evidence from studies of age distribution, the demography of urothelial malignancies, a special study of diagnostic criteria, data on sales of analgesics, and a study of regional areas of high incidence lend some support to that view. Changes in prescription and self-medication practices over the last 20 years have almost eradicated analgesic nephropathy from the U.K. and Sweden, two countries in which there was previously a high frequency of ESRF due to AN. In other countries where action has been taken more recently, cases are still reported fairly frequently, and this seems likely to continue for several years to come.

Remission of nephrotic syndrome in amyloidosis associated with a hypernephroma.

Nephrotic syndrome due to renal amyloidosis in association with hypernephroma underwent gradual but complete remission with loss of proteinuria after unilateral nephrectomy. Remission persisted for over five years despite the development of intracranial metastatic disease and the administration of dexamethasone, but relapse occurred 6 months before eventual death. This case history appears to be unique amongst the descriptions of tumor-associated amyloidosis.

The effect of hyperacetatemia on cardiac output during regular hemodialysis.

We used impedance cardiography to monitor changes in cardiac output in 22 adult patients with terminal renal failure during hemodialysis against a dialyzate containing acetate. In 7 patients arterial acetate levels rose progressively during dialysis while in the remainder they remained low and steady. Patients who developed hyperacetatemia were able to maintain an elevated cardiac output during dialysis in contrast to the patients with stable acetate levels in whom cardiac output fell. These results strengthen our previous conclusion that acetate as used in conventional regular hemodialysis does not have a cardiodepressant action. The reported benefits of bicarbonate dialysis therefore involve other factors.

Incidence and significance of rising blood acetate levels during hemodialysis.

Recent work suggests that rising arterial acetate levels occur in some patients undergoing hemodialysis and that they may be responsible for some dialysis problems, particularly cardiovascular instability. Blood acetate levels and acetate flux rates have been determined in 20 adult and 4 pediatric patients during hemodialysis as well as in 4 patients with combined renal and hepatic failure. Rising acetate levels occurred in 25% of the adult patients, although they were stable in the children and the patients with renal and hepatic failure. The occurrence of hypotension during dialysis was unrelated to a high blood acetate level.

Reversible renal failure in malignant hypertension.

Acute renal failure requiring dialysis to sustain life may be due to malignant hypertension. If the blood pressure is controlled during a period of dialysis, then it is possible that the renal lesions may heal, with some recovery of renal function. This report describes eight patients with acute renal failure due to malignant hypertension who required temporary dialysis. In all eight cases adequate control of blood pressure was achieved and all recovered renal function such that dialysis could be discontinued. The longest period of follow-up was five years, and one patient achieved a creatinine clearance of 23 ml/min. Renal histology, available in five cases, showed changes of malignant hypertension only, with no evidence of other renal lesions. A review of the literature is presented and the potentially reversible nature of acute oliguric renal failure due to malignant hypertension is emphasized.

Dialysis treatment and psoriasis in Europe.

One hundred and fifty out of 944 European dialysis centers reported experience with patients suffering from psoriasis. Ninety-three centers returned special questionnaires on 97 patients with end stage renal failure (ESRF patients) and on 49 patients dialyzed for psoriasis but who had normal renal function (NRF patients). Improvement of skin disease was reported in 17 out of 27 NRF patients according to both "objective criteria" and the patients' personal opinions. However, most of these patients had been on dialysis for less than one year (9.9 +/- 11.1 months) which is too short to allow for the spontaneous recurrence of psoriasis. In contrast, 60% of ESRF patients had been on dialysis for 45 +/- 3.1 months. Skin disease definitely improved in 20% of these patients after commencement of dialysis. This proportion is greater than the expected spontaneous long-term remission of psoriasis.

Active intervention dramatically reduces CAPD-associated infection.

In 1987 a preventive programme was initiated to address the problem of high hospital and community-acquired CAPD infection. It concentrated on reducing Staphylococcus aureus carriage, improving aseptic operative technique, intensive training for nursing staff and patients in stringent aseptic care of the exit site, and avoidance of contact of the exit site with unsterile water. This programme was associated with an overall 10-fold reduction in exit site infection, a 2-fold reduction in peritonitis, and a 4.5-fold reduction in catheter loss from infection. These reductions have been sustained. Preventing infection in CAPD patients requires persistence and commitment but improves the patient's quality of life and reduces the cost of treatment.

High cost dialysis and transplantation--dilemmas for nephrologists and nations.

The linked successes of dialysis and transplantation pose dilemmas for nephrologists struggling to meet the clinical need and for health care planners wondering where to find the resources required. The low rate of acceptance of new patients in the UK compares unfavourably with the service given in other countries. Successful rationing is achieved by a sparse distribution of centres and of specialists and operates through a low rate of referral of patients to nephrologists. Political initiative is beginning to emerge to redress the underprovision of facilities by setting realistic targets before regional health authorities.