Peripheral nonulcerative keratitis as a presenting sign of microscopic polyangiitis.

PURPOSE: To report a 16-year-old woman who had peripheral keratitis as a presenting sign of microscopic polyangiitis (MPA), which rapidly progressed to acute renal failure. METHOD: Case report. RESULTS: The patient's vasculitis was diagnosed by renal biopsy, which was evaluated with histologic, immunofluorescence, and electron microscopy. The diagnosis was confirmed by laboratory study, which showed a positive antimyeloperoxidase antibody. CONCLUSION: MPA may rarely present with ocular findings and should be considered in the differential diagnosis when a patient has peripheral keratitis.     

Studies on patients establish Crohn's disease as a manifestation of impaired innate immunity

The fruitless search for the cause of Crohn's disease has been conducted for more than a century. Various theories, including autoimmunity, mycobacterial infection and aberrant response to food and other ingested materials, have been abandoned for lack of robust proof. This review will provide the evidence, obtained from patients with this condition, that the common predisposition to Crohn's is a failure of the acute inflammatory response to tissue damage. This acute inflammation normally attracts large numbers of neutrophil leucocytes which engulf and clear bacteria and autologous debris from the inflamed site. The underlying predisposition in Crohn's disease is unmasked by damage to the bowel mucosa, predominantly through infection, which allows faecal bowel contents access to the vulnerable tissues within. Consequent upon failure of the clearance of these infectious and antigenic intestinal contents, it becomes contained, leading to a chronic granulomatous inflammation, producing cytokine release, local tissue damage and systemic symptoms. Multiple molecular pathologies extending across the whole spectrum of the acute inflammatory and innate immune response lead to the common predisposition in which defective monocyte and macrophage function plays a central role. Family linkage and exome sequencing together with GWAS have identified some of the molecules involved, including receptors, molecules involved in vesicle trafficking, and effector cells. Current therapy is immunosuppressant, which controls the symptoms but accentuates the underlying problem, which can only logically be tackled by correcting the primary lesion/s by gene therapy or genome editing, or through the development of drugs that stimulate innate immunity.     

Closed–suction compared with Penrose drainage after free flap reconstruction in the head and neck

Microsurgical free flaps are common in head and neck reconstruction, and their techniques and outcomes have continuously improved during the past decades. However, there are variations in practice among surgeons between the use of closed-suction drainage systems and Penrose drains. The proponents of Penrose drains propose that the negative pressure generated by the closed-suction drainage system may harm the microvascular anastomosis. We know of no previous studies that have compared the two drains for microvascular free flap reconstruction, so our aim was to compare them in a single-centre, retrospective review of all patients who had microvascular free flap reconstruction of the head and neck region in our department between 1 November 2010 and 1 September 2017. During this period 84 patients had 87 free flap reconstructions in the head and neck, 43 of which had Penrose, and 44 closed-suction, drainage. We compared the number of complications between the groups including haematomas, seromas, wound infections, anastomostic thrombosis, anastomotic revision, and need for re-exploration. There were no significant differences between the groups, despite a trend toward fewer negative explorations in the closed-suction group. There were no differences in complications between suction and passive drainage systems after microvascular free flaps, which suggests that closed suction drainage could be safely used after free flap reconstruction in the head and neck.     

Induction of diuresis and natriuresis for renal protection: Update on the RenalGuard system™

“Forced diuresis” is a technique that involves inducing a high urine flow rate. In most circumstances, diuretics and intravenous fluid replacement are necessary. Forced diuresis is recommended in a number of circumstances to improve or protect kidney function. The technique can be difficult to manage in clinical practice, often leading to net volume loss or excess. In this article, we review the data on the use of the RenalGuard system?. RenalGuard® accurately matches urine output and intravenous fluid input in real time and prevents any net volume changes. To date, RenalGuard® has been studied for prevention of acute kidney injury in patients undergoing cardiac angiography, percutaneous coronary intervention, and transcatheter aortic valve implantation. The possible mechanisms involved in producing a benefit are discussed.     

Fixing the game: are between-silo differences in funding arrangements handicapping some interventions and giving others a head-start?

Given resource scarcity, not all potentially beneficial health services can be funded. Choices are made, if not explicitly, implicitly as some health services are funded and others are not. But what are the primary influences on those choices? We sought to test whether funding decisions are linked to cost effectiveness and to quantify the influence of funding arrangements and community values arguments. We tested this via empirical analysis of 245 Australian health-care interventions for which cost-effectiveness estimates had been published. The likelihood of government funding was modelled as a function of cost effectiveness, patient/target group characteristics, intervention characteristics and publication characteristics, using multiple regression analysis. We found that higher cost effectiveness ratios were a significant predictor of funding rejection, but that cost effectiveness was not related to the level of funding. Intervention characteristics linked to funding and delivery arrangements and community values arguments were significant predictors of funding outcomes. Our analysis supports the hypothesis that funding and delivery arrangements influence both whether an intervention is funded and funding level; even after controlling for community values and cost effectiveness. It suggests that adopting partial priority setting processes without regard to opportunity cost can have the perverse effect of compounding allocative inefficiencies. Copyright © 2009 John Wiley & Sons, Ltd.     

COMBINATION ANTI-PARATUBERCULOSIS THERAPY WITH CLARITHROMYCIN, RIFABUTIN and CLOFAZIMINE IN THE TREATMENT OF CROHN'S DISEASE. A PRELIMINARY REPORT ON THE AUSTRALIAN MULTICENTRE TRIAL

Mycobacterium paratuberculosis has been proposed as the cause of Crohn's disease, although this remains controversial. Observational studies of antibiotics with activity against this organism have led to the establishment of an Australian multicentre placebo-controlled trial of clarithromycin, rifabutin and clofazimine in patients with active Crohn's disease. All subjects receive treatment with a tapering regimen of prednisolone for the initial 16 weeks, combined with either antibiotics or matching placebos. If remission is achieved at the end of this period and prednisolone has been ceased they continue the trial medications for 2 years. The primary outcomes – remission rates at 1, 2 and 3 years – aim to determine whether these antibiotics are of long-term benefit in Crohn's disease. Secondary outcomes include rate of remission at 4 months, safety and quality of life.
As of May 2001, 171 of the required 212 subjects have been enrolled. Eighty-seven of 146 potential subjects have reached 16 weeks in remission (60%). Eighty of these are ongoing (92%). Only five withdrawals from the trial have occurred for adverse events thought probably related to trial medications – four subjects with raised LFTs and one who developed a rash. Other withdrawals have been mainly due to lack of response or worsening of Crohn's disease (37), hypomania from steroids (one patient) and pregnancy (one patient on placebo). There have been 11 withdrawals for protocol violations. An Independent Data Monitoring Committee has analysed progress of the trial and unanimously recommended that it continue.
This study is the largest and longest suitably powered randomised controlled trial of antibiotics undertaken in Crohn's disease. It will determine whether this antibiotic combination alters the natural history of this disorder.
This study is being supported by Pharmacia Australia Pty Limited.