Potential therapeutic effects of peroxisome proliferator-activated receptors on corneal diseases.

The cornea is an avascular tissue in the eye that has multiple functions in the eye to maintain clear vision which can significantly impair one's vision when subjected to damage. Peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptor proteins comprising three different peroxisome proliferator-activated receptor (PPAR) isoforms, namely, PPAR alpha (α), PPAR gamma (γ), and PPAR delta (δ), have emerged as potential therapeutic targets for treating corneal diseases. In this review, we summarised the current literature on the therapeutic effects of PPAR agents on corneal diseases. We discussed the role of PPARs in the modulation of corneal wound healing, suppression of corneal inflammation, neovascularisation, fibrosis, stimulation of corneal nerve regeneration, and amelioration of dry eye by inhibiting oxidative stress within the cornea. We also discussed the underlying mechanisms of these therapeutic effects. Future clinical trials are warranted to further attest to the clinical therapeutic efficacy.

Introducing WASHOUT: A Large-scale Observational Study of Inpatient Haematuria.

WASHOUT is an international, multicentre, prospective observational study aiming to describe the management of unscheduled haematuria admissions. Preregistration can be done using the following link: https://redcap.link/WASHOUT.

Spontaneous haemorrhagic cholecystitis secondary to the use of novel anticoagulants (rivaroxaban).

Haemorrhagic cholecystitis is a rare complication of acute cholecystitis. It carries a high risk of morbidity and mortality. Risk factors for haemorrhagic cholecystitis include cholelithiasis, trauma, malignancy and the use of anticoagulants. There have only been a few reported cases of haemorrhagic cholecystitis secondary to the use of novel oral anticoagulants (NOACs). The demographic transition of an ageing population will potentially increase the utilisation of NOACs. Therefore, the incidence of haemorrhagic cholecystitis secondary to NOACs will likely increase. Awareness and prompt diagnosis is paramount to avoid morbidity and mortality associated with haemorrhagic cholecystitis.

Management of infected arteriovenous grafts for haemodialysis: Outcomes and strategies using a novel objective scoring system.

BACKGROUND: In haemodialysis patients with exhausted autogenous options, prosthetic arteriovenous grafts (AVGs) are frequently utilised as tertiary vascular access. However, the prosthetic nature of AVGs precipitates an increased risk of infection which may translate to excess morbidity and life-threatening complications. The current evidence remains divided on the optimal treatment strategy for arteriovenous graft infections (AVGi) with arguments for conservative management by antibiotics, salvaging with graft revision or total/subtotal excision. To address this gap, we assessed the outcomes of AVGi patients treated in our institution, developing an AVGi severity classification model and a proposed treatment algorithm to guide AVGi management. METHODS: We conducted a single centre retrospective review of outcomes of patients with AVGi managed either by sole antibiotics therapy, graft revision or surgical excision between June 2016 and May 2021. Outcomes of AVGi patients across differing treatment groups were compared, including 1-year mortality, 6-month and 1-year functional vascular access. We also analysed the outcomes of tunnelled haemodialysis lines (THL), which were used as a temporary vascular access in several AVGi patients in our study. RESULTS: A total of 34 AVGi patients were managed within that time frame and included in the study (5 conservatively management by antibiotics, 5 graft revisions and 24 surgical excision) with a mean age of 60.4 ± 14.4 years (67.6% males). Overall 1-year mortality was 14.7%. A 6-month functional vascular access status across the three groups stood at 60%, 60% and 10% while 1-year functional vascular access status was 60%, 75% and 42% respectively. CONCLUSIONS: When clinically appropriate, conservative management by antibiotics or salvage/graft revision can present as prudent AVGi treatment options. The adoption of our proposed severity classification system and treatment algorithm provides a more thorough objective assessment of the infection and helps guide the clinical decision-making process.

Serum anion gap revisited: a verified reference interval for contemporary use.

BACKGROUND: The anion gap (AG) is often used to evaluate acid-base disorders. The reference interval for normal AG is used to differentiate between raised (gap) or normal AG (non-gap) acidosis. Historically accepted AG values may not be valid with the evolution of modern analytical techniques and the reference interval requires revalidation. AIMS: To determine the reference interval for AG based on current laboratory techniques. METHODS: During a health-screening exercise, 284 participants with no major illnesses volunteered surplus blood for analysis. The samples were tested in an internationally accredited clinical laboratory. AG was calculated by [Na+ ] - [Cl- ] - [HCO3 - ] and AGK by [Na+ ] + [K+ ] - [Cl- ] - [HCO3 - ]. The reference interval was determined at 2.5th-97.5th percentiles. Analysis was further undertaken for a subcohort of 156 individuals with no suboptimal health indicators. RESULTS: Median age was 35 years, body mass index 23.4 kg/m2 and the glomerular filtration rate was 106 mL/min/1.73 m2 . Median AG was 13 mmol/L and the reference interval for normal AG is 10-18 mmol/L with a 99% level of confidence. Statistically significant differences in AG were detected for sex, race, obesity and serum albumin, but the difference was 1 mmol/L between subgroups. The reference interval was the same for the sub-cohort of 156 individuals. Median AGK was 17.7 mmol/L and reference interval was 14.6-22.5 mmol/L. CONCLUSIONS: The AG reference interval of 10-18 mmol/L is valid for laboratories with similar reference intervals for electrolytes. Lower values expected with current laboratory techniques were not observed. The median AG of 13 mmol/L may be used to differentiate gap acidosis, non-gap acidosis or mixed acid-base disorders.

Weight-Based Assessment of Fluid Overload in Patients with Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) with fluid overload is associated with poor outcomes. While percentage fluid overload (PFO) using intake/output charts (PFOi/o) has been validated as a marker of overload, accurate PFOi/o measurements may not be possible in a general ward. We propose an alternative weight-based PFO calculation: PFOw = [(maximum weight - baseline weight) ÷ baseline weight] × 100%. METHODS: This is a prospective, observational pilot study on general ward inpatients with AKI who were referred for nephrology consult. PFOw was compared with PFOi/o, and both were evaluated for associations with dialysis requirement, AKI stage 2 or 3, and 90-day mortality. RESULTS: Fifty-eight patients with a median age of 67.5 years (interquartile range 18.0) were recruited. Of which, 33 (56.9%) were males and 41 (70.7%) had preexisting CKD 3 or higher. We found no correlation between PFOi/o and PFOw (R2 = 0.015, p = 0.531). A higher PFOw was observed in AKI stage 2 or 3 (p = 0.005) and in patients requiring dialysis (p = 0.001). On multivariate analysis, each percentage increase in PFOw was associated with increased odds of AKI stage 2 or 3 (odds ratio 1.37 [95% CI 1.05-1.78], p = 0.020) and dialysis need (odds ratio 1.69 [95% CI 1.20-2.39], p = 0.003). Twenty-nine patients had complete quantitative data to calculate PFOi/o. Multivariate analysis of these 29 patients showed that PFOw correlated with AKI stage 2 or 3 and dialysis requirement, while PFOi/o had no correlation with these events. The area under the curve receiver operating characteristics of PFOw was 0.706 for AKI stage 2 or 3 and 0.819 for AKI requiring dialysis. The optimal PFOw cutoff was determined at ≥1%. Three deaths occurred within 90 days, and all had PFOw ≥ 1%, although the log-rank test did not achieve statistical significance (p = 0.050). CONCLUSION: The proposed PFOw is a potential prognostic indicator for general ward patients with AKI. PFOw ≥ 1% is associated with poor renal outcomes.

Postcolonoscopy splenic rupture: the under-reporting of an unpropitious phenomena?

Splenic rupture secondary to colonoscopy is a rare but potentially fatal complication. Given the disparity between the small number of case reports with the incidence reported by some investigators, we contend that the former is not representative of the true extent of this sequela. We present a case report of postcolonoscopy splenic rupture, where the patient had a bizarre initial presentation of chest pain and collapse; and only developed haemodynamic instability and abdominal pain on day 2 postprocedure. Diagnosis was made with a CT scan, and resolution of symptoms was achieved with a splenectomy.

The curious case of biliary emesis and bowel obstruction from Bouveret syndrome.

Bouveret syndrome is a rare complication of biliary lithiasis. This sequela is caused by the passage of the gallstone via a bilioenteric fistula, resulting in an impacted gallstone in the duodenum or stomach. The common presentation of non-specific symptoms contributes to the diagnostic uncertainty and delay, which is strongly associated with adverse outcomes. We report an uncomplicated stone extraction via open gastrotomy in an elderly man afflicted with bowel obstruction and biliary vomit secondary to Bouveret syndrome.

Mixed-expired and end-tidal CO2 distinguish between ventilation and perfusion defects during exercise testing in patients with lung and heart diseases.

BACKGROUND: Mismatching of ventilation to perfusion is found in patients with COPD, left ventricular failure (LVF), and pulmonary vascular diseases. Such mismatching may be due to ventilation or perfusion defects or both. Our primary hypothesis was that pressures of mixed-expired CO2 pressure (Peco(2)), end-tidal Pco(2) pressure (Petco(2)), and their ratios would differ between groups during exercise testing, depending on whether the ventilation/perfusion (V/Q) abnormality was dominantly caused by airways or perfusion defects. METHODS: We administered incremental cycle ergometry tests to 25 normal subjects and three groups of 25 patients, each group with uncomplicated COPD, LVF, or primary pulmonary arterial hypertension (PAH). We compared Peco(2), Petco(2), and their ratios at rest, unloaded pedaling, anaerobic threshold, and peak exercise. RESULTS: Although each patient group had mean peak O(2) uptake of approximately 50% of predicted normal, the levels and patterns of change for each group for Peco(2), Petco(2), and their ratios were surprisingly distinctive. As hypothesized, the COPD group always had markedly lower Peco(2)/Petco(2) ratios than all other groups (p < 0.001). In addition, patients with LVF had slightly lower Peco(2)/Petco(2) ratios at heavy exercise than normal subjects (p < 0.05). At all times, except for COPD group Petco(2) at peak exercise, each group had significantly lower Petco(2) and Peco(2) than normal subjects (p < 0.001). In patients with PAH, the Petco(2) decline with exercise was distinctive. CONCLUSIONS: The levels and changes in Peco(2), Petco(2), and their ratios during cardiopulmonary exercise testing are distinctive and explained by the differing pathophysiologies of V/Q mismatching in these disorders.