Development of a sustained-release voriconazole-containing thermogel for subconjunctival injection in horses

PURPOSE. To determine in vitro release profiles, transcorneal permeation, and ocular injection characteristics of a voriconazole-containing thermogel suitable for injection into the subconjunctival space (SCS). METHODS. In vitro release rate of voriconazole (0.3% and 1.5%) from poly (DL-lactide-coglycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) thermogel was determined for 28 days. A Franz cell diffusion chamber was used to evaluate equine transcorneal and transscleral permeation of voriconazole (1.5% topical solution, 0.3% and 1.5% voriconazole-thermogel) for 24 hours. Antifungal activity of voriconazole released from the 1.5% voriconazole-thermogel was determined via the agar disk diffusion method. Ex vivo equine eyes were injected with liquid voriconazole-thermogel (4°C). Distension of the SCS was assessed ultrasonographically and macroscopically. SCS voriconazole-thermogel injections were performed in a horse 1 week and 2 hours before euthanasia and histopathologic analysis of ocular tissues performed. RESULTS. Voriconazole was released from the PLGA-PEG-PLGA thermogel for more than 21 days in all groups. Release followed first-order kinetics. Voriconazole diffused through the cornea and sclera in all groups. Permeation was greater through the sclerae than corneas. Voriconazole released from the 1.5% voriconazole-thermogel showed antifungal activity in vitro. Voriconazole-thermogel was easily able to be injected into the dorsal SCS where it formed a discrete gel deposit. Voriconazole-thermogel was easily injected in vivo and did not induce any adverse reactions. CONCLUSIONS. Voriconazole-containing thermogels have potential application in treatment of keratomycosis. Further research is required to evaluate their performance in vivo

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Update on fungal respiratory disease in horses

Fungal respiratory disease is a rare occurrence in horses. Fungal organisms are ubiquitous in the equine environment; however, there is a geographic predisposition for disease development, with fungal respiratory infections seen more commonly by practitioners working in tropical or subtropical environments. Diagnosis and treatment of fungal respiratory infections pose a challenge for the equine practitioner, and the prognosis for complete resolution of infection is often guarded; however, new antifungal medications are likely to improve treatment success. This article summarizes the available literature regarding the cause, diagnosis, and treatment of equine fungal respiratory disease

Peritoneal fluid analysis in equine post‐partum emergencies admitted to a referral hospital: a retrospective study of 110 cases

Background: Peritoneal fluid analysis has both diagnostic and prognostic value in colic but is little reported in the post-partum mare. Multiple conditions may present similarly in this period, and peritoneal fluid findings may aid a prompt diagnosis. Objectives: To describe the peritoneal fluid findings and their association with diagnosis in mares presenting to a single referral hospital for treatment of post-partum emergencies. Study design: A retrospective clinical study. Methods: Clinical records of 110 Thoroughbred mares were reviewed. Details of peritoneal fluid analysis from samples obtained at admission were recorded, in addition to history, physical examination, presenting clinicopathological data. Cases were classified by their primary diagnosis into groups of gastrointestinal tract (GIT), urogenital trauma (UGT) and post parturient haemorrhage (PPH). Univariable analysis was performed to compare findings between groups, using one-way ANOVA and post hoc Tukey/Kruskal-Wallis, as appropriate. A multinomial logistic regression was performed for variables significant in the univariable analysis. Results: When separated into their diagnostic categories, 33/110 (30%) mares were classified as GIT, 55/110 (50%) UGT and 22/110 (20%) PPH. Peritoneal fluid packed cell volume (PCV), nucleated cell count (WBCC) and cytological findings were significantly different between diagnostic categories. The likelihood of diagnosis of PPH increased with an increase in peritoneal fluid PCV, the absence of degenerate neutrophils on peritoneal fluid cytology and a decrease in the peritoneal fluid WBCC. Overall survival to discharge was 55%. Main limitations: The study is referral hospital-based and retrospective in nature. Missing data reduced the power of analysis for several variables. Conclusions: Peritoneal fluid analysis may guide diagnosis in post-partum emergencies, but no one factor is uniformly diagnostic. Mares with PPH presented with a non-septic peritonitis with higher peritoneal PCV