Vision-threatening retinal abnormalities in chronic kidney disease stages 3 to 5

SUMMARY: BACKGROUND AND OBJECTIVES: Retinal abnormalities are common in inherited and acquired renal disease. This study determined the prevalence of retinal abnormalities in chronic kidney disease (CKD) stages 3 to 5. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One hundred fifty patients with CKD stages 3 to 5 and 150 age- and gender-matched hospital patients with CKD stages 1 to 2 underwent bilateral retinal photography. These images were reviewed for incidental abnormalities, microvascular (Wong and Mitchell classification) and diabetic retinopathy (Airlie House criteria), and macular degeneration (Seddon classification). RESULTS: Three (2%) patients with CKD stages 3 to 5 had retinal features characteristic of inherited renal disease (atrophy in Myopathy, Encephalopathy, Lactic Acidosis, Stroke-like episodes [MELAS] syndrome; and 2 with drusen in dense deposit disease). Fifty-nine (39%) patients had moderate-severe microvascular retinopathy (hemorrhages, exudates, etc.) compared with 19 (13%) with CKD stages 1 to 2. Forty-one (28%) had moderate-severe diabetic retinopathy (microaneurysms, exudates, etc.) compared with 16 (11%) with CKD stages 1 to 2. Ten (7%) had severe macular degeneration (geographic atrophy, hemorrhage, exudates, membranes) compared with one (1%) with CKD stages 1 to 2. Renal failure was an independent risk factor for microvascular retinopathy, diabetic retinopathy, and macular degeneration. Eleven (7.3%) patients with renal failure and one (0.7%) with CKD stages 1 to 2 had previously unrecognized vision-threatening retinal abnormalities that required immediate ophthalmologic attention. CONCLUSIONS: Retinal abnormalities are common in CKD stages 3 to 5, and are more severe and more likely to threaten vision than in hospital patients with CKD stages 1 to 2

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Unilateral autoimmune inner ear disease in a patient with lung cancer treated with nivolumab

A 69-year-old male presented with early stage non-small cell lung cancer in 2016. The tumor was resected; however, the patient experienced recurrence 2 years later and subsequently received paclitaxel/carboplatin concurrently with radiotherapy. Within weeks of completing this treatment, he developed a symptomatic pancoast tumor secondary to disease progression and commenced second line nivolumab. Following the second dose of nivolumab, he developed acute unilateral right hearing loss. He commenced intravenous methylprednisolone followed by a slow taper of oral prednisolone. With steroids, he noted a gradual improvement in hearing, confirmed by audiology. Restaging imaging post-nivolumab demonstrated a complete metabolic response. Two prior cases have reported bilateral sensorineural hearing loss post-immune checkpoint inhibitor (ICI). We postulate the hearing impairment relates to the development of autoimmune inner ear disease. To our knowledge, this is the only case of a patient experiencing unilateral loss of hearing following an ICI

Is Alpha-B Crystallin an Independent Marker for Prognosis in Lung Cancer?

Background: Alpha B-crystallin (CRYAB) is an oncogene that increases tumour survival by promoting angiogenesis and preventing apoptosis. CRYAB is an independent prognostic marker in epithelial tumours including head and neck squamous cell carcinoma and breast cancer where it is predictive of nodal status and associated with poor outcome. We explored the role of CRYAB in non-small-cell lung cancer (NSCLC). Methods: Immunohistochemical analysis was performed on 50 samples. Following staining with anti-alpha-B crystallin antibody, a blinded pathologist scored samples for nuclear (N) and cytoplasmic (C) staining intensity. Analysis was performed using Cox's proportional hazards model. Results: There were 32 adenocarcinomas and 18 squamous cell carcinomas. The median tumour size was T2, grade 2 moderately differentiated, and 10 patients had nodal spread. Recurrence was seen in 22 patients (46%). Mortality was 48%, with median time to mortality 871 days. N staining was detected in eight samples (16%), and C staining in 20 (40%), with both N and C staining positive in five (10%). Staining for CRYAB predicted neither recurrence (N stain p= 0.78, C stain p= 0.38) nor mortality (N stain p= 0.86, C stain p= 0.66). Conclusion: CRYAB did not predict outcomes in patients treated for NSCLC. Larger studies are required to validate this finding

Management and Outcomes Following Surgery for Gastrointestinal Typhoid: An International, Prospective, Multicentre Cohort Study

Background: Gastrointestinal perforation is the most serious complication of typhoid fever, with a high disease burden in low-income countries. Reliable, prospective, contemporary surgical outcome data are scarce in these settings. This study aimed to investigate surgical outcomes following surgery for intestinal typhoid. Methods: Two multicentre, international prospective cohort studies of consecutive patients undergoing surgery for gastrointestinal typhoid perforation were conducted. Outcomes were measured at 30 days and included mortality, surgical site infection, organ space infection and reintervention rate. Multilevel logistic regression models were used to adjust for clinically plausible explanatory variables. Effect estimates are expressed as odds ratios (ORs) alongside their corresponding 95% confidence intervals. Results: A total of 88 patients across the GlobalSurg 1 and GlobalSurg 2 studies were included, from 11 countries. Children comprised 38.6% (34/88) of included patients. Most patients (87/88) had intestinal perforation. The 30-day mortality rate was 9.1% (8/88), which was higher in children (14.7 vs. 5.6%). Surgical site infection was common, at 67.0% (59/88). Organ site infection was common, with 10.2% of patients affected. An ASA grade of III and above was a strong predictor of 30-day post-operative mortality, at the univariable level and following adjustment for explanatory variables (OR 15.82, 95% CI 1.53–163.57, p = 0.021). Conclusions: With high mortality and complication rates, outcomes from surgery for intestinal typhoid remain poor. Future studies in this area should focus on sustainable interventions which can reduce perioperative morbidity. At a policy level, improving these outcomes will require both surgical and public health system advances

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc