Effectiveness and future implications of COVID-19-related risk stratification for managing retinopathy of prematurity: The Indian twin cities retinopathy of prematurity study report number 10

Purpose:To evaluate the effectiveness and future implications of COVID-related risk stratification for managing retinopathy of prematurity (ROP).Methods:A prospective study was conducted at a tertiary eye care center from the beginning of the lockdown in India from 23 March 2020 till the end of the first phase of lockdown on 29 May 2020. We evaluated 200 prematurely born infants (< 34 weeks of gestational age) using the new safety guideline protocols for low-risk babies developed in conjunction with the Indian ROP Society for care during the COVID-19 pandemic. Low risk included babies born at more than 30 weeks of gestational age, post menstrual age 34 weeks or above at presentation, more than 1000 grams of birth weight, and stable systemically with good weight gain.Results:New guidelines were implemented in 106 (53%) infants who were low risk while 94 (47%) infants with high risk were followed up as per the old guidelines. Out of the 106 infants (212 eyes) managed by the new guidelines, good outcome (group 1) was seen in 102 (96.2%) infants. Twenty-seven of the 102 infants had some form of ROP and 5 of these infants needed treatment. None of the low-risk babies with no detachment at presentation managed by new guidelines required surgery later (group 2). Two (1.9%) infants came with retinal detachment at presentation and underwent successful surgery (group 3) and two infants (1.9%) were lost to follow up.Conclusion:New risk stratification during the COVID-19 pandemic was an efficient and safe strategy in managing low-risk ROP babies.     

Cross-sectional observational analysis of the genetic referral practices across pediatric ophthalmology outpatient departments in an urban setting

Purpose:To analyze the genetic referral practices of pediatric ophthalmologists in an urban setting.Methods: (1) The first limb of the study: cross-sectional, observational study among children visiting the outpatient department of pediatric ophthalmology across five centers in Mumbai. All pediatric patients were screened separately by pediatric ophthalmologists and a clinical geneticist for their ophthalmic and systemic complaints. Children were marked for referral to genetics (RTG) by both the specialists based on identification of distinctive features (red flag) and were requested to meet a local geneticist. (2a) Twenty-three months later, patients who had been marked for RTG were contacted telephonically to follow-up if they had met the geneticist. (2b) Additionally, the last 20 proformas from each center were checked retrospectively to note the RTG marked by the ophthalmologist alone.Results: (1) In the first aspect of the study, 126 patients (male: female = 1.2:1) were included. Forty-nine (38.3%) patients were referred for genetic evaluation, of which three (6.1%), 31 (63.26%), and 15 (30.6%) cases were referred by the ophthalmologist alone, geneticist alone, and by both the specialists, respectively. Glaucoma (100%), nystagmus (86%), and leukocoria (83%) were the most prominent ocular diagnoses in cases referred for genetic evaluation. Facial dysmorphism (55.1%) and neurodevelopmental delays (51%) were among the most common systemic red flags found in patients referred to genetics. (2a) Twenty-three months later, on contacting the 49 patients marked for RTG, only one family had met the geneticist. (2b) Retrospective evaluation of 100 proformas: only three patients were marked for RTG by ophthalmologist alone.Conclusion: This study found that the genetic referrals by pediatric ophthalmologist were far lesser than those by geneticist. The study highlights an area of knowledge gap among pediatric ophthalmologists, prompting a need for heightened awareness in this area.     

Autosomal recessive progeroid syndrome due to homozygosity for a TOMM7 variant

Multiple genetic loci have been reported for progeroid syndromes. However, the molecular defects in some extremely rare forms of progeria have yet to be elucidated. Here, we report a 21-year-old man of Chinese ancestry who has an autosomal recessive form of progeria, characterized by severe dwarfism, mandibular hypoplasia, hyperopia, and partial lipodystrophy. Analyses of exome sequencing data from the entire family revealed only 1 rare homozygous missense variant (c.86C>T; p.Pro29Leu) in TOMM7 in the proband, while the parents and 2 unaffected siblings were heterozygous for the variant. TOMM7, a nuclear gene, encodes a translocase in the outer mitochondrial membrane. The TOMM complex makes up the outer membrane pore, which is responsible for importing many preproteins into the mitochondria. A proteomic comparison of mitochondria from control and proband-derived cultured fibroblasts revealed an increase in abundance of several proteins involved in oxidative phosphorylation, as well as a reduction in abundance of proteins involved in phospholipid metabolism. We also observed elevated basal and maximal oxygen consumption rates in the fibroblasts from the proband as compared with control fibroblasts. We concluded that altered mitochondrial protein import due to biallelic loss-of-function TOMM7 can cause severe growth retardation and progeroid features.     

Mitigating ipatasertib‐induced glucose increase through dose and meal timing modifications

Ipatasertib, an AKT inhibitor, in combination with prednisone and abiraterone, is under evaluation for the treatment of metastatic castration‐resistant prostate cancer (mCRPC). Hyperglycemia is an on‐target effect of ipatasertib. An open‐label, single‐arm, single‐sequence, signal‐seeking study (n = 25 mCRPC patients) was conducted to evaluate the glucose changes across four different treatment periods: ipatasertib alone, ipatasertib‐prednisone combination, ipatasertib‐prednisone‐abiraterone combination (morning dose), and ipatasertib‐prednisone‐abiraterone combination (evening dose). Continuous glucose monitoring (CGM) was used in this study to compare the dynamic glucose changes across the different treatment periods. Four key parameters: average glucose, peak glucose and % time in range (70–180 and >180 mg/dl) were evaluated for this comparison. Ipatasertib‐prednisone‐abiraterone combination when administered in the morning after an overnight fast significantly increased average glucose, peak glucose and % time in range >180 mg/dl compared to ipatasertib monotherapy. Ipatasertib, when co‐administered with abiraterone, increased ipatasertib and M1 (G‐037720) metabolite exposures by approximately 1.5‐ and 2.2‐fold, respectively. Exposure–response analysis results show that increased exposures of ipatasertib in combination with abiraterone are associated with increased glucose levels. When ipatasertib‐prednisone‐abiraterone combination was administered as an evening dose compared to a morning dose, lowered peak glucose and improved % time in range was observed. The results from this study suggest that dosing ipatasertib after an evening meal followed by overnight fasting can be an effective strategy for managing increased glucose levels.

Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Clinical development of PI3K/AKT inhibitors has been particularly challenging given their toxicity profiles, hyperglycemia being one of the on‐target effects. WHAT QUESTION DID THIS STUDY ADDRESS? This study evaluated the real‐time changes in glucose levels post‐ipatasertib administration using a continuous glucose‐monitoring wearable device. This study further evaluated morning versus evening dosing of ipatasertib in combination with prednisone and abiraterone. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? The results from this study suggest that offering ipatasertib, an AKT inhibitor, as an evening dose after evening meal may offer a better option at de‐risking hyperglycemia incidences. The study also provides preliminary information that a low dose of steroids does not lead to a marked increase in glucose levels when administered in combination with ipatasertib. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This is a novel clinical pharmacology study, wherein a safety finding was investigated using an innovative continuous glucose‐monitoring device and results were discussed in the context of pharmacokinetic results and drug–drug interactions. The conclusions and the methodology are supportive of further investigations to mitigate hyperglycemia risk for oncology drugs that inhibit the AKT/PI3K pathway, as this class of drugs are known to cause an increase in blood glucose.     

Coronary artery bypass grafting in active or recent COVID-19 infection: a systematic review

IntroductionEven though there have been few studies on coronary artery bypass grafting (CABG), data on patients with coronavirus disease-2019 (COVID-19) infection show that cardiac surgery has poor outcomes in this subset. From the available studies in the literature, we conducted a systematic review with the aim of determining the outcome of COVID-19 patients who underwent CABG.MethodsBetween December 2019 and October 2022, searches were conducted in PubMed, the Directory of Open Access Journals, and Google Scholar to find studies reporting results of COVID-19 patients undergoing CABG. We extracted data on the clinical profile and outcomes of the patients from the eligible studies. The quality of the studies was assessed using a standardised tool.ResultsThe total sample size across the 12 included studies was 99 patients who underwent CABG in active disease or within 30 days of COVID-19 infection. The median and interquartile range (IQR) for the length of time spent on a mechanical ventilator, stay in the intensive care unit (ICU), and the total hospital stay were 0.9 (0.47–2), 4.5 (2.5–8), and 12.5 (8.5–22.5) days respectively. Seventy-six patients developed postoperative complications, and there were eleven deaths.ConclusionThe findings of the present study indicate that mortality risk goes down when the time between COVID-19 diagnosis and surgery increases. When compared to data from other high-risk urgent or emergent CABG patients around the world who were not infected with COVID-19, patients who underwent CABG in the COVID-19 subgroup had similar postoperative outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12055-023-01495-7.     

Baveno-VII criteria to predict decompensation and initiate non-selective beta-blocker in compensated advanced chronic liver disease patients

Background/AimsThe utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients.MethodscACLD patients were stratified into three categories (CSPH excluded, grey zone, and CSPH). The risks of decompensation across different CSPH categories were estimated using competing risk regression for clustered data, with death and hepatocellular carcinoma as competing events. The performance of “treating definite CSPH” strategy to prevent decompensation using non-selective beta-blocker (NSBB) was compared against other strategies in decision curve analysis.ResultsOne thousand one hundred fifty-nine cACLD patients (36.8% had CSPH) were included; 7.2% experienced decompensation over a median follow-up of 40 months. Non-invasive assessment of CSPH predicts a 5-fold higher risk of liver decompensation in cACLD patients (subdistribution hazard ratio, 5.5; 95% confidence interval, 4.0–7.4). “Probable CSPH” is suboptimal to predict decompensation risk in cACLD patients. CSPH exclusion criteria reliably exclude cACLD patients at risk of decompensation, regardless of etiology. Among the grey zone, the decompensation risk was negligible among viral-related cACLD, but was substantially higher among the non-viral cACLD group. Decision curve analysis showed that “treating definite CSPH” strategy is superior to “treating all varices” or “treating probable CSPH” strategy to prevent decompensation using NSBB.ConclusionsNon-invasive assessment of CSPH may stratify decompensation risk and the need for NSBB in cACLD patients.     

Role of 0.01% atropine in high myopic children of Moradabad,India (RAMCOM Study)

Purpose:Low-concentration atropine is an emerging therapy for myopia progression, but its efficacy remains uncertain among high myopic children. This study aimed to evaluate the efficacy and safety of low-concentration atropine eye drop (0.01%) in high myopic children.Methods:A non-randomized, parallel-group, longitudinal interventional cohort study. Myopic children were divided into two groups: (1) the intervention arm of children who received one drop of topical 0.01% atropine once a day at bedtime and (2) the control arm, in which enrolled children who were on observation only. Repeated measurements of spherical equivalent refractive errors (SERs) were performed at baseline and 1 and 2 years after treatment.Results:A total of 37 eyes were enrolled in the intervention arm (allocated to 0.01% atropine at year 1 follow-up) and 23 eyes in the control arm. After 1 year of 0.01% atropine therapy, the myopia progression was 0.15 ± 0.9 D in the intervention group versus 1.1 ± 1 D in the control group (P = 0.001). Similarly, after 2 years of treatment, the myopia progression was 0.3 ± 1.1 D in the intervention group versus 1.4 ± 1.1 D in the control group (P ≤ 0.001).Conclusion:Compared to no treatment, 0.01% atropine treatment had shown better effect on myopia progression in high myopic children.