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Sirolimus (mammalian target of rapamycin inhibitor) is a potent immunosuppressive agent, used in patients receiving hematopoietic stem cell transplant (HSCT) for Graft vs Host disease prophylaxis. Compared to calcineurin inhibitors, sirolimus has no neurotoxicity or nephrotoxicity, but sirolimus causes dose-dependent thrombocytopenia, leukopenia, delayed wound healing, hyperlipidemia, and hypertriglyceridemia. Here we report a case of acute pancreatitis and diabetic ketoacidosis in a patient with sickle cell disease post haploidentical family donor HSCT which was managed conservatively without plasmapheresis. Based on our review of the literature, this is the first reported case of developing acute pancreatitis as an adverse effect of sirolimus-induced hypertriglyceridemia leading to diabetic ketoacidosis in a recipient of HSCT., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cancer is one of the leading causes of morbidity and mortality. Current treatments include chemotherapy, radiotherapy, etc., are known to be associated with several side effects. Hence, complementary and alternative medicine is growing in acceptance around the world, particularly Ayurvedic formulations. MAK is one of the most scientifically acclaimed formulations with potential anti-neoplastic and chemoprotective properties., Objective: To study literature available on the anti-neoplastic and chemoprotective effects of MAK., Material and Methods: A systematic literature review was conducted using multiple web-based sources: Google Scholar (185), PubMed (33), DHARA (49), AYUSH research portal (2), EBSCO (66), and CTRI (1) for all studies published before February 2021 using keywords: Maharishi Amrit Kalash, Amrit Kalash, Amrit, MAK-4, MAK-5, MAK-7, and others. A manual search was conducted on the reference list of all included articles to identify additional studies. Studies with cancer and/or chemotoxicity outcomes were selected manually. Evidence from both preclinical and clinical level studies have been included in the current review., Results: Out of total 79 studies on applications of MAK, 13 studies were found to state its anti-neoplastic and chemoprotective effects. The studies showed role of MAK in initiation of neoplastic transformation of cancer cells (1), carcinogenesis inhibition (4), metastases inhibition/reduction (1), cancer growth inhibition (4), induction of morphological and biochemical differentiation of cancer cells (3), and reduction in chemotoxicity (4). In studies with controlled clinical trial design (3), MAK use among patients with cancer showed a significant reduction in anorexia, vomiting, and other side effects associated with chemotherapy. A general improvement in quality-of-life scores (Karnofsky Performance Status) and well-being was also observed among patients using MAK., Conclusion: Evidence from pre-clinical studies show promising results for use of MAK as an anti-cancer and a chemoprotective agent. More clinical studies are needed to assess the impact of MAK use for tumour regression among patients with cancer. Current scoping review provides sufficient evidence on MAK to be considered for further exploration for its anti-cancer/chemoprotective effects in bigger randomized clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs). The main risk factor is elevated intraocular pressure (IOP), but the actual cause of the disease remains unknown. Emerging evidence indicates that metabolic dysfunction plays a central role. The aim of the current study was to determine and compare the effect of universal hypoxia on the metabolomic signature in plasma samples from healthy controls ( n = 10), patients with normal-tension glaucoma (NTG, n = 10), and ocular hypertension (OHT, n = 10). By subjecting humans to universal hypoxia, we aim to mimic a state in which the mitochondria in the body are universally stressed. Participants were exposed to normobaric hypoxia for two hours, followed by a 30 min recovery period in normobaric normoxia. Blood samples were collected at baseline, during hypoxia, and in recovery. Plasma samples were analyzed using a non-targeted metabolomics approach based on liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Multivariate analyses were conducted using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and univariate analysis using the Wilcoxon signed-rank test and false discovery rate (FDR) correction. Unique metabolites involved in fatty acid biosynthesis and ketone body metabolism were upregulated, while metabolites of the kynurenine pathway were downregulated in OHT patients exposed to universal hypoxia. Differential affection of metabolic pathways may explain why patients with OHT initially do not suffer or are more resilient from optic nerve degeneration. The metabolomes of NTG and OHT patients are regulated differently from control subjects and show dysregulation of metabolites important for energy production. These dysregulated processes may potentially contribute to the elevation of IOP and, ultimately, cell death of the RGCs.

Background: Acute liver failure in the pediatric population is often accompanied by deranged metabolism, severe encephalopathy and coagulopathy. A liver transplant is the most viable option for the management of such patients. Therapeutic plasma exchange (TPE) is helpful in improving the liver biochemistry profile, thereby, increasing their likelihood of undergoing a liver transplant METHOD: The study was conducted over a period of 3 years (January 2018 to December 2021). Indications mainly consisted of ALF with hepatic encephalopathy, worsening liver parameters in spite of medical management, and candidacy for undergoing a liver transplant. Plasma exchange was performed daily or alternatively until the patient recovered, succumbed, or was stable enough to undergo a transplant. Biochemical parameters serum bilirubin, ALT, AST serum ammonia serum urea, serum creatinine were recorded before and after TPE sessions., Results: The study group comprised 14 patients of which a total of 28 TPE was performed. There were a total of 5 cases of cryptogenic ALF, 4 of Wilson disease, 2 cases each of infection-related ALF and autoimmune hepatitis, and a single case of drug-induced hepatitis. A total of 5 out of 14 patients underwent a liver transplant and amongst the 9 who did not undergo a transplant, 4 patients expired due to septic shock syndrome; the remaining 5 were discharged in a stable condition following TPE sessions. The disease-free survival was 78.9% and the transplant-free survival was 35.71%., Conclusion: TPE plays a crucial role in improving the biochemistry profile of the liver in children with liver failure., Competing Interests: Conflicts of interest There are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To identify prognostic factors associated with 90-day mortality in patients with oesophageal perforation (OP), and characterize the specific timeline from presentation to intervention, and its relation to mortality., Background: OP is a rare gastro-intestinal surgical emergency with a high mortality rate. However, there is no updated evidence on its outcomes in the context of centralized esophago-gastric services; updated consensus guidelines; and novel non-surgical treatment strategies., Methods: A multi-center, prospective cohort study involving eight high-volume esophago-gastric centers (January 2016 to December 2020) was undertaken. The primary outcome measure was 90-day mortality. Secondary measures included length of hospital and ICU stay, and complications requiring re-intervention or re-admission. Mortality model training was performed using random forest, support-vector machines, and logistic regression with and without elastic net regularisation. Chronological analysis was performed by examining each patient's journey timepoint with reference to symptom onset., Results: The mortality rate for 369 patients included was 18.9%. Patients treated conservatively, endoscopically, surgically, or combined approaches had mortality rates of 24.1%, 23.7%, 8.7%, and 18.2%, respectively. The predictive variables for mortality were Charlson comorbidity index, haemoglobin count, leucocyte count, creatinine levels, cause of perforation, presence of cancer, hospital transfer, CT findings, whether a contrast swallow was performed, and intervention type. Stepwise interval model showed that time to diagnosis was the most significant contributor to mortality., Conclusions: Non-surgical strategies have better outcomes and may be preferred in selected cohorts to manage perforations. Outcomes can be significantly improved through better risk-stratification based on afore-mentioned modifiable risk factors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To assess the characteristics of completed panretinal photocoagulation (PRP), using ultra-widefield imaging in proliferative diabetic retinopathy., Methods: Quantitative assessment of ultra-widefield imaging images of 133 patients with proliferative diabetic retinopathy with completed PRP was made using ImageJ software. The parameters assessed included distance of laser spots from the optic disk, foveal center, superior and inferior arcades, and extent of the maximum width of laser. Areas assessed were total area of the image, area of the inner limit within which laser spots are restricted, minimum areas of unlasered patches, total area lasered, and ideal area to be covered by PRP., Results: Two hundred one images were assessed for the final analysis. The mean distance of laser spots was 4.2 ± 2.4 mm from the optic disk (nasal) and 6.6 ± 2.5 mm from the foveal center (temporal). The mean distance of laser spots from the superior arcade vessel was 3.2 ± 1.9 mm and 6.2 ± 4.4 mm from the inferior arcade. The mean area of the retina that should have been ideally lasered was found to be 900 ± 267 mm 2 , and the actual area lasered was found to be 681 ± 254.4 mm 2 ., Conclusion: Approximately one-quarter area of the retina continues to remain ischemic because of the lack of inadequate coverage of PRP. Further longitudinal studies are recommended, using ultra-widefield imaging to objectively assess the adequacy of PRP and its role in modulating the course of progression of the retinopathy.

Introduction: Mushrooms containing amatoxin are found worldwide and represent a challenging poisoning for the clinician and consulting poison center. This study evaluates the experience of a large poison system with possible amatoxin-containing mushroom ingestion calls., Methods: A 10-year retrospective review of the California Poison Control System database was performed for amatoxin mushroom ingestion calls resulting in hospitalization. Cases found were abstracted and data statistically analyzed for association with a composite endpoint of death, liver transplant, and/or the need for dialysis., Results: Amatoxin-containing mushroom calls are infrequent with the vast majority (98.4 percent) coming from Northern California during the rainier first and fourth quarters (October through March) of the year. Elevated initial aminotransferase activities and international normalized ratios were predictive of the composite negative outcome. The mortality plus liver transplant and hemodialysis composite rate was 8.2 percent, consistent with current literature., Conclusion: The California Poison Control System has relatively few amatoxin-containing mushroom ingestion calls that result in hospitalization but those that are reported mostly occur in Northern California. Treatment bias towards the sickest patients may explain the association of intravenous fluid use or treatment with acetylcysteine or silibinin with meeting the composite outcome. The initial presence of elevated hepatic aminotransferase activity and international normalized ratios are poor prognostic indicators and are likely reflective of late presentation, an advanced toxic phase of amatoxin poisoning, and/or delays in time to obtain poison center consultation.

Purpose: The efficacy of additional barrage laser posterior to ridge in advanced stage 3 or stage 4 retinopathy of prematurity (ROP) is established, but its role in early stages is not defined. The objective was to study the efficacy of additional posterior barrage laser in type I zone 2 disease., Methods: In a randomized trial, patients with type I zone 2 ROP were recruited between February 2016 and May 2017. One eye of each baby was randomized into study and control groups, respectively. Laser photocoagulation anterior to ridge was given in the control group, and additional posterior barrage laser was performed in the study group. The outcome measures were time to complete ridge regression and final cycloplegic refraction at 3 months post-laser., Results: Forty patients (40 eyes per group) completed the required follow-up. The mean birth weight and gestational age were 1357 ± 338 g and 29.72 ± 2.57 weeks, respectively. The mean post-conceptional age during laser was 36.67 ± 3.23 weeks. The number of eyes achieving ridge regression in control and study groups was 8/40 (20%) and 27/40 (67%) at 2 weeks (P = 0.001) and 39/40 (97%) and 40/40 (100%) at 4 weeks (P = 0.4). The mean time to complete ridge regression was 3.74 ± 1.17 weeks and 2.62 ± 0.91 weeks in control and study groups, respectively (P < 0.001). The mean spherical equivalent at 12 weeks in control and study groups was -1.9 ± 2.3 Diopters and -2.4 ± 2.6 Diopters, respectively (P = 0.41)., Conclusions: Additional posterior barrage laser leads to significantly faster regression of type 1 zone 2 ROP without increasing induced myopia and thereby might be a useful adjunct to conventional treatment in selected cases., Trial Registration Number: CTRI/2018/05/013779., Competing Interests: None

Alzheimer's disease (AD) represents a major diagnostic challenge, as early detection is crucial for effective intervention. This review examines the diagnostic challenges facing current AD evaluations and explores the emerging field of retinal alterations as early indicators. Recognizing the potential of the retina as a noninvasive window to the brain, we emphasize the importance of identifying retinal biomarkers in the early stages of AD. However, the examination of AD is not without its challenges, as the similarities shared with other retinal diseases introduce complexity in the search for AD-specific markers. In this review, we address the relevance of using the retina for the early diagnosis of AD and the complex challenges associated with the search for AD-specific retinal biomarkers. We provide a comprehensive overview of the current landscape and highlight avenues for progress in AD diagnosis by retinal examination.

Background: Currently, two classification systems, namely Stephens and Sanders, based on axial CT images, and Zwipp and Rammelt, which consider deformities, are used for calcaneus malunions. Existing classifications have limitations due to their pure anatomical basis, and the complexity of the problem, involving both bone and soft tissues. As a solution, the senior author proposed a novel ADIENS classification system for calcaneal malunion, based on pain generators. This study aimed to introduce and evaluate the inter- and intra-observer reliability of a new classification system for calcaneal malunions., Methods: This retrospective cohort study included adult cases with post-traumatic calcaneus malunion. Three experienced foot and ankle surgeon volunteers underwent training session on the classification system, which classifies malunions based on A arthritis, D deformity, E exostosis, I implant issues, N nerve issues, and S soft tissue issues. Post-training, two rounds of classification exercises were conducted. Inter-rater and intra-rater agreements were determined using Gwet's AC coefficient., Results: Out of 15 cases, 6 were of Stephen and Sanders types, and 8 were of Zwipp and Rammelt types, the rest fell out of these classifications. Inter-rater agreement for ADEINS classification was noted to be 'very good' for all six domains. Intra-observer agreements were 'very good' for four out of six domains of classification and 'fair' for two domains of classification., Conclusion: Pain generators-based new ADEINS classification has demonstrated good intra- and inter-observer reliability and seemed user-friendly. However, results need to be replicated in a larger, multicentric cohort before wider clinical applicability., Level of Evidence: Level IV, retrospective study., Competing Interests: Conflict of InterestThe authors have no conflicts of interest to declare relevant to this article's content., (© Indian Orthopaedics Association 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities., Methods: Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020-October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting., Results: Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30-60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6-7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03)., Conclusion: Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Objectives: In view of anecdotal reports of sudden unexplained deaths in India's apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case-control study., Methods: This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1 st October 2021-31 st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI)., Results: Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not., Interpretation Conclusions: COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death., (Copyright © 2023 Copyright: © 2023 Indian Journal of Medical Research.)

Owing to its simplicity, transvaginal oocyte retrieval (TVOR) has become the standard procedure for oocyte retrieval. Despite being an easy procedure, TVOR is still associated with rare but serious complications. A high index of suspicion is required for early diagnosis of complications. We present two cases of bladder haematoma, which presented to us post-TVOR., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Human Reproductive Sciences.)

Background: Tibialis posterior tendon, deltoid ligament and spring ligament are the three most important structures on the medial aspect of the foot. They contribute to the stability of the foot and ankle and also to the maintenance of the arches of the foot. These structures get affected and dimensions get disrupted in various traumatic and degenerative conditions. Normal range of dimensions of these structures has not been studied in an Indian population. Our objective is to define the normal thicknesses of these structures using a cadaveric model. We also hypothesize that longer the foot, higher stresses on these structures and hence thicker they will be. We aim to assess this hypothesis as well., Methods: Dissection of the medial aspect of the foot was done on twenty cadaveric below knee specimens. Tibialis posterior tendon was identified and its thickness was measured. Deltoid and plantar calcaneonavicular ligaments were identified. Their lengths and thicknesses were measured. Length of the feet was also measured prior to dissection. Statistical analysis was done using the data obtained., Results: Mean tibialis posterior thickness was 7.0165 ± 0.387 mm. Mean deltoid thickness was 5.124 ± 0.28 mm. Its mean length was 21.328 ± 2.22 mm. Mean plantarcalcaneonavicular ligament thickness was 2.491 ± 1.120 mm. Thicknesses of the tibialis posterior tendon and plantarcalcaneonavicular ligament correlated significantly with the length of the foot., Conclusion: The thicknesses of the tibialis posterior tendon and plantar calcaneonavicular ligament are shown to be a function of and significantly proportional to the length of the foot. This helps the surgeon to estimate the thicknesses which the structures had prior to the pathology, in order to recreate the non-pathological anatomy after a tendon transfer or a reconstruction procedure. The normal thicknesses of tibialis posterior, deltoid and plantar calcaneonavicular ligaments are described for an Indian setting and deviations can be used to assess various pathologies of the foot and ankle affecting these structures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Delhi Orthopedic Association. All rights reserved.)

Tunicates are marine, non-vertebrate chordates that comprise the sister group to the vertebrates. Most tunicates have a biphasic lifecycle that alternates between a swimming larva and a sessile adult. Recent advances have shed light on the neural basis for the tunicate larva's ability to sense a proper substrate for settlement and initiate metamorphosis. Work in the highly tractable laboratory model tunicate Ciona robusta suggests that sensory neurons embedded in the anterior papillae transduce mechanosensory stimuli to trigger larval tail retraction and initiate the process of metamorphosis. Here, we take advantage of the low-cost and simplicity of Ciona by using tissue-specific CRISPR/Cas9-mediated mutagenesis to screen for genes potentially involved in mechanosensation and metamorphosis, in the context of an undergraduate 'capstone' research course. This small screen revealed at least one gene, Vamp1/2/3, which appears crucial for the ability of the papillae to trigger metamorphosis. We also provide step-by-step protocols and tutorials associated with this course, in the hope that it might be replicated in similar CRISPR-based laboratory courses wherever Ciona are available., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Purpose: To analyze the topographic distribution of neovascularization (NV) and capillary nonperfusion (CNP) using ultra-wide field fluorescein angiography (UWFFA) in patients with proliferative diabetic retinopathy (PDR)., Methods: This was a prospective, single-center, observational study in which all patients who presented between March 2019 and December 2020 and satisfied the inclusion criteria were recruited. In our study, patients with treatment-naïve PDR without any fibrovascular proliferation underwent UWFFA. The images were analyzed qualitatively for the topographic distribution of NV and the CNP area was quantified. The number of lesions picked by UWFFA was compared with 7 standard field (7SF) image using overlay of 7SF. The main outcome measure was characteristics of neovascularization, such as the number, location, and area of CNP, measured using UWFFA, which was considered with 95% confidence intervals (CI)., Results: Two hundred and fifty-three eyes of 187 patients with a mean age of 56.03 ± 8 years were included. Mean neovascularization elsewhere (NVE) was 2.91 ± 3.43. Maximum NVEs were seen in the superotemporal (ST; 0.9 ± 1.13) quadrant, followed by the inferotemporal (IT; 0.7 ± 1.08), inferonasal (IN; 0.66 ± 1.02) and superonasal (SN; 0.66 ± 1.01) quadrants. Maximum CNP area was seen in the SN (13.75 ± 8.83 disc diameter square [DD 2 ]) quadrant, followed by the IN (13.48 ± 8.59 DD 2 ), IT (11.34 ± 8.37 DD 2 ), and ST (11.3 ± 8.34 DD 2 ) quadrants. Mean CNP area was maximum in patients with only neovascularization of disc (NVD; 64.99 ± 41.47 DD 2 ), followed by both NVD and NVE (61.37 ± 35.61 DD 2 ), and was minimum in patients with only NVE (36.44 ± 22.03 DD 2 ). Eighty-one (32%) eyes out of 253 had NVE and 189 (75%) out of 253 had CNP area outside 7SF (overlay) of Early Treatment Diabetic Retinopathy Study (ETDRS)., Conclusion: Diabetic NV lesions and CNP areas are distributed asymmetrically throughout the retina and are not restricted to the posterior pole. Compared to conventional 7SF imaging, UWFFA reveals significantly more retinal vascular pathology in patients with PDR.

Background: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity., Methods: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration., Results: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis ( P  = 0.89) or polynomial model ( P  = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration., Conclusion: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Background: The COVID-19 pandemic brought rapid and major changes to research, and those wishing to carry out Patient and Public Involvement (PPI) activities faced challenges, such as restrictions on movement and contact, illness, bereavement and risks to potential participants. Some researchers moved PPI to online settings during this time but remote consultations raise, as well as address, a number of challenges. It is important to learn from PPI undertaken in this period as face-to-face consultation may no longer be the dominant method for PPI., Methods: UK stay-at-home measures announced in March 2020 necessitated immediate revisions to the intended face-to-face methods of PPI consultation for the ESORT Study, which evaluated emergency surgery for patients with common acute conditions. PPI plans and methods were modified to all components being online. We describe and reflect on: initial plans and adaptation; recruitment; training and preparation; implementation, contextualisation and interpretation. Through first-hand accounts we show how the PPI processes were developed, experienced and viewed by different partners in the process., Discussion and Conclusions: While concerns have been expressed about the possible limiting effects of forgoing face-to-face contact with PPI partners, we found important benefits from the altered dynamic of the online PPI environment. There were increased opportunities for participation which might encourage the involvement of a broader demographic, and unexpected benefits in that the online platform seemed to have a 'democratising' effect on the meetings, to the benefit of the PPI processes and outcomes. Other studies may however find that their particular research context raises particular challenges for the use of online methods, especially in relation to representation and inclusion, as new barriers to participation may be raised. It is important that methodological challenges are addressed, and researchers provide detailed examples of novel methods for discussion and empirical study., Patient and Public Contribution: We report a process which involved people with lived experience of emergency conditions and members of the public. A patient member was involved in the design and implementation, and two patients with lived experience contributed to the manuscript., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Purpose: To compare disease regression in cases of Fluorescein Angiography (FA) guided laser vs. conventional laser treatment in infants with Aggressive retinopathy of prematurity (AROP)., Methods: 60 eyes of 30 infants of AROP were randomized into two groups. In both the group's FA was done once. Montage of the fundus, FA images was created and the vascular area, avascular areas, and skip areas after laser treatment were demarcated and measured. In group 1, FA-guided laser treatment was done whereas in group 2 they were lasered without seeing FA. Infants were followed up every week to look for skip areas and disease regression., Results: The mean vascular retinal area in group 1 and group 2 on fundus images was 302.7 sq. mm and 245.8 sq. mm respectively, while the same on FA was 285.2 sq. mm and 221.3 sq. mm respectively, suggesting overestimation of the vascular area on fundus imaging compared to FA which enabled more objective estimation of avascular loop areas. Retinal skip areas in group 1 and group 2 after 1st laser were 18.7 sq. mm and 73.1 sq. mm respectively (P = 0.001), after 2nd laser was 3.7 sq. mm and 19.2 sq. mm (P = 0.003), which suggests FA-guided laser led to significantly fewer skip areas. Infants had regression in 4.1 ± 0.3 wks and 4.2 ± 0.4 wks in groups 1 and 2, respectively., Conclusion: FA-guided laser ensured lesser skip areas and more complete laser treatment, though regression was similar in both groups., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: COVID-19 was declared as a Public Health Emergency of International Concern on 30th January 2020. Compared to the general population, healthcare workers and their families have been identified to be at a higher risk of getting infected with COVID-19. Therefore, it is crucial to understand the risk factors responsible for the transmission of SARS-CoV-2 infection among health workers in different hospital settings and to describe the range of clinical presentations of SARS-CoV-2 infection among them., Methodology: A nested case-control study was conducted among healthcare workers who were involved in the care of COVID-19 cases for assessing the risk factors associated with it. To get a holistic perspective, the study was conducted in 19 different hospitals from across 7 states (Kerala, Tamil Nadu, Andhra Pradesh, Karnataka, Maharashtra, Gujarat, and Rajasthan) of India covering the major government and private hospitals that were actively involved in COVID-19 patient care. The study participants who were not vaccinated were enrolled using the incidence density sampling technique from December 2020 to December 2021., Results: A total of 973 health workers consisting of 345 cases and 628 controls were recruited for the study. The mean age of the participants was observed to be 31.17 ± 8.5 years, with 56.3% of them being females. On multivariate analysis, the factors that were found to be significantly associated with SARS-CoV-2 were age of more than 31 years (adjusted odds ratio [aOR] 1.407 [95% CI 1.53-1.880]; p  = 0.021), male gender (aOR 1.342 [95% CI 1.019-1.768]; p  = 0.036), practical mode of IPC training on personal protective equipment (aOR 1. 1.935 [95% CI 1.148-3.260]; p  = 0.013), direct exposure to COVID-19 patient (aOR 1.413 [95% CI 1.006-1.985]; p  = 0.046), presence of diabetes mellitus (aOR 2.895 [95% CI 1.079-7.770]; p  = 0.035) and those received prophylactic treatment for COVID-19 in the last 14 days (aOR 1.866 [95% CI 0.201-2.901]; p  = 0.006)., Conclusion: The study was able to highlight the need for having a separate hospital infection control department that implements IPC programs regularly. The study also emphasizes the need for developing policies that address the occupational hazards faced by health workers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 George, Tomy, Retnakumar, Narlawar, Bhardwaj, Krishnan, Rao, Patel, Bilimale, Baby, Mathew, Cassini, Simniceanu, Yin, Allegranzi, Ahmad, Rahman, Mohiuddin, Thakre, Bhansali, Vohra, Krishnan, Logaraj, Maheriya, Gharat, Dipu, Solomon, Sharma, Shwethashree, Hegde, Ansari and Misra.)

The distal tibiofibular syndesmosis (DTFS) is more frequently injured than previously thought. Early diagnosis and appropriate treatment is essential to avoid long term complications like chronic instability, early osteoarthritis and residual pain. Management of these injuries require a complete understanding of the anatomy of DTFS, and the role played by the ligaments stabilizing the DTFS and ankle. High index of suspicion, appreciating the areas of focal tenderness and utilizing the provocative maneuvers help in early diagnosis. In pure ligamentous injuries radiographs with stress of weight bearing help to detect subtle instability. If these images are inconclusive, then further imaging with MRI, CT scan, stress examination under anesthesia, and arthroscopic examination facilitate diagnosis. An injury to syndesmosis frequently accompanies rotational fractures and all ankle fractures need to be stressed intra-operatively under fluoroscopy after fixation of the osseous components to detect syndesmotic instability. Non-operative treatment is appropriate for stable injuries. Unstable injuries should be treated operatively. Anatomic reduction of the syndesmosis is critical, and currently both trans-syndesmotic screws and suture button fixation are commonly used for syndesmotic stabilization. Chronic syndesmotic instability (CSI) requires debridement of syndesmosis, restoration of ankle mortise with or without syndesmotic stabilization. Arthrodesis of ankle is used a last resort in the presence of significant ankle arthritis. This article reviews anatomy and biomechanics of the syndesmosis, the mechanism of pure ligamentous injury and injury associated with ankle fractures, clinical, radiological and arthroscopic diagnosis and surgical treatment.

Background: Medial aspect of foot is unexplored due to its complex anatomy. Masterknot of Henry is an important landmark in this region, which plays a key role during tendon transfer procedures especially in those involving the flexor hallucis longus and flexor digitorum longus. We aim to determine the exact anatomical location of masterknot of Henry with respect to the bony prominences of the medial aspect of the foot and compare these measurements to the length of the foot., Methods: Twenty cadaveric below-knee specimens were dissected. Structures on the medial side of the foot were exposed. Distance of the masterknot of Henry from surrounding bony landmarks was measured. Depth of the masterknot from skin of the plantar aspect was also measured. Means of all parameters were calculated. Relation between measurements and the foot length was determined using correlation and regression analysis. P value of less than 0.05 was considered significant., Results: Distance of masterknot of Henry from navicular tuberosity was found to be fairly constant of 19.965 mm. Foot length was found to be correlating with the distance between masterknot of Henry and medial malleolus, navicular tuberosity and its depth from the skin., Conclusions: Navicular tuberosity can be considered an important surface landmark for the location of masterknot of Henry. Correlation of length of the feet with various measurements helps to find the masterknot considering the foot length to be an important variable. Good knowledge of surface anatomy leads to shorter operating time and less morbidity during procedures involving the flexor hallucis longus and flexor digitorum longus., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Indian Orthopaedics Association 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: There is currently a lack of evidence-based guidelines regarding surveillance for recurrence after esophageal and gastric (OG) cancer surgical resection, and which symptoms should prompt endoscopic or radiological investigations for recurrence. The aim of this study was to develop a core symptom set using a modified Delphi consensus process that should guide clinicians to carry out investigations to look for suspected recurrent OG cancer in previously asymptomatic patients., Methods: A web-based survey of 42 questions was sent to surgeons performing OG cancer resections at high volume centers. The first section evaluated the structure of follow-up and the second, determinants of follow-up. Two rounds of a modified Delphi consensus process and a further consensus workshop were used to determine symptoms warranting further investigations. Symptoms with a 75% consensus agreement as suggestive of recurrent cancer were included in the core symptom set., Results: 27 surgeons completed the questionnaires. A total of 70.3% of centers reported standardized surveillance protocols, whereas 3.7% of surgeons did not undertake any surveillance in asymptomatic patients after OG cancer resection. In asymptomatic patients, 40.1% and 25.9% of centers performed routine imaging and endoscopy, respectively. The core set that reached consensus, consisted of eight symptoms that warranted further investigations included; dysphagia to solid food, dysphagia to liquids, vomiting, abdominal pain, chest pain, regurgitation of foods, unexpected weight loss and progressive hoarseness of voice., Conclusion: There is global variation in monitoring patients after OG cancer resection. Eight symptoms were identified by the consensus process as important in prompting radiological or endoscopic investigation for suspected recurrent malignancy. Further randomized controlled trials are necessary to link surveillance strategies to survival outcomes and evaluate prognostic value., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Background: This study assessed the impact of the first COVID-19 wave in England on outcomes for acute appendicitis, gallstone disease, intestinal obstruction, diverticular disease, and abdominal wall hernia., Methods: Emergency surgical admissions for patients aged 18 years and older to 124 NHS Trust hospitals between January and June in 2019 and 2020 were extracted from Hospital Episode Statistics. The risk of 90-day mortality after admission during weeks 11-19 in 2020 (national lockdown) and 2019 (pre-COVID-19) was estimated using multilevel logistic regression with case-mix adjustment. The primary outcome was all-cause mortality at 90 days., Results: There were 12 231 emergency admissions and 564 deaths within 90 days during weeks 11-19 in 2020, compared with 18 428 admissions and 542 deaths in the same interval in 2019. Overall, 90-day mortality was higher in 2020 versus 2019, with an adjusted OR of 1.95 (95 per cent c.i. 0.78 to 4.89) for appendicitis, 2.66 (1.81 to 3.92) for gallstone disease, 1.99 (1.44 to 2.74) for diverticular disease, 1.70 (1.13 to 2.55) for hernia, and 1.22 (1.01 to 1.47) for intestinal obstruction. After emergency surgery, 90-day mortality was higher in 2020 versus 2019 for gallstone disease (OR 3.37, 1.26 to 9.02), diverticular disease (OR 2.35, 1.16 to 4.73), and hernia (OR 2.34, 1.23 to 4.45). For intestinal obstruction, the corresponding OR was 0.91 (0.59 to 1.41). For admissions not leading to emergency surgery, mortality was higher in 2020 versus 2019 for gallstone disease (OR 2.55, 1.67 to 3.88), diverticular disease (1.90, 1.32 to 2.73), and intestinal obstruction (OR 1.30, 1.06 to 1.60)., Conclusion: Emergency admission was reduced during the first lockdown in England and this was associated with higher 90-day mortality., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Purpose: To study the effect of subthreshold micropulse yellow laser treatment on central serous chorioretinopathy (CSC) and to compare two laser protocols. As per our knowledge, there are no studies comparing the two protocols of subthreshold laser., Methods: Twenty-three patients with non-resolving CSC of at least three months duration were treated with subthreshold laser (577 nm). Ten patients were treated with 5% duty cycle (group A) and 13 patients with 10% duty cycle (group B). At one month, best corrected visual acuity (BCVA), central macular thickness (CMT), subretinal fluid (SRF), choroidal thickness (CT) and choroidal vascularity index (CVI) were evaluated., Results: In group A, BCVA improved from 0.508 ± 504 to 0.174 ± 0.171 (P = 0.0058), CMT improved from 349.8 ± 168.9 micrometers (μm) to 183.3 ± 70.312 μm (P = 0.0093) and SRF reduced from 202.4 ± 158.024 to 43.8 ± 46.599 μm (P = 0.0069). In group B, BCVA improved from 0.437 ± 0.426 to 0.289 ± 0.470 (P = 0.0026), CMT improved from 280.846 ± 72.668 to 196.769 ± 72.62 μm (P = 0.0002) and SRF reduced from 110.385 ± 57.687 μm to 52.538 ± 52.111 μm (P = 0.0064). No significant difference was found in BCVA and CMT between the groups (P = 0.8716 and P = 0.8523, respectively). CSC completely resolved in 50% of cases in group A and in 69.2% of cases in group B. This difference was not statistically significant (0.423); however, the odds ratio of resolution was 2.25 times more with 10% duty cycle. No change was observed on fundus autofluorescence (FAF) following laser., Conclusion: Subthreshold micropulse laser can lead to resolution of SRF in 60.87% of cases (groups A and B combined). Ten per cent duty cycle had higher odds of resolution without causing any RPE damage., Competing Interests: None

Introduction: Major surgery accounts for a substantial proportion of health service activity, due not only to the primary procedure, but the longer-term health implications of poor short-term outcome. Data from small studies or from outside the UK indicate that rates of complications and failure to rescue vary between hospitals, as does compliance with best practice processes. Within the UK, there is currently no system for monitoring postoperative complications (other than short-term mortality) in major non-cardiac surgery. Further, there is variation between national audit programmes, in the emphasis placed on quality assurance versus quality improvement, and therefore the principles of measurement and reporting which are used to design such programmes., Methods and Analysis: The PQIP patient study is a multi-centre prospective cohort study which recruits patients undergoing major surgery. Patient provide informed consent and contribute baseline and outcome data from their perspective using a suite of patient-reported outcome tools. Research and clinical staff complete data on patient risk factors and outcomes in-hospital, including two measures of complications. Longer-term outcome data are collected through patient feedback and linkage to national administrative datasets (mortality and readmissions). As well as providing a uniquely granular dataset for research, PQIP provides feedback to participating sites on their compliance with evidence-based processes and their patients' outcomes, with the aim of supporting local quality improvement., Ethics and Dissemination: Ethical approval has been granted by the Health Research Authority in the UK. Dissemination of interim findings (non-inferential) will form a part of the improvement methodology and will be provided to participating centres at regular intervals, including near-real time feedback of key process measures. Inferential analyses will be published in the peer-reviewed literature, supported by a comprehensive multi-modal communications strategy including to patients, policy makers and academic audiences as well as clinicians., (© 2022. The Author(s).)

Objective: To evaluate the prognostic role of pretreatment CD4 + , CD8 + T lymphocytes in predicting response to definite chemo radiotherapy in advanced cervical cancer. Design: A hospital-based prospective one-year follow-up study., Method: This observational study was conducted on 74 patients with advanced cervical cancer. Pretreatment CD4 + and CD8 + levels in cervical cancer tissue and peripheral blood was noted and quantitatively assessed in patients with complete remission or persistent disease after one year of follow-up., Results: There was a statistically significant association of tumour volume with the remission or persistence of disease. In peripheral blood, mean CD4 + score and CD4 + /CD8 + ratio were significantly higher while mean CD8 + score is significantly lower in patients with remission. Similar results were seen in tumour tissue as well. On Receiver Operating Curve analysis, the cut-off value of CD4 + , CD8 + and CD4 + /CD8 + ratio in predicting remission or persistent disease in peripheral blood was 20.09, 18.51 and 0.41 while in tumor tissue was 19.71, 20.99 and 0.20, respectively., Conclusion: The patients with tumor volume < 100 cm 2 have much higher chances of remission. The patients with higher CD4 + and CD4 + / CD8 + ratio, both in peripheral blood as well as tumor tissue, have higher chances of remission. The cut-off value of CD4 + , CD8 + and CD4 + /CD8 + ratio in predicting remission or persistent disease in peripheral blood was 20.09, 18.51 and 0.41 while in tumor tissue was 19.71, 20.99 and 0.20, respectively., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© Federation of Obstetric & Gynecological Societies of India 2022.)

Anemia is one of the most pressing public health issues in the world with iron deficiency a major public health issue worldwide. The highest prevalence of anemia is in developing countries. The complete blood count is a blood test used to diagnose the prevalence of anemia. While earlier studies have framed the problem of diagnosis as a binary classification problem, this paper frames it as a multi class (three classes) classification problem with mild, moderate and severe classes. The three classes for the anemia classification (mild, moderate, severe) are so chosen as the world health organization (WHO) guidelines formalize this categorization based on the Haemoglobin (HGB) values of the chosen sample of patients in the Complete Blood Count (CBC) patient data set. Complete blood count test data was collected in an outpatient clinical setting in India. We used Feature selection with Majority voting to identify the key attributes in the input patient data set. In addition, since the original data set was imbalanced we used Synthetic Minority Oversampling Technique (SMOTE) to balance the data set. Four data sets including the original data set were used to perform the data experiments. Six standard machine learning algorithms were utilised to test our four data sets, performing multi class classification. Benchmarking these algorithms was performed and tabulated using both10 fold cross validation and hold out methods. The experimental results indicated that multilayer perceptron network was predominantly giving good recall values across mild and moderate class which are early and middle stages of the disease. With a good prediction model at early stages, medical intervention can provide preventive measure from further deterioration into severe stage or recommend the use of supplements to overcome this problem., Competing Interests: The authors have declared that no competing interests exist.

Background: Progressive retinal ganglion cell (RGC) dysfunction and death are common characteristics of retinal neurodegenerative diseases. Recently, hydroxycarboxylic acid receptor 1 (HCA 1 R, GPR81) was identified as a key modulator of mitochondrial function and cell survival. Thus, we aimed to test whether activation of HCA 1 R with 3,5-Dihydroxybenzoic acid (DHBA) also promotes RGC survival and improves energy metabolism in mouse retinas., Methods: Retinal explants were treated with 5 mM of the HCA 1 R agonist, 3,5-DHBA, for 2, 4, 24, and 72 h. Additionally, explants were also treated with 15 mM of L-glutamate to induce toxicity. Tissue survival was assessed through lactate dehydrogenase (LDH) viability assays. RGC survival was measured through immunohistochemical (IHC) staining. Total ATP levels were quantified through bioluminescence assays. Energy metabolism was investigated through stable isotope labeling and gas chromatography-mass spectrometry (GC-MS). Lactate and nitric oxide levels were measured through colorimetric assays., Results: HCA 1 R activation with 3,5-DHBAincreased retinal explant survival. During glutamate-induced death, 3,5-DHBA treatment also increased survival. IHC analysis revealed that 3,5-DHBA treatment promoted RGC survival in retinal wholemounts. 3,5-DHBA treatment also enhanced ATP levels in retinal explants, whereas lactate levels decreased. No effects on glucose metabolism were observed, but small changes in lactate metabolism were found. Nitric oxide levels remained unaltered in response to 3,5-DHBA treatment., Conclusion: The present study reveals that activation of HCA 1 R with 3,5-DHBA treatment has a neuroprotective effect specifically on RGCs and on glutamate-induced retinal degeneration. Hence, HCA 1 R agonist administration may be a potential new strategy for rescuing RGCs, ultimately preventing visual disability.

Purpose: To compare pneumatic vitreolysis and pars plana vitrectomy in the management of focal symptomatic vitreomacular traction (VMT)., Method: Patients aged 18 years or older, with idiopathic focal symptomatic VMT and best-corrected visual acuity <20/40, without any other retinal pathology were randomized to undergo pneumatic vitreolysis (Group 1) or pars plana vitrectomy (Group 2). The primary outcome measure was resolution of traction confirmed with optical coherence tomography at 3 months. Secondary outcome measures were to compare changes in best-corrected visual acuity, central foveal thickness, and complications if any., Results: A total of 30 eyes of 30 patients were included with 15 eyes in each group. Vitreomacular traction resolved successfully in 12 of 15 (80%) eyes in Group 1 and in all (100%) eyes in Group 2 (P = 0.224). The mean visual acuity improved from 0.80 ± 0.26 (20/126 Snellen's equivalent) to 0.70 ± 0.46 logMAR (20/100 Snellen's equivalent) in Group 1 (P = 0.71) and from 0.904 ± 0.44 (20/160 Snellen's equivalent) to 0.47 ± 0.26 logMAR (20/59 Snellen's equivalent) in Group 2 (P = 0.0016). Although 4 of 15 (26.66%) eyes in Group 1 had formation of full-thickness macular hole and 7 eyes required resurgery (4 for full-thickness macular hole and 3 for unresolved VMT), none in the pars plana vitrectomy group had any complications requiring resurgery (P = 0.0063). Two eyes in the pars plana vitrectomy group had intraoperative deroofing of the fovea leading to full-thickness macular hole., Conclusion: Pars plana vitrectomy is better than pneumatic vitreolysis as a single intervention in the management of focal symptomatic VMT.

Background: Enhanced recovery pathways are associated with improved postoperative outcomes. However, as enhanced recovery pathways have become more complex and varied, compliance has reduced. The 'DrEaMing' bundle re-prioritises early postoperative delivery of drinking, eating, and mobilising. We investigated relationships between DrEaMing compliance, postoperative hospital length of stay (LOS), and complications in a prospective multicentre major surgical cohort., Methods: We interrogated the UK Perioperative Quality Improvement Programme dataset. Analyses were conducted in four stages. In an exploratory cohort, we identified independent predictors of DrEaMing. We quantified the association between delivery of DrEaMing (and its component variables) and prolonged LOS in a homogenous colorectal subgroup and assessed generalisability in multispecialty patients. Finally, LOS and complications were compared across hospitals, stratified by DrEaMing compliance., Results: The exploratory cohort comprised 22 218 records, the colorectal subgroup 7230, and the multispecialty subgroup 5713. DrEaMing compliance was 59% (13 112 patients), 60% (4341 patients), and 60% (3421), respectively, but varied substantially between hospitals. Delivery of DrEaMing predicted reduced odds of prolonged LOS in colorectal (odds ratio 0.51 [0.43-0.59], P<0.001) and multispecialty cohorts (odds ratio 0.47 [0.41-0.53], P<0.001). At the hospital level, complications were not the primary determinant of LOS after colorectal surgery, but consistent delivery of DrEaMing was associated with significantly shorter LOS., Conclusions: Delivery of bundled and unbundled DrEaMing was associated with substantial reductions in postoperative LOS, independent of the effects of confounder variables. Consistency of process delivery, and not complications, predicted shorter hospital-level length of stay. DrEaMing may be adopted by perioperative health systems as a quality metric to support improved patient outcomes and reduced hospital length of stay., Competing Interests: Declaration of interest All authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The genus Providencia , earlier considered a rare pathogen, is now increasingly recognized as a notorious opportunistic pathogen capable of causing serious nosocomial infections, mainly urinary tract infections (UTIs). Treating these infections is an onerous task given the resistance seen in clinical strains to many currently available antimicrobials. The objective of the present study is to provide an overall view into the prevalence of Providencia spp. causing UTIs, their antibiotic susceptibility pattern, and respective clinical outcomes., Materials and Methods: This is a retrospective observational study carried out in a tertiary care teaching referral hospital located in Jaipur, India from March 2021 to May 2021. All Providencia spp. strains isolated from urine samples were included in the study. Data were entered in Microsoft Office Excel worksheet. Results are presented in numbers and percentages., Results: Out of 1,261 urine samples processed in the laboratory during the study period, 426 were culture positive and the majority were gram-negative isolates and included Escherichia coli (46.0%) and Klebsiella spp. (28.0%). Providencia spp. was the fourth most common gram-negative pathogen (6.0%). The median age of patients was 65 years. The male:female ratio was 3:2 and maximum patients belonged to the 30-60-year age-group. Diabetes was the commonest associated comorbidity. All patients had an indwelling urinary catheter. Three (20.0%) patients succumbed to infections., Conclusion: Providencia is an opportunistic pathogen that cannot be neglected due to escalating antibiotic resistance. Effective infection control and antibiotic stewardship policies are required to prevent the development of further antibiotic resistance., How to Cite This Article: Rajni E, Jain A, Garg VK, Sharma R, Vohra R, Jain SS. Providencia Causing Urinary Tract Infections: Are We Reaching a Dead End? Indian J Crit Care Med 2022;26(4):446-451., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; Jaypee Brothers Medical Publishers (P) Ltd.)

Background: Severe acute respiratory syndrome corona virus 2(SARS-CoV-2), the causative agent of corona virus disease-2019(COVID- 19) which has led to a global pandemic. The true extent of the burden of COVID-19 may be underestimated, and there is need to know the current prevalence of SARS-CoV-2 antibody in population., Methods: The present study was a cross-sectional study to assess prevalence of SARS-CoV- 2 IgG antibody among 586 healthy voluntary blood donors who donated whole blood between mid-December 2020 to January 2021. A chemiluminescence assay was used to detect the presence of SARS-CoV-2 IgG antibody in serum samples in addition to recommended transfusion transmitted infections tests and Signal to Cut Off (S/C) > 1 was considered as reactive for antibody as per manufacturer's instructions., Results: In the present study, 586 healthy voluntary blood donors were enrolled and were screened for SARS- CoV-2 IgG antibody. Out of 586 donors, 52 donors had indeterminate values of SARS-CoV-2 IgG antibody. A total of 534 healthy voluntary blood donors' samples were included in the present study for analysis. Out of total 534 healthy blood donors, 42.88% (229) were found to be seropositive while 57.11% (305) were found to be seronegative., Conclusion: A 43% positivity of SARS-CoV-2 IgG antibody among healthy blood donors was detected which is an indication of presence of infection at community level and majority of the population already has been exposed to SARS-CoV-2 infection. However, there was no statistically significant association of type of blood group and age with seropositivity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Baricitinib, typically applied as a treatment for rheumatoid arthritis, has recently attracted the attention of clinicians and researchers as a potential treatment for COVID-19. Naturally, there has been a need for the preparation of the isotope-labelled analogue of baricitinib to probe the pharmacokinetics of baricitinib in this new role. As such, we have developed a simple synthetic route to deuterated [ 2 H 5 ]baricitinib, facilitating its formation over four steps and in a 29% overall yield based on starting [ 2 H 5 ]ethanethiol (19% if we start with [ 2 H 5 ]bromoethane instead). A critical component of the overall process involves the synthesis of [ 2 H 5 ]ethanesulfonyl chloride, and we describe in detail the two routes that were explored to optimize this step., (© 2022 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.)

Purpose: Real-life comparison of three intravitreal drug regimens used in cases of endophthalmitis at a tertiary care center in India., Methods: In this prospective, comparative study, patients of bacterial endophthalmitis were grouped according to intravitreal antibiotic drug regimens into Group 1 (ceftazidime and vancomycin), Group 2 (piperacillin + tazobactam and vancomycin), and Group 3 (imipenem and vancomycin). Forty-eight hours after injection nonresponding/worsening patients underwent vitrectomy. Vitreous samples were subjected to microbiological and pharmacokinetic tests., Results: A total of 64 patients were included and divided into Group 1: 29, Group 2: 20, and Group 3: 15 cases. Also, 75% of patients were post-surgical endophthalmitis, whereas 25% were post-traumatic. Improvement in vision (V 90-0 ) and vision at 3 months (V 90 ) were comparable between the three groups. Visual recovery was poorer in post-traumatic cases. In post-surgical cases, visual recovery was poorer in those presenting beyond 72 h of onset of symptoms (P = 0.0002). Polymerase chain reaction (PCR) positivity (66%) was higher than BACTEC TM (33%) and culture (14%). Antibiotic resistance was comparable amongst the three groups. Most patients (62/64) further underwent vitrectomy. Ceftazidime and vancomycin achieved vitreous concentrations more than the minimum inhibitory concentration (MIC) at 48 h after the first injection., Conclusion: The choice of antibiotics did not affect the rate of vitrectomy and final vision in a real-life scenario. Ceftazidime and vancomycin can still be used as first-line intravitreal antibiotics owing to their comparable microbial sensitivity profile and adequate ocular bioavailability., Competing Interests: None

Glaucoma is a common ocular neurodegenerative disease characterized by the progressive loss of retinal ganglion cells and their axons. It is the most common cause of irreversible blindness. With an increasing number of glaucoma patients and disease progression despite treatment, it is paramount to develop new and effective therapeutics. Emerging new candidates are the receptor agonists of the incretin hormone glucagon-like-peptide-1 (GLP-1), originally used for the treatment of diabetes. GLP-1 receptor (GLP-1R) agonists have shown neuroprotective effects in preclinical and clinical studies on neurodegenerative diseases in both the brain (e.g., Alzheimer's disease, Parkinson's disease, stroke and diabetic neuropathy) and the eye (e.g., diabetic retinopathy and AMD). However, there are currently very few studies investigating the protective effects of GLP-1R agonists in the treatment of specifically glaucoma. Based on a literature search on PubMed, the Cochrane Library, and ClinicalTrials.gov, this review aims to summarize current clinical literature on GLP-1 receptor agonists in the treatment of neurodegenerative diseases to elucidate their potential in future anti-glaucomatous treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mouhammad, Vohra, Horwitz, Thein, Rovelt, Cvenkel, Williams, Azuara-Blanco and Kolko.)

Purpose: To describe a rare case of endogenous endophthalmitis due to Citrobacter with subretinal abscess and the role of the novel technique of intralesional antibiotic for its treatment., Methods: A retrospective case report., Result: A 45-year-old male presenting with painful, progressive diminution of vision in the left eye was diagnosed to have endogenous endophthalmitis due to Citrobacter with subretinal abscess. After the failure of the initial intravitreal injection of ceftazidime and vancomycin, successful resolution of abscess was achieved by pars plana vitrectomy with 41-gauge (G) needle assisted intralesional injection of piperacillin and tazobactam combination., Conclusion: We treated a case of Citrobacter associated endogenous endophthalmitis with subretinal abscess with intralesional injection of piperacillin and tazobactam combination. 41-G needle can be used safely to inject antibiotic into the subretinal space through a small self-sealing retinotomy with minimum risk of retinal detachment and encouraging results.

Pancreatic ductal adenocarcinomas are characterized by a complex and robust tumor microenvironment (TME) consisting of fibrotic tissue, excessive levels of hyaluronan (HA), and immune cells. We utilized quantitative multi-parametric magnetic resonance imaging (mp-MRI) methods at 14 Tesla in a genetically engineered KPC ( Kras LSL-G12D/+ , Trp53 LSL-R172H/+ , Cre) mouse model to assess the complex TME in advanced stages of tumor development. The whole tumor, excluding cystic areas, was selected as the region of interest for data analysis and subsequent statistical analysis. Pearson correlation was used for statistical inference. There was a significant correlation between tumor volume and T2 (r = -0.66), magnetization transfer ratio (MTR) (r = 0.60), apparent diffusion coefficient (ADC) (r = 0.48), and Glycosaminoglycan-chemical exchange saturation transfer (GagCEST) (r = 0.51). A subset of mice was randomly selected for histological analysis. There were positive correlations between tumor volume and fibrosis (0.92), and HA (r = 0.76); GagCEST and HA (r = 0.81); and MTR and CD31 (r = 0.48). We found a negative correlation between ADC low-b (perfusion) and Ki67 (r = -0.82). Strong correlations between mp-MRI and histology results suggest that mp-MRI can be used as a non-invasive tool to monitor the tumor microenvironment.

Preterm babies with retinopathy of prematurity (ROP) can become blind if they do not receive appropriate timely intervention. The presence of cataract in these individuals in addition to visual deprivation amblyopia, also delays proper screening, adequate treatment, and makes follow-up assessment difficult. Anatomical differences in these infants and amblyopia management, especially in unilateral cataract, are other important concerns, and hence, management of these cases with cataract and ROP is challenging. In this review, studies where ROP cases were associated with cataract, were evaluated with a focus on preterm individuals less than 6 months age. Preterm babies are at increased risk of developing cataract because of systemic factors. In addition, those with ROP may have cataract associated with retinal detachment or treatment received. The type of cataract, risk factors, and pathophysiology associated with each cause varies. This review highlights these different aspects of cataract in ROP including causes, pathophysiology, types of cataracts, and management. The management of these cases is critical in terms of the timing of cataract surgery and the challenges associated with surgery and posterior segment management for ROP. Anatomical differences, preoperative retina status, pupillary dilatation, neovascularization of iris in aggressive posterior ROP, fundus examination, amblyopia, and follow-up are various important aspects in the management of the same. The preoperative workup, intraoperative challenges, postoperative care, and rehabilitation in these individuals are discussed., Competing Interests: None

Introduction: During the coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2, deaths from opiate drug overdoses reached their highest recorded annual levels in 2020. Medication-assisted treatment for opiate use disorder has demonstrated efficacy in reducing opiate overdoses and all-cause mortality and improving multiple other patient-centered outcomes. Treatment of tramadol dependence in particular poses unique challenges due to its combined action as opioid agonist and serotonin-norepinephrine reuptake inhibitor. Tramadol puts patients with dependence at risk for atypical withdrawal syndromes when attempting to reduce use. Little evidence is available to guide treatment of tramadol dependence., Case Report: We present a case of high-dose tramadol addiction that began with misuse of medically prescribed tramadol for treatment of musculoskeletal back pain. The patient's use reached oral consumption of 5000-6000 milligrams of illicit tramadol daily. She complained of common complications of tramadol use disorder including memory impairment, excessive sedation, and tramadol-induced seizures. The patient was referred to the emergency department in a withdrawal crisis seeking treatment where she was successfully managed with buprenorphine and phenobarbital and then linked to ongoing outpatient treatment., Conclusion: Our report adds to the limited guidance currently available on the acute management of tramadol withdrawal and treatment of tramadol use disorder. Our case suggests the initiation of high-dose buprenorphine may be an effective and feasible option for emergency clinicians.

Purpose: Available literature on peripapillary pachychoroid syndrome (PPS) is very limited. The purpose of this study is to evaluate features of PPS using multimodal imaging and shed further light on this entity., Methods: This is a retrospective case series at a tertiary eye-care center. Patients with features of pachychoroid with preferential choroidal thickening in nasal macula along with pachyvessels were identified and included for analysis. The patients underwent fundus photography, fundus autofluorescence, optical coherence tomography, fundus fluorescein angiography, and indocyanine angiography. Images were separately analyzed by two different retina specialists., Results: A total of 27 eyes of 14 patients with mean age of 52.2 years were included. Seven patients had bilateral PPS, whereas six had unilateral; one patient had only one seeing eye. A total of 21 eyes with PPS were studied. 52.4% of the eyes revealed retinal pigment epithelium gravitational tracks, outer retinal atrophy, and serous PEDs. None of the eyes showed choroidal folds. Fundus fluorescein angiography showed late leakage at macula in 33% eyes. Fundus autofluorescence showed features of PPS to be similar to central serous chorioretinopathy in most cases., Conclusion: Peripapillary pachychoroid syndrome shares common findings with central serous chorioretinopathy and seems to be a subset of central serous chorioretinopathy than a separate entity in pachychoroid disease spectrum.

Estrogen is essential in maintaining various physiological features in women, and a decline in estrogen levels are known to give rise to numerous unfortunate symptoms associated with menopause. To alleviate these symptoms hormone replacement therapy with estrogen is often used, and has been shown to be fruitful in improving quality of life in women suffering from postmenopausal discomforts. An often forgotten condition associated with menopause is the optic nerve disorder, glaucoma. Thus, estrogen may also have an impact in maintaining the retinal ganglion cells (RGCs), which make up the optic nerve, thereby preventing glaucomatous neurodegeneration. This review aims to provide an overview of possible associations of estrogen and the glaucoma subtype, primary open-angle glaucoma (POAG), by evaluating the current literature through a PubMed-based literature search. Multiple in vitro and in vivo studies of RGC protection, as well as clinical and epidemiological data concerning the well-defined retinal neurodegenerative disorder POAG have been reviewed. Over all, deficiencies in retinal estrogen may potentially instigate RGC loss, visual disability, and eventual blindness. Estrogen replacement therapy may therefore be a beneficial future treatment. However, more studies are needed to confirm the relevance of estrogen in glaucoma prevention., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Visual changes are some of the earliest symptoms that patients with Alzheimer's disease (AD) experience. Pathophysiological processes such as amyloid-β plaque formation, vascular changes, neuroinflammation, and loss of retinal ganglion cells (RGCs) have been detected in the retina of AD patients and animal models. However, little is known about the molecular processes that underlie retinal neurodegeneration in AD. The cellular architecture and constant sensory activity of the retina impose high metabolic demands. We thus hypothesized that energy metabolism might be compromised in the AD retina similarly to what has been observed in the AD brain. To address this question, we explored cellular alterations and retinal metabolic activity in the 5 × FAD mouse model of AD. We used 8-month-old female 5 × FAD mice, in which the AD-related pathology has been shown to be apparent. We observed that RGC density is selectively affected in the retina of 5 × FAD mice. To map retinal metabolic activity, we incubated isolated retinal tissue with [U- 13 C] glucose and analyzed tissue extracts by gas chromatography-mass spectrometry. We found that the retinas of 5 × FAD mice exhibit glucose hypometabolism. Moreover, we detected decreased glutamine synthesis in 5 × FAD retinas but no changes in the expression of markers of Müller glia, the main glial cell type responsible for glutamate uptake and glutamine synthesis in the retina. These findings suggest that AD presents with metabolic alterations not only in the brain but also in the retina that may be detrimental to RGC activity and survival, potentially leading to the visual impairments that AD patients suffer., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The fear of contracting a serious illness caused by a contagious disease limits economic activity even after reopening. Widespread testing alone will not alleviate this problem. We argue that targeted testing in concert with targeted transfers is essential. We propose a model with these features to determine where agents should be tested and how they should be incentivized. Agents with a low wage, a high risk of infection, and who bear a large cost of falling ill should be tested at work. When testing is very costly, agents with high wages and low expected costs associated with falling ill should be tested at home., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.)

Candidemia is one of the significant causes of mortality amongst critically ill patients in Intensive Care Units (ICUs). This study aimed to assess the incidence, risk factors and antifungal susceptibility pattern in candidemia cases admitted in ICU in a tertiary care hospital in Jaipur, Rajasthan from June 2021 to November 2021. Candida species isolated from blood culture of clinically suspected patients of sepsis were defined as candidemia cases. Blood culture and antifungal susceptibility testing were performed as per standard laboratory protocol. Analyses of risk factors was done between candidemia cases and matched controls in a ratio of 1 : 3. Forty-six candidemic cases and 150 matched controls were included in the study. C. tropicalis was the most prevalent species (22/46; 48%) followed by C. auris (8/46; 17%) and C. albicans (7/46; 15%). Candida species showed good sensitivity to echinocandins (97%) followed by amphotericin B (87%) and voriconazole (80%). In multivariate analysis, longer stay in ICU, presence of an indwelling device, use of immunosuppressive drugs and positive SARS-CoV-2 infection were associated with increased risk of candidemia. The constant evaluation of risk factors is required as prediction of risks associated with candidemia may help to guide targeted preventive measures with reduced morbidity and mortality.

Purpose: To compare the anatomical and functional outcomes of drainage through posterior retinotomy versus perfluorocarbon liquid (PFCL)-assisted drainage in vitreoretinal surgery for rhegmatogenous retinal detachment and to study intraoperative and postoperative complications., Methods: This was a prospective randomized study of 52 cases who underwent vitreoretinal surgery for rhegmatogenous retinal detachment. Group 1 underwent PFCL-assisted drainage through preexisting break, whereas Group 2 had posterior retinotomy to drain subretinal fluid. Cases were evaluated for retinal reattachment rates, visual outcomes, optical coherence tomography parameters, and postoperative metamorphopsia. The patients were followed up for minimum period of 3 months., Results: Two groups were comparable in terms of demographic and preoperative parameters. Both groups had single surgery success rate of 100% by the end of follow-up. Final best-corrected visual acuity in Group 1 was 0.61 ± 0.33 and 0.61 ± 0.32 in Group 2 (P = 0.77). Optical coherence tomography parameters (foveal contour, retinal layers, central macular thickness, and epiretinal membrane formation) were similar between the two groups. Subjective metamorphopsia was present in 30.77% (8 of 26) patients in Group-1 and 69.23% (18 of 26) patients in Group-2 (P = 0.034). One eye had retained subretinal PFCL away from the macula in Group 1., Conclusion: Anatomical and functional outcomes were similar in vitrectomy using PFCL-assisted drainage versus posterior retinotomy drainage. Postoperative metamorphopsia was lesser in patients who underwent PFCL-assisted drainage through the pre-existing break.

Purpose: Stress and Type A personality are established risk factors for the development of central serous chorioretinopathy (CSC). Meditation is known to have a positive effect on reducing stress levels. This study aimed to assess the effect of short-term meditation training in patients of CSC., Methods: A pilot study was conducted where 40 patients diagnosed with acute and non-resolving CSC were randomly assigned to either of two groups - meditation training and routine care (without meditation). The primary outcome measure was time to resolution of CSC based on optical coherence tomography and fluorescein angiography. Secondary outcome measures were changes in anxiety score (State-Trait Anxiety Inventory [STAI] scores) and blood pressure. The patients were followed up for a minimum period of 4 months., Results: Twenty cases were included in each group. The demographic pattern, baseline swept-source optical coherence tomography parameters, and STAI scores were similar in both groups. The time to disease resolution was 9.4 ± 4.22 weeks in the meditation group and 19.5 ± 2.79 weeks in the nonmeditation group (P < 0.001). At 4 months, CSC had failed to resolve in 60% of patients with routine care compared with 8% in cases following short-term meditation training. STAI scores showed a reduction in stress levels in the meditation group. Furthermore, statistically significant improvement in systolic and diastolic blood pressures was also observed following meditation training., Conclusion: Short-term meditation training may be a useful approach in the management of patients with CSC as it tends to reduce stress and prehypertension, and promotes earlier resolution of the condition. However, patient's motivation to complete and pursue the meditation training is a significant barrier., Competing Interests: None

Purpose: To determine the utility of optical coherence tomography-angiography (OCT-A) in diabetic retinopathy (DR) and comparison versus fluorescein angiography (FA) in vision-threatening diabetic retinopathy (VTDR)., Methods: In this cross-sectional observational study, 60 eyes with no DR (NDR), 60 eyes with non-proliferative diabetic retinopathy (NPDR), and 60 eyes with proliferative diabetic retinopathy (PDR) underwent OCT-A. FA was done in VTDR. OCT-A of the NDR eyes was analyzed by two independent retina specialists. Vessel density (VD) (mm/mm 2 ), perfusion density (PD) (%), and foveal avascular zone (FAZ) (mm 2 ) area was analyzed among the groups. Montage angiography with vitreoretinal interface (VRI) segmentation was done in PDR. A qualitative comparison was done between OCT-A and FA for features of DR., Results: OCT-A detected 16.66% of the eyes with microaneurysm and 57.5% of the patients with capillary non-perfusion (CNP) areas in the NDR group. The inter-grader coefficient between the two observers was 0.820 for microaneurysm and 0.880 for CNP. The mean VD in NDR, NPDR, and PDR was 16.865, 13.983, and 11.643 mm/mm 2 . The mean PD in NDR, NPDR, and PDR was 30.595, 26.853, and 23.193%. The VD and PD values were statistically significant (P < 0.001). The mean FAZ area was not statistically significant (NPDR and PDR) (P > 0.05). The VRI showed elevated neovascularization in four eyes. OCT-A delineated microaneurysm and FAZ in 97/97 eyes who underwent FA. The FA failed to delineate FAZ in 2/37 NPDR eyes and 13/60 PDR eyes. The CNP areas (OCT-A) were detectable in all eyes. The FA demonstrated CNP areas in 17/37 and 36/60 eyes in NPDR and PDR, respectively. The FA could show peripheral CNP., Conclusion: The OCT-A helps in the early diagnosis of DR by providing vascular indices which are consistent with disease progression. OCT-A is non-invasive and ideal for follow-up. FA is a dynamic test with a larger field of view., Competing Interests: None