Diabetes IN hospital - Glucose and Outcomes in the COVID-19 pandemic (DINGO COVID-19): the 2020 Melbourne hospital experience prior to novel variants and vaccinations.

BACKGROUND AND AIMS: A relationship between diabetes, glucose and COVID-19 outcomes has been reported in international cohorts. This study aimed to assess the relationship between diabetes, hyperglycaemia and patient outcomes in those hospitalised with COVID-19 during the first year of the Victorian pandemic prior to novel variants and vaccinations. DESIGN, SETTING: Retrospective cohort study from March to November 2020 across five public health services in Melbourne, Australia. PARTICIPANTS: All consecutive adult patients admitted to acute wards of participating institutions during the study period with a diagnosis of COVID-19, comprising a large proportion of patients from residential care facilities and following dexamethasone becoming standard-of-care. Admissions in patients without known diabetes and without inpatient glucose testing were excluded. RESULTS: The DINGO COVID-19 cohort comprised 840 admissions. In 438 admissions (52%), there was no known diabetes or in-hospital hyperglycaemia, in 298 (35%) patients had known diabetes, and in 104 (12%) patients had hyperglycaemia without known diabetes. ICU admission was more common in those with diabetes (20%) and hyperglycaemia without diabetes (49%) than those with neither (11%, P < 0.001 for all comparisons). Mortality was higher in those with diabetes (24%) than those without diabetes or hyperglycaemia (16%, P = 0.02) but no difference between those with in-hospital hyperglycaemia and either of the other groups. On multivariable analysis, hyperglycaemia was associated with increased ICU admission (adjusted odds ratio (aOR) 6.7, 95% confidence interval (95% CI) 4.0-12, P < 0.001) and longer length of stay (aOR 173, 95% CI 11-2793, P < 0.001), while diabetes was associated with reduced ICU admission (aOR 0.55, 95% CI 0.33-0.94, P = 0.03). Neither diabetes nor hyperglycaemia was independently associated with in-hospital mortality. CONCLUSIONS: During the first year of the COVID-19 pandemic, in-hospital hyperglycaemia and known diabetes were not associated with in-hospital mortality, contrasting with published international experiences. This likely mainly relates to hyperglycaemia indicating receipt of mortality-reducing dexamethasone therapy. These differences in published experiences underscore the importance of understanding population and clinical treatment factors affecting glycaemia and COVID-19 morbidity within both local and global contexts.

Squalene hopene cyclases and oxido squalene cyclases: potential targets for regulating cyclisation reactions.

Squalene hopene cyclases (SHC) convert squalene, the linear triterpene to fused ring product hopanoid by the cationic cyclization mechanism. The main function of hopanoids, a class of pentacyclic triterpenoids in bacteria involves the maintenance of membrane fluidity and stability. 2, 3-oxido squalene cyclases are functional analogues of SHC in eukaryotes and both these enzymes have fascinated researchers for the high stereo selectivity, complexity, and efficiency they possess. The peculiar property of the enzyme squalene hopene cyclase to accommodate substrates other than its natural substrate can be exploited for the use of these enzymes in an industrial perspective. Here, we present an extensive overview of the enzyme squalene hopene cyclase with emphasis on the cloning and overexpression strategies. An attempt has been made to explore recent research trends around squalene cyclase mediated cyclization reactions of flavour and pharmaceutical significance by using non-natural molecules as substrates.

An Unusual Antenatal Presentation of a Mature Pericardial Teratoma Masquerading as Congenital Pulmonary Airway Malformation.

We report an antenatal presentation of a huge pericardial mature teratoma that was referred as congenital pulmonary airway malformation (CPAM) in the late third trimester of pregnancy. Initial ultrasound evaluation revealed a huge predominantly cystic lesion with mixed echogenicity in the left hemithorax. A provisional diagnosis of pleural tumor was considered in view of previous scans at 20‒28 weeks being normal and associated pleural effusion. Magnetic resonance imaging of the fetus reported the lesion to be CPAM which was supported by postnatal computed tomographic imaging done on day 2 of life. However, intraoperatively, the lesion was found to be of pericardial origin which on subsequent histopathological examination was confirmed to be mature teratoma. We recommend considering potential differential diagnosis other than CPAM, especially when the lesion is found for the first time in the late third trimester.

Lethal Cenani Lenz syndrome in two consecutive pregnancies: Further extension of phenotype from Maldives.

Cenani Lenz syndrome is a rare autosomal recessive disorder associated with variable degree of limb malformations, dysmorphism, and renal agenesis. It is caused due to pathogenic variants in the LRP4 gene, which plays an important role in limb and renal development. Mutations in the APC gene have also been occasionally associated with CLS. The phenotypic spectrum ranges from mild to very severe perinatal lethal type depending on the type of variant. We report a pathogenic variant, c.2710 del T (p.Trp904GlyfsTer5) in theLRP4 gene, in a fetus with lethal Cenani Lenz syndrome with antenatal presentation of tetraphocomelia and symmetrical involvement of hands and feet.

Environmental Adaptations of an Extremely Plant Beneficial Bacillus subtilis Dcl1 Identified Through the Genomic and Metabolomic Analysis.

Bacterial endophytes ubiquitously colonize the internal tissues of plants and promote the plant growth through diverse mechanisms. The current study describes the mechanistic basis of plant-specific adaptations present in an extremely beneficial endophytic bacterium. Here, the endophytic Bacillus subtilis Dcl1 isolated from the dried rhizome of Curcuma longa was found to have the drought tolerance, IAA and ACC deaminase production and phosphate solubilization properties. The whole genome sequencing and annotation further showed the genome of B. subtilis Dcl1 to have the size of 4,321,654 bp. This also showed the presence of genes for IAA, H2S, acetoin, butanediol, flagella and siderophore production along with phosphate solubilization and biofilm formation for the B. subtilis Dcl1. In addition, the genes responsible for the synthesis of surfactin, iturin, fengycin, bacillibactin, bacillaene, bacilysin, chitinase, chitosanase, protease and glycoside hydrolase could also be annotated from the genome of B. subtilis Dcl1. Identification of genes for the glycine betaine, glutamate and trehalose further indicated the drought stress tolerance features of B. subtilis Dcl1. The presence of the genetic basis to produce the catalase, superoxide dismutase, peroxidases, gamma-glutamyltranspeptidase, glutathione and glycolate oxidase also indicated the plant oxidative stress protective effect of B. subtilis Dcl1. Identification of these properties and the demonstration of its plant probiotic effect in Vigna unguiculata confirmed the applicability of B. subtilis Dcl1 as a biofertilizer, biocontrol and bioremediator agent to enhance the agricultural productivity.

Drought-tolerant and plant growth-promoting endophytic Staphylococcus sp. having synergistic effect with silicate supplementation.

Endophytic bacteria have been reported to have symbiotic, mutualistic, commensalistic or trophobiotic relationships with various plant parts. As part of its adaptation, many endophytic organisms are known to exhibit properties with multiple beneficial effects to the plant system. Even though many bacterial genera have been identified to have endophytic association, isolation of those which were previously demonstrated well for human association is quite interesting. In the study, endophytic bacteria Ceb1 isolated from the rhizome of Curcuma longa was identified by 16S rDNA sequencing as Staphylococcus sp. Further, Ceb1 was observed to have the ability to tolerate drought stress. While screening for the plant growth-promoting traits, Ceb1 was found to be positive for IAA production both under drought-stressed and normal conditions as confirmed by HPLC. The Ceb1 priming with Vigna unguiculata was observed to enhance the growth parameters of the plant. Analysis of Ceb1-treated plants by ICP-MS further showed modulation of both macro- and micronutrients. Upon drought stress induction in Vigna unguiculata, Ceb1 was found to provide synergistic plant growth-promoting effect to the plant along with the supplemented silicate sources. Under the changing agroclimatic conditions, exploring the plant stress-alleviating effects of endophytes is highly significant.

4-4' Diaponeurosporenic Acid, the C30 Carotenoid Pigment in Endophytic Pseudomonas Mendocina with Squalene Cyclase Activity.

Even though organisms with squalene hopene cyclase activity involved in hopanoid synthesis has been reported earlier, their existence along with carotenoid synthesis is rarely reported. Here, we report the existence of hopanoid and C30 carotenoid biosynthetic pathway in Pseudomonas mendocina, the squalene hopene cyclase producing endophyte of the medicinal plant Murraya koenigii. The enzyme squalene hopene cyclase from Pseudomonas mendocina is involved in the synthesis of dehydrosqualene-mediated alternate pathway for carotenoid biosynthesis. The hopanoids are involved in membrane stability and integrity, and the carotene chromophores are involved in the photo protection of the cell. The orange-colored C30 carotenoid pigment 4-4' diaponeurosporenic acid in the extracellular extract of Pseudomonas mendocina with squalene cyclase activity was detected by the combination of UV/Vis spectrometry, FTIR, and Mass Spectrometry. 4-4' diaponeurosporenic acid could be traced as the end product of the carotenoid pathway and belonged to the xanthophyll group of carotenoids.

Pro-inflammatory cytokines and their epistatic interactions in genetic susceptibility to schizophrenia.

BACKGROUND: In schizophrenia, genetic background may provide a substrate for intrinsic maldevelopment of the brain through environmental influences, by recruiting neurotrophic factors and cytokines, to trigger the changes that lead to impaired neuronal functions. Cytokines being the key regulators of immune/inflammatory reactions are also known to influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. Therefore, functional polymorphisms in cytokine genes may result in imbalances in the pro- and anti-inflammatory cytokine production. METHODS: We screened polymorphisms in pro- and anti-inflammatory cytokine genes using a case-control association study in a South Indian population. The role of allele, genotype, haplotype, and diplotypes of these cytokine genes and their epistatic interactions were assessed in contributing to the risk of developing schizophrenia. Meta-analysis for the reported associations was also monitored for global significance. RESULTS: The pro-inflammatory cytokine gene polymorphisms in IL1Ars1800587, IL6rs1800796, TNFArs361525, and IFNGrs2069718 were associated with schizophrenia. The study also provides significant evidence for strong epistatic interactions among pro-inflammatory cytokine genes IL6 and IFNG in the development of schizophrenia. In silico analysis suggested that associated risk variants were indicative of altered transcriptional activity with higher production of IL1α, IL-6, TNF-α, and IFN-ɤ cytokines. Meta-analysis indicated heterogeneity among study population while IL1Ars1800587 was found to be globally significant. CONCLUSIONS: It is important to identify the nature of inflammatory response that can be amplified by the environment, to influence either Th1 response or Th2 response. The associated functional variants in the study are involved with increased expression resulting in higher production of the pro-inflammatory cytokines IL-1α, IL-6, TNF-α, and IFN-γ. The interaction of immunological stressors with these high producer alleles of pro-inflammatory cytokines may suggest that even a lower threshold may be sufficient to induce a resultant chronic effect on the psycho-social and environmental stressors that may result in the development and pathogenesis of schizophrenia. Understanding environmental factors that influence the expression of these pro-inflammatory cytokine genes or their interaction can possibly help in dissecting the phenotypic variation and therapeutic response to antipsychotics in schizophrenia.

Sodium levels of human pancreatic donors are a critical factor for determination of islet efficacy and survival.

Organs from hypernatremia (elevated Na+) donors when used for transplantation have had dismal outcomes. However, islet isolation from hypernatremic donors for both transplantation and research applications has not yet been investigated. A retrospective analysis of in vivo and in vitro islet function studies was performed on islets isolated from hypernatremic (serum sodium levels≥160 meq/l) and normal control (serum sodium levels≤155 meq/l) donors. Twelve isolations from 32 hypernatremic and 53 isolations from 222 normal donors were randomly transplanted into diabetic NOD Scid mice. Sodium levels upon pancreas procurement were significantly elevated in the hypernatremia group (163.5±0.6 meq/l) compared with the normal control group (145.9±0.4 meq/l) (P<0.001). The postculture islet recovery rate was significantly lower in the hypernatremia (59.1±3.8%) group compared with the normal (73.6±1.8%) group (P=0.005). The duration of hypernatremia was inversely correlated with the recovery rate (r2=0.370, P<0.001). Furthermore, the percentage of successful graft function when transplanted into diabetic NOD Scid mice was significantly lower in the hypernatremia (42%) group compared with the normal control (85%) group (P<0.001). The ability to predict islet graft function posttransplantation using donor sodium levels and duration of hypernatremia was significant (ROC analysis, P=0.022 and 0.042, respectively). In conclusion, duration of donor hypernatremia is associated with reduced islet recovery postculture. The efficacy of islets from hypernatremia donors diminished when transplanted into diabetic recipients.

The zinc finger transcription factor Jing is required for dendrite/axonal targeting in Drosophila antennal lobe development.

An important role in olfactory system development is played by transcription factors which act in sensory neurons or in their interneuron targets as cell autonomous regulators of downstream effectors such as cell surface molecules and signalling systems that control neuronal identity and process guidance. Some of these transcriptional regulators have been characterized in detail in the development of the neural elements that innervate the antennal lobe in the olfactory system of Drosophila. Here we identify the zinc finger transcription factor Jing as a cell autonomously acting transcriptional regulator that is required both for dendrite targeting of projection neurons and local interneurons as well as for axonal targeting of olfactory sensory neurons in Drosophila olfactory system development. Immunocytochemical analysis shows that Jing is widely expressed in the neural cells during postembryonic development. MARCM-based clonal analysis of projection neuron and local interneuron lineages reveals a requirement for Jing in dendrite targeting; Jing loss-of-function results in loss of innervation in specific glomeruli, ectopic innervation of inappropriate glomeruli, aberrant profuse dendrite arborisation throughout the antennal lobe, as well as mistargeting to other parts of the CNS. ey-FLP-based MARCM analysis of olfactory sensory neurons reveals an additional requirement for Jing in axonal targeting; mutational inactivation of Jing causes specific mistargeting of some olfactory sensory neuron axons to the DA1 glomerulus, reduction of targeting to other glomeruli, as well as aberrant stalling of axons in the antennal lobe. Taken together, these findings indicate that Jing acts as a key transcriptional control element in wiring of the circuitry in the developing olfactory sensory system in Drosophila.

Methylome-wide and meQTL analysis helps to distinguish treatment response from non-response and pathogenesis markers in schizophrenia.

Schizophrenia is a complex condition with entwined genetic and epigenetic risk factors, posing a challenge to disentangle the intermixed pathological and therapeutic epigenetic signatures. To resolve this, we performed 850K methylome-wide and 700K genome-wide studies on the same set of schizophrenia patients by stratifying them into responders, non-responders, and drug-naïve patients. The key genes that signified the response were followed up using real-time gene expression studies to understand the effect of antipsychotics at the gene transcription level. The study primarily implicates hypermethylation in therapeutic response and hypomethylation in the drug-non-responsive state. Several differentially methylated sites and regions colocalized with the schizophrenia genome-wide association study (GWAS) risk genes and variants, supporting the convoluted gene-environment association. Gene ontology and protein-protein interaction (PPI) network analyses revealed distinct patterns that differentiated the treatment response from drug resistance. The study highlights the strong involvement of several processes related to nervous system development, cell adhesion, and signaling in the antipsychotic response. The ability of antipsychotic medications to alter the pathology by modulating gene expression or methylation patterns is evident from the general increase in the gene expression of response markers and histone modifiers and the decrease in class II human leukocyte antigen (HLA) genes following treatment with varying concentrations of medications like clozapine, olanzapine, risperidone, and haloperidol. The study indicates a directional overlap of methylation markers between pathogenesis and therapeutic response, thereby suggesting a careful distinction of methylation markers of pathogenesis from treatment response. In addition, there is a need to understand the trade-off between genetic and epigenetic observations. It is suggested that methylomic changes brought about by drugs need careful evaluation for their positive effects on pathogenesis, course of disease progression, symptom severity, side effects, and refractoriness.

How hairfall saved the patient from cancer twice - A postmenopausal patient with synchronous endometrial and endocervical carcinomas presenting with endocrine symptoms.

Ovarian stromal hyperthecosis is an uncommon nonneoplastic cause of ovarian hyperandrogenism mainly in postmenopausal women. Here, we present a case of a postmenopausal woman who presented with features of virilization like alopecia and hirsutism. During its workup, two malignancies were diagnosed at a very early stage. Microscopic focus of endometrial adenocarcinoma in a polyp and similar focus of endocervical adenocarcinoma in the subsequent hysterectomy specimen were noted. Presence of synchronous malignancies in the uterus is very rare and it being detected in a patient who presented with a non-related symptom of hairfall makes it an interesting case scenario.

Comparative study of surgical outcomes of twin-site phacotrabeculectomy with mitomycin C in primary open-angle glaucoma versus primary angle-closure glaucoma.

Purpose: To compare the surgical outcomes of twin-site phacotrabeculectomy with Mitomycin C (MMC) in primary open-angle glaucoma (POAG) versus primary angle-closure glaucoma (PACG). Methods: Prospective, comparative, observational study. Patients with visually significant cataract and primary glaucoma were divided into two groups: POAG and PACG. They underwent twin-site phacotrabeculectomy with MMC and followed up on days 1, 15, 1 month, 6 months, and 12 months. Baseline and follow-up visits were compared to find the differences in intraocular pressure (IOP), antiglaucoma medications (AGM), success rates, anterior chamber depth (ACD), and axial length (AXL). Results: There were 50 eyes each in POAG and PACG groups. Mean IOP reduction from baseline to 12 months (21.22 ± 6.0 to 11.40 ± 2.8-POAG group vs 24.16 ± 7.6 to 12.42 ± 3.2-PACG group) was statistically significant in both groups (P < 0.001), but no significant difference between groups (P = 0.095). There was a statistically significant decline in the number of AGM in POAG [1.66 (0.7) to 0.38 (0.7), P < 0.001] and PACG [2.10 (0.7) to 0.70 (0.8), P < 0.001]; the decline was more in POAG (P = 0.012) at last visit. Probability of overall (complete and qualified) success at 12 months postop was 72.0% [95% confidence interval (CI): 57.4-82.4] in PACG and 84.0% (95% CI: 70.5-91.7) in POAG group. There was a significant increase in ACD and a decrease in AXL in both groups (P < 0.001). More interventions were required in the PACG group (38, P = 0.012). Conclusion: Phacotrabeculectomy with MMC causes a significant reduction in IOP and improvement in biometric parameters in both POAG and PACG. Patients with PACG required more postoperative interventions, while a lesser number of antiglaucoma medications were needed in POAG patients.

Association of molecular subgroups with pathological parameters in endometrial carcinomas.

BACKGROUND: The integration of molecular features into the already existing pathological classification of endometrial carcinomas will offer significant prognostic information. As the literature search reveals, there are no studies from India that have classified these carcinomas based on molecular subtypes. The aim of the study was to classify endometrial carcinomas into four subtypes based on their molecular and immunohistochemical features and to find out the association of each of these molecular subtypes with the other pathological parameters. METHODS: A prospective study was done on 37 consecutive cases of fresh hysterectomy specimens, biopsy-proven as endometrial carcinomas between November 2019 and August 2020. Three immunohistochemical markers (p53, mismatch repair proteins,MutS homolog6 and Postmeiotic seggregation 2 respectively[MSH6, and PMS2]), along with DNA (deoxyribonucleic acid) sequencing of selected regions of the POLE gene was performed in each of the 37 cases. Endometrial carcinomas were subclassified into four subtypes, and the association of each of these four subtypes with the other pathological parameters was also explored. Statistical analysis was done using the IBM Statistical Package for the Social Science (SPSS) Version 20.0 software (IBM SPSS, USA). RESULTS: Among the 37 cases studied, eight (21.6%) cases were p53 abnormal, eight (21.6%) cases showed MMR-D (mismatch repair deficient), one case (2.7%) showed mutation of POLE, and 21 cases (56.8%) were assembled under p53 wild-type. Higher grade endometrial carcinomas showed more (80.0%) p53 abnormal (P < 0.001). All the p53 wild-type (100%) were of Type 1 endometrial carcinoma subtype (P = 0.001) and low-grade type (90.5%; P = 0.005). CONCLUSION: Our study confirms that the type of carcinoma and grade correlates with p53 expression, p53 abnormal being associated with higher grade and type 2 endometrial carcinomas, whereas p53 wild-type is associated with low-grade and type 1 endometrial carcinoma. There was only one case of the POLE subtype identifiable in our study.

Establishing an effective antimicrobial stewardship program at four secondary-care hospitals in India using a hub-and-spoke model.

Background: The high burden of antimicrobial resistance in India necessitates the urgent implementation of antimicrobial stewardship programs (ASPs) in all healthcare settings in India. Most ASPs are based at tertiary-care centers, with sparse data available regarding the effectiveness of an ASP in a low-resource primary/secondary-care setting. Methods: We adopted a hub-and-spoke model to implement ASPs in 4 low-resource, secondary-care healthcare settings. The study included 3 phases measuring antimicrobial consumption data. In the baseline phase, we measured days on antimicrobial therapy (DOTs) with no feedback provided. This was followed by the implementation of a customized intervention package. In the postintervention phase, prospective review and feedback were offered by a trained physician or ASP pharmacist, and days of therapy (DOT) were measured. Results: In the baseline phase, 1,459 patients from all 4 sites were enrolled; 1,233 patients were enrolled in the postintervention phase. Both groups had comparable baseline characteristics. The key outcome, DOT per 1,000 patient days, was 1,952.63 in the baseline phase and significantly lower in the post-intervention period, at 1,483.06 (P = .001). Usage of quinolone, macrolide, cephalosporin, clindamycin, and nitroimidazole significantly decreased in the postintervention phase. Also, the rate of antibiotic de-escalation was significantly higher in the postintervention phase than the baseline phase (44% vs 12.5%; P < .0001), which suggests a definite trend toward judicious use of antibiotics. In the postintervention phase, 79.9% of antibiotic use was justified. Overall, the recommendations given by the ASP team were fully followed in 946 cases (77.7%), partially followed in 59 cases (4.8%), and not followed in 137 cases (35.7%). No adverse events were noted. Conclusion: Our hub-and-spoke model of ASP was successful in implementing ASPs in secondary-care hospitals in India, which are urgently needed.

Endometriosis in clear cell and endometrioid carcinoma ovary: its impact on clinicopathological characteristics and survival outcomes.

Background: Malignant transformation in endometriosis was first described by Sampson in 1925. There is now sufficient evidence of its association specifically with endometrioid (EOC) and clear cell ovarian cancer (CCOC). Whether endometriosis-associated ovarian cancer (EAOC) is a distinct clinicopathological entity from non-endometriosis-associated ovarian cancer (NEAOC) remains uncertain. Objectives: This study aimed to assess the impact of endometriosis on clinical characteristics and survival outcomes in EOC and CCOC. Methods: This is a retrospective single-institution analysis of patients diagnosed with CCOC AND EOC between 2010 and 2021. Demographic and clinical presentation data were obtained from medical records. Patients were followed up till March 2023. Statistical analysis was done using the IBM SPSS Statistics 20 Windows. Results: Of the 77 cases of CCOC and EOC ovary, 38 had histopathologically proven endometriosis. There was no difference in age (51.62 and 50.05 years, respectively), body mass index, parity, menopausal status and CA 125 levels at presentation. Ascites was more frequent in the absence of endometriosis (30% versus 8.1%, p = 0.015). However, this did not translate to a statistical difference in the stage, with the majority presenting in the early stage. (94% versus 83%). All 78 patients underwent primary cytoreduction with equal rates of optimal resection.There was no difference in the mean disease-free interval between EAOC and NEAOC (107.6 and 109.4 months, p 0.484). Recurrences were predominantly pelvic in both groups. The disease-specific survival was 111.7 and 120.1 months, respectively, with and without endometriosis. This was however not statistically significant (p 0.751). Conclusion: In the Indian population, endometriosis did not have any impact on the age at presentation, CA 125 levels, stage of the disease and survival outcomes in EOC and CCOC ovary.

Validating saliva as a biological sample for cost-effective, rapid and routine screening for SARS-CoV-2.

PURPOSE: Compared to nasopharyngeal/oropharyngeal swabs (N/OPS-VTM), non-invasive saliva samples have enormous potential for scalability and routine population screening of SARS-CoV-2. In this study, we investigate the efficacy of saliva samples relative to N/OPS-VTM for use as a direct source for RT-PCR based SARS-CoV-2 detection. METHODS: We collected paired nasopharyngeal/oropharyngeal swabs and saliva samples from suspected positive SARS-CoV-2 patients and tested using RT-PCR. We used generalized linear models to investigate factors that explain result agreement. Further, we used simulations to evaluate the effectiveness of saliva-based screening in restricting the spread of infection in a large campus such as an educational institution. RESULTS: We observed a 75.4% agreement between saliva and N/OPS-VTM, that increased drastically to 83% in samples stored for less than three days. Such samples processed within two days of collection showed 74.5% test sensitivity. Our simulations suggest that a test with 75% sensitivity, but high daily capacity can be very effective in limiting the size of infection clusters in a workspace. Guided by these results, we successfully implemented a saliva-based screening in the Bangalore Life Sciences Cluster (BLiSC) campus. CONCLUSION: These results suggest that saliva may be a viable alternate source for SARS-CoV-2 surveillance if samples are processed immediately. Although saliva shows slightly lower sensitivity levels when compared to N/OPS-VTM, saliva collection is logistically advantageous. We strongly recommend the implementation of saliva-based screening strategies for large workplaces and in schools, as well as for population-level screening and routine surveillance as we learn to live with the SARS-CoV-2 virus.

Innovator Versus Biosimilar Ranibizumab in Polypoidal Choroidal Vasculopathy: Real-World Evidence.

INTRODUCTION: To analyze the efficacy and safety profile of the intravitreal ranibizumab biosimilar molecule, Razumab® (Intas Pharmaceuticals, Ahmedabad, India; BRm; Razumab®) and the innovator ranibizumab drug (IRm; LUCENTIS®) in Indian patients with polypoidal choroidal vasculopathy (PCV) under real-world conditions. METHODS: This was a retrospective study of treatment-naïve and previously treated PCV eyes undergoing intravitreal therapy with either BRm or IRm from January 2019 to September 2020 as three loading doses followed by a pro-re-nata (PRN) regimen. Changes in the best-corrected visual acuity (BCVA), subretinal fluid (SRF), intraretinal fluid (IRF), SRF height, and subfoveal choroidal thickness (SFCT) and the safety profiles were assessed at weeks 12, 24, and 52, respectively. RESULTS: A total of 22 eyes received IRm and 19 eyes underwent BRm therapy, respectively. Both the groups were comparable in age (P = 0.41) and gender distribution, although the BRm arm had significantly more eyes that were previously treated (P < 0.00001) with a greater median number of injections (P < 0.0001). At week 52, both groups had similar gains in visual acuity (P = 0.19), SRF resolution (P = 0.8), IRF resolution (P = 0.47), and SRF height (P = 0.71). The IRm eyes exhibited a significant improvement in BCVA (P = 0.001) at all visits with a greater mean number of injections (IRm: 5.41 ± 0.94; BRm: 4 ± 1.45; P = 0.0004), while the BRm eyes showed a similar increase in BCVA but did not reach statistical significance until week 52. The SFCT decreased significantly in the BRm arm at week 52 (P = 0.045). One eye (5.26%) in the BRm arm experienced mild anterior uveitis, which was treated with topical corticosteroids. In either arm, no other ocular or systemic adverse effects were observed. CONCLUSIONS: Our real-world data demonstrated the ranibizumab biosimilar Razumab to have comparable visual acuity outcomes to the innovator ranibizumab molecule with an adequate safety profile in the management of PCV. Although these encouraging results support its use as a viable alternative to the innovator molecule, further prospective studies in a diverse patient population are needed to validate our findings.