Repurposing surgical wards in pandemics - An appraisal of outcomes of COVID-19 patients treated in Orthopaedic wards.

Background: The COVID-19 pandemic resulted in a shift in the way healthcare resources were used. While India faced limited effects in the first COVID wave primarily due to strict lockdown of the county, it was one of the worst affected in the second wave and at one time reported the highest number of daily cases. To address the lack of intensive care units (ICU) beds, the surgical wards of our institute were repurposed to take care of patients requiring supplementary oxygen and other supportive care till either they improved or an ICU bed was available. The medical personnel in charge of the surgical wards were entrusted with the care of patients with support from intensive care support teams (ICST). Aims: We aimed to examine the clinical details of patients admitted in the repurposed orthopaedic wards during the second COVID wave and to evaluate the factors that might affect the clinical outcomes in such patients. Methods: This was a retrospective review of records of patients admitted in the repurposed orthopaedic wards between 16 April 2021 and 20 May 2021. Details related to demography, COVID-19 presentation, COVID-19-related management and clinical course, including transfers to ICUs, and outcomes in terms of either discharge to home or death were recorded. They were analysed using statistical software. Results: One hundred and twenty three patients were treated during the said period. Twenty patients died during treatment, resulting in a mortality rate of 16.3%. Age, gender, RT-PCR status, pre-existing comorbidities, SpO2 at admission, method of supplemental oxygen supply, total leukocyte counts, haemoglobin values, serum C-reactive protein, Lactate dehydrogenase (LDH) and creatinine values had no statistically significant association with death of a patient during treatment. Conclusion: Based on the results, one can state that clinicians of surgical specialities having background knowledge of internal medicine from undergraduate education can manage patients of COVID-19 with support from ICST with reasonable outcomes. In case of future pandemics, surgical wards can be repurposed to tide over exigencies. Additionally, primary care physicians, who are often the first point of contact for patients, can allay their apprehensions adequately in future pandemics, thus preventing widespread panic and burdening of healthcare resources.

Helicobacter pylori present in caries sample among dental caries patients.

Helicobacter pylori is Gram negative bacteria, the reason for causing peptic ulcer. There is suggestion between the presence of H. pylori in oral cavity and gastritis. The present study aimed to detect H. pylori in dental caries samples. The study included 29 dental caries patients from both sexes (13 males and 16 females), with different age groups (children and adult), and nine apparently healthy subject as a control group (2 males & 7 females). Dental caries samples were collected and investigated for this study from patients with dental caries who visited the Dental Faculty in the College of Dentistry, University of Babylon, Iraq. H. pylori antigen was detected using an enzyme linked immunosorbent assay (ELISA) technique. Of the 29 dental caries patients, 19 (65.51%) patients were positive for H. pylori antigen test. Most of them were in the age group 20-30 (9 patients) & 30-40 (8 patients). The age groups (10-20) & (40-50) years shows 100% positivity for H. pylori antigen. Also, result was recorded significant higher difference's between H. pylori positive antigen between dental caries patients and H. pylori positive antigen among control group. (t=2.697,df=5, p≤ 0.05). Pearson correlation recorded significantly higher association between the presence of H. pylori antigen and the dental caries infection among test group (r=1, p≤ 0.000), 4 (44.5%) of the 9 control subjects, without dental caries, were positive for H. pylori antigen test. In summary, the H. pylori positive antigen test was recorded in both dental caries patients (65.51%) and in the control group (62.5 %). In conclusion, H. pylori antigen was present in dental caries patients. This could indicate that the bacteria H. pylori present in dental caries samples may contribute to caries processes.

Postoperative Outcomes After Emergency Surgery in COVID-19 Patients: An Ambispective Matched Cohort Study.

Purpose There is limited data from the Indian subcontinent regarding the surgical outcomes of coronavirus disease (COVID-19) patients. In this observational study, we aimed to evaluate the postoperative outcomes after emergency surgery in COVID-19 patients compared to concurrent age and gender-matched controls. We also sought to analyze the possible predictors of postoperative mortality in COVID-19 patients. Methods This matched cohort study was conducted in a tertiary care teaching hospital in central India, between 1st July 2021 and 30th June 2022. COVID-19-positive patients undergoing emergency surgery under anesthesia were recruited as cases. Age and gender-matched COVID-19-negative patients undergoing a similar nature of surgery in the same period served as concurrent controls. The cases and controls were compared for the 30-day mortality and perioperative complications. Results The COVID-19-positive surgical cohort had a 12.3 times greater 30-day postoperative overall mortality risk as compared to a matched cohort of patients with a negative COVID-19 test. A positive COVID-19 status was associated with more postoperative complications of acute respiratory distress syndrome (ARDS), sepsis, shock, and persistent hyperglycemia. On analysis of predictors of mortality, the presence of preoperative dyspnea, ARDS, American Society of Anesthesiologists Physical Status (ASA-PS) Class IIIE/IVE, increase in sequential organ failure assessment (SOFA) score, Quick SOFA>1, higher creatinine, bilirubin, and lower albumin were observed to be associated with increased mortality. Conclusions Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients undergoing emergency surgery is significantly associated with higher postoperative complications and increased 30-day postoperative mortality.

The analgesic efficacy of ultrasound-guided erector spinae plane block versus ultrasound-guided caudal epidural block for abdominal surgery in pediatric patients - A patient and assessor-blind, randomized controlled study.

Background: Literature on the efficacy and safety of erector spinae plane block (ESPB) in pediatric patients is limited. Hence, we aimed to compare ESPB versus caudal epidural block (CEB) in children undergoing abdominal surgery. Methods: In this patient and assessor-blind study, fifty-two ASA I-II patients, between 1 to 9 years of age, were randomized into groups of 26 each. ESPB group received unilateral or bilateral ultrasound (USG)-guided ESPB with 0.5 ml/kg of 0.25% bupivacaine per side. CEB group received USG-guided CEB with 1 ml/kg of 0.25% bupivacaine. The primary objective was to estimate the proportion of patients requiring postoperative rescue analgesia. The secondary objectives were to assess postoperative Face, Legs, Activity, Cry and Consolability (FLACC) scale scores, duration of analgesia, and consumption of rescue analgesic drugs. Results: More patients in the ESPB group (88.4%), compared to the CEB group (42.3%), required rescue analgesics (P value <0.001). FLACC scores in the ESPB group, though satisfactory, were inferior, to the CEB group. The duration of postoperative analgesia was shorter in the ESPB group by 9.54 h (95% CI: 4.51 to 14.57 h, P value <0.001). The median (IQR) consumption of rescue paracetamol was significantly higher in the ESPB group (20 mg/kg (10,20) compared to the CEB group (0.0 mg/kg (0.0,10) P value <0.001)). No adverse effects were reported. Conclusion: In children undergoing abdominal surgery, both ESPB and CEB were safe and efficacious. CEB provided a longer duration and better quality of analgesia. ESPB may be considered when CEB is contraindicated or difficult.

Novel B-DNA dermatophyte assay for demonstration of canonical DNA in dermatophytes: Histopathologic characterization by artificial intelligence.

We describe a novel assay and artificial intelligence-driven histopathologic approach identifying dermatophytes in human skin tissue sections (ie, B-DNA dermatophyte assay) and demonstrate, for the first time, the presence of dermatophytes in tissue using immunohistochemistry to detect canonical right-handed double-stranded (ds) B-DNA. Immunohistochemistry was performed using anti-ds-B-DNA monoclonal antibodies with formalin-fixed paraffin-embedded tissues to determine the presence of dermatophytes. The B-DNA assay resulted in a more accurate identification of dermatophytes, nuclear morphology, dimensions, and gene expression of dermatophytes (ie, optical density values) than periodic acid-Schiff (PAS), Grocott methenamine silver (GMS), or hematoxylin and eosin (H&E) stains. The novel assay guided by artificial intelligence allowed for efficient identification of different types of dermatophytes (eg, hyphae, microconidia, macroconidia, and arthroconidia). Using the B-DNA dermatophyte assay as a clinical tool for diagnosing dermatophytes is an alternative to PAS, GMS, and H&E as a fast and inexpensive way to accurately detect dermatophytosis and reduce the number of false negatives. Our assay resulted in superior identification, sensitivity, life cycle stages, and morphology compared to H&E, PAS, and GMS stains. This method detects a specific structural marker (ie, ds-B-DNA), which can assist with diagnosis of dermatophytes. It represents a significant advantage over methods currently in use.

An ncRNA transcriptomics-based approach to design siRNA molecules against SARS-CoV-2 double membrane vesicle formation and accessory genes.

BACKGROUND: The corona virus SARS-CoV-2 is the causative agent of recent most global pandemic. Its genome encodes various proteins categorized as non-structural, accessory, and structural proteins. The non-structural proteins, NSP1-16, are located within the ORF1ab. The NSP3, 4, and 6 together are involved in formation of double membrane vesicle (DMV) in host Golgi apparatus. These vesicles provide anchorage to viral replicative complexes, thus assist replication inside the host cell. While the accessory genes coded by ORFs 3a, 3b, 6, 7a, 7b, 8a, 8b, 9b, 9c, and 10 contribute in cell entry, immunoevasion, and pathological progression. METHODS: This in silico study is focused on designing sequence specific siRNA molecules as a tool for silencing the non-structural and accessory genes of the virus. The gene sequences of NSP3, 4, and 6 along with ORF3a, 6, 7a, 8, and 10 were retrieved for conservation, phylogenetic, and sequence logo analyses. siRNA candidates were predicted using siDirect 2.0 targeting these genes. The GC content, melting temperatures, and various validation scores were calculated. Secondary structures of the guide strands and siRNA-target duplexes were predicted. Finally, tertiary structures were predicted and subjected to structural validations. RESULTS: This study revealed that NSP3, 4, and 6 and accessory genes ORF3a, 6, 7a, 8, and 10 have high levels of conservation across globally circulating SARS-CoV-2 strains. A total of 71 siRNA molecules were predicted against the selected genes. Following rigorous screening including binary validations and minimum free energies, final siRNAs with high therapeutic potential were identified, including 7, 2, and 1 against NSP3, NSP4, and NSP6, as well as 3, 1, 2, and 1 targeting ORF3a, ORF7a, ORF8, and ORF10, respectively. CONCLUSION: Our novel in silico pipeline integrates effective methods from previous studies to predict and validate siRNA molecules, having the potential to inhibit viral replication pathway in vitro. In total, this study identified 17 highly specific siRNA molecules targeting NSP3, 4, and 6 and accessory genes ORF3a, 7a, 8, and 10 of SARS-CoV-2, which might be used as an additional antiviral treatment option especially in the cases of life-threatening urgencies.

Evaluation of quality of abstracts of randomized controlled trials on procedural sedation in children after publication of CONSORT guidelines for abstracts: A systematic review.

The extension of the Consolidated Standards of Reporting Trials (CONSORT) statement provides guidelines for abstracts of randomized controlled trials (RCTs). This study was done to assess the reporting quality of abstracts of RCTs, on procedural sedation in children and identify factors associated with better quality. A PubMed search was conducted from inception of database till July 2017 to identify RCTs on procedural sedation in children. Search terms used were (procedural [All Fields] AND sedation [All Fields]) AND ("child" [MeSH Terms] OR "child" [All Fields] OR "children" [All Fields]) were included in the analysis, while primary RCTs, published in the English language unstructured abstracts, secondary analysis of primary RCTs and studies not exclusively on children we excluded. Our search strategy initially yielded 582 abstracts. Out of these, 535 abstracts were excluded. 47 articles were included in the final analysis. We extracted basic information and data on CONSORT items from abstracts. Each abstract was assessed using a 16-item composite abstract score (CAS) based on the CONSORT guidelines. This abstract quality was further explored by Method Score and by Result Score. Regression analysis was conducted to analyze factors associated with reporting quality. In majority of the abstracts, only objectives and conclusion were adequately reported. Inadequately reported items in >90% of abstracts included randomization, trial status, registration & funding. There was no significant difference in the CAS of abstracts (mean ± SD) published in & before 2008 (12.63 ± 4.0), to those published after 2009 (12.48 ± 4.23). Similarly, there was no significant difference in Result Score and Method Score of the abstracts. After the publication of 'CONSORT for abstracts' guideline, the quality of abstracts of RCTs on procedural sedation has shown suboptimal improvement. We suggest stricter adherence to guidelines by editors and reviewers. A checklist for adherence to CONSORT guidelines could be introduced during submission for the same.

Awake Prone-Positioning in Patients on Non-Invasive Ventilation for Management of SARS-CoV-2 Pneumonia: A Systematic Review.

INTRODUCTION: Patients with corona virus disease-19 (COVID-19)-induced acute hypoxemic respiratory failure (AHRF) are often on non-invasive ventilation (NIV) and use of awake prone positioning (PP) may pose concern in terms of feasibility, efficacy and side effects. This systematic review was undertaken to evaluate the feasibility and efficacy of awake PP along with NIV in them. MATERIALS AND METHODS: A systematic literature search was conducted from the inception of COVID-19 until 15 August 2021. Various factors including feasibility, interface used, outcome, efficacy, side effects and limitations in both intensive care unit (ICU) and Non-ICU setups were noted. RESULTS: A total of 12 original articles and six case series including 359 patients were involved. Out of it, 40% (n = 122) of patients were in ICU and 60% (n = 237) in Non-ICU areas. Four clinical studies and four case series including 114 patients had evaluated PP along with helmet continuous positive airway pressure (CPAP). All had found PP with helmet CPAP to be feasible and efficacious; however, only one study documented the sustained improvement in oxygenation i.e., 12 h after PP. CONCLUSIONS: The present systematic review observed moderate to serious risk of bias amongst the included studies along with heterogeneity in terms of varied respiratory support amongst patients. However, the use of awake PP in patients on NIV has been found to be feasible and efficacious with no adverse events.

Management of Accidental Succinylcholine Ingestion: Navigating Uncharted Waters.

Accidental oral ingestion of intravenous drugs is rare and under-reported, which may lead to serious morbidity and worsen the outcome for the patient. Though oral ingestion of sedatives and opioid drugs is reported, literature regarding the ingestion of muscle relaxants and subsequent management is limited. We report an interesting case of oral intake of 10 ml (500 mg) of injection Succinylcholine, a depolarizing muscle relaxant, by a psychiatric patient awaiting electroconvulsive therapy (ECT) in the pre-procedure room. We hereby report the subsequent sequence of events along with the suggested recommendations to be followed in the case of such an eventuality. To the best of our knowledge, this is the first case report of oral ingestion of a depolarizing neuromuscular blocking drug and its subsequent consequences.

Awake Prone Positioning in the Management of COVID-19 Pneumonia: A Systematic Review.

Background: The aim was to investigate the efficacy of prone positioning (PP) in the management of coronavirus disease-2019 (COVID-19) pneumonia in various setups, with various modes of oxygen therapy and its optimal duration. Materials and methods: A systematic literature search was conducted from inception until May 15, 2021. Patients with a validated diagnosis of COVID-19 and receiving PP were included. Various factors, including intensive care unit (ICU) or non-ICU setup, mode of oxygen therapy, outcome, duration of proning, and limitations, were noted. Results: We retrieved 36 articles with a total of 1,385 patients for qualitative analysis. Out of 36 articles, there were 17 original articles, 09 case series, and 10 case reports. Out of 1,385 participants, 78.9% (n = 1,093) and 21.0% (n = 292) of patients were managed in ICU and non-ICU setup, respectively. Awake PP with high flow nasal cannula (HFNC) was found to be a promising technique; however, the result was inconclusive with helmet continuous positive airway pressure (CPAP). No study has evaluated the optimal duration of awake PP and the associated long-term outcomes. Conclusion: We encourage the use of early awake self-proning in the management of COVID19 disease. However, the evidence in terms of its use in non-ICU setup, the optimal duration of PP, and various oxygenation devices are insufficient, thereby mandating further well-designed multicentric studies to evaluate its efficacy as an adjunct in the management of COVID-19 pneumonia in context to the aforementioned factor. How to cite this article: Chilkoti GT, Mohta M, Saxena AK, Ahmad Z, Sharma CS. Awake Prone Positioning in the Management of COVID-19 Pneumonia: A Systematic Review. Indian J Crit Care Med 2021;25(8):896-905.

Risk Recognition and Multidisciplinary Approach for Non-Cardiac Surgeries in Paediatric Cardiac Patients: A Retrospective Observational Study.

Background Congenital heart disease (CHD), a structural and functional heart disease, is the commonest birth defect with an incidence of one in 125 live births worldwide with ventricular septal defect (VSD), atrial septal defect (ASD) and tetralogy of Fallot (TOF) constituting the majority. Surgery for associated extra-cardiac anomalies (airway, skeletal, genitourinary, and gastrointestinal) may be required in 30% of these patients. Delivery of uneventful anaesthesia in these children requires an understanding of not only paediatric anaesthesia but also of the pathophysiology of the cardiac lesion and its associated risks. Aims The purpose of this retrospective review was to highlight the approach to the anaesthetic management and outcomes of patients with significant cardiac lesions presenting for non-cardiac surgeries. Material and methods A retrospective chart review of all children with congenital heart disease (CHD) (repaired or unrepaired) who were posted for a non-cardiac surgery in this tertiary care Paediatric super-specialty hospital from January 1, 2018 to December 31, 2019 was carried out. Data on demographics, peri-operative management, and clinical course was retrieved. Inclusion criteria were paediatric patients (0-18 years) of either gender with a diagnosis of a CHD (repaired or unrepaired) undergoing any non-cardiac surgeries (NCS) under anaesthesia/Monitored Anaesthesia Care (MAC). Exclusion criteria were procedures only under local anaesthesia (LA) or a minor procedure done solely under sedation not involving an anaesthesiologist. Results During the study period, we found five eligible cases who underwent a total of six procedures. Five procedures were elective and one was an emergency. Preoperative optimization was conducted by a multidisciplinary team including paediatric surgeons, anaesthesiologists, physicians, and cardio-thoracic surgeons. Anaesthesia was conducted by at least a consultant paediatric anaesthesiologist. Overall all patients tolerated anaesthesia well without any adverse events or complications. All six anaesthetic encounters were safe and uneventful.

Cervical epidural analgesia combined with general anesthesia for head and neck cancer surgery: A randomized study.

BACKGROUND AND AIMS: The role of cervical epidural analgesia in head and neck cancer surgery is not fully explored. The aim of this study was to evaluate cervical epidural analgesia in terms of opioid and anesthetic requirements and stress response in patients undergoing head and neck cancer surgery. MATERIAL AND METHODS: After institutional ethical committee approval and written informed consent, 30 patients undergoing elective head and neck cancer surgery were randomized into two groups: Group E (cervical epidural analgesia with general anesthesia), and group G (general anesthesia alone). In group E, an 18 gauge epidural catheter was placed at cervical (C) 6 - thoracic (T) 1 level. After test dose, a bolus of 10 ml of 0.2% ropivacaine was given followed by continuous infusion. Technique of general anesthesia and post-operative management was standardized in both the groups. Opioid and anesthetic drug requirement was observed. Blood glucose and serum cortisol levels were measured at baseline; post-incision and after surgery. RESULTS: There was significant reduction in the requirement of morphine (P < 0.001), isoflurane (P = 0.004) and vecuronium (P = 0.001) in group E. Post-operative, blood glucose and serum cortisol levels were significantly reduced (P = 0.0153 and 0.0074, respectively). Early post-operative pain was reduced with the lesser requirement of post-operative morphine. CONCLUSIONS: The use of combined cervical epidural analgesia with general anesthesia reduces opioid, anesthetic drug requirement and stress response as compared to general anesthesia alone in patients undergoing head and neck cancer surgery.

Design and synthesis of new energy restriction mimetic agents: Potent anti-tumor activities of hybrid motifs of aminothiazoles and coumarins.

The incidence of obesity-related diseases like diabetes, cardiovascular diseases, and different types of cancers shed light on the importance of dietary control as preventive and treatment measures. However, long-term dietary control is challenging to achieve in most individuals. The use of energy restriction mimetic agents (ERMAs) as an alternative approach to affect the energy machinery of cancer cells has emerged as a promising approach for cancer therapy. ERMAs limit the high need for energy in rapidly growing tumor cells, with their survival rate strongly dependent on the robust availability of energy. In this context, initial phenotypic screening of an in-house pilot compound library identified a new class of aminothiazole anchored on coumarin scaffold as potent anticancer lead drug candidates with potential activity as ERMA. The identified chemotypes were able to inhibit glucose uptake and increase ROS content in cancer cells. Compounds 9b, 9c, 9i, 11b, and 11c were highly active against colorectal cancer cell lines, HCT116 and HT-29, with half-maximal inhibitory concertation (IC50) range from 0.25 to 0.38 µM. Further biological evaluations of 9b and 9f using Western blotting, caspase activity, glucose uptake, ROS production, and NADPH/NADP levels revealed the ability of these lead drug candidates to induce cancer cell death via, at least in part, energy restriction. Moreover, the assessment of 9b and 9f synergistic activity with cisplatin showed promising outcomes. The current work highlights the significant potential of the lead compounds, 9b, and 9f as potential anticancer agents via targeting the cellular energy machinery in cancer cells.

Molecular insight for the role of key residues of calreticulin in its binding activities: A computational study.

Calreticulin (CRT) is localized to and has functions in multiple cellular compartments, including the cell surface, the endoplasmic reticulum, and the extracellular matrix. Mutagenesis studies have identified several residues on a concave ß-sheet surface of CRT critical for CRT binding to carbohydrate and other proteins/peptides. How the mutations of these key residues in CRT affect the conformation and dynamics of CRT, further influencing CRT binding to carbohydrates and other proteins to signal the important biological activities remain unknown. In this study, we investigated the effect of three key point mutations (C105A, C137A and W319A) on CRT conformation and dynamics via atomistic molecular dynamics simulations. Results show that these three key residues mutations induced the changes of CRT local backbone flexibility and secondary structure of CRT N-domain, which could further affect CRT's binding activity. C137A mutation led to dramatic decrease of the overall size of CRT due to the P-domain fold back to the globular domain and formed new inter-domain contacts, which can cause blockage of CRT's binding with other large substrates. Furthermore, for CRT concave ß-strand surface patch containing lectin binding site, CRT C105A, C137A and W319A point mutation resulted in the changes in solvent accessible surface area, key residues' side chain atom positions and dynamical correlated motions between residues. All these changes could directly affect CRT binding behavior. Results of this study provide molecular and structural insights into understanding the role of key residues of CRT in its binding behavior.

Comparison of Knowledge, Attitudes, and Practices of Educated and Uneducated Adults Regarding Human Immunodeficiency Virus in Karachi, Pakistan.

BACKGROUND: Despite the high prevalence of human immunodeficiency virus (HIV) in Pakistan, no prior work has been done to specifically highlight the importance of education as a social vaccine against HIV. Therefore, our study focuses on differences in knowledge and practices regarding HIV and acquired immunodeficiency syndrome (AIDS) among educated and uneducated adults. METHODOLOGY: A cross-sectional study was carried out in which data was collected from all over Karachi. An individual was designated as educated if he had received education above primary school level. Individuals who had studied till primary school or less were considered uneducated. The questionnaire was split into four sections that assessed respondents' demographics, knowledge, attitudes, and practices regarding HIV/AIDS. Chi square test was used as the primary statistical test. RESULTS: Out of the 446 adult participants, 235 (52.7%) were educated and 211 (47.3%) were uneducated. Educated participants were significantly more likely to have heard about HIV (183 vs. 39, p < 0.001) and had better knowledge about the symptoms of HIV/AIDS (p < 0.001). Among the participants who knew about AIDS, a greater percentage of uneducated (n = 28, 53%) than educated individuals (n = 68, 37%) believed that people suffering from AIDS should be isolated (p = o.o16) and that HIV can spread through water (40% vs 20% respectively, p < 0.001). Both educated (n = 49, 27%) and uneducated (n = 46, 89%) adults believed that awareness would help prevent the spread of HIV (p = 0.978) and were willing to educate their children about it (p = 0.696). CONCLUSION: Our study revealed a gap in the knowledge about HIV/AIDS between educated and uneducated adults. There is an urgent need for awareness programs that especially reach out to the uneducated masses that are otherwise uninformed about HIV and are under high risk of acquiring HIV.

Pregabalin in Monitored Anesthesia Care for Ear-nose-throat Surgery.

AIM: The aim of this study was to determine intraoperative sedative and perioperative analgesic requirement and associated side effects of pregabalin (150 mg) for monitored anesthesia care during ear-nose-throat (ENT) surgeries. MATERIALS AND METHODS: The study design was randomized and single-blinded; fifty patients undergoing elective ambulatory ENT surgeries under monitored anesthesia care were randomly allocated to receive either placebo (Group P) or pregabalin (Group PG) 150 mg, orally 1 h before surgery. All patients were then given intravenous (i.v.) midazolam 2 mg and fentanyl 1 µg/kg and local anesthesia at the site. Sedation was induced by administering an i.v. bolus of propofol 0.8 mg/kg and was maintained by continuous infusion of propofol. Level of sedation was assessed by Ramsay scale, and propofol infusion was titrated accordingly. Intraoperative pain was assessed by verbal rating scale (VRS) score. Patient having VRS >4 or complaint of pain was given fentanyl (0.5 µg/kg) i.v. bolus. Intraoperative sedative and analgesic requirement were recorded. Postoperative visual analog scale scores and requirement of analgesics were recorded for the first 24 h after surgery. Diclofenac 75 mg intramuscular (i.m.) was administered as rescue analgesic. Side effects (nausea/vomiting, sedation, dizziness, blurred vision) were also recorded. RESULTS: Intraoperative propofol (212 ± 11 mg vs. 174 ± 9 mg; P = 0.013) and fentanyl (120 ± 8 µg vs. 94 ± 6 µg; P = 0.02) consumption was significantly lower in Group PG. Time to first analgesic request was longer (6.1 ± 0.4 h vs. 9.5 ± 1.2 h) with lesser requirement of analgesics (diclofenac) in the postoperative period. Incidence of side effects (sedation, nausea, vomiting) was found to be similar in both the groups. CONCLUSION: Premedication with pregabalin (150 mg) reduces intraoperative sedative and perioperative analgesic requirement in patients undergoing ENT surgeries under monitored anesthesia care with tolerable side effects.

Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry.

Pre-targeting combined with bioorthogonal chemistry is emerging as an effective way to create new radiopharmaceuticals. Of the methods available, the inverse electron demand Diels-Alder (IEDDA) cycloaddition between a radiolabeled tetrazines and trans-cyclooctene (TCO) linked to a biomolecule has proven to be a highly effective bioorthogonal approach to imaging specific biological targets. Despite the fact that technetium-99m remains the most widely used isotope in diagnostic nuclear medicine, there is a scarcity of methods for preparing 99mTc-labeled tetrazines. Herein we report the preparation of a family of tridentate-chelate-tetrazine derivatives and their Tc(I) complexes. These hitherto unknown compounds were radiolabeled with 99mTc using a microwave-assisted method in 31% to 83% radiochemical yield. The products are stable in saline and PBS and react rapidly with TCO derivatives in vitro. Their in vivo pre-targeting abilities were demonstrated using a TCO-bisphosphonate (TCO-BP) derivative that localizes to regions of active bone metabolism or injury. In murine studies, the 99mTc-tetrazines showed high activity concentrations in knees and shoulder joints, which was not observed when experiments were performed in the absence of TCO-BP. The overall uptake in non-target organs and pharmacokinetics varied greatly depending on the nature of the linker and polarity of the chelate.

A Bone-Seeking trans-Cyclooctene for Pretargeting and Bioorthogonal Chemistry: A Proof of Concept Study Using 99mTc- and 177Lu-Labeled Tetrazines.

A high yield synthesis of a novel, small molecule, bisphosphonate-modified trans-cyclooctene (TCO-BP, 2) that binds to regions of active bone metabolism and captures functionalized tetrazines in vivo, via the bioorthogonal inverse electron demand Diels-Alder (IEDDA) cycloaddition, was developed. A 99mTc-labeled derivative of 2 demonstrated selective localization to shoulder and knee joints in a biodistribution study in normal mice. Compound 2 reacted rapidly with a 177Lu-labeled tetrazine in vitro, and pretargeting experiments in mice, using 2 and the 177Lu-labeled tetrazine, yielded high activity concentrations in shoulder and knee joints, with minimal uptake in other tissues. Pretargeting experiments with 2 and a novel 99mTc-labeled tetrazine also produced high activity concentrations in the knees and shoulders. Critically, both radiolabeled tetrazines showed negligible uptake in the skeleton and joints when administered in the absence of 2. Compound 2 can be utilized to target functionalized tetrazines to bone and represents a convenient reagent to test novel tetrazines for use with in vivo bioorthogonal pretargeting strategies.