Publications by authors named "Ravi Sharma"

360 Publications

EUS-guided transmural drainage of hemorrhagic pancreatic fluid collections without associated arterial pseudoaneurysms.

Endosc Ultrasound 2021 Sep 3. Epub 2021 Sep 3.

Department of Surgical Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.4103/EUS-D-21-00045DOI Listing
September 2021

Endoscopic ultrasound-guided transmural drainage of post-traumatic pancreatic fluid collections.

Ann Gastroenterol 2021 Sep-Oct;34(5):751-755. Epub 2021 Feb 26.

Department of Surgical Gastroenterology (Rajesh Gupta), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: Pancreatic injury is an uncommon consequence of abdominal trauma, and surgery has been the conventional treatment. The role and timing of endoscopic ultrasound (EUS)-guided treatment of the consequences of traumatic pancreatic injury is unclear. Our study evaluated the safety and efficacy of EUS-guided transmural drainage of post-traumatic pancreatic fluid collections (PFC).

Methods: A retrospective analysis of 13 patients (mean age 20.2±4.4 years; 12 males) with post-traumatic PFC treated with EUS-guided transmural drainage over the last 10 years was performed. Patient demographics, imaging findings, size of PFC, details of endoscopic transmural drainage procedure, outcome details, as well complications were retrieved from our database.

Results: The patients underwent drainage at 26.8±7.4 days after abdominal trauma, and the mean size of PFC was 11.8±3.2 cm with 2 patients having multiple fluid collections. Ten patients had PFC with a well-formed wall and 3 patients had an incompletely formed wall. Endoscopic drainage was technically successful in all 13 patients and 11 patients underwent transmural drainage with multiple plastic stents whereas 2 patients were treated with lumen apposing metal stents. The PFC resolved in all patients over a mean period of 2.7±0.4 weeks. One patient developed gastrointestinal bleeding 6 days after the procedure, successfully treated with angio-embolization.

Conclusion: EUS-guided transmural drainage of post-traumatic PFC is safe and effective and can be safely performed at an early phase (<4 weeks) after pancreatic trauma.
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http://dx.doi.org/10.20524/aog.2021.0607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375657PMC
February 2021

The relationship between cardiac dosimetry and tumour quadrant location in left sided whole breast and chest wall adjuvant radiotherapy.

Breast Dis 2021 Aug 16. Epub 2021 Aug 16.

Aberdeen Royal Infirmary, Foresterhill, Aberdeen, Scotland, UK.

Background: Radiotherapy after breast surgery decreases locoregional recurrence and improves survival. This is not without risks from radiation exposure and could have implications in clinical practice. Our study investigates the correlation between tumour location and radiation dose to the heart.

Methods: Left-sided breast cancer patients who had radiotherapy at Aberdeen Royal Infirmary in 2010 were identified. Tumour location was established from notes and imaging. Radiotherapy planning scans were reviewed, and cardiac doses calculated. The mean cardiac dose, maximum dose and volume of the heart in the field, along with V5-V40, were determined.

Results: 40 patients had mastectomies and 118 breast conserving surgery. The median percentage of the heart in the field and the Interquartile Range was 0.59% (0.03-1.74) for all patients, with the highest for lower inner quadrant (LIQ) tumours 1.20% (0.29-2.40), followed by mastectomy 0.94% (0.02-1.82). The mean heart dose showed a higher median for mastectomies 1.59 Gy (1.00-1.94), followed by LIQ tumours 1.58 Gy (1.31-2.28), with an overall median of 1.42 Gy (1.13-1.95). The median percentage of the heart in the field, the mean cardiac dose and V5-V30 did not reach statistical significance, however, V40 and the maximum dose did.

Conclusions: The benefits of radiotherapy after breast cancer surgery are established, but with potential harm from cardiac exposure. Our cohort showed higher radiation exposure to the heart in patients with LIQ tumours and mastectomies but reached significance only for V40 and maximum dose. This highlights tumour location as a potentially important risk factor for cardiac exposure with breast radiotherapy.
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http://dx.doi.org/10.3233/BD-201025DOI Listing
August 2021

Management of Obstetric Analgesia in the Developing Countries during the Coronavirus Disease Pandemic: A Narrative Review.

Anesth Essays Res 2020 Oct-Dec;14(4):545-549. Epub 2021 May 27.

Department of Anaesthesiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

Coronavirus disease (COVID), also known as COVID-19, has brought the immense challenges for the health-care system globally. All the branches of medicine are equally involved in managing these patients. During this pandemic, care of obstetric patients in terms of obstetric analgesia becomes crucial. Hence, the purpose of this review was to draft a basic model of strategies related to the provision of safe obstetric analgesia during this coronavirus pandemic, which will assist the health-care providers across the developing countries to formulate their own protocols depending upon the resource availability. All research articles related to obstetric analgesia during the COVID-19 pandemic from January 2020 to December 01, 2020 available on PubMed, Cochrane, Google scholar, and Embase are included in this study. The keywords used for data search were "obstetric analgesia during COVID-19," "coronavirus pandemic," "Labor pain," "obstetric pain management guidelines," and "regional anesthesia during COVID-19." Eventually, our review yielded the most recentmodel for the provision of safe and effective obstetric analgesia practices during the COVID-19 pandemic across the developing countries.
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http://dx.doi.org/10.4103/aer.AER_10_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294418PMC
May 2021

Percutaneous Management of a Contained Annular Rupture Occurring With Self-Expanding Transcatheter Aortic Valve Replacement.

JACC Case Rep 2020 Oct 21;2(12):1852-1858. Epub 2020 Oct 21.

CardioVascular Institute, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts.

Annular rupture is a rare catastrophic event during transcatheter aortic valve replacement, often life threatening and requiring emergent surgical repair. We describe, herein, a case of contained annular rupture successfully managed percutaneously with coiling and polymer injection. This is a novel technique to manage this complication. ().
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http://dx.doi.org/10.1016/j.jaccas.2020.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299247PMC
October 2020

Contrast-enhanced endoscopic ultrasound features of tubercular lymphadenopathy.

Trop Doct 2021 Jul 4:494755211028057. Epub 2021 Jul 4.

Department of Surgical Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

There is lack of data on the contrast-enhanced endoscopic ultrasound features of tubercular lymph node; our retrospective analysis of 37 patients with enlarged mediastinal and abdominal lymph nodes showed heterogeneous enhancement in the great majority (70%).
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http://dx.doi.org/10.1177/00494755211028057DOI Listing
July 2021

Biomechanical Factors Influencing Fixation Angle in Occipitocervical Fusion.

Neurol India 2021 May-Jun;69(3):780-781

Additional Professor, Department of Neurosurgery, 720, CNC, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.4103/0028-3886.319241DOI Listing
June 2021

Atypical Symptoms of Cervical Spondylosis: Is Anterior Cervical Discectomy and Fusion Useful? - An Institutional Experience.

Neurol India 2021 May-Jun;69(3):595-601

Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.

Background: A significant proportion of patients with cervical spondylosis can present with atypical symptoms like vertigo, tinnitus, nausea, vomiting, headache, blurred vison, palpitations and gastrointestinal (GI) discomfort. The role of ACDF in alleviating these atypical symptoms remains unexplored.

Objective: The current study attempts to investigate the role of anterior cervical discectomy and fusion (ACDF) in alleviating atypical symptoms associated with cervical spondylosis.

Materials And Methods: The patients with cervical spondylosis who underwent ACDF between January 2011 and December 2015 were contacted by phone. Data regarding the severity and frequency of atypical symptoms was collected by a structured questionnaire. Wilcoxon signed rank test was used to compare the severity and frequency of these symptoms before the surgery and at last follow up.

Results: A total of 467 patients underwent ACDF for cervical spondylosis between January 2011 and December 2015, of which 358 patients were interviewed telephonically. 99 of 358 (27.65%) patients who met the eligibility criteria were included in the final analysis. The severity and frequency of vertigo, headache, nausea, vomiting and GI discomfort significantly improved at last follow-up (P < 0.001) compared to pre-operative period. Significant improvement in hypertension was also seen (P = 0.001). Improvements in severity and frequency of tinnitus (P = 0.083), palpitation (P = 0.317) and blurring of vision (P = 1.00) were not significant.

Conclusions: ACDF might improve the atypical symptoms like vertigo, headache, nausea, vomiting and GI discomfort in patients with cervical spondylosis. Some patients also show improvement in hypertension following surgery.
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http://dx.doi.org/10.4103/0028-3886.317235DOI Listing
June 2021

Detection of serum cross-reactive antibodies and memory response to SARS-CoV-2 in pre-pandemic and post-COVID-19 convalescent samples.

J Infect Dis 2021 Jun 23. Epub 2021 Jun 23.

Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, veterinary and Ecological Sciences, University of Liverpool, UK.

Background: A notable feature of COVID-19 is that children are less susceptible to severe disease. Children are known to experience more infections with endemic human coronaviruses (HCoVs) compared to adults. Little is known whether HCoV infections lead to cross-reactive anti-SARS-CoV-2 antibodies.

Methods: We investigated the presence of cross-reactive anti-SARS-CoV-2 IgG antibodies (to spike(S)1, S1-receptor-binding receptor (S1-RBD) and nucleocapsid protein(NP)), by enzyme-linked immunosorbent assays, and neutralizing activity by a SARS-CoV-2 pseudotyped virus neutralisation assay, in pre-pandemic sera collected from children(n=50) and adults(n=45), and compared with serum samples from convalescent COVID-19 patients(n=16).

Results: A significant proportion of children (up to 40%) had detectable cross-reactive antibodies to SARS-CoV-2 S1, S1-RBD and NP antigens, and the anti-S1 and -S1-RBD antibody levels correlated with anti-HCoV-HKU1 and -OC43 S1 antibody titers in pre-pandemic samples(p<0.001). There were marked increases of anti-HCoV-HKU1 and -OC43 S1 (but not anti-NL63 and -229E S-RBD) antibody titres in serum samples from convalescent COVID-19 patients(p<0.001), indicating an activation of cross-reactive immunological memory to β-coronavirus spike.

Conclusions: We demonstrated cross-reactive anti-SARS-CoV-2 antibodies in pre-pandemic serum samples from children and young adults. Promoting this cross-reactive immunity and memory response derived from common HCoV may be an effective strategy against SARS-COV-2 and future novel coronaviruses.
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http://dx.doi.org/10.1093/infdis/jiab333DOI Listing
June 2021

Analysis of Neurosurgical Cases Before and During the Coronavirus Disease 2019 Pandemic from a Tertiary-Care Centre in India.

World Neurosurg 2021 08 12;152:e635-e644. Epub 2021 Jun 12.

Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.

Objective: We present the unique administrative issues as well as specific patient-related and surgeon-related challenges and solutions implemented while treating neurosurgical patients during the coronavirus disease 2019 (COVID-19) pandemic vis-à-vis pre-COVID-19 times at our tertiary-care center.

Methods: This is a retrospective study comparing the outcome of the neurosurgical patients treated from the beginning of lockdown in India on March 25, 2020 to November 30, 2020 with that of same period in the previous year, 2019.

Results: There were 687 neurosurgery admissions during the study period compared with 2550 admissions in 2019. The total number of surgeries performed in neurosurgery also showed a similar trend, with only 654 surgeries in 2020 compared with 3165 surgeries in 2019. During COVID-19 times, 474 patients were operated on including both trauma and nontrauma cases. Of the 50 patients with suspected/indeterminate COVID-19 who were operated on, 5 turned out to be positive for COVID-19. Significant differences were seen in the mortality (P < 0.01) and morbidity (P < 0.01) among patients with trauma on comparing COVID and pre-COVID periods. Similarly, a significant difference was observed in the mortality (P < 0.001) and morbidity (P < 0.001) in patients who did not have trauma.

Conclusions: The higher mortality and morbidity during the COVID pandemic is primarily attributable to poorer baseline clinical status. Our experience from this COVID period might not only help us in tackling subsequent waves but also help other institutions in the developing world to be better prepared for similar circumstances.
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http://dx.doi.org/10.1016/j.wneu.2021.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197626PMC
August 2021

Parturient Controlled Epidural Analgesia with and without Basal Infusion of Ropivacaine and Fentanyl: A Randomized Trial.

Anesth Essays Res 2020 Jul-Sep;14(3):390-394. Epub 2021 Mar 22.

Department of Anesthesiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Introduction: Parturient controlled epidural analgesia (PCEA) is an established method of providing safe and effective labor analgesia.

Objective: The aim of this single-blind, randomized controlled trial was to compare the efficacy of PCEA with or without basal infusion (BI) of ropivacaine and fentanyl for the effective management of labor pain associated with normal vaginal delivery.

Materials And Methods: A total of 78 nulliparous parturients with vertex presentation at term and with cervical dilatation of 3-5 cm demanding for epidural analgesia (EA) were enrolled in the study. EA was initiated and maintained with ropivacaine 0.125% and fentanyl 2 μg/mL. Following an initial epidural loading volume of 8-10 mL, parturients were randomly allocated in two groups of 39 each. PCEA group received bolus of 5 mL at 200 mL/h with lockout interval of 15 min and with maximum volume of local anaesthetic was 20 mL/h and PCEA + BI group - receiving added BI rate of 5 mL/h along with same programmed parameters of PCEA pump.

Results: No statistically significant difference was observed between the groups in terms of demographic characteristics, duration of labor, delivery methods, maternal satisfaction as well as Apgar score. Mean demand bolus in group PCEA + BI was 0.39 ± 0.59, whereas in group PCEA was 3.31 ± 0.77 ( < 0.05). Mean volume of drug used in group PCEA + BI was 25.57 ± 2.75 mL, while in group PCEA was 22.42 ± 4.56 mL ( = 0.0005). In PCEA + BI group, Visual Analog Scale (VAS) score was 0.07 ± 0.35 at 60 min and 0.06 ± 0.33 at 120 min, whereas in PCEA group, VAS was 0.32 ± 0.62 at 60 min and 0.26 ± 0.50 at 120 min ( = 0.05), respectively.

Conclusion: BI when added to PCEA, it significantly reduces breakthrough labor pain and demand boluses without prolonging labor duration but at the cost of increased requirement of drug volume when compared to PCEA only group.
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http://dx.doi.org/10.4103/aer.AER_116_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159052PMC
March 2021

Microsurgical suturing assessment scores: a systematic review.

Neurosurg Rev 2021 Jun 2. Epub 2021 Jun 2.

Department of Neurosurgery, Cardiothoracic and Neurosciences Centre, All India Institute of Medical Sciences, New Delhi, 110029, India.

Several scoring scales for the assessment of microsurgical skills have been established and validated with the same basic parameters. The study aims to review the existing scales to highlight those parameters, which can be utilized uniformly across all neurosurgical training centers. An online search was conducted and all the surgical scores pertinent to microsurgical suturing were reviewed. The scales were compared to identify parameters, which were important for skill development and assessment in neurosurgical trainees. Seven assessment scales were identified which assessed the trainee's proficiency in microsurgical suturing. The objective structured assessment of technical skills (OSATS) and Northwestern Objective Microanastomosis Assessment Tool (NOMAT) were identified as the most widely used and validated assessment scales. The newer scales University of Western Ontario microsurgical skills acquisition/assessment (UWOMSA) and structured assessment of microsurgery (SAMS) were notable for the division of the skills. The knot strength, suture separation, and suture intervals were the most important parameters in all scales. Each scale has its strength in the assessment of the microsurgical proficiency of neurosurgical trainees. However, a more uniform scale that can be applied as per the level of the neurosurgical trainee is necessary.
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http://dx.doi.org/10.1007/s10143-021-01569-3DOI Listing
June 2021

Analysis of Droplet Splatter Patterns During Coblation Tonsil Surgery in the Covid-19 Pandemic.

Ann Otol Rhinol Laryngol 2021 May 22:34894211018909. Epub 2021 May 22.

Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.

Objectives: To assess droplet splatter around the surgical field and surgeon during simulated Coblation tonsil surgery to better inform on mitigation strategies and evaluate choice of personal protective equipment.

Methods: This was an observational study performed using a life-size head model to simulate tonsil surgery and fluorescein-soaked strawberries to mimic tonsils. The Coblation wand was activated over the strawberries for 5 minutes. This was repeated 5 times with 2 surgeons (totalling 10 data sets). The presence of droplet around the surgical field and anatomical subsites on the surgeon was assessed in binary fashion: present or not present. The results were collated as frequency of droplet detection and illustrated as a heatmap; 0 = white, 1-2 = yellow, 3-4 = orange, and 5 = red.

Results: Fluorescein droplets were detected in all 4 quadrants of the surgical field. The frequency of splatter was greatest in the upper (nearest to surgeon) and lower quadrants. There were detectable splatter droplets on the surgeon; most frequently occurring on the hands followed by the forearm. Droplets were also detected on the visor, neck, and chest albeit less frequently. However, none were detected on the upper arms.

Conclusion: Droplet splatter can be detected in the immediate surgical field as well as on the surgeon. Although wearing a face visor does not prevent splatter on the surgical mask or around the eyes, it should be considered when undertaking tonsil surgery as well as a properly fitted goggle.

Level Of Evidence: 5.
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http://dx.doi.org/10.1177/00034894211018909DOI Listing
May 2021

Efficacy of antimicrobial medicated ventricular catheters: a network meta-analysis with trial sequential analysis.

Neurosurg Rev 2021 May 19. Epub 2021 May 19.

Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India.

There is paucity of evidence regarding relative performance of antibiotic-medicated (AM), silver-medicated (SM) and non-medicated (NM) ventricular catheters in controlling infection rate. We aim to quantitatively synthesize the current evidence after addition of the three-armed British Antibiotic and Silver Impregnated Catheters for ventriculoperitoneal Shunts (BASICS) trial, understand the need for further evidence using trial sequential analysis (TSA) and incorporate the indirect evidence using network meta-analysis (NMA). Randomized controlled trials (RCTs) comparing AM, SM and NM ventriculoperitoneal shunt (VPS) or external ventricular drain (EVD) were included. Antibiotic-medicated VPS show a significantly lower infection rate as compared to non-medicated VPS (RR 0.44; 95% CI: 0.27-0.73; p = 0.001), however, TSA reveals need for further evidence. SM including both EVD as well as VPS were found to be inferior to AM while no significant difference was found in comparison to the NM catheters. In NMA for VPS, the AM were found to be significantly better than SM (RR 0.41, 95% CI: 0.22-0.75) as well as NM (RR 0.42; 95% CI: 0.25-0.71) with a SUCRA of 99.8% and a mean rank of 1. However, antibiotic medicated shunts did not show a statistically significant association with reoperation rate (RR 0.99; 95% CI:0.81-1.20; p = 0.9) with no further need for evidence as per TSA.
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http://dx.doi.org/10.1007/s10143-021-01532-2DOI Listing
May 2021

Ambient fine particulate matter exposure and incident mild cognitive impairment and dementia.

J Am Geriatr Soc 2021 Aug 26;69(8):2185-2194. Epub 2021 Apr 26.

Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background/objective: Poor air quality is implicated as a risk factor for cognitive impairment and dementia. Few studies have examined these associations longitudinally in well-characterized population-based cohorts with standardized annual assessment of both mild cognitive impairment (MCI) and dementia. We investigated the association between estimated ambient fine particulate matter (PM ) and risk of incident MCI and dementia in a post-industrial region known for historically poor air quality.

Setting/participants: Adults aged 65+ years in a population-based cohort (n = 1572).

Measurements: Census tract level PM from Environmental Protection Agency (EPA) air quality monitors; Clinical Dementia Rating (CDR)®.

Design: We estimated ambient PM exposure (μg/m , single-year and 5-year averages) by geocoding participants' residential addresses to census tracts with daily EPA PM measurements from 2002 to 2014. Using Bayesian spatial regression modeling adjusted for age, sex, education, smoking history, and household income, we examined the association between estimated PM exposure and risk of incident MCI (CDR = 0.5) and incident dementia (CDR ≥ 1.0).

Results: Modeling estimated single-year exposure, each 1 μg/m higher ambient PM was associated with 67% higher adjusted risk of incident dementia (hazard ratio [HR] = 1.669, 95% credible interval [CI]: 1.298, 2.136) and 75% higher adjusted risk of incident MCI (HR = 1.746, 95% CI: 1.518, 2.032). Estimates were higher when modeling 5-year ambient PM exposure for incident dementia (HR = 2.082, 95% CI: 1.528, 3.015) and incident MCI (HR = 3.419, 95% CI: 2.806, 4.164).

Conclusions: Higher estimated ambient PM was associated with higher risk of incident MCI and dementia, particularly when considering longer-term exposure, and independent of demographic characteristics and smoking history. Targeting poor air quality may be a reasonable population-wide intervention to reduce the risk of cognitive impairment in older adults, particularly in regions exceeding current recommendations for safe exposure to PM .
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http://dx.doi.org/10.1111/jgs.17188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373708PMC
August 2021

The shared susceptibility epitope of HLA-DR4 binds citrullinated self-antigens and the TCR.

Sci Immunol 2021 Apr;6(58)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

Individuals expressing HLA-DR4 bearing the shared susceptibility epitope (SE) have an increased risk of developing rheumatoid arthritis (RA). Posttranslational modification of self-proteins via citrullination leads to the formation of neoantigens that can be presented by HLA-DR4 SE allomorphs. However, in T cell-mediated autoimmunity, the interplay between the HLA molecule, posttranslationally modified epitope(s), and the responding T cell repertoire remains unclear. In HLA-DR4 transgenic mice, we show that immunization with a Fibβ-74cit peptide led to a population of HLA-DR4 tetramer T cells that exhibited biased T cell receptor (TCR) β chain usage, which was attributable to selective clonal expansion from the preimmune repertoire. Crystal structures of pre- and postimmune TCRs showed that the SE of HLA-DR4 represented a main TCR contact zone. Immunization with a double citrullinated epitope (Fibβ-72,74cit) altered the responding HLA-DR4 tetramer T cell repertoire, which was due to the P2-citrulline residue interacting with the TCR itself. We show that the SE of HLA-DR4 has dual functionality, namely, presentation and a direct TCR recognition determinant. Analogous biased TCR β chain usage toward the Fibβ-74cit peptide was observed in healthy HLA-DR4 individuals and patients with HLA-DR4 RA, thereby suggesting a link to human RA.
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http://dx.doi.org/10.1126/sciimmunol.abe0896DOI Listing
April 2021

Optimal policy for attention-modulated decisions explains human fixation behavior.

Elife 2021 03 26;10. Epub 2021 Mar 26.

Department of Neurobiology, Harvard Medical School, Boston, United States.

Traditional accumulation-to-bound decision-making models assume that all choice options are processed with equal attention. In real life decisions, however, humans alternate their visual fixation between individual items to efficiently gather relevant information (Yang et al., 2016). These fixations also causally affect one's choices, biasing them toward the longer-fixated item (Krajbich et al., 2010). We derive a normative decision-making model in which attention enhances the reliability of information, consistent with neurophysiological findings (Cohen and Maunsell, 2009). Furthermore, our model actively controls fixation changes to optimize information gathering. We show that the optimal model reproduces fixation-related choice biases seen in humans and provides a Bayesian computational rationale for this phenomenon. This insight led to additional predictions that we could confirm in human data. Finally, by varying the relative cognitive advantage conferred by attention, we show that decision performance is benefited by a balanced spread of resources between the attended and unattended items.
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http://dx.doi.org/10.7554/eLife.63436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064754PMC
March 2021

and functional characterization of human HLA-DRB1∗04 restricted T cell receptors.

J Transl Autoimmun 2021 3;4:100087. Epub 2021 Mar 3.

Division of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.

Recent advances in single-cell sequencing technologies enable the generation of large-scale data sets of paired TCR sequences from patients with autoimmune disease. Methods to validate and characterize patient-derived TCR data are needed, as well as relevant model systems that can support the development of antigen-specific tolerance inducing drugs. We have generated a pipeline to allow streamlined generation of 'artificial' T cells in a robust and reasonably high throughput manner for and studies of antigen-specific and patient-derived immune responses. Hereby chimeric (mouse-human) TCR alpha and beta constructs are re-expressed in three different formats for further studies: () transiently in HEK cells for peptide-HLA tetramer validation experiments, () stably in the TCR-negative 58 ​T cell line for functional readouts such as IL-2 production and NFAT-signaling, and lastly () in human HLA-transgenic mice for studies of autoimmune disease and therapeutic interventions. As a proof of concept, we have used human HLA-DRB1∗04:01 restricted TCR sequences specific for a type I diabetes-associated GAD peptide, and an influenza-derived HA peptide. We show that the same chimeric TCR constructs can be used in each of the described assays facilitating sequential validation and prioritization steps leading to humanized animal models.
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http://dx.doi.org/10.1016/j.jtauto.2021.100087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980064PMC
March 2021

Corneal reconstruction in chemically damaged cornea using temperature responsive surface assisted mesenchymal stem cell transplantation in rabbits.

Graefes Arch Clin Exp Ophthalmol 2021 Jul 22;259(7):1859-1870. Epub 2021 Mar 22.

Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh, 160012, India.

Purpose: Transplantation of autologous stem cells over damaged cornea seems to be a promising approach for corneal reconstruction. Use of a biocompatible carrier is still a challenge in bedside translation of transplantation. We investigated corneal reconstruction and tissue remodelling by transplantation of mesenchymal stem cells (MSCs) using temperature responsive membranes in chemically damaged rabbit cornea model.

Methods: MSCs were cultured from rabbit's bone marrow and transplanted over alkali injured cornea, using either temperature responsive membrane or fibrin glue method. Endogenous levels of MSCs were assessed to decide the optimal time point for transplanting cells. MSC transplanted corneas were harvested at different time points post-transplantation. Corneal repair markers were evaluated using histopathology, immunohistochemistry (IHC) and real time qPCR. The quality of cornea reconstructed was evaluated and compared using corneal opacity scoring and immunohistochemistry (IHC).

Results: Use of temperature responsive surface as carrier resulted in uniform and homogenous delivery of MSCs sheet over the damaged corneal surface. Corneal transparency improved day 7 onwards post-MSC transplantation in rabbit chemically injured cornea. Complete re-epithelialization of injured cornea was observed 15 days after MSC transplantation. Restoration of vimentin, α-smooth muscle actin and collagen levels in MSC transplanted cornea was observed post-transplantation. Further, differentiation of MSCs into mature corneal epithelial cells was also observed upon transplantation.

Conclusions: The extent of corneal repair was apparently better using temperature responsive surfaces. The surface provides biocompatible niche for MSCs and can be a method of choice in clinics for cell transplantation over the damaged ocular surfaces.
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http://dx.doi.org/10.1007/s00417-021-05132-0DOI Listing
July 2021

Predictive factors and timelines of rebleeding in aneurysmal SAH: what have we gleaned?

Acta Neurochir (Wien) 2021 05 19;163(5):1479-1480. Epub 2021 Mar 19.

Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1007/s00701-021-04772-9DOI Listing
May 2021

A systematic review of emerging information technologies for sustainable data-centric health-care.

Int J Med Inform 2021 05 19;149:104420. Epub 2021 Feb 19.

Department of Accounting and Information Systems, College of Business and Law, University of Canterbury, Christchurch, New Zealand. Electronic address:

Background: Of the Sustainable Development Goals (SDGs), the third presents the opportunity for a predictive universal digital healthcare ecosystem, capable of informing early warning, assisting in risk reduction and guiding management of national and global health risks. However, in reality, the existing technology infrastructure of digital healthcare systems is insufficient, failing to satisfy current and future data needs.

Objective: This paper systematically reviews emerging information technologies for data modelling and analytics that have potential to achieve Data-Centric Health-Care (DCHC) for the envisioned objective of sustainable healthcare. The goal of this review is to: 1) identify emerging information technologies with potential for data modelling and analytics, and 2) explore recent research of these technologies in DCHC.

Findings: A total of 1619 relevant papers have been identified and analysed in this review. Of these, 69 were probed deeply. Our analysis found that the extant research focused on elder care, rehabilitation, chronic diseases, and healthcare service delivery. Use-cases of the emerging information technologies included providing assistance, monitoring, self-care and self-management, diagnosis, risk prediction, well-being awareness, personalized healthcare, and qualitative and/or quantitative service enhancement. Limitations identified in the studies included vendor hardware specificity, issues with user interface and usability, inadequate features, interoperability, scalability, and compatibility, unjustifiable costs and insufficient evaluation in terms of validation.

Conclusion: Achievement of a predictive universal digital healthcare ecosystem in the current context is a challenge. State-of-the-art technologies demand user centric design, data privacy and protection measures, transparency, interoperability, scalability, and compatibility to achieve the SDG objective of sustainable healthcare by 2030.
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http://dx.doi.org/10.1016/j.ijmedinf.2021.104420DOI Listing
May 2021

A Case Series of Late Gastrointestinal Fistulization in 16 Patients with Walled-Off Necrosis.

Dig Dis Sci 2021 Mar 2. Epub 2021 Mar 2.

Department of Surgical Gastroenterology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

Background: Gastrointestinal fistulization (GIF) is a rare and potentially fatal complication of acute necrotizing pancreatitis (ANP). There is paucity of data on clinical course and outcome of GIF in walled of necrosis (WON).

Objective: To evaluate frequency, clinical as well as imaging findings and outcome of spontaneous symptomatic GIF in patients with WON.

Methods: Retrospective analysis of database of patients with asymptomatic WON on regular follow-up over last six years to identify patients with symptomatic GIF.

Results: Out of 138 patients with asymptomatic WON seen during the study period, 16 (11.5%) patients (all males; mean age 41.7 ± 9.9 years) developed symptomatic GIF. The mean size of WON in patients who developed GIF was 9.5 ± 2.4 cm, and fistulization occurred after 65.1 ± 17.8 days of the onset of ANP. The site of fistulization was stomach, duodenum, jejunum, colon, and esophagus in seven (43.7%), five (31.2%), one (6.2%), two (12.5%), and one (6.2%) patients, respectively. GIF resulted in spontaneous resolution in two patients (stomach 1 and esophagus 1). The remaining patients with gastric (six patients) and duodenal (five patients) fistulization were successfully treated endoscopically by placing multiple plastic stents in the necrotic cavity after balloon dilatation of the fistulous tract. Patients with colonic fistulization required surgery. None of the patients succumbed to the illness.

Conclusion: Symptomatic GIF of WON usually occurs within the first three months of onset of ANP. It commonly occurs in either stomach or duodenum and can be successfully managed endoscopically.
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http://dx.doi.org/10.1007/s10620-021-06900-yDOI Listing
March 2021

Heterotopic caval valve implantation for the management of severe tricuspid regurgitation: a case series.

Eur Heart J Case Rep 2021 Jan 28;5(1):ytaa428. Epub 2020 Dec 28.

Department of Anesthesia, Critical Care and Pain Medicine. Beth Israel Deaconess Medical Center, Harvard Medical School, One, Deaconess Road, Boston, MA 02215, USA.

Background: Severe tricuspid regurgitation (TR) is a complex condition that can be difficult to treat medically, and often surgical intervention is prohibited due to the high morbidity and mortality associated with this intervention. In patients who have failed maximal medical therapy and have progressive symptoms related to their severe TR, heterotopic caval valve implantation (CAVI) offers potential for symptom relief for these patients.

Case Summary: We present two cases of patients with severe TR with symptoms of heart failure that were refractory to medical therapy. Due to extensive comorbidities in these patient's surgical intervention was deemed unsuitable and the decision was made to proceed with heterotopic CAVI in order to try and control their symptoms. Both patients successfully underwent the procedure and had an Edwards SAPIEN 3 valve (Edwards Lifesciences, Irvine, CA, USA) implanted in the inferior vena cava/right atrium junction. In both patients, there was improvement in the postoperative haemodynamics as measured by invasive and non-invasive methods. Successful discharge was achieved in both patients with improvement in their symptoms.

Discussion: Selective use of heterotopic CAVI to treat symptomatic severe TR that is refractory to medical therapy may be a viable option to improve symptoms in those patients that are unsuitable for surgical intervention.
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http://dx.doi.org/10.1093/ehjcr/ytaa428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898562PMC
January 2021

"Identification of Nafamostat and VR23 as COVID-19 drug candidates by targeting 3CL and PL."

J Mol Struct 2021 Jun 15;1233:130094. Epub 2021 Feb 15.

Department of Microbiology, Assam University, Silchar-788011, Assam, India.

The sudden increase in the COVID-19 epidemic affected by novel coronavirus 2019 has jeopardized public health worldwide. Hence the necessities of a drug or therapeutic agent that heal SARS-CoV-2 infections are essential requirements. The viral genome encodes a large Polyprotein, further processed by the main protease/ 3C-like protease (3CL) and papain-like proteases (PL) into 16 nonstructural proteins to form a viral replication complex. These essential functions of 3CL and PL in virus duplication make these proteases a promising target for discovering potential therapeutic candidates and possible treatment for SARS-CoV-2 infection. This study aimed to screen a unique set of protease inhibitors library against 3CL and PL of the SARS-CoV-2. A molecular docking study was performed using PyRx to reveal the binding affinity of the selected ligands and molecular dynamic simulations were executed to assess the three-dimensional stability of protein-ligand complexes. The pharmacodynamics parameters of the inhibitors were predicted using admetSAR. The top two ligands (Nafamostat and VR23) based on docking scores were selected for further studies. Selected ligands showed excellent pharmacokinetic properties with proper absorption, bioavailability and minimal toxicity. Due to the emerging and efficiency of remdesivir and dexamethasone in healing COVID-19 patients, ADMET properties of the selected ligands were thus compared with it. MD Simulation studies up to 100 ns revealed the ligands' stability at the target proteins' binding site residues. Therefore, Nafamostat and VR23 may provide potential treatment options against SARS-CoV-2 infections by potentially inhibiting virus duplication though more research is warranted.
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http://dx.doi.org/10.1016/j.molstruc.2021.130094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884051PMC
June 2021

CoreValve bioprosthesis dysfunction treated with a Sapien 3 valve-in-valve transcatheter aortic valve replacement and BASILICA technique.

Catheter Cardiovasc Interv 2021 Aug 17;98(2):403-406. Epub 2021 Feb 17.

Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Structural deterioration of transcatheter heart valve (THV) has been previously described. With the expansion of transcatheter aortic valve replacement (TAVR) indications toward treating lower risk patients with longer life expectancy, there will be increased necessity of managing the patients with THV dysfunction including those at risk for coronary obstruction or sinus sequestration. Coronary access also remains a challenge in such cases with THV dysfunction undergoing valve-in-transcatheter heart valve (ViTHV) TAVR. A unique and first reported case of THV deterioration treated with Sapien 3 ViTHV-TAVR inside a 31 mm CoreValve bioprosthesis along with left coronary leaflet laceration using the BASILICA technique has been presented.
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http://dx.doi.org/10.1002/ccd.29544DOI Listing
August 2021

Alternative splicing of ceramide synthase 2 alters levels of specific ceramides and modulates cancer cell proliferation and migration in Luminal B breast cancer subtype.

Cell Death Dis 2021 02 10;12(2):171. Epub 2021 Feb 10.

Amity Institute of Integrative Sciences and Health, Amity University Haryana, Panchgaon, Manesar, Gurgaon, 122413, Haryana, India.

Global dysregulation of RNA splicing and imbalanced sphingolipid metabolism has emerged as promoters of cancer cell transformation. Here, we present specific signature of alternative splicing (AS) events of sphingolipid genes for each breast cancer subtype from the TCGA-BRCA dataset. We show that ceramide synthase 2 (CERS2) undergoes a unique cassette exon event specifically in Luminal B subtype tumors. We validated this exon 8 skipping event in Luminal B cancer cells compared to normal epithelial cells, and in patient-derived tumor tissues compared to matched normal tissues. Differential AS-based survival analysis shows that this AS event of CERS2 is a poor prognostic factor for Luminal B patients. As Exon 8 corresponds to catalytic Lag1p domain, overexpression of AS transcript of CERS2 in Luminal B cancer cells leads to a reduction in the level of very-long-chain ceramides compared to overexpression of protein-coding (PC) transcript of CERS2. We further demonstrate that this AS event-mediated decrease of very-long-chain ceramides leads to enhanced cancer cell proliferation and migration. Therefore, our results show subtype-specific AS of sphingolipid genes as a regulatory mechanism that deregulates sphingolipids like ceramides in breast tumors, and can be explored further as a suitable therapeutic target.
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http://dx.doi.org/10.1038/s41419-021-03436-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876150PMC
February 2021

Safety and Efficacy of Early (<4 Weeks of Illness) Endoscopic Transmural Drainage of Post-acute Pancreatic Necrosis Predominantly Located in the Body of the Pancreas.

J Gastrointest Surg 2021 Feb 5. Epub 2021 Feb 5.

Department of Surgical Gastroenterology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

Background: Endoscopic transmural drainage is usually not performed for pancreatic necrotic collection (PNC) < 4 weeks after onset of acute necrotizing pancreatitis (ANP) because of lack of encapsulating wall and increased risk of complications.

Objective: Study safety and efficacy of early (<4 weeks) endoscopic transluminal drainage in patients with symptomatic PNC.

Methods: Retrospective analysis of data base of patients with PNC treated with endoscopic transmural drainage within 4 weeks of onset of ANP (early drainage) was done. The outcomes and complications were compared with patients with PNC who underwent delayed endoscopic drainage (≥4 weeks of onset of ANP).

Results: Thirty-four patients (26 males; mean age: 35.9 ± 8.6 years) underwent early and 136 patients (115 males; mean age: 37.9 ± 9.4 years) underwent delayed endoscopic drainage. The PNC was significantly larger (12.3 ± 2.1 cm vs 10.5 ± 2.7 cm, p <0.001) with increased solid component (47.7 ± 8.9% vs 28.3 ± 11.7%, p <0.001) in the early group. Clinical success was achieved in 94% patients in the early group and all patients in the delayed group. Direct endoscopic necrosectomy was performed more frequently in the early group (50% vs 7.4%; p<0.001). There was increased mortality (5.7% vs 0%), need for rescue surgical necrosectomy (5.7% vs 0%), and clinically significant bleeding (20% vs 1.5%, p<0.001) in the early group as compared to the delayed group.

Conclusion: Early endoscopic drainage of PNC is feasible and seems to be safe as well as effective but is associated with increased risk of complications as compared to delayed drainage.
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http://dx.doi.org/10.1007/s11605-021-04945-yDOI Listing
February 2021

Endoscopic dilatation of tight difficult pancreatic duct strictures: Soehendra stent retriever or wire guided cystotome.

Pancreatology 2021 Mar 3;21(2):498-499. Epub 2021 Jan 3.

Department of Surgical Gastroenterology, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012, India.

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http://dx.doi.org/10.1016/j.pan.2020.12.020DOI Listing
March 2021

Identifying the natural polyphenol catechin as a multi-targeted agent against SARS-CoV-2 for the plausible therapy of COVID-19: an integrated computational approach.

Brief Bioinform 2021 03;22(2):1346-1360

Amity Institute of Integrative Sciences and Health, Amity Institute of Integrative Sciences and Health, Amity University, Haryana.

The global pandemic crisis, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines have not turned to be realistic within the timeframe needed to combat this pandemic. Here, we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, whichare crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection. Virtual screening of 75 FDA-approved potential antiviral drugs against the target proteins, spike (S) glycoprotein, human angiotensin-converting enzyme 2 (hACE2), 3-chymotrypsin-like cysteine protease (3CLpro), cathepsin L (CTSL), nucleocapsid protein, RNA-dependent RNA polymerase (RdRp) and non-structural protein 6 (NSP6), resulted in the selection of seven drugs which preferentially bind to the target proteins. Further, the molecular interactions determined by molecular dynamics simulation revealed that among the 75 drug molecules, catechin can effectively bind to 3CLpro, CTSL, RBD of S protein, NSP6 and nucleocapsid protein. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of -5.09 kcal/mol (CTSL) to -26.09 kcal/mol (NSP6). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values: -7.59 to -37.39 kcal/mol. Thus, the structural insights of better binding affinity and favorable molecular interaction of catechin toward multiple target proteins signify that catechin can be potentially explored as a multi-targeted agent against COVID-19.
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http://dx.doi.org/10.1093/bib/bbaa378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799228PMC
March 2021

Impact of different visualization devices on accuracy, efficiency, and dexterity in neurosurgery: a laboratory investigation.

Neurosurg Focus 2021 01;50(1):E18

Objective: Extracorporeal telescopes (exoscopes) have been the latest addition to the neurosurgeons' armamentarium, acting as a bridge between operating microscopes and endoscopes. However, to the authors' knowledge there are no published preclinical laboratory studies of the accuracy, efficiency, and dexterity of neurosurgical training for the use of 2D or 3D exoscopes compared with microscopes.

Methods: In a controlled experimental setup, 22 participating neurosurgery residents performed simple (2D) and complex (3D) motor tasks with three visualization tools in alternating sequence: a 2D exoscope, 3D exoscope, and microscope, using a block randomization model based on the neurosurgeons' prior training experience (novice, intermediate, and senior: n = 6, 12, and 4, respectively). Performance scores (PS; including error and efficiency scores) and dexterity scores (DS) were calculated to objectify the accuracy, efficiency, and finesse of task performance. Repeated measures ANOVA analysis was used to compare the PS, DS, and cumulative scores (CS) of candidates using the three visualization aids. Bland-Altman plots and intraclass correlation coefficients were generated to quantify intraobserver and interobserver agreement for DS. Subgroup analysis was performed to assess the impact of participants' prior training. A postexercise survey was conducted to assess the comfort level (on a 10-point analog scale) of the participants while using each visualization tool for performing the suturing task.

Results: PS, DS, and CS were significantly impacted by the visualization tool utilized for 2D motor tasks (p < 0.001 for each), with the microscope faring better than the 2D exoscope (p = 0.04) or 3D exoscope (p = 0.008). The PS for the 3D object transfer task was significantly influenced by the visualization aid used (p = 0.007), with the microscope and 3D exoscope faring better than the 2D exoscope (p = 0.04 for both). The visualization instrument used significantly affected the DS and CS for the suturing task (p < 0.001 for both), with the microscope again scoring better than the 2D exoscope (p < 0.001) or 3D exoscope (p = 0.005). The impact of the visualization aid was more apparent in participants with a shorter duration of residency (novice, p = 0.03; intermediate, p = 0.0004). Participants also felt the greatest operational comfort while working with a microscope, 3D exoscope, and 2D exoscope, in that order (p < 0.0001).

Conclusions: Compared with 3D and 2D exoscopes, an operating microscope provides better dexterity and performance and a greater operational comfort level for neurosurgeons while they are performing 2D or 3D motor tasks. For performing complex 3D motor tasks, 3D exoscopes offer selective advantages in dexterity, performance, and operational comfort level over 2D exoscopes. The relative impact of visualization aids on surgical proficiency gradually weakens as the participants' residency duration increases.
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http://dx.doi.org/10.3171/2020.10.FOCUS20786DOI Listing
January 2021
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