Publications by authors named "Niraj Kumar"

194 Publications

Sleep Disorders in Patients with Parkinson's Disease during COVID-19 Pandemic: A Case-Control Study.

Ann Indian Acad Neurol 2022 May-Jun;25(3):394-400. Epub 2022 Jun 24.

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

Objective: To assess the impact of coronavirus disease 2019 (COVID-19) pandemic on sleep disorders among Parkinson's disease (PD) patients using validated questionnaires.

Materials And Methods: This prospective study involved 50 PD patients and 50 age, gender, and body mass index-matched controls. All participants underwent assessment of cognition using Montreal Cognitive Assessment scale, sleep quality using Parkinson's disease sleep scale-2 (PDSS-2; for PD patients) and Pittsburgh Sleep Quality Index (PSQI; for PD patients and healthy controls), excessive daytime sleepiness (EDS) using Epworth sleepiness scale (ESS), insomnia symptoms and severity using insomnia severity index (ISI), restless legs syndrome (RLS) using International RLS Study Group criteria, rapid eye movement sleep behavior disorder (RBD) using RBD Single-Question Screen (RBD1Q), and depression using Patient Health Questionnaire-9 scale.

Results: Eighty-eight percent of PD patients reported one or more sleep disorders, compared to 28% controls. While 72% of PD patients reported poor sleep quality (PDSS-2 ≥15, PSQI >5), 60% had insomnia, 58% reported RBD, 50% had EDS, and 36% reported RLS. Depressive symptoms were reported by 70% patients. PD patients with and without poor sleep quality were comparable with regards to demographic and clinical variables, except for depressive symptoms ( < 0.001). Depressive symptoms showed a significant association with EDS ( = 0.008), RBD ( < 0.001), and insomnia ( = 0.001).

Conclusion: Prevalence of sleep disorders increased in PD patients during the COVID-19 pandemic. Prevalence of EDS, RBD, and RLS in PD patients was higher compared to that reported in studies during the pre-COVID-19 times. Presence of depressive symptoms was a significant correlate of presence of sleep disorders in PD patients.
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http://dx.doi.org/10.4103/aian.aian_255_22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350758PMC
June 2022

Development & validation of scales to assess stigma related to COVID-19 in India.

Indian J Med Res 2022 01;155(1):156-164

Department of Microbiology, ICMR-Regional Medical Research Centre, Bhubaneswar, Odisha, India.

Background & Objectives: COVID-19 pandemic has triggered social stigma towards individuals affected and their families. This study describes the process undertaken for the development and validation of scales to assess stigmatizing attitudes and experiences among COVID-19 and non-COVID-19 participants from the community.

Methods: COVID-19 Stigma Scale and Community COVID-19 Stigma Scale constituting 13 and six items, respectively, were developed based on review of literature and news reports, expert committee evaluation and participants' interviews through telephone for a multicentric study in India. For content validity, 61 (30 COVID-19-recovered and 31 non-COVID-19 participants from the community) were recruited. Test-retest reliability of the scales was assessed among 99 participants (41 COVID-19 recovered and 58 non-COVID-19). Participants were administered the scale at two-time points after a gap of 7-12 days. Cronbach's alpha, overall percentage agreement and kappa statistics were used to assess internal consistency and test-retest reliability.

Results: Items in the scales were relevant and comprehensible. Both the scales had Cronbach's α above 0.6 indicating moderate-to-good internal consistency. Test-retest reliability assessed using kappa statistics indicated that for the COVID-19 Stigma Scale, seven items had a moderate agreement (0.4-0.6). For the Community COVID-19 Stigma Scale, four items had a moderate agreement.

Interpretation & Conclusions: Validity and reliability of the two stigma scales indicated that the scales were comprehensible and had moderate internal consistency. These scales could be used to assess COVID-19 stigma and help in the development of appropriate stigma reduction interventions for COVID-19 infected, and mitigation of stigmatizing attitudes in the community.
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http://dx.doi.org/10.4103/ijmr.ijmr_2455_21DOI Listing
January 2022

Genome-Wide Polygenic Score Predicts Large Number of High Risk Individuals in Monogenic Undiagnosed Young Onset Parkinson's Disease Patients from India.

Adv Biol (Weinh) 2022 Jul 10:e2101326. Epub 2022 Jul 10.

Hyderabad, 500084, India.

Parkinson's disease (PD) is a genetically heterogeneous neurodegenerative disease with poorly defined environmental influences. Genomic studies of PD patients have identified disease-relevant monogenic genes, rare variants of significance, and polygenic risk-associated variants. In this study, whole genome sequencing data from 90 young onset Parkinson's disease (YOPD) individuals are analyzed for both monogenic and polygenic risk. The genetic variant analysis identifies pathogenic/likely pathogenic variants in eight of the 90 individuals (8.8%). It includes large homozygous coding exon deletions in PRKN and SNV/InDels in VPS13C, PLA2G6, PINK1, SYNJ1, and GCH1. Eleven rare heterozygous GBA coding variants are also identified in 13 (14.4%) individuals. In 34 (56.6%) individuals, one or more variants of uncertain significance (VUS) in PD/PD-relevant genes are observed. Though YOPD patients with a prioritized pathogenic variant show a low polygenic risk score (PRS), patients with prioritized VUS or no significant rare variants show an increased PRS odds ratio for PD. This study suggests that both significant rare variants and polygenic risk from common variants together may contribute to the genesis of PD. Further validation using a larger cohort of patients will confirm the interplay between monogenic and polygenic variants and their use in routine genetic PD diagnosis and risk assessment.
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http://dx.doi.org/10.1002/adbi.202101326DOI Listing
July 2022

Predictors of post-TAVI conduction abnormalities in patients with bicuspid aortic valves.

Open Heart 2022 07;9(2)

Cardiology, Barts Health NHS Trust, London, UK

Objectives: This study evaluates predictors of conduction abnormalities (CA) following transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valves (BAV).

Background: TAVI is associated with CA that commonly necessitate a permanent pacemaker. Predictors of CA are well established among patients with tricuspid aortic valves but not in those with BAV.

Methods: This is a single-centre, retrospective, observational study of patients with BAV treated with TAVI. Pre-TAVI ECG and CT scans and procedural characteristics were evaluated in 58 patients with BAV. CA were defined as a composite of high-degree atrioventricular block, new left bundle branch block with a QRS >150 ms or PR >240 ms and right bundle branch block with new PR prolongation or change in axis. Predictors of CA were identified using regression analysis and optimum cut-off values determined using area under the receiver operating characteristic curve analysis.

Results: CA occurred in 35% of patients. Bioprosthesis implantation depth, the difference between membranous septum (MS) length and implantation depth (MSID) and device landing zone (DLZ) calcification adjacent to the MS were identified as univariate predictors of CA. The optimum cut-off for MSID was 1.25 mm. Using this cut-off, low MSID and DLZ calcification adjacent to MS predicted CA, adjusted OR 8.79, 95% CI 1.88 to 41.00; p=0.01. Eccentricity of the aortic valve annulus, type of BAV and valve calcium quantity and distribution did not predict CA.

Conclusions: In BAV patients undergoing TAVI, short MSID and DLZ calcification adjacent to MS are associated with an increased risk of CA.
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http://dx.doi.org/10.1136/openhrt-2022-001995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258482PMC
July 2022

Role of artificial intelligence in defibrillators: a narrative review.

Open Heart 2022 07;9(2)

Cardiff University College of Biomedical and Life Sciences, Cardiff, UK.

Automated external defibrillators (AEDs) and implantable cardioverter defibrillators (ICDs) are used to treat life-threatening arrhythmias. AEDs and ICDs use shock advice algorithms to classify ECG tracings as shockable or non-shockable rhythms in clinical practice. Machine learning algorithms have recently been assessed for shock decision classification with increasing accuracy. Outside of rhythm classification alone, they have been evaluated in diagnosis of causes of cardiac arrest, prediction of success of defibrillation and rhythm classification without the need to interrupt cardiopulmonary resuscitation. This review explores the many applications of machine learning in AEDs and ICDs. While these technologies are exciting areas of research, there remain limitations to their widespread use including high processing power, cost and the 'black-box' phenomenon.
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http://dx.doi.org/10.1136/openhrt-2022-001976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258481PMC
July 2022

Environmental sustainability in robotic and laparoscopic surgery: systematic review.

Br J Surg 2022 Jun 21. Epub 2022 Jun 21.

Division of Surgery and Interventional Science, University College London, London, UK.

Background: Minimally invasive surgical (MIS) techniques are considered the gold standard of surgical interventions, but they have a high environmental cost. With global temperatures rising and unmet surgical needs persisting, this review investigates the carbon and material footprint of MIS and summarizes strategies to make MIS greener.

Methods: The MEDLINE, Embase, and Web of Science databases were interrogated between 1974 and July 2021. The search strategy encompassed surgical setting, waste, carbon footprint, environmental sustainability, and MIS. Two investigators independently performed abstract/full-text reviews. An analysis of disability-adjusted life years (DALYs) averted per ton of carbon dioxide equivalents (CO2e) or waste produced was generated.

Results: From the 2456 abstracts identified, 16 studies were selected reporting on 5203 MIS procedures. Greenhouse gas (GHG) emissions ranged from 6 kg to 814 kg CO2e per case. Carbon footprint hotspots included production of disposables and anaesthetics. The material footprint of MIS ranged from 0.25 kg to 14.3 kg per case. Waste-reduction strategies included repackaging disposables, limiting open and unused instruments, and educational interventions. Robotic procedures result in 43.5 per cent higher GHG emissions, 24 per cent higher waste production, fewer DALYs averted per ton of CO2, and less waste than laparoscopic alternatives.

Conclusion: The increased environmental impact of robotic surgery may not sufficiently offset the clinical benefit. Utilizing alternative surgical approaches, reusable equipment, repackaging, surgeon preference cards, and increasing staff awareness on open and unused equipment and desflurane avoidance can reduce GHG emissions and waste.
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http://dx.doi.org/10.1093/bjs/znac191DOI Listing
June 2022

Linear Morphea: A Mimicker of Motor Neuron Disease.

Ann Indian Acad Neurol 2022 Mar-Apr;25(2):278-280. Epub 2022 Jan 7.

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

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http://dx.doi.org/10.4103/aian.AIAN_431_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175433PMC
January 2022

Development & validation of scales to assess stigma related to COVID-19 in India.

Indian J Med Res 2022 May 20. Epub 2022 May 20.

Department of Microbiology, ICMR-Regional Medical Research Centre, Bhubaneswar, Odisha, India.

Background & Objectives: COVID-19 pandemic has triggered social stigma towards individuals affected and their families. This study describes the process undertaken for the development and validation of scales to assess stigmatizing attitudes and experiences among COVID-19 and non-COVID-19 participants from the community.

Methods: COVID-19 Stigma Scale and Community COVID-19 Stigma Scale constituting 13 and six items, respectively, were developed based on review of literature and news reports, expert committee evaluation and participants' interviews through telephone for a multicentric study in India. For content validity, 61 (30 COVID-19-recovered and 31 non-COVID-19 participants from the community) were recruited. Test-retest reliability of the scales was assessed among 99 participants (41 COVID-19 recovered and 58 non-COVID-19). Participants were administered the scale at two-time points after a gap of 7-12 days. Cronbach's alpha, overall percentage agreement and kappa statistics were used to assess internal consistency and test-retest reliability.

Results: Items in the scales were relevant and comprehensible. Both the scales had Cronbach's α above 0.6 indicating moderate-to-good internal consistency. Test-retest reliability assessed using kappa statistics indicated that for the COVID-19 Stigma Scale, seven items had a moderate agreement (0.4-0.6). For the Community COVID-19 Stigma Scale, four items had a moderate agreement.

Interpretation & Conclusions: Validity and reliability of the two stigma scales indicated that the scales were comprehensible and had moderate internal consistency. These scales could be used to assess COVID-19 stigma and help in the development of appropriate stigma reduction interventions for COVID-19 infected, and mitigation of stigmatizing attitudes in the community.
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http://dx.doi.org/10.4103/ijmr.ijmr_2455_21DOI Listing
May 2022

Identification of metabolite extraction method for targeted exploration of antimicrobial resistance associated metabolites of Klebsiella pneumoniae.

Sci Rep 2022 05 27;12(1):8939. Epub 2022 May 27.

Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad - Gurugram Expressway, PO box #04, Faridabad, 121001, India.

Antimicrobial resistant Klebsiella pneumoniae (K. pneumoniae), as being a pathogen of critical clinical concern, urgently demands effective therapeutic options. However, the discovery of novel antibiotics over the last three decades has declined drastically and necessitates exploring novel strategies. Metabolomic modulation has been the promising approach for the development of effective therapeutics to deal with AMR; however, only limited efforts have been made to-date, possibly due to the unavailability of suitable metabolites extraction protocols. Therefore, in order to establish a detailed metabolome of K. pneumoniae and identify a method for targeted exploration of metabolites that are involved in the regulation of AMR associated processes, metabolites were extracted using multiple methods of metabolites extraction (freeze-thaw cycle (FTC) and sonication cycle (SC) method alone or in combination (FTC followed by SC; FTC + SC)) from K. pneumoniae cells and then identified using an orbitrap mass analyzer (ESI-LC-MS/MS). A total of 151 metabolites were identified by using FTC, 132 metabolites by using FTC+SC, 103 metabolites by using SC and 69 metabolites common among all the methods used which altogether enabled the identification of 199 unique metabolites. Of these 199, 70 metabolites were known to have an association with AMR phenotype and among these, the FTC + SC method yielded better (identified 55 metabolites), quantitatively and qualitatively compared to FTC and SC alone (identified 51 and 41 metabolites respectively). Each method of metabolite extraction showed a definite degree of biasness and specificity towards chemical classes of metabolites and jointly contributed to the development of a detailed metabolome of the pathogen. FTC method was observed to give higher metabolomic coverage as compared to SC alone and FTC + SC. However, FTC + SC resulted in the identification of a higher number of AMR associated metabolites of K. pneumoniae compared to FTC and SC alone.
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http://dx.doi.org/10.1038/s41598-022-12153-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142494PMC
May 2022

COVID-19 transmission among vaccinated laboratory workers during the second wave in eastern Uttar Pradesh, India.

J Med Virol 2022 Aug 23;94(8):3512-3514. Epub 2022 Apr 23.

Indian Council of Medical Research-Regional Medical Research Centre Gorakhpur (ICMR-RMRC Gorakhpur), Gorakhpur, Uttar Pradesh, India.

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http://dx.doi.org/10.1002/jmv.27788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088332PMC
August 2022

Disrupted Sleep During a Pandemic.

Sleep Med Clin 2022 Mar;17(1):41-52

Department of Psychiatry, Division of Sleep Medicine, All India Institute of Medical Sciences, Rishikesh 249203, India. Electronic address:

The COVID-19 pandemic affected sleep in several people. Though most of the studies argued that age, gender, employment, finances, responsibilities, and exposure to sunlight governed sleep-wake schedule and sleep disturbances, there is also scientific evidence to suggest that these issues could have aroused because of the infiltration of the central nervous system (CNS) by SARS-CoV-2. Sleep disturbances must be addressed during the pandemic as sleep disturbances and systemic inflammation run in a vicious cycle; quality of sleep and timing of vaccination can influence the immune response to vaccination and subjects having obstructive sleep apnea (OSA) are at higher risk for having SARS-CoV-2 infection-related complications.
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http://dx.doi.org/10.1016/j.jsmc.2021.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863400PMC
March 2022

Replication of Dengue Virus in K562-Megakaryocytes Induces Suppression in the Accumulation of Reactive Oxygen Species.

Front Microbiol 2021 11;12:784070. Epub 2022 Jan 11.

Translational Health Science and Technology Institute, National Capital Region (NCR) Biotech Science Cluster, Faridabad, India.

Dengue virus can infect human megakaryocytes leading to decreased platelet biogenesis. In this article, we report a study of Dengue replication in human K562 cells undergoing PMA-induced differentiation into megakaryocytes. PMA-induced differentiation in these cells recapitulates steps of megakaryopoiesis including gene activation, expression of CD41/61 and CD61 platelet surface markers and accumulation of intracellular reactive oxygen species (ROS). Our results show differentiating megakaryocyte cells to support higher viral replication without any apparent increase in virus entry. Further, Dengue replication suppresses the accumulation of ROS in differentiating cells, probably by only augmenting the activity of the transcription factor NFE2L2 without influencing the expression of the coding gene. Interestingly pharmacological modulation of NFE2L2 activity showed a simultaneous but opposite effect on intracellular ROS and virus replication suggesting the former to have an inhibitory effect on the later. Also cells that differentiated while supporting intracellular virus replication showed reduced level of surface markers compared to uninfected differentiated cells.
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http://dx.doi.org/10.3389/fmicb.2021.784070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787197PMC
January 2022

Genome Sequencing Reveals a Mixed Picture of SARS-CoV-2 Variant of Concern Circulation in Eastern Uttar Pradesh, India.

Front Med (Lausanne) 2021 7;8:781287. Epub 2022 Jan 7.

Indian Council of Medical Research (ICMR)-Regional Medical Research Centre, Gorakhpur, India.

Uttar Pradesh is the densely populated state of India and is the sixth highest COVID-19 affected state with 22,904 deaths recorded on November 12, 2021. Whole-genome sequencing (WGS) is being used as a potential approach to investigate genomic evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In this study, a total of 87 SARS-CoV-2 genomes-49 genomes from the first wave (March 2020 to February 2021) and 38 genomes from the second wave (March 2021 to July 2021) from Eastern Uttar Pradesh (E-UP) were sequenced and analyzed to understand its evolutionary pattern and variants against publicaly available sequences. The complete genome analysis of SARS-CoV-2 during the first wave in E-UP largely reported transmission of G, GR, and GH clades with specific mutations. In contrast, variants of concerns (VOCs) such as Delta (71.0%) followed by Delta AY.1 (21.05%) and Kappa (7.9%) lineages belong to G clade with prominent signature amino acids were introduced in the second wave. Signature substitution at positions S:L452R, S:P681R, and S:D614G were commonly detected in the Delta, Delta AY.1, and Kappa variants whereas S:T19R and S:T478K were confined to Delta and Delta AY.1 variants only. Vaccine breakthrough infections showed unique mutational changes at position S:D574Y in the case of the Delta variant, whereas position S:T95 was conserved among Kappa variants compared to the Wuhan isolate. During the transition from the first to second waves, a shift in the predominant clade from GH to G clade was observed. The identified spike protein mutations in the SARS-CoV-2 genome could be used as the potential target for vaccine and drug development to combat the effects of the COVID-19 disease.
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http://dx.doi.org/10.3389/fmed.2021.781287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777020PMC
January 2022

Exposure to household air pollution from solid cookfuels and childhood stunting: a population-based, cross-sectional study of half a million children in low- and middle-income countries.

Int Health 2022 Jan 12. Epub 2022 Jan 12.

Institute of Applied Health Research, University of Birmingham, Birmingham, B15 2TT, UK.

Background: Household air pollution from the incomplete combustion of solid cookfuels in low- and middle-income countries (LMICs) has been largely ignored as a potentially important correlate of stunting. Our objective was to examine the association between solid cookfuel use and stunting in children aged <5 y.

Methods: We used data from 59 LMICs' population-based cross-sectional demographic and health surveys; 557 098 children aged <5 y were included in our analytical sample. Multilevel logistic regression was used to examine the association between exposure to solid cookfuel use and childhood stunting, adjusting for child sex, age, maternal education and number of children living in the household. We explored the association across key subgroups.

Results: Solid cookfuel use was associated with child stunting (adjusted OR 1.58, 95% CI 1.55 to 1.61). Children living in households using solid cookfuels were more likely to be stunted if they lived in rural areas, the poorest households, had a mother who smoked tobacco or were from the Americas.

Conclusions: Focused strategies to reduce solid cookfuel exposure might contribute to reductions in childhood stunting in LMICs. Trial evidence to assess the effect of reducing solid cookfuel exposure on childhood stunting is urgently needed.
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http://dx.doi.org/10.1093/inthealth/ihab090DOI Listing
January 2022

Infantile Ascending Hereditary Spastic Paralysis with Extrapyramidal and Extraocular Manifestations Associated with a Novel Mutation.

Mov Disord Clin Pract 2022 Jan 28;9(1):118-121. Epub 2021 Nov 28.

Department of Neurology All India Institute of Medical Sciences Rishikesh India.

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http://dx.doi.org/10.1002/mdc3.13372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721836PMC
January 2022

Wilson's Disease Update: An Indian Perspective.

Ann Indian Acad Neurol 2021 Sep-Oct;24(5):652-663. Epub 2021 Oct 14.

Department of Neurology, Medanta Hospital, Gurugram, Haryana, India.

Wilson's disease (WD) is an autosomal recessive disorder due to ATP7B gene mutation, resulting in defective copper metabolism, with the liver and brain being primarily affected. WD being a treatable disorder, early diagnosis and proper management may result in near complete recovery. It has received significant attention over the past 50 years, with several Indian contributions. This study collates published Indian studies on WD in Pubmed and Embase databases and puts them in perspective. Several Indian case series suggest WD may be more prevalent than thought. Commonly detected ATP7B mutation in India is p.C271X. Although initial Indian series reported significant osseomuscular presentation, neuropsychiatric and hepatic manifestations dominated the later reports. A significant male predominance is observed in the Indian series. Pure hepatic presentation starts earlier than neurological or osseomuscular WD. A positive family history may be seen in nearly 50% of Indian WD cases, with a high rate of consanguinity. Up to two-third of the Indian cases may be initially misdiagnosed, with a mean diagnostic delay of up to 2 years. Abnormalities in serum ceruloplasmin and 24-hour urinary copper has been reported in more than four-fifth cases. Brain MRI is abnormal in nearly all neurological WD cases. Copper chelation remains the mainstay of therapy, with D-penicillamine being the most widely used chelator in India. Global Assessment Scale for WD is a comprehensive tool for clinical monitoring. Hepatic presentation carries a five-time higher mortality risk than neurological, with up to 90% Indian neurological WD cases recovering back to pre-morbid functionality with adequate therapy.
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http://dx.doi.org/10.4103/aian.AIAN_171_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8680915PMC
October 2021

Emergency surgery for type A aortic dissection in octogenarians-Do we still err on the side of caution?

J Card Surg 2022 Mar 8;37(3):616-617. Epub 2022 Jan 8.

Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, UK.

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http://dx.doi.org/10.1111/jocs.16211DOI Listing
March 2022

The Results From the COMALIGN Study.

JACC Cardiovasc Interv 2021 12;14(23):2635

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http://dx.doi.org/10.1016/j.jcin.2021.10.010DOI Listing
December 2021

Incidence of posterior vessel wall puncture during ultrasound guided vascular access: Short axis versus long axis approach.

J Anaesthesiol Clin Pharmacol 2021 Jul-Sep;37(3):342-346. Epub 2021 Oct 12.

Department of Community Medicine, Armed Forces Medical College, Pune, Maharashtra, India.

Background And Aims: Posterior vessel wall puncture (PVWP) is a common complication of ultrasound (US) guided central venous cannulation. We evaluated and compared the frequency of PWVP of internal jugular vein using short axis (SA) and long axis (LA) approach of US-guided needle cannulation. As a secondary objective incidence of carotid puncture was assessed.

Material And Methods: Prospective, single-blinded, cross over, observational study at Urban Level I Neuroanesthesiology and Critical Care Department. Residents receiving standard education on ultrasound-guided central venous cannulation were asked to place an US-guided catheter using either short axis or long axis approach on a human torso mannequin. During the procedure, the path of the needle was carefully observed by the investigator for any PVWP and carotid puncture without interference with the placement procedure. The confidence level of the resident for the intraluminal placement of the needle tip was measured on a 10-point Likert scale.

Results: Forty residents participated in the study. The incidence of PVWP in SA and LA group was 40% and 17.5% respectively and was statistically significant (p = 0.026). There was no incidence of carotid artery puncture in either of the group. The mean confidence of intraluminal placement of needle was significantly higher in the LA group (8.32) as compared to the SA group (5.95).

Conclusion: Lower incidence of PVWP was seen in LA as compared to the SA approach during US-guided IJV cannulation in phantom in residents having previous experience of CVC (central venous cannulation) in landmark technique only. Participants were more confident about intraluminal needle placement in the LA group compared to the SA group.
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http://dx.doi.org/10.4103/joacp.JOACP_185_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562459PMC
October 2021

Sensory Trick in Painful Legs and Moving Toes Syndrome.

Neurol India 2021 Sep-Oct;69(5):1436-1437

Department of Clinical Neurological Sciences, Western University, London, ON, Canada.

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http://dx.doi.org/10.4103/0028-3886.329607DOI Listing
November 2021

An investigation to the prolonged requirement (>7 days) of vasopressors in cervical spinal cord injury patients-a retrospective analysis.

Spinal Cord Ser Cases 2021 11 2;7(1):96. Epub 2021 Nov 2.

Department of Neuroanaesthesia and critical care, All India Institute of Medical Sciences, New Delhi, 110029, India.

Study Design: Retrospective chart review.

Objectives: The primary aim was to identify the number of patients requiring vasopressors beyond the first week of cervical spinal cord injury (SCI). Secondary objectives were to note the type, duration and doses of vasopressors and any association between prolonged vasopressors use and outcome.

Setting: Neurosurgical intensive care of a tertiary trauma care centre.

Methods: After Ethical approval we retrospectively collected the data of patients of isolated cervical SCI admitted to neurosurgical intensive care from January to December 2017. Vasopressor requirement for sepsis or cardiac arrest was excluded.

Results: Out of 80 patients analysed, 54 (67.5%) received vasopressors. The prolonged requirement of vasopressors was observed in 77.7%. Our preferred agent was dopamine (64.8%). We found out that longer requirement (in days) of high dose of dopamine was associated with higher survival (p = 0.03).

Conclusion: Our results describe a significant portion of cervical SCI patients need ongoing vasopressor to maintain a mean arterial pressure >65 mm of Hg beyond first week. We observed patients who required longer duration of high dose dopamine had a higher chance of survival suggesting some unknown mechanism of high dose of dopamine. This is first such observation, further studies are needed to substantiate.
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http://dx.doi.org/10.1038/s41394-021-00459-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563917PMC
November 2021

Emerging roles of autophagy in the development and treatment of urothelial carcinoma of the bladder.

Expert Opin Ther Targets 2021 09 27;25(9):787-797. Epub 2021 Oct 27.

Department of Biochemistry, University of Lucknow, Lucknow, India.

Introduction: High recurrence rates, frequent surveillance strategies, and current multidisciplinary treatment approaches make urothelial carcinoma of bladder (UCB) one of the most expensive cancers to clinically manage. Recent studies have demonstrated a role for autophagy in bladder tumorigenesis. It serves as a tumor suppressor by maintaining genomic integrity and preventing tumor proliferation during initial stages of tumor development. Nevertheless, once established, cancer cells may utilize protective autophagy to endure cellular stress and survive in the adverse environment. Its excessive stimulation supports cancer cells' resistance to therapeutic modalities.

Areas Covered: PubMed and Google Scholar electronic databases were searched for recently published studies. This review summarizes emerging roles of autophagy in development/progression of UCB and treatment resistance and explores novel therapeutic targets for prevention of cancer invasion, metastatic spread', and disease relapse.

Expert Opinion: The development of novel therapies via targeting of autophagy may augment current treatment regimens and improve clinical outcomes. Synthetic compounds or plant-based metabolites are reported to enhance cancer therapies by modulating autophagic flux. Successful autophagy-focused therapeutic intervention requires a mechanistic understanding of autophagic effects on tumor initiation and progression and the development of efficient biomarkers to monitor it in tumor tissues.
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http://dx.doi.org/10.1080/14728222.2021.1992384DOI Listing
September 2021

The impact of the COVID-19 pandemic on global neurosurgical education: a systematic review.

Neurosurg Rev 2022 Apr 8;45(2):1101-1110. Epub 2021 Oct 8.

Department of Medicine, UCL Medical School, 74 Huntley St, London, WC1E 6DE, UK.

The COVID-19 pandemic has disrupted neurosurgical training worldwide, with the shutdown of academic institutions and the reduction of elective surgical procedures. This impact has disproportionately affected LMICs (lower- and/or middle-income countries), already burdened by a lack of neurosurgical resources. Thus, a systematic review was conducted to examine these challenges and innovations developed to adapt effective teaching and learning for medical students and neurosurgical trainees. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and The Cochrane Handbook of Systematic Reviews of Interventions. MEDLINE, PubMed, Embase and Cochrane databases were accessed, searching and screening literature from December 2019 to 5th December 2020 with set inclusion and exclusion criteria. Screening identified 1254 articles of which 26 were included, providing data from 96 countries. Twenty-three studies reported transition to online learning, with 8 studies also mentioned redeployment into COVID wards with 2 studies mentioning missed surgical exposure as a consequence. Of 7 studies conducted in LMICs, 3 reported residents suffering financial insecurities from reduced surgical caseload and recession. Significant global disruption in neurosurgical teaching and training has arisen from the COVID-19 pandemic. Decreased surgical exposure has negatively impacted educational provision. However, advancements in virtual technology have allowed for more affordable, accessible training especially in LMICs. Using this, initiatives to reduce physical and mental stress experienced by trainees should be paramount.
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http://dx.doi.org/10.1007/s10143-021-01664-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497188PMC
April 2022

Spinal Intramedullary Neurocysticercosis An Unusual Cause of Paraparesis.

J Assoc Physicians India 2021 Sep;69(9):11-12

Additional Professor, Department of Neurology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand.

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September 2021

Neurological safety and efficacy of darifenacin and mirabegron for the treatment of overactive bladder in patients with history of cerebrovascular accident: A prospective study.

Neurourol Urodyn 2021 11 13;40(8):2041-2047. Epub 2021 Sep 13.

Department of Urology and Renal Transplant, Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.

Objectives: To evaluate the neurological safety and clinical efficacy of darifenacin and mirabegron in patients with a history of cerebrovascular accident (CVA) who had overactive bladder (OAB) symptoms.

Methods: This prospective randomized study, approved by the institute's ethics committee, was carried out at a tertiary care center from December 2018 to June 2020. Treatment naïve adult patients with a past history of CVA with stable neurological status for atleast past 3 months with symptoms of OAB for 3 or more months were included. Eligible patients received either darifenacin or mirabegron for a period of 3 months and various parameters on the 3-day International Consultation on Incontinence Questionnaire (ICIQ) bladder diary, the Montreal Cognitive Assessment-Basic score (MoCA-B), and the adverse events at 3 months posttreatment were compared to that at the baseline.

Results: A total of 60 patients were included, 30 in each arm. After 3 months of treatment with darifenacin or mirabegron, the majority of the ICIQ bladder diary parameters improved and there was no deterioration in the cognitive function as noted on the MoCA-B score in either of the arms. On intergroup comparison, the mean change in bladder diary parameters and the MoCA-B scores was similar between the two groups.

Conclusion: Darifenacin and mirabegron, in the short term, do not adversely affect the cognitive function in patients with a history of CVA with OAB symptoms. Both are safe and effective treatment options in patients with OAB post-CVA.
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http://dx.doi.org/10.1002/nau.24793DOI Listing
November 2021

Syringomyelia after spinal anaesthesia: A case report.

Trop Doct 2022 Jan 13;52(1):178-181. Epub 2021 Aug 13.

Additional Professor and Head, Department of Neurology, All India Institute of Medical Sciences, Rishikesh.

Lumbar spinal or epidural anaesthesia has a lower complication rate compared to general anaesthesia. An occasional patient may develop spinal cord injury during the procedure and develop neurological complications. We report an interesting case of paraparesis due to dorsal spinal cord involvement and syrinx formation following spinal anaesthesia for abdominal surgery.
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http://dx.doi.org/10.1177/00494755211037783DOI Listing
January 2022

Stress distribution and patient satisfaction in flexible and cast metal removable partial dentures: Finite element analysis and randomized pilot study.

J Oral Biol Craniofac Res 2021 Oct-Dec;11(4):478-485. Epub 2021 Jul 5.

Department of Prosthodontics, Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, 110029, India.

Purpose: To compare stress distribution in polyacetyl based flexible RPD (FRPD) with cast metal RPD (CRPD) by using three-dimensional finite element analysis (FEA) and patient satisfaction by using OHIP-14 questionnaire in participants with Kennedy's class I partially edentulous mandibular arch rehabilitated with CRPD and FRPD.

Material And Methods: For FEA, 3D models of Kennedy's class I partially edentulous mandibular arch, CRPD in chrome-cobolt alloy, and polyacetyl based FRPD were geometrically modelled and subjected to a vertical load of 100 ​N bilaterally. The in vivo comparison of satisfaction was assessed by enrolling 22 participants with Kennedy's class I partially edentulous mandibular arch. After randomization, 11 participants were rehabilitated by CRPD (group C), and 11 participants by polyacetyl based FRPD (group F). OHIP-14 questionnaire in Hindi language was filled at 1 week and 1 year after denture insertion.

Results: Von Mises stress distribution in CRPD was maximum in mesial rest seat of the primary abutment (100 ​MPa) and minimum for edentulous ridge (7 ​MPa on bone and 6 ​MPa on mucosa). Von Mises stress distribution for polyaccetyl based FRPD was maximum in ridge (25 ​MPa) and minimum in periodontal ligament of the second premolar (3 ​MPa). Patient satisfaction in group F was significantly more than in group C at end of 1 year ( ​= ​.0158).

Conclusion: FRPD is useful in periodontally compromised abutment teeth and CRPD in resorbed ridge conditions. Patient satisfaction is more with polyacetyl based flexible RPD when compared with cast metal RPD at the end of 1 year.
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http://dx.doi.org/10.1016/j.jobcr.2021.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319529PMC
July 2021

Protein synthesis in Mycobacterium tuberculosis as a potential target for therapeutic interventions.

Mol Aspects Med 2021 Oct 31;81:101002. Epub 2021 Jul 31.

Structural Biology & Translation Regulation Laboratory, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, 121 001, India. Electronic address:

Mycobacterium tuberculosis (Mtb) causes one of humankind's deadliest diseases, tuberculosis. Mtb protein synthesis machinery possesses several unique species-specific features, including its ribosome that carries two mycobacterial specific ribosomal proteins, bL37 and bS22, and ribosomal RNA segments. Since the protein synthesis is a vital cellular process that occurs on the ribosome, a detailed knowledge of the structure and function of mycobacterial ribosomes is essential to understand the cell's proteome by translation regulation. Like in many bacterial species such as Bacillus subtilis and Streptomyces coelicolor, two distinct populations of ribosomes have been identified in Mtb. Under low-zinc conditions, Mtb ribosomal proteins S14, S18, L28, and L33 are replaced with their non-zinc binding paralogues. Depending upon the nature of physiological stress, species-specific modulation of translation by stress factors and toxins that interact with the ribosome have been reported. In addition, about one-fourth of messenger RNAs in mycobacteria have been reported to be leaderless, i.e., without 5' UTR regions. However, the mechanism by which they are recruited to the Mtb ribosome is not understood. In this review, we highlight the mycobacteria-specific features of the translation apparatus and propose exploiting these features to improve the efficacy and specificity of existing antibiotics used to treat tuberculosis.
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http://dx.doi.org/10.1016/j.mam.2021.101002DOI Listing
October 2021

Non-COVID Neurological Emergencies: A Silent Killer Going Unnoticed during COVID-19 Pandemic.

J Neurosci Rural Pract 2021 Jul 22;12(3):461-469. Epub 2021 Feb 22.

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

 This study assesses the impact of coronavirus disease 2019 (COVID-19) on the pattern of neurological emergencies reaching a tertiary care center.  This is a retrospective and single center study involving 295 patients with neurological emergencies mainly including acute stroke, status epilepticus (SE), and tubercular meningitis visiting emergency department (ED) from January 1 to April 30, 2020 and divided into pre- and during lockdown, the latter starting from March 25 onward. The primary outcome was number of neurological emergencies visiting ED per week in both periods. Secondary outcomes included disease severity at admission, need for mechanical ventilation (MV), delay in hospitalization, in-hospital mortality, and reasons for poor compliance to ongoing treatment multivariate binary logistic regression was used to find independent predictors of in-hospital mortality which included variables with <0.1 on univariate analysis. Structural break in the time series analysis was done by using Chow test.  There was 53.8% reduction in number of neurological emergencies visiting ED during lockdown (22.1 visits vs. 10.2 visits per week, = 0.001), significantly affecting rural population ( = 0.004). Presenting patients had comparatively severe illness with increased requirement of MV ( < 0.001) and significant delay in hospitalization during lockdown ( < 0.001). Poor compliance to ongoing therapy increased from 34.4% in pre-lockdown to 64.7% patients during lockdown ( < 0.001), mostly due to nonavailability of drugs ( < 0.001). Overall, 35 deaths were recorded, with 20 (8.2%) in pre-lockdown and 15 (29.4%) during lockdown ( = 0.001). Lockdown, nonavailability of local health care, delay in hospitalization, severity at admission, and need for MV emerged as independent predictors of poor outcome in stroke and delay in hospitalization in SE.  COVID-19 pandemic and associated lockdown resulted in marked decline in non-COVID neurological emergencies reporting to ED, with more severe presentations and significant delay from onset of symptoms to hospitalization.
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http://dx.doi.org/10.1055/s-0040-1722810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289548PMC
July 2021

Impact of COVID-19 Pandemic on Parkinson's Disease: A Tale of Fears and Sorrows!

Ann Indian Acad Neurol 2021 Mar-Apr;24(2):121-123. Epub 2021 Apr 6.

Department of Psychiatry and Division of Sleep Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

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http://dx.doi.org/10.4103/aian.AIAN_97_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232492PMC
April 2021
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