Publications by authors named "Manish Gupta"

321 Publications

A prospective randomized trial comparing accelerated concurrent chemoradiotherapy with conventional concurrent chemoradiotherapy in locally advanced carcinoma cervix (IIA-IVA).

J Cancer Res Ther 2021 Jul-Sep;17(4):1012-1016

Department of Radiation Oncology, Tertiary Cancer Centre, IGMC, Shimla, Himachal Pradesh, India.

Introduction: Cervical cancer ranks fourth in women worldwide. The management requires a multidisciplinary approach. Concomitant chemoradiotherapy with cisplatin, followed by brachytherapy, is the standard approach. Accelerated radiotherapy (ART) can be used to decrease the treatment duration which can further lead to better outcomes.

Materials And Methods: Stages II, III, and IVA of carcinoma cervix were studied for 1 year. Ninety patients were randomized in control and study arms, 45 patients in each arm. The total dose of radiation was 50 Gy/25#/5 weeks from Monday to Friday in the control arm and 50 Gy/25#/4 weeks from Monday to Saturday in the study arm, with injection cisplatin 40 mg/m intravenous infusion weekly in both the arms.

Results: The response was similar in both the arms at the first follow-up as well as at median follow-up. However, acute toxicities in the ART arm were more, but they were managed conservatively.

Conclusion: ART can be used in patients of cervical cancers to decrease the total treatment time. The results were similar in both the groups but need to be studied over more number of patients.
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http://dx.doi.org/10.4103/jcrt.JCRT_626_19DOI Listing
September 2021

The Rare Cases of Parotid Gland Arteriovenous Malformations.

Case Rep Otolaryngol 2021 2;2021:6072155. Epub 2021 Sep 2.

School of Medical Science and Research, Sharda University, Greater Noida, India.

Arteriovenous malformation (AVM) results from errors in vascular development during embryogenesis; absent capillary beds lead to shunting directly from the arterial to venous circulation. Although it is common in the head and neck region, AVMs located in the parotid gland are quite rare. Here, we report two cases of arteriovenous malformation of the parotid gland that presented to our out-patient setup with swelling in the parotid region and were diagnosed as arteriovenous malformation on histopathological study after surgical resection.
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http://dx.doi.org/10.1155/2021/6072155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429032PMC
September 2021

Disjoining Pressure of Water in Nanochannels.

Nano Lett 2021 Sep 30;21(18):7769-7774. Epub 2021 Aug 30.

Department of Mechanical and Aerospace Engineering, Syracuse University, Syracuse, New York 13244, United States.

The disjoining pressure of water was estimated from wicking experiments in 1D silicon dioxide nanochannels of heights of 59, 87, 124, and 1015 nm. The disjoining pressure was found to be as high as ∼1.5 MPa while exponentially decreasing with increasing channel height. Such a relation resulting from the curve fitting of experimentally derived data was implemented and validated in computational fluid dynamics. The implementation was then used to simulate bubble nucleation in a water-filled 59 nm nanochannel to determine the nucleation temperature. Simultaneously, experiments were conducted by nucleating a bubble in a similar 58 nm nanochannel by laser heating. The measured nucleation temperature was found to be in excellent agreement with the simulation, thus independently validating the disjoining pressure relation developed in this work. The methodology implemented here integrates experimental nanoscale physics into continuum simulations thus enabling numerical study of various phenomena where disjoining pressure plays an important role.
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http://dx.doi.org/10.1021/acs.nanolett.1c02726DOI Listing
September 2021

Expression of podoplanin in tumor cells and lymphatic vessels in both tumoral and peritumoral areas and correlation with metastatic potential of oral squamous cell carcinoma.

J Oral Maxillofac Pathol 2021 Jan-Apr;25(1):131-135. Epub 2021 May 14.

Department of Oral Medicine and Radiology, Santosh Deemed to be University, Ghaziabad, Uttar Pradesh, India.

Aim: This study aims to study the expression of podoplanin in tumor cells as well as the lymphatic vessels (LVs) in both tumoral and peritumoral areas and correlate the importance of the lymphatic microvascular density (LMVD) in oral squamous cell carcinoma (OSCC) and its metastatic potential.

Materials And Methods: D2-40 expression and LV density (LVD) were assessed using antibody D240, in 45 diagnosed cases of all the three grades of OSCC. D2-40 expression was evaluated in both epithelial cells as well as the LVs.

Results: D2-40 expression in OSCC showed two different patterns - diffuse and focal. LMVD was calculated and difference in peritumoral and intra tumoral LVs was also assessed. A marked increase was seen we progressed from well-differentiated tumor to poorly differentiated ones, but this difference was found to be statistically nonsignificant. D2-40 immunostaining also highlighted the presence of lymphatic invasion present within the tumors which was detected by the presence of tumor emboli within the LVs. Overall, no significant correlation was found between D240 epithelial positivity and LVD.

Conclusion: The expression of podoplanin in tumor cells and lymphatics when correlated with histopathological status and clinically with the lymph node status can definitely help in the adjuvant therapies used in OSCC.
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http://dx.doi.org/10.4103/jomfp.jomfp_481_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272477PMC
May 2021

Invasive Fungal Infection Complicating Treatment With Ibrutinib.

Cureus 2021 Jun 29;13(6):e16009. Epub 2021 Jun 29.

Internal Medicine, Danbury Hospital, Yale School of Medicine, Danbury, USA.

Ibrutinib is a selective Bruton's tyrosine kinase inhibitor (BTKi) approved for the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. Invasive fungal infections (IFIs) have recently been reported in patients on BTKis despite the absence of significant immunocompromise raising great interest among oncologists regarding the mechanism by which BTKi's permit fungal infections. Here, we describe a fatal case of cerebral aspergillosis in a patient with relapsed CLL while on treatment with ibrutinib. There are few hypotheses on the mechanism by which ibrutinib permits fungal infections. As it becomes more widely used in B-cell cancers, clinicians should be aware of the potential for decreased anti-fungal immunity with this drug.
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http://dx.doi.org/10.7759/cureus.16009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319755PMC
June 2021

A prospective longitudinal study to evaluate bone health, implication of FRAX tool and impact on quality of life (FACT-P) in advanced prostate cancer patients.

Am J Clin Exp Urol 2021 15;9(3):211-220. Epub 2021 Jun 15.

King George's Medical University Lucknow, India.

Background: Androgen-deprivation therapy (ADT) as a treatment modality in advanced prostate cancer has deleterious effect on bone mineral density (BMD) and quality of life (QOL). Using FRAX (Fracture Risk Assessment) model, candidates at high risk of fractures can be predicted and appropriate treatment can be initiated at early step to prevent skeletal-related events. Objectives of the present study were to evaluate bone health, implication of FRAX tool in advanced prostate cancer and to see the impact of ADT and Bone-directed therapy (BDT) on FRAX and FACT-P QOL scores.

Material & Method: We conducted a prospective longitudinal study of 83 localized and metastatic prostate cancer patients from March 2017 to Dec 2020. FRAX tool using BMD femoral neck (GE-Lunar) was used to compute the probability of 10-year Major osteoporotic fracture (MOF) and hip fracture risk %. Patients who received monthly Zolendronic acid with or without Vitamin-D/calcium supplementation were classified as BDT group. FRAX and FACT-P were measured at baseline and 12 months follow-up and compared between different therapeutic modalities to see the impact on clinical outcomes.

Results: Majority of patients had skeletal metastasis (78.3%) and high-grade disease at presentation. Secondary osteoporosis was the most commonly (82.05%) observed clinical risk factor (CRF) followed by smoking (19.23%). Hip fracture risk ≥3% accounted for larger proportion of patients than did MOF risk ≥20% (21.2% and 2.5%, respectively). Statistically significant reduction was observed in both MOF and hip fracture risk in BDT group, while worsening on ADT. ADT duration correlated positively with both MOF and hip fracture risk (R=0.148, P<0.001 and R=0.164, P<0.001, respectively). FRAX score accurately predict future fracture events in majority (80%) of high-risk patients. Statistically and clinically significant worsening in PWB, EWB, PCS, FACT-P Total, FACT-P TOI and FAPSI scores were observed in patients on ADT. Statistically and clinically significant improvement was noted in physical well-being in BDT group. However, other QOL domains and FACT-P total scores remained stable.

Conclusions: ADT caused duration depended worsening of FRAX and FACT-P score in these patients while improvements of FRAX were seen on BDT. FRAX tool is advantageous in identifying the patients who require early intervention or therapy to decrease skeletal-related events.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303024PMC
June 2021

Multiparametric magnetic resonance imaging to characterize cabotegravir long-acting formulation depot kinetics in healthy adult volunteers.

Br J Clin Pharmacol 2021 Jul 8. Epub 2021 Jul 8.

ViiV Healthcare, Research Triangle Park, NC, USA.

Aim: Cabotegravir long-acting (LA) intramuscular (IM) injection is being investigated for HIV preexposure prophylaxis due to its potent antiretroviral activity and infrequent dosing requirement. A subset of healthy adult volunteers participating in a Phase I study assessing cabotegravir tissue pharmacokinetics underwent serial magnetic resonance imaging (MRI) to assess drug depot localization and kinetics following a single cabotegravir LA IM targeted injection.

Methods: Eight participants (four men, four women) were administered cabotegravir LA 600 mg under ultrasonographic-guided injection targeting the gluteal muscles. MRI was performed to determine injection-site location in gluteal muscle (IM), subcutaneous (SC) adipose tissue and combined IM/SC compartments, and to quantify drug depot characteristics, including volume and surface area, on Days 1 (≤2 hours postinjection), 3 and 8. Linear regression analysis examined correlations between MRI-derived parameters and plasma cabotegravir exposure metrics, including maximum observed concentration (C ) and partial area under the concentration-time curve (AUC) through Weeks 4 and 8.

Results: Cabotegravir LA depot locations varied by participant and were identified in the IM compartment (n = 2), combined IM/SC compartments (n = 4), SC compartment (n = 1) and retroperitoneal cavity (n = 1). Although several MRI parameter and exposure metric correlations were determined, total depot surface area on Day 1 strongly correlated with plasma cabotegravir concentration at Days 3 and 8, C and partial AUC through Weeks 4 and 8.

Conclusion: MRI clearly delineated cabotegravir LA injection-site location and depot kinetics in healthy adults. Although injection-site variability was observed, drug depot surface area correlated with both plasma C and partial AUC independently of anatomical distribution.
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http://dx.doi.org/10.1111/bcp.14977DOI Listing
July 2021

Recent Advances in the Discovery of Antiviral Metabolites from Fungi.

Curr Pharm Biotechnol 2021 Jun 15. Epub 2021 Jun 15.

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Raebareli, New Transit Campus, Lucknow 226002, India.

As the world manages the impact of a global pandemic caused by COVID-19, the discovery of new antiviral agents has become way more relevant and urgent. Viruses are submicroscopic infectious agents that replicate inside the living cells of different organisms. These viruses use nucleic acids (both DNA and RNA) for further replication and maturity inside the cells. Some of the viruses responsible for various human and plant diseases belong to the classes of Picornaviridae, Retroviridae, Orthomyxoviridae, Flaviviridae, Pneumoviridae, Virgaviridae, and Hepadnaviridae, and their treatment options are limited or non-existent. The consistent reemergence and resistance development in the viral strains demands the discovery and development of new antiviral drugs possessing better efficacy. Bio-active compounds isolated from fungi can be the source of new compounds with enhanced potency and new mechanisms of action. Fungi are known to produce a diverse lot of secondary metabolites due to their existence in harsh climates which are often inhabitable for many organisms. Due to these unique environments, fungi produce a variety of secondary metabolites of different chemical classes like alkaloids, quinones, furanone, pyrones, benzopyranoids, xanthones, terpenes, steroids, peptides, and many acyclic compounds. Fungal metabolites are known to display a wide range of bioactive attributes, i.e., anticancer, antibacterial, antifungal, and anti-Alzheimer's, along with antiviral properties. In this review article, we report over 300 antiviral compounds from fungal sources during the period of 2009 to 2019. The source of these compounds is marine and endophytic fungi and they are arranged based on their antiviral action against different viral families. These compounds are promising in their use and development as future antiviral drugs.
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http://dx.doi.org/10.2174/1389201022666210615120720DOI Listing
June 2021

The Effect of Biofeedback Therapy Combined with Comprehensive Nursing Intervention on the Quality of Life of Patients with Functional Constipation Based on Dynamic Magnetic Resonance Defecation.

J Healthc Eng 2021 13;2021:9947373. Epub 2021 May 13.

Bakhtar University, Kabul, Afghanistan.

In order to study the quality of life of patients with functional constipation based on dynamic magnetic resonance defecation, the biofeedback therapy combined with comprehensive nursing intervention was used to diagnose and treat the patients, so as to explore its clinical efficacy and its impact on patients' quality of life. The obstructed defecation surgical treatment carries frequent recurrences, and dynamic magnetic resonance imaging defecography evaluated and elucidated the underlying anatomic features. This research selected 80 patients who came to our hospital for treatment of functional constipation and evaluated and recorded various clinical indicators before and after treatment in the form of questionnaire survey. The results showed that the clinical symptom scores of patients with functional constipation before and after treatment were greatly different ( < 0.05). Thus, the biofeedback therapy combined with comprehensive nursing intervention showed a good clinical effect in the treatment of patients with functional constipation and significantly improved the quality of life of patients, showing high clinical application and promotion value. A convenient diagnostic procedure is represented by the dynamic magnetic resonance imaging in females, especially pelvic floor organs dynamic imaging during defecation.
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http://dx.doi.org/10.1155/2021/9947373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137299PMC
May 2021

Surgical Occlusion of Leaking Bronchus by a Serratus Anterior Flap in a Child with Langerhans Cell Histiocytosis.

J Indian Assoc Pediatr Surg 2021 Mar-Apr;26(2):123-125. Epub 2021 Mar 4.

Department of Paediatric Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

Langerhans cell histiocytosis is an uncommon disease of childhood. Intrathoracic transposition flaps have been described for a management of number of conditions. We discuss our experience of the use of serratus anterior flap for the obliteration of a pulmonary bulla with a communicating airway, in a 1½-year-old pediatric patient with multisystem Langerhans cell histiocytosis who presented with recurrent pneumothorax with empyema due to rupture of bullae.
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http://dx.doi.org/10.4103/jiaps.JIAPS_66_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152404PMC
March 2021

Pseudocyst in Neck: A Case Report on Rare Complication of Ventriculoperitoneal Shunt.

Case Rep Otolaryngol 2021 30;2021:6656506. Epub 2021 Apr 30.

Department of ENT, Maharishi Markandeshwar Institute of Medical Sciences & Research,MMDU, Ambala, India.

Introduction: Ventriculoperitoneal shunt is a common neurosurgical procedure, for the definitive management of hydrocephalus. Shunt failures may occur due to various causes but are usually due to infections in adults and catheter occlusion in the paediatric population. . The 13-year-old girl presented with a right lateral neck swelling. In detailed history, she was found to be an old case of ventriculoperitoneal shunt. The clinical examination and radiological investigation revealed proximal dislodgment of the stent from the cranium, causing persistent cerebrospinal fluid (CSF) leak and pseudocyst formation in the neck.

Conclusion: The case highlights CSF pseudocyst formation as a rare differential for lateral neck swellings.
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http://dx.doi.org/10.1155/2021/6656506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110417PMC
April 2021

The Art of Designing DNA Nanostructures with CAD Software.

Molecules 2021 Apr 15;26(8). Epub 2021 Apr 15.

Peter Debye Institute for Soft Matter Physics, Leipzig University, Linnéstraße 5, 04103 Leipzig, Germany.

Since the arrival of DNA nanotechnology nearly 40 years ago, the field has progressed from its beginnings of envisioning rather simple DNA structures having a branched, multi-strand architecture into creating beautifully complex structures comprising hundreds or even thousands of unique strands, with the possibility to exactly control the positions down to the molecular level. While the earliest construction methodologies, such as simple Holliday junctions or tiles, could reasonably be designed on pen and paper in a short amount of time, the advent of complex techniques, such as DNA origami or DNA bricks, require software to reduce the time required and propensity for human error within the design process. Where available, readily accessible design software catalyzes our ability to bring techniques to researchers in diverse fields and it has helped to speed the penetration of methods, such as DNA origami, into a wide range of applications from biomedicine to photonics. Here, we review the historical and current state of CAD software to enable a variety of methods that are fundamental to using structural DNA technology. Beginning with the first tools for predicting sequence-based secondary structure of nucleotides, we trace the development and significance of different software packages to the current state-of-the-art, with a particular focus on programs that are open source.
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http://dx.doi.org/10.3390/molecules26082287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071251PMC
April 2021

Antiretroviral Drugs Regulate Epigenetic Modification of Cardiac Cells Through Modulation of H3K9 and H3K27 Acetylation.

Front Cardiovasc Med 2021 9;8:634774. Epub 2021 Apr 9.

Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States.

Antiretroviral therapy (ART) has significantly reduced the rate of mortality in HIV infected population, but people living with HIV (PLWH) show higher rates of cardiovascular disease (CVD). However, the effect of antiretroviral (ARV) drug treatment on cardiac cells is not clear. In this study, we explored the effect of ARV drugs in cardiomyocyte epigenetic remodeling. Primary cardiomyocytes were treated with a combination of four ARV drugs (ritonavir, abacavir, atazanavir, and lamivudine), and epigenetic changes were examined. Our data suggest that ARV drugs treatment significantly reduces acetylation at H3K9 and H3K27 and promotes methylation at H3K9 and H3K27, which are histone marks for gene expression activation and gene repression, respectively. Besides, ARV drugs treatment causes pathological changes in the cell through increased production of reactive oxygen species (ROS) and cellular hypertrophy. Further, the expression of chromatin remodeling enzymes was monitored in cardiomyocytes treated with ARV drugs using PCR array. The PCR array data indicated that the expression of epigenetic enzymes was differentially regulated in the ARV drugs treated cardiomyocytes. Consistent with the PCR array result, SIRT1, SUV39H1, and EZH2 protein expression was significantly upregulated in ARV drugs treated cardiomyocytes. Furthermore, gene expression analysis of the heart tissue from HIV+ patients showed that the expression of SIRT1, SUV39H1, and EZH2 was up-regulated in patients with a history of ART. Additionally, we found that expression of SIRT1 can protect cardiomyocytes in presence of ARV drugs through reduction of cellular ROS and cellular hypertrophy. Our results reveal that ARV drugs modulate the epigenetic histone markers involved in gene expression, and play a critical role in histone deacetylation at H3K9 and H3K27 during cellular stress. This study may lead to development of novel therapeutic strategies for the treatment of CVD in PLWH.
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http://dx.doi.org/10.3389/fcvm.2021.634774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062764PMC
April 2021

Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer.

Front Oncol 2021 23;11:645475. Epub 2021 Mar 23.

Department of Zoology, Central University of Punjab, Bathinda, India.

Dysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was significantly down-regulated (~5.87-fold; < 0.0001) in NSCLC patients ( = 80) compared to matched control plasma samples from healthy subjects ( = 80). Kaplan-Meier survival analysis revealed that NSCLC patients with lower levels of circulating miR-320a had overall poorer prognosis and survival rates compared to patients with higher levels ( < 0.0001). Moreover, the diagnostic and prognostic potential of miR-320a correlated with clinicopathological characteristics such as tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis. Functionally, depletion of miR-320a in human A549 lung adenocarcinoma cells induced their metastatic potential and reduced apoptosis, which was reversed by exogenous re-expression of miR-320a mimics, indicating that miR-320a has a tumor-suppressive role in NSCLC. These results were further supported by high levels of epithelial-mesenchymal transition (EMT) marker proteins (e.g., Beta-catenin, MMP9, and E-cadherin) in lung cancer cells and tissues immunoblot and immunohistochemistry experiments. Moreover, through bioinformatics and dual-luciferase reporter assays, we demonstrated that was a direct target of miR-320a. In addition, AKT3-associated PI3K/AKT/mTOR protein-signaling pathways were elevated with down-regulated miR-320a levels in NSCLC. These composite data indicate that circulating miR-320a may function as a tumor-suppressor miRNA with potential as a prognostic marker for NSCLC patients.
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http://dx.doi.org/10.3389/fonc.2021.645475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021852PMC
March 2021

Congenital lateral facial teratoma: A case report and review of literature.

Afr J Paediatr Surg 2021 Apr-Jun;18(2):99-103

Department of Pediatric Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

Facial teratomas are uncommon tumours in children that distort the face and may be associated with functional problems. They are less common than cervical teratomas though they are often grouped together and considered an emergency due to their tendency to cause respiratory compromise. They tend to be large and cause cosmetic issues; hence usually noticed early and medical help sought promptly by parents. The close proximity of facial teratomas to structures like eyes, parotid gland, facial nerve, vessels and brain makes them challenging and requires a patient and meticulous exploration during surgery. We present a case of an 11 month old girl with left sided temporal teratoma. Well planning of the incision and complete excision of the tumour with careful sparing of the facial nerves and parotid gland yielded good result.
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http://dx.doi.org/10.4103/ajps.AJPS_77_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232360PMC
June 2021

Influence of Etiology and Onset of Deformity on Spatiotemporal, Kinematic, Kinetic, and Electromyography Gait Variables in Patients with Scoliosis-A Prospective, Comparative Study.

Spine (Phila Pa 1976) 2021 Mar;46(6):374-382

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

Study Design: Prospective comparative study.

Objective: The aim of this study was to compare the spatiotemporal, kinematic, kinetic and electromyographic (EMG) gait variables in patients with adolescent idiopathic scoliosis (AIS) and congenital scoliosis and to compare these gait variables of scoliosis patients with healthy controls.

Summary Of Background Data: Earlier studies have solely focussed on the possibility of altered gait patterns in AIS patients; not much light has been shed on the differences in gait patterns in congenital and adolescent scoliosis patients.

Methods: Forty scoliosis patients (20 each with AIS and congenital scoliosis) and 20 healthy volunteers were prospectively recruited. After thorough clinical and radiological examination, all patients underwent gait analysis in accordance with standard protocols.The outcome measures included spatiotemporal, kinetic, kinematic and EMG activity. Composite indices for gait analysis-Gait Profile Score (GPS) and Gait Deviation Index (GDI)-were also calculated. Relevant statistical tests were applied to compare the different groups.

Results: No significant difference was found between the AIS and congenital scoliosis groups with respect to baseline demographic and radiological parameters. The two subgroups of scoliosis patients (AIS and congenital) did not differ significantly with respect to any of the measured gait analysis parameters. However, when compared to the healthy age-matched control group, the scoliosis patients differed significantly with respect to gait speed, stride length, step length, GDI, GPS and peak EMG activation for erector spinae, biceps femoris, semimembranosus, rectus femoris, gastrocnemious, and tibialis anterior.

Conclusion: Our findings confirm the previous findings of literature regarding the alteration in gait patterns in scoliosis patients when compared to normal individuals. However, the lack of difference in gait analysis variables between AIS and congenital scoliosis patients suggests that this alteration in gait is secondary to the existence of the deformity and does not correlate with the onset or etiology of deformity.Level of Evidence: 2.
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http://dx.doi.org/10.1097/BRS.0000000000003796DOI Listing
March 2021

Intramedullary Headless Screw Fixation of Distal Metacarpal Fractures - the Birmingham Experience.

J Hand Surg Asian Pac Vol 2021 Mar;26(1):52-59

Hand Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Trust, Birmingham, UK.

Surgical fixation using intramedullary headless screws (IHS) is a relatively new technique for metacarpal fracture repair. However, there are very few studies investigating the outcomes of this procedure. We present the surgical and functional outcomes of a consecutive series of 30 metacarpal fractures treated by a single surgeon over a 2.5-year period using IHS. We retrospectively reviewed the records of 30 metacarpal fractures in 27 patients who underwent IHS fixation from March 2016 to October 2018. There were 29 fractures of the metacarpal neck and 1 was to the metacarpal head. All fractures underwent the procedure by a single operating surgeon. Individual joint movements along with total active movement (TAM) was measured at postoperative follow-up appointments 4-8 weeks after surgery. Fracture healing was confirmed with plain radio-graphs. Patients were also recalled in March 2019 for their latest functional measurements. A QuickDASH (disabilities of the arm, shoulder and hand) questionnaire was used to assess for any residual functional disability. All fractures healed within acceptable radiological parameters with no mal-unions or rotational deformities. The average TAM at initial follow-up was 245°, which improved to 264° at the March 2019 review. All patients returned to work in an average of 6 weeks. The final functional QuickDASH score was an average of 2.9/100 (range 0-18.2). 2/27 patients required further surgery for stiffness before regaining excellent TAM. No patient required metalwork removal. There were no other complications. Our findings suggest that IHS fixation is an effective alternative technique for the treatment of metacarpal fractures. It is a relatively simple procedure, which provides good stable fixation, allowing for early mobilisation. It has few complications and does not routinely require removal of the implant.
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http://dx.doi.org/10.1142/S2424835521500089DOI Listing
March 2021

A Prospective Observational Study Comparing Long-Course Conventional Neoadjuvant Chemoradiotherapy with Short-Course Radiotherapy Followed by Consolidation Chemotherapy with Delayed Surgery in Locally Advanced Rectal Cancer.

South Asian J Cancer 2020 Jun 14;9(2):80-85. Epub 2020 Dec 14.

Department of Radiation Oncology, Regional Cancer Centre, Indira Gandhi Medical College & Hospital, Shimla, Himachal Pradesh, India.

 Polish and Australian randomized studies compared short-course radiotherapy (RT) with immediate surgery and long-course chemoradiotherapy (CRT) with delayed surgery. In these studies, similar long-term survival and local control have been reported for both these approaches, but pathological complete response (pCR) is not better with short-course RT. Moreover, studies have shown better tumor downstaging with delayed surgery. In this context, the use of short-course RT with delayed surgery may have some advantages and needs to be tested in clinical trials.  This was a two-arm, prospective, observational study, in which preoperative short-course RT followed by two cycles of chemotherapy was compared with the conventional neoadjuvant CRT in locally advanced rectal cancer. The primary end points were the rate of complete response and toxicity profile. The secondary end points were the rate of R0 resection, overall survival, and progression-free survival. The data obtained from the two arms were analyzed using Pearson's chi-square test to determine the statistical significance between the two treatment arms.  The pCR rate was 6.7% in the study arm and 0 in the control arm ( = 0.343). The RO resection rates were 92.8 and 92.3% in the study and control arms, respectively. The rates of grade 3and 4 acute toxicity in the study and control arms were 14.2 and 61.5%, respectively ( = 0.011). The rates of grade 3 and 4 late toxicity in the study and control arms were 21.4 and 15.3%, respectively ( = 0.686).  The pCR rates and the late toxicities in both arms are comparable. The major advantages of the 5 × 5 Gy regimen with chemotherapy in a neoadjuvant setting are a significant reduction in acute toxicities and better patient compliance along with similar efficacy as that of the standard regimen.
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http://dx.doi.org/10.1055/s-0040-1721220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745749PMC
June 2020

Cervical Infantile Fibrosarcoma: a rare cause of paediatric parapharyngeal neck mass.

Autops Case Rep 2020 Nov 20;10(4):e2020189. Epub 2020 Nov 20.

All India Institute of Medical Sciences, Department of Paediatric Surgery, Rishikesh, Uttarakhand, India.

Soft tissue tumors are not uncommon in childhood and comprise entities that range from common to very rare malignancies. Infantile fibrosarcoma (IFS) is a rare pediatric malignancy mainly seen in the first two years of life. The data about the incidence of infantile fibrosarcoma occurring in the neck in the Indian subcontinent is scarce. To the best of our knowledge, only one case of infant cervical IFS has been reported previously in the Indian subcontinent. We present another case of an eight-year-old male patient with a rapidly growing mass on the left side of the neck. He was successfully treated with a combined modality of surgery and chemotherapy with a good outcome. Among the soft tissue tumors of childhood, IFS is a rare entity. It has a good prognosis and lesser chance of distant metastasis as compared to adult fibrosarcoma. Though surgical excision is the mainstay of treatment, chemotherapy also has a significant role in the treatment of primary tumor and metastasis. We discuss the stated case to bring to the notice this uncommon cause, which can be considered as a differential diagnosis of upper cervical swellings. A better understanding of this entity would help in early diagnosis and aggressive treatment, reducing the overall morbidity and mortality.
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http://dx.doi.org/10.4322/acr.2020.189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703127PMC
November 2020

Retained wooden foreign body in groin in a child: A case report and review of literature.

Afr J Paediatr Surg 2020 Jul-Dec;17(3 & 4):127-130

Department of Pediatric Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

Wooden foreign body (WFB) injuries in children are common. They may report with acute presentation or be delayed as retained foreign body giving rise to complications. Cases with superficial skin penetration by these foreign bodies and acute presentation may be convenient to diagnose and remove. However, localising deeply impacted and chronically retained WFB is challenging, as they are usually not radiopaque and have a tendency to move deeper into the surrounding soft tissues with time. Foreign body retained for prolonged duration may present with either cellulitis, deep tissue infections, sinus, restriction of joint movements, necrotising fasciitis, osteomyelitis or tumour-like mass. We present an 8-year-old boy with discharging sinuses in the right iliac fossa and medial aspect of the right upper thigh, due to an impacted WFB for 3 months. Prompt radiological imaging and surgical removal helped him recover completely.
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http://dx.doi.org/10.4103/ajps.AJPS_22_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051621PMC
May 2021

A novel technique of abdominoplasty for prune belly syndrome.

Afr J Paediatr Surg 2020 Jul-Dec;17(3 & 4):108-110

Department of Paediatric Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

Prune belly syndrome is an extremely rare congenital condition occurring predominantly in males. This triad syndrome comprises of partial or complete deficient abdominal wall muscles, undescended testes and dilated urinary collecting system. We present the case of a 2-year-old male patient, who presented with classic prune belly syndrome, operated with modification in classical Monfort technique of abdominoplasty. The basis of this approach was to save and use the supraumbilical abdominal wall which has better tensile strength. The infraumbilical skin was mostly discarded. The outcome was better in terms of cosmetic appearance as the scar was limited to the lower abdomen and better anterior abdominal wall strength.
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http://dx.doi.org/10.4103/ajps.AJPS_55_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051631PMC
May 2021

Modulation of Autophagy by SARS-CoV-2: A Potential Threat for Cardiovascular System.

Front Physiol 2020 30;11:611275. Epub 2020 Nov 30.

Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States.

Recently, we have witnessed an unprecedented increase in the number of patients suffering from respiratory tract illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 virus is a single-stranded positive-sense RNA virus with a genome size of ~29.9 kb. It is believed that the viral spike (S) protein attaches to angiotensin converting enzyme 2 cell surface receptors and, eventually, the virus gains access into the host cell with the help of intracellular/extracellular proteases or by the endosomal pathway. Once, the virus enters the host cell, it can either be degraded autophagy or evade autophagic degradation and replicate using the virus encoded RNA dependent RNA polymerase. The virus is highly contagious and can impair the respiratory system of the host causing dyspnea, cough, fever, and tightness in the chest. This disease is also characterized by an abrupt upsurge in the levels of proinflammatory/inflammatory cytokines and chemotactic factors in a process known as cytokine storm. Certain reports have suggested that COVID-19 infection can aggravate cardiovascular complications, in fact, the individuals with underlying co-morbidities are more prone to the disease. In this review, we shall discuss the pathogenesis, clinical manifestations, potential drug candidates, the interaction between virus and autophagy, and the role of coronavirus in exaggerating cardiovascular complications.
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http://dx.doi.org/10.3389/fphys.2020.611275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734100PMC
November 2020

Percutaneous cervical cordotomy for cancer-related pain: prospective multimodal outcomes evaluation.

BMJ Support Palliat Care 2020 Dec 4. Epub 2020 Dec 4.

Palliative Medicine, University Hospital Aintree, Liverpool, UK.

Background: Percutaneous cervical cordotomy (PCC) offers pain relief to patients with unilateral treatment-refractory cancer-related pain. There is insufficient evidence about any effects of this intervention on patients' quality of life.

Method: Comprehensive multimodal assessment to determine how PCC affects pain, analgesic intake and quality of life of patients with medically refractory, unilateral cancer-related pain.This study was set in a multidisciplinary, tertiary cancer pain service. Patient outcomes immediately following PCC were prospectively recorded. Patients were also followed up at 4 weeks.

Results: Outcome variables collected included: background and breakthrough pain numerical rating scores before PCC, at discharge and 4 weeks postprocedure; oral morphine equivalent opioid dose changes, Patient's Global Impression of Change, Eastern Cooperative oncology group performance status and health related quality of life score, that is, EuroQol-5 dimension-5 level (EQ-5D).

Conclusions: Despite significant improvement in pain and other standard outcomes sustained at 4 weeks, there was little evidence of improvement in EQ-5D scores. In patients with terminal cancer, improved pain levels following cordotomy for cancer-related pain does not appear to translate into improvements in overall quality of life as assessed with the generic EQ-5D measure.
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http://dx.doi.org/10.1136/bmjspcare-2019-002084DOI Listing
December 2020

An Otorhinolaryngologists Perspective on Using Face Masks by Health Care Professionals Based on an Online Survey.

Indian J Otolaryngol Head Neck Surg 2020 Oct 28:1-6. Epub 2020 Oct 28.

Department of Internal Medicine, Government Medical College and Hospital, 1156-C GMCH Campus, Sector 32-B, Chandigarh, 160030 India.

Acute respiratory infections pose a constant threat to society and health care professionals. The effectiveness of face masks covering mouth and nose in reducing aerosol spread and curbing respiratory infection acquisition is well-studied. Despite enough beneficial evidence in favour of wearing masks, general population and the health care workers needs to be convinced to wear it and often enforcement is required for the same. This study was designed to study various barriers perceived and experienced with poor mask usage among hospital staff from an otorhinolaryngological perspective. An online survey was conducted to study the awareness of health care professionals and other hospital staff about advantages and disadvantages of mask use. Total 100 questionnaire based responses were obtained using this method. The participants included the ministerial staff, nursing and paramedical staff and faculty and residents of various medical and surgical specialties. The data thus collected was analyzed to identify the perceived benefits and limitations in mask usage. The participants wore surgical mask more commonly (50%) as compared to N95 respirator and cloth mask. 58% of the participants were using masks due to professional need. Majority (40%) used masks for a period ranging from 4 to 8 h in a day. Most of the participants realized that the masks offered protection from aerosols (90%) and more than 60% also mentioned that it helped in avoiding touching the face inadvertently. 62% participants complained of fogging of vision while wearing masks and approximately 50% reported pain due to tight elastic bands, difficulty breathing through mask and excessive sweating in the masked area In non-pharmaceutical measures to contain the aerosol-associated pandemics, face masks play an important precautionary role. It is cheap, easy to use and protects against respiratory infections, pollution and allergies. Certain minor issues like fogging of spectacles, and difficulty breathing through mask may need revisions in mask fabric and design.
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http://dx.doi.org/10.1007/s12070-020-02248-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591694PMC
October 2020

Nano-Enabled sensors for detection of arsenic in water.

Water Res 2021 Jan 21;188:116538. Epub 2020 Oct 21.

Deakin University, Geelong, Faculty of Science, Engineering & Built Environment, Waurn Ponds, Victoria 3216, Australia. Electronic address:

The elevated cases of arsenic contamination reported across the globe have made its early detection and remediation an active area of research. Although, the World Health Organisation has set the maximum provisional value for arsenic in drinking water at 10 parts per billion, yet concentrations as high as 5000 parts per billion are still reported. In human beings, chronic arsenic exposure can culminate into lethal diseases such as cancer. Thus, there is a need for urgent emergence of efficient and reliable detection system. This paper offers an overview of the state-of-art knowledge on current arsenic detection mechanisms. The central agenda of this paper is to develop an understanding into the nano-enabled methods for arsenic detection with an emphasis on strategic fabrication of nanostructures and the modulation of nanomaterial chemistry in order to strengthen the knowledge into novel nano-enabled solutions for arsenic contamination. Towards the end prospects for arsenic detection in water are also prompted.
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http://dx.doi.org/10.1016/j.watres.2020.116538DOI Listing
January 2021

Optimization and Formulation of Nanostructured and Self-Assembled Caseinate Micelles for Enhanced Cytotoxic Effects of Paclitaxel on Breast Cancer Cells.

Pharmaceutics 2020 Oct 18;12(10). Epub 2020 Oct 18.

Tropical Medicine and Biology Multidisciplinary Platform, Monash University, Jalan Lagoon Selatan, Bandar Sunway 47500, Petaling Jaya, Selangor, Malaysia.

Background: Paclitaxel (PTX) is a widely used anti-cancer drug for treating various types of solid malignant tumors including breast, ovarian and lung cancers. However, PTX has a low therapeutic response and is linked with acquired resistance, as well as a high incidence of adverse events, such as allergic reactions, neurotoxicity and myelosuppression. The situation is compounded when its complex chemical structure contributes towards hydrophobicity, shortening its circulation time in blood, causing off-target effects and limiting its therapeutic activity against cancer cells. Formulating a smart nano-carrier may overcome the solubility and toxicity issues of the drug and enable its more selective delivery to the cancerous cells. Among the nano-carriers, natural polymers are of great importance due to their excellent biodegradability, non-toxicity and good accessibility. The aim of the present research is to develop self-assembled sodium caseinate nanomicelles (NaCNs) with PTX loaded into the hydrophobic core of NaCNs for effective uptake of the drug in cancer cells and its subsequent intracellular release.

Methods: The PTX-loaded micelle was characterized with high-performance liquid chromatography (HPLC), Fourier Transform Infrared Spectra (FTIR), High Resolution-Transmission Electron Microscope (HR-TEM), Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-Ray (EDX). Following treatment with PTX-loaded NaCNs, cell viability, cellular uptake and morphological changes were analyzed using MCF-7 and MDA-MB 231 human breast cancer cell lines.

Results: We found that PTX-loaded NaCNs efficiently released PTX in an acidic tumor environment, while showing an enhanced cytotoxicity, cellular uptake and in-vivo anti-tumor efficacy in a mouse model of breast cancer when compared to free drug and blank micelles. Additionally, the nanomicelles also presented improved colloidal stability for three months at 4 °C and -20 °C and when placed at a temperature of 37 °C.

Conclusions: We conclude that the newly developed NaCNs is a promising carrier of PTX to enhance tumor accumulation of the drug while addressing its toxicity issues as well.
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http://dx.doi.org/10.3390/pharmaceutics12100984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589039PMC
October 2020

Evaluation of Automated Delivery of Propofol Using a Closed-Loop Anesthesia Delivery System in Patients Undergoing Thoracic Surgery: A Randomized Controlled Study.

J Cardiothorac Vasc Anesth 2021 Apr 13;35(4):1089-1095. Epub 2020 Sep 13.

Department of Anaesthesiology, Pain, and Perioperative Medicine, Sir Ganga Ram Hospital, New Delhi, India.

Objective: Automated propofol total intravenous anesthesia (TIVA) administered by a closed-loop anesthesia delivery system (CLADS) exhibits greater efficiency than conventional manual methods, but its use in major thoracic surgery is limited.

Design: Prospective, single-blind, randomized controlled study.

Setting: Single-center tertiary care hospital.

Participants: Patients undergoing thoracic surgery.

Interventions: Patients were randomly allocated to receive CLADS-driven (CLADS group) or manually controlled (manual group) propofol TIVA.

Measurements And Main Results: Anesthesia depth consistency (primary objective) and anesthesia delivery performance, propofol usage, work ergonomics, intraoperative hemodynamics, and recovery profile (secondary objectives) were analyzed. No differences were found for anesthesia depth consistency (percentage of time the bispectral index was within ± 10 of target) (CLADS group: 82.5% [78.5%-87.2%] v manual group: 86.5% [74.2%-92.5%]; p = 0.581) and delivery performance, including median performance error (CLADS group: 3 [-4 to 6] v manual group: 1 [-2.5 to 6]); median absolute performance error (CLADS group: 10 [10-12] v manual group:10 [8-12]); wobble (CLADS group: 10 [8-12] v manual group: 9 [6-10.5]); and global score (CLADS group: 24.2 [21.2-29.3] v manual group: 22.1 [17.3-32.3]) (p > 0.05). However, propofol requirements were significantly lower in the CLADS group for induction (CLADS group: 1.27 ± 0.21] mg/kg v manual group: 1.78 ± 0.51 mg/kg; p = 0.014) and maintenance (CLADS group: 4.02 ± 0.99 mg/kg/h v manual group: 5.11 ± 1.40 mg/kg/h; p = 0.025) of TIVA. Ergonomically, CLADS-driven TIVA was found to be significantly superior to manual control (infusion adjustment frequency/h) (manual infusion: 9.6 [7.8-14.9] v CLADS delivery [none]).

Conclusions: In thoracic surgery patients, CLADS-automated propofol TIVA confers significant ergonomic advantage along with lower propofol usage.
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http://dx.doi.org/10.1053/j.jvca.2020.09.101DOI Listing
April 2021

Structure-based drug repurposing to inhibit the DNA gyrase of Mycobacterium tuberculosis.

Biochem J 2020 11;477(21):4167-4190

School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India.

Drug repurposing is an alternative avenue for identifying new drugs to treat tuberculosis (TB). Despite the broad-range of anti-tubercular drugs, the emergence of multi-drug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis (Mtb) H37Rv, as well as the significant death toll globally, necessitates the development of new and effective drugs to treat TB. In this study, we have employed a drug repurposing approach to address this drug resistance problem by screening the drugbank database to identify novel inhibitors of the Mtb target enzyme, DNA gyrase. The compounds were screened against the ATPase domain of the gyrase B subunit (MtbGyrB47), and the docking results showed that echinacoside, doxorubicin, epirubicin, and idarubicin possess high binding affinities against MtbGyrB47. Comprehensive assessment using fluorescence spectroscopy, surface plasmon resonance spectroscopy (SPR), and circular dichroism (CD) titration studies revealed echinacoside as a potent binder of MtbGyrB47. Furthermore, ATPase, and DNA supercoiling assays exhibited an IC50 values of 2.1-4.7 µM for echinacoside, doxorubicin, epirubicin, and idarubicin. Among these compounds, the least MIC90 of 6.3 and 12 μM were observed for epirubicin and echinacoside, respectively, against Mtb. Our findings indicate that echinacoside and epirubicin targets mycobacterial DNA gyrase, inhibit its catalytic cycle, and retard mycobacterium growth. Further, these compounds exhibit potential scaffolds for optimizing novel anti-mycobacterial agents that can act on drug-resistant strains.
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http://dx.doi.org/10.1042/BCJ20200462DOI Listing
November 2020

Laparoscopic retrieval of impacted and broken dormia basket using a novel approach.

J Minim Access Surg 2020 Oct-Dec;16(4):415-417

Department of Radiodiagnosis, AIIMS, Jodhpur, Rajasthan, India.

We encountered a 73-year-old patient who presented with right upper abdominal pain and jaundice. On evaluation, he was found to have cholelithiasis with choledocholithiasis. Endoscopic retrograde cholangiography was attempted, but during the procedure, the wire snapped and the dormia basket got retained in the common bile duct (CBD). Laparoscopic CBD exploration was performed and the basket with calculus was found impacted in the lower CBD. The basket was disengaged by holding its tip through another dormia introduced through choledochoscope and basket with all calculi retrieved. Clearance of CBD was ascertained with choledochoscopy and CBD was closed primarily. He did well in the post-operative period and was discharged on the 5 post-operative day. At 1-year follow-up, the patient was doing well. Laparoscopic CBD exploration is a feasible and safe option for the retained dormia basket. We utilised the 'dormia with dormia technique' to retrieve the impacted basket which has not been reported before.
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http://dx.doi.org/10.4103/jmas.JMAS_245_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597889PMC
September 2020

Melatonin as a protective agent in cardiac ischemia-reperfusion injury: Vision/Illusion?

Eur J Pharmacol 2020 Oct 26;885:173506. Epub 2020 Aug 26.

Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, 32827, USA. Electronic address:

Melatonin, an emphatic endogenous molecule exerts protective effects either via activation of G-protein coupled receptors (Melatonin receptors, MTR 1-3), tumor necrosis factor receptor (TNFR), toll like receptors (TLRS), nuclear receptors (NRS) or by directly scavenging the free radicals. MTRs are extensively expressed in the heart as well as in the coronary vasculature. Accumulating evidences have indicated the existence of a strong correlation between reduction in the circulating level of melatonin and precipitation of heart attack. Apparently, melatonin exhibits cardioprotective effects via modulating inextricably interlinked pathways including modulation of mitochondrial metabolism, mitochondrial permeability transition pore formation, nitric oxide release, autophagy, generation of inflammatory cytokines, regulation of calcium transporters, reactive oxygen species, glycosaminoglycans, collagen accumulation, and regulation of apoptosis. Convincingly, this review shall describe the various signaling pathways involved in salvaging the heart against ischemia-reperfusion injury.
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http://dx.doi.org/10.1016/j.ejphar.2020.173506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025154PMC
October 2020
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