Publications by authors named "Gaurav Agarwal"

187 Publications

COVID-19 in Solid Organ Transplantation: Results of the National COVID Cohort Collaborative.

Transplant Direct 2021 Nov 6;7(11):e775. Epub 2021 Oct 6.

Division of Nephology, Department of Medicine, University of Nebraska Medical Center, Omaha, NE.

Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality in solid organ transplant (SOT) recipients. The National COVID Cohort Collaborative was developed to facilitate analysis of patient-level data for those tested for COVID-19 across the United States.

Methods: In this study, we identified a cohort of SOT recipients testing positive or negative for COVID-19 (COVID+ and COVID-, respectively) between January 1, 2020, and November 20, 2020. Univariable and multivariable logistic regression were used to determine predictors of a positive result among those tested. Outcomes following COVID-19 diagnosis were also explored.

Results: Of 18 121 SOT patients tested, 1925 were positive (10.6%). COVID+ SOT patients were more likely to have a kidney transplant and be non-White race. Comorbidities were common in all SOT patients but significantly more common in those who were COVID+. Of COVID+ SOT, 42.9% required hospital admission. COVID+ status was the strongest predictor of acute kidney injury (AKI), rejection, and graft failure in the 90 d after testing. A total of 40.9% of COVID+ SOT experienced a major adverse renal or cardiac event, 16.3% experienced a major adverse cardiac event, 35.3% experienced AKI, and 1.5% experienced graft loss.

Conclusions: In the largest US cohort of COVID+ SOT recipients to date, we identified patient factors associated with the diagnosis of COVID-19 and outcomes following infection, including a high incidence of major adverse renal or cardiac event and AKI.
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http://dx.doi.org/10.1097/TXD.0000000000001234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500600PMC
November 2021

Sex and Organ-Specific Risk of Major Adverse Renal or Cardiac Events in Solid Organ Transplant Recipients with COVID-19.

Am J Transplant 2021 Oct 12. Epub 2021 Oct 12.

Division of Nephology, Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.

While older males are at highest risk for poor COVID-19 outcomes, it is not known if this applies to the immunosuppressed recipient of a solid organ transplant (SOT), nor how the type of allograft transplanted may impact outcomes. In a cohort study of adult (>18 years) patients testing positive for COVID-19 (Jan 01, 2020-June 21, 2021) from 56 sites across the United States identified using the National COVID Cohort Collaborative (N3C) Enclave, we used multivariable Cox proportional hazards models to assess time to MARCE after COVID-19 diagnosis in those with and without SOT. We examined the exposure of age-stratified recipient sex overall and separately in kidney, liver, lung, and heart transplant recipients. 3,996 (36.4%) SOT and 91,646 (4.8%) non-SOT patients developed MARCE. Risk of post-COVID outcomes differed by transplant allograft type with heart and kidney recipients at highest risk. Males with SOT were at increased risk of MARCE, but to a lesser degree than the non-SOT cohort (HR 0.89, 95% CI 0.81-0.98 for SOT and HR 0.61, 95% CI 0.60-0.62 for non-SOT (females versus males)). This represents the largest COVID-19 SOT cohort to date and the first-time sex-age stratified and allograft-specific COVID-19 outcomes have been explored in those with SOT.
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http://dx.doi.org/10.1111/ajt.16865DOI Listing
October 2021

Pan-Genome-Wide Analysis of Identified Genes Linked to Pathogenicity in Onion.

Front Microbiol 2021 19;12:684756. Epub 2021 Aug 19.

Department of Plant Pathology, Coastal Plain Experimental Station, University of Georgia, Tifton, GA, United States.

Pantoea ananatis, a gram negative and facultative anaerobic bacterium is a member of a spp. complex that causes center rot of onion, which significantly affects onion yield and quality. This pathogen does not have typical virulence factors like type II or type III secretion systems but appears to require a biosynthetic gene-cluster, HiVir/PASVIL (located chromosomally comprised of 14 genes), for a phosphonate secondary metabolite, and the '' gene cluster (located in plasmid and comprised of 11 genes) that aids in bacterial colonization in onion bulbs by imparting tolerance to thiosulfinates. We conducted a deep pan-genome-wide association study (pan-GWAS) to predict additional genes associated with pathogenicity in using a panel of diverse strains ( = 81). We utilized a red-onion scale necrosis assay as an indicator of pathogenicity. Based on this assay, we differentiated pathogenic ( = 51)- vs. non-pathogenic ( = 30)-strains phenotypically. Pan-genome analysis revealed a large core genome of 3,153 genes and a flexible accessory genome. Pan-GWAS using the presence and absence variants (PAVs) predicted 42 genes, including 14 from the previously identified HiVir/PASVIL cluster associated with pathogenicity, and 28 novel genes that were not previously associated with pathogenicity in onion. Of the 28 novel genes identified, eight have annotated functions of site-specific tyrosine kinase, N-acetylmuramoyl-L-alanine amidase, conjugal transfer, and HTH-type transcriptional regulator. The remaining 20 genes are currently hypothetical. Further, a core-genome SNPs-based phylogeny and horizontal gene transfer (HGT) studies were also conducted to assess the extent of lateral gene transfer among diverse strains. Phylogenetic analysis based on PAVs and whole genome multi locus sequence typing (wgMLST) rather than core-genome SNPs distinguished red-scale necrosis inducing (pathogenic) strains from non-scale necrosis inducing (non-pathogenic) strains of . A total of 1182 HGT events including the HiVir/PASVIL and cluster genes were identified. These events could be regarded as a major contributing factor to the diversification, niche-adaptation and potential acquisition of pathogenicity/virulence genes in .
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http://dx.doi.org/10.3389/fmicb.2021.684756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417944PMC
August 2021

Pan-Genome of Novel subsp. Reveals Genes Involved in Onion Pathogenicity and Evidence of Lateral Gene Transfer.

Microorganisms 2021 Aug 18;9(8). Epub 2021 Aug 18.

Department of Plant Pathology, Coastal Plain Experiment Station, University of Georgia, Tifton, GA 31793, USA.

subsp. () is a causative agent of leafspot on foxtail millet and pearl millet; however, novel strains were recently identified that are pathogenic on onions. Our recent host range evaluation study identified two pathovars; subsp. pv. pv. nov. and subsp. pv. pv. nov. that are pathogenic on onions and millets or on millets only, respectively. In the current study, we developed a pan-genome using the whole genome sequencing of newly identified/classified strains from both pathovars [pv. ( = 4) and pv. ( = 13)]. The full spectrum of the pan-genome contained 7030 genes. Among these, 3546 (present in genomes of all 17 strains) were the core genes that were a subset of 3682 soft-core genes (present in ≥16 strains). The accessory genome included 1308 shell genes and 2040 cloud genes (present in ≤2 strains). The pan-genome showed a clear linear progression with >6000 genes, suggesting that the pan-genome of is open. Comparative phylogenetic analysis showed differences in phylogenetic clustering of spp. using PAVs/wgMLST approach in comparison with core genome SNPs-based phylogeny. Further, we conducted a horizontal gene transfer (HGT) study using strains from both pathovars along with strains from other species, namely, subsp. LMG 2715, LMG 2665 LMG L15, and LMG 24248. A total of 317 HGT events among four species were identified with most gene transfer events occurring between pv. and pv. . Pan-GWAS analysis predicted a total of 154 genes, including seven gene-clusters, which were associated with the pathogenicity phenotype (necrosis on seedling) on onions. One of the gene-clusters contained 11 genes with known functions and was found to be chromosomally located.
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http://dx.doi.org/10.3390/microorganisms9081761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399035PMC
August 2021

Whole-genome characterization and comparative genomics of a novel freshwater cyanobacteria species: Pseudanabaena punensis.

Mol Phylogenet Evol 2021 Jul 28;164:107272. Epub 2021 Jul 28.

Institute of Genomics for Crop Abiotic Stress Tolerance, Department of Plant and Soil Science, Texas Tech University, Lubbock, TX, USA. Electronic address:

Cyanobacteria are emerging as a potential source of novel, beneficial bioactive compounds. However, some cyanobacteria species can harm water quality and public health through the production of toxins. Therefore, surveying the occurrence and generating genomic resources of cyanobacteria producing harmful compounds could help develop the control methods necessary to manage their growth and limit the release contaminants into the water bodies. Here, we describe a novel strain, Pseudanabaena punensis isolated from the open ends of pipelines supplying freshwater. This isolate was characterized morphologically, biochemically and by whole-genome sequence analysis. We also provide genomic information for P. punensis to help understand and highlight the features unique to this isolate. Morphological and genetic (analysis using 16S rRNA and rbcL genes) data were used to assign this novel strain to phylogenetic and taxonomic groups. The isolate was identified as a filamentous and non-heterocystous cyanobacteria. Based on morphological and 16S rRNA phylogeny, this isolate shares characteristics with the Pseudanabaenaceae family, but remains distinct from well-characterized species suggesting its polyphyletic assemblage. The whole-genome sequence analysis suggests greater genomic and phenotypic plasticity. Genome-wide sequence and comparative genomic analyses, comparing against several closely related species, revealed diverse and important genes associated with synthesizing bioactive compounds, multi-drug resistance pathway, heavy metal resistance, and virulence factors. This isolate also produces several important fatty acids with potential industrial applications. The observations described in this study emphasize both industrial applications and risks associated with the freshwater contamination, and therefore genomic resources provided in this study offer an opportunity for further investigations.
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http://dx.doi.org/10.1016/j.ympev.2021.107272DOI Listing
July 2021

Left Ventricular Intramyocardial Dissecting Hematomas.

JACC Case Rep 2021 Jan 7;3(1):94-98. Epub 2020 Oct 7.

Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences & Research, Bengaluru, Karnataka, India.

Intramyocardial dissection is a rare complication of myocardial infarction, trauma, and percutaneous intervention. It is usually caused by hemorrhagic dissection among the spiral myocardial fibers. We hereby report the case of a patient with left ventricular intramyocardial dissection who presented with acute decompensated heart failure. ().
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http://dx.doi.org/10.1016/j.jaccas.2020.07.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305111PMC
January 2021

Metastases from renal cell carcinoma-Report of three unpredictable cases and literature review.

Indian J Cancer 2021 Apr-Jun;58(2):273-277

Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India.

The capacity to metastasize after long periods of discovery and resection of the primary renal lesion or to present as metastasis with undisclosed primary lesions grant renal cell carcinomas (RCC) a formidable and unpredictable behavior. We report three unusual cases of metastasis from RCC. The first patient presented with metastatic clear cell adenocarcinoma in the right shoulder muscles, with unknown primary and revealed an undetected clear cell right RCC on radiology. The second patient presented with a hemorrhagic nasal metastasis of RCC. A history of nephrectomy for RCC, 10 years prior to the development of nasal metastasis was elicited. The third patient presented with axillary and later abdominal wall metastasis of papillary RCC. He had a history of RCC 3 years prior to the discovery of metastasis. RCC has the propensity to appear as a metastatic carcinoma with unknown primary, requiring exclusion of several diagnostic pathologic entities. The appearance of metastasis many years after disease quiescence is challenging and clinicians need to be sensitized to the need for long-term surveillance in RCC. Though the prognosis remains poor, immune checkpoint inhibitors are currently the modalities of choice in such cases.
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http://dx.doi.org/10.4103/ijc.IJC_160_20DOI Listing
June 2021

Thyroid dysfunctions and autoimmunity in breast cancer patients: a prospective case-control study.

Arch Endocrinol Metab 2021 May;64(6):743-750

Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Objective: The relationship of thyroid dysfunction and autoimmunity with breast cancer (BC) continues to be contentious. The primary aim of this study was to estimate the prevalence of thyroid dysfunctions and autoimmunity in BC patients, and the secondary aims were to investigate the relationship of thyroid dysfunction with the clinicopathological profile of and therapy received by BC patients.

Methods: This was a single-center prospective case-control study (March 2015-May 2017). Women with BC (n = 191), age-matched healthy controls (n = 166) and malignant controls (patients with cervical cancer, n = 87) were enrolled. Basal serum free thyroxin (fT4), thyrotropin (TSH) and anti-thyroid peroxidase (TPO) antibody levels were measured in all three groups; fT4, TSH and TPO measures were repeated after chemotherapy and at the 1-year follow-up (one year after diagnosis) in the BC patients.

Results: The prevalence of overall hypothyroidism and autoimmunity (p = 0.106) did not differ significantly between the three groups, but the rate of clinical hypothyroidism was significantly higher in the BC group than in the healthy control group and the malignant control group (12.2% 3.0% 4.6%, respectively; p = 0.001). BC patients had significantly lower mean basal TSH concentrations than the healthy controls (p = 0.017). The postchemotherapy TSH concentrations were significantly lower (p = 0.001), and the fT4 concentrations were higher, albeit not significantly (p = 1.00), than the respective basal concentrations. The reverse was true for the follow-up values, in which the TSH (p = 1.00) values were higher and the fT4 (p = 0.03) concentrations were lower than the respective basal concentrations. An additional 6% of the BC patients developed clinical hypothyroidism during follow-up. Hypothyroid (p = 0.02) and TPO-positive (p = 0.004) patients had significantly smaller tumors, but their other clinicopathological features were comparable to those without thyroid dysfunction.

Conclusion: The prevalence of clinical hypothyroidism requiring thyroxine replacement was significantly high in BC patients and increased further during follow-up. Hence, BC patients should be considered a high-risk group that should receive routine screening for hypothyroidism.
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http://dx.doi.org/10.20945/2359-3997000000284DOI Listing
May 2021

Comments on "Breast-Conserving Therapy is Associated with Improved Survival compared with Mastectomy for Early-Stage Breast Cancer: A Propensity Score Matched Comparison Using the National Cancer Database".

Ann Surg Oncol 2021 May 24. Epub 2021 May 24.

Endocrine & Breast Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

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http://dx.doi.org/10.1245/s10434-021-10149-0DOI Listing
May 2021

Development and validation of a Questionnaire to study practices and diversities in Plexus and Peripheral nerve blocks.

Indian J Anaesth 2021 Mar 13;65(3):197-201. Epub 2021 Mar 13.

Department of Anaesthesia, Care Hospital, Bhubaneswar, Odisha, India.

Background And Aims: Regional anaesthesia techniques are a part of perioperative medicine that affects both perioperative and long-term outcomes. We have a paucity of the data on the usage and practices of plexus and peripheral nerve blocks (PNBs). To the best of our knowledge, this is the first effort to validate a survey for plexus and PNBs. Subsequently, this questionnaire could be used for the survey to look for the trends and disparities in PNB practices and further to develop a national registry in the future.

Methods: Thirty questions were prepared after evidence-based search and reviewed by experts for suggestions. Changes were done and the questionnaire with the grading sheet was sent to 19 experts. The responses were analysed to calculate the content validity index (CVI) item-wise (I-CVI), scale-wise (S-CVI), and modified kappa statistics. The I-CVI of 0.78 and an S-CVI/average of 0.90 was taken as acceptable with more than six experts.

Results: Fourteen experts out of 19 assessed and graded the questions as per the provided sheet and submitted suggestions through the mail. Question reframing, option reconsideration, and change from single to multiple choices were incorporated as per the suggestions of the experts. Mean I-CVI for relevance, simplicity, clarity, and ambiguity was 0.99, 0.98, 0.98, and 0.99, respectively. S-CVI/average was 0.98, 0.97, 0.98, and 0.99 for relevance, simplicity, clarity, and ambiguity, respectively.

Conclusion: We conclude that this questionnaire has met the content validity criteria and can be used to study plexus and PNBs practices.
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http://dx.doi.org/10.4103/ija.IJA_1161_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989482PMC
March 2021

Letter to the Editor: The Impact of Neoadjuvant Chemotherapy on Margin Re-excision in Breast-Conserving Surgery.

World J Surg 2021 Feb 26. Epub 2021 Feb 26.

Department of Endocrine & Breast Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Uttar Pradesh, Raebareli Road, Lucknow, 226014, India.

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http://dx.doi.org/10.1007/s00268-021-06018-2DOI Listing
February 2021

Hereditary Medullary Thyroid Carcinoma: Genotype, Phenotype and Outcomes in a North Indian Cohort.

World J Surg 2021 06 19;45(6):1785-1793. Epub 2021 Feb 19.

Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, UP, 226014, India.

Background: Aggressiveness of hereditary medullary thyroid carcinoma (hMTC) has been conventionally described to correlate with American Thyroid Association (ATA) risk groups based on RET mutations. Recent evidence increasingly contradicts this notion. We studied the RET genotype and its correlation with disease phenotype and survival outcomes in a cohort of hMTC patients.

Methods: In a retrospective cohort of 55 hMTC patients from 23 families treated at a north Indian tertiary care institute over 15-years, RET genotype was correlated with disease phenotype (clinical, biochemical, and pathological attributes) and outcomes in terms of biochemical cure (normalization of serum calcitonin), structural cure, overall survival (OS) and disease specific survival (DSS).

Results: Forty-nine patients had Multiple Endocrine Neoplasia (MEN)-type 2A syndrome, 02 had MEN-2B, and 4 had familial MTC. Two patients belonged to highest ATA risk, 41 to high-risk, and 12 to moderate risk categories. Age of the patients or stage of disease at presentation did not differ significantly between the ATA risk groups. Though the baseline serum calcitonin was significantly higher in highest risk category, the biochemical cure rates were not significantly different. At a median follow up of 48 months (Inter-quartile range 18-84, range 12-192) structural cure rates in ATA moderate and high risk groups were significantly higher than highest risk group (p = 0.04). No significant difference in OS between the three ATA groups of hMTC among the patients who underwent surgical treatment was observed (p = 0.098).

Conclusions: The ATA moderate and high risk groups have better structural cure rates compared to ATA highest risk group. The biochemical cure and overall survival rates did not significantly differ between ATA risk-groups, and were impacted by the disease stage at presentation. The current ATA risk-groups do not reliably predict the outcomes in terms of biochemical cure and survival in hMTC patients.
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http://dx.doi.org/10.1007/s00268-021-05993-wDOI Listing
June 2021

Breathability and Safety Testing of Personal Protective Equipment: "Human-comfort" Factor Remains Undefined.

Indian J Crit Care Med 2021 Jan;25(1):12-15

Department of Gastromedicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Healthcare systems all over the world have been enormously affected by the COVID-19 pandemic. Healthcare workers (HCWs) taking care of these patients need personal protective equipments (PPEs) standardized for full protection from droplets and aerosols carrying viral load to variable distances. There has been a surge of manufacturers supplying these protective gears in India and regulatory agencies have issued technical specifications pertaining to PPEs focusing solely on synthetic blood penetration tests (SBPTs) and keeping the upper limit of non-woven fabric to 95 g/m (GSM). These PPE specifications are silent on air permeability (AP) and water/moisture vapor transmission rate (WVTR/MVTR) of the fabric. As a result, most of the PPE kits, despite having appropriate SBPT certifications from regulatory agencies, have extremely poor permeability and breathability. The acceptability of PPEs by HCWs can be vastly improved when the end-users are proactively invited to participate in "comfort testing" of PPEs before getting issuance of certification for marketing. "Field testing" or "end-user trials" in which HCWs don the PPE and assess it for comfort while performing different types of clinical work, e.g., in intensive care units (ICUs), operation theaters, cath labs, etc., also takes into account a hitherto often ignored "human-comfort-factor" that not only enhances the understanding of HCWs about the need for the PPEs but can also motivate them to use it without worrying about discomfort. We hereby propose that comfort fit testing (COmfort and Material Fit is an Obviously Required Test) should be a part of the mandatory testing and certification process for PPE, so that the industry invests wisely in manufacturing PPE kits that are not only certified for fabric but are also tested for comfort factors. Kapoor A, Baronia AK, Azim A, Agarwal G, Prasad N, Mishra R, . Breathability and Safety Testing of Personal Protective Equipment: "Human-comfort" Factor Remains Undefined. Indian J Crit Care Med 2021;25(1):12-15.
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http://dx.doi.org/10.5005/jp-journals-10071-23598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874299PMC
January 2021

Identification of Two Novel Pathovars of subsp. Affecting sp. and Millets.

Phytopathology 2021 Oct 14:PHYTO11200508R. Epub 2021 Oct 14.

Department of Plant Pathology, Coastal Plain Experiment Station, University of Georgia, Tifton, GA 31793.

subsp. is a causative agent of leafspot of foxtail millet and pearl millet; however, novel strains were recently identified that are pathogenic on onion. We phenotypically and genotypically characterized 17 . subsp. strains from onion and other sources (pearl millet, foxtail millet, guar pulse, verbena, and corn). Based on the host range evaluation, we propose two pathovars: . subsp. pv. pv. nov. and . subsp. pv. pv. nov. . subsp. pv. pv. nov. causes symptoms on spp. (leek, onion, chive, and Japanese bunching onion) and on foxtail millet, pearl millet, and oat. However, . subsp. pv. pv. nov. can only infect the members of family (foxtail millet, pearl millet, and oat). We also propose that the type strain of . subsp. (LMG 2632) should be designated as a pathotype strain of . subsp. pv. and recommend that the strain PNA 14-12 be designated as the pathotype strain of . subsp. pv. . The digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI), and multilocus sequence analysis study showed that the two pathovars are genotypically closely related. Our study also showed that . subsp. pathovars and . subsp. share high genotypic relatedness and cannot be differentiated by dDDH and ANI values. Although the newly proposed pathovars are not clearly distinguishable by their fatty acid and methyl esterase profiles and substrate use patterns, a fatty acid (unknown with retention time: 10.9525) and a few metabolites (3-methyl glucose, Na butyrate, and fusidic acid) can be potentially used to distinguish them. We also report the distribution of previously known pathogenicity (HiVir, ) and virulence () factors of spp. in the new pathovars. The impact of these new pathovars in the center rot pathosystem of onion is yet to be determined.
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http://dx.doi.org/10.1094/PHYTO-11-20-0508-RDOI Listing
October 2021

Impact of Subclinical Borderline Inflammation on Kidney Transplant Outcomes.

Transplant Direct 2021 Feb 26;7(2):e663. Epub 2021 Jan 26.

Department of Medicine, University of Alabama School of Medicine, Birmingham, AL.

Background: Surveillance biopsies permit early detection of subclinical inflammation before clinical dysfunction, but the impact of detecting early subclinical phenotypes remains unclear.

Methods: We conducted a single-center retrospective cohort study of 441 consecutive kidney transplant recipients between 2015 and 2018 with surveillance biopsies at 6 months post-transplant. We tested the hypothesis that early subclinical inflammation (subclinical borderline changes, T cell-mediated rejection, or microvascular injury) is associated with increased incidence of a composite endpoint including acute rejection and allograft failure.

Results: Using contemporaneous Banff criteria, we detected subclinical inflammation in 31%, with the majority (75%) having a subclinical borderline phenotype (at least minimal inflammation with mild tubulitis [>i0t1]). Overall, subclinical inflammation was independently associated with the composite endpoint (adjusted hazard ratio, 2.88; 1.11-7.51;  = 0.03). The subgroup with subclinical borderline inflammation, predominantly those meeting the Banff 2019 i1t1 threshold, was independently associated with 5-fold increased hazard for the composite endpoint ( = 0.02). Those with concurrent subclinical inflammation and subclinical chronic allograft injury had worse outcomes. The effect of treating subclinical inflammation was difficult to ascertain in small heterogeneous subgroups.

Conclusions: Subclinical acute and chronic inflammation are common at 6 months post-transplant in kidney recipients with stable allograft function. The subclinical borderline phenotype with both tubulitis and interstitial inflammation was independently associated with poor long-term outcomes. Further studies are needed to elucidate the role of surveillance biopsies for management of allograft inflammation in kidney transplantation.
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http://dx.doi.org/10.1097/TXD.0000000000001119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837932PMC
February 2021

Field Screen and Genotyping of against Two Begomoviruses in Georgia, USA.

Insects 2021 Jan 10;12(1). Epub 2021 Jan 10.

Department of Plant Pathology, Coastal Plain Experimental Station, University of Georgia, Tifton, GA 31793, USA.

The production and quality of (snap bean) have been negatively impacted by leaf crumple disease caused by two whitefly-transmitted begomoviruses: cucurbit leaf crumple virus (CuLCrV) and sida golden mosaic Florida virus (SiGMFV), which often appear as a mixed infection in Georgia. Host resistance is the most economical management strategy against whitefly-transmitted viruses. Currently, information is not available with respect to resistance to these two viruses in commercial cultivars. In two field seasons (2018 and 2019), we screened spp. genotypes ( = 84 in 2018; = 80 in 2019; most of the genotypes were common in both years with a few exceptions) for resistance against CuLCrV and/or SiGMFV. We also included two commonly grown Lima bean () varieties in our field screening. Twenty spp. genotypes with high to moderate-levels of resistance (disease severity ranging from 5%-50%) to CuLCrV and/or SiGMFV were identified. Twenty-one spp. genotypes were found to be highly susceptible with a disease severity of ≥66%. Furthermore, based on the greenhouse evaluation with two genotypes-each (two susceptible and two resistant; identified in field screen) exposed to viruliferous whiteflies infected with CuLCrV and SiGMFV, we observed that the susceptible genotypes accumulated higher copy numbers of both viruses and displayed severe crumple severity compared to the resistant genotypes, indicating that resistance might potentially be against the virus complex rather than against the whiteflies. Adult whitefly counts differed significantly among Phaseolus genotypes in both years. The whole genome of these spp. [snap bean ( = 82); Lima bean ( = 2)] genotypes was sequenced and genetic variability among them was identified. Over 900 giga-base (Gb) of filtered data were generated and >88% of the resulting data were mapped to the reference genome, and SNP and Indel variants in spp. genotypes were obtained. A total of 645,729 SNPs and 68,713 Indels, including 30,169 insertions and 38,543 deletions, were identified, which were distributed in 11 chromosomes with chromosome 02 harboring the maximum number of variants. This phenotypic and genotypic information will be helpful in genome-wide association studies that will aid in identifying the genetic basis of resistance to these begomoviruses in spp.
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http://dx.doi.org/10.3390/insects12010049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827361PMC
January 2021

Comment on: Risk Factors of Redo Surgery After Unilateral Focused Parathyroidectomy - Conclusions From a Comprehensive Nationwide Database of 13,247 Interventions Over 6 Years.

Ann Surg 2020 Dec 23;Publish Ahead of Print. Epub 2020 Dec 23.

Department of Endocrine & Breast Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India.

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http://dx.doi.org/10.1097/SLA.0000000000004724DOI Listing
December 2020

Comparative retrospective analysis of locoregional recurrence in unselected breast cancer patients treated with conventional versus hypofractionated radiotherapy at a tertiary cancer center?

J Cancer Res Ther 2020 Oct-Dec;16(6):1314-1322

Department of Radiotherapy, SGPGIMS, Lucknow, Uttar Pradesh, India.

Background: Role of hypofractionated radiotherapy (HFRT) in early breast cancer is established; comparatively, there are limited data for HFRT in locally advanced breast cancer (LABC). We report the impact of HFRT in unselected breast cancer patients in comparison with historically treated patients with conventional fractionated radiotherapy (CFRT).

Patients And Methods: Records of 463 breast cancer patients treated between January 09 and July 13 with CFRT (50 Gy/25 fr) or HFRT (42.4 Gy in 16 fractions or 40 Gy in 15 fractions) in two sequential periods were retrospectively reviewed. The analysis was done in August 2018. The primary endpoint was to compare the differences in locoregional recurrence rate.

Results: Of the 463 patients, 209 received CFRT and 254 received HFRT. The median age was 48 years (interquartile range: 40-56), premenopausal (CFRT: 23% vs. HFRT 39%, P = 0.005). The most common pathology was infiltrating ductal carcinoma (81%) with Grade III tumors (45%), estrogen receptor (+) was seen in 44%, triple-negative breast cancer in 34%, and Her2Neu (3+) were seen in 27%. Two hundred and fifty-four patients (54.5%) had undergone breast-conserving surgery (BCS) and 209 patients (45%) modified radical mastectomy (MRM). Nodal radiotherapy was delivered in 76% versus 64% in patients receiving CFRT versus HFRT, respectively (P = 0.005). With a median follow-up of 46 months in CFRT and 57 months in HFRT, 9/209 (4.3%) patients in CFRT and 7/254 (2.7%) in HFRT had locoregional relapse (LRR). The 4 years#39; actuarial local recurrence-free survival (LRFS) in CFRT versus HFRT was 95% versus 97% (P = 0.37). The mean estimated LRFS (local relapse-free survival) for CFRT is 113.4 months and for HFRT 94.2 months (P = 0.3).

Conclusions: The risk of local recurrence among patients of breast cancer treated with HFRT after BCS or MRM was not worse when compared to CFRT.
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http://dx.doi.org/10.4103/jcrt.JCRT_389_18DOI Listing
February 2021

Soybean transporter database: A comprehensive database for identification and exploration of natural variants in soybean transporter genes.

Physiol Plant 2021 Apr 14;171(4):756-770. Epub 2020 Dec 14.

Division of Plant Science, National Center for Soybean Biotechnology, University of Missouri, Columbia, Missouri, USA.

Transporters, a class of membrane proteins that facilitate exchange of solutes including diverse molecules and ions across the cellular membrane, are vital component for the survival of all organisms. Understanding plant transporters is important to get insight of the basic cellular processes, physiology, and molecular mechanisms including nutrient uptake, signaling, response to external stress, and many more. In this regard, extensive analysis of transporters predicted in soybean and other plant species was performed. In addition, an integrated database for soybean transporter protein, SoyTD, was developed that will facilitate the identification, classification, and extensive characterization of transporter proteins by integrating expression, gene ontology, conserved domain and motifs, gene structure organization, and chromosomal distribution features. A comprehensive analysis was performed to identify highly confident transporters by integrating various prediction tools. Initially, 7541 transmembrane (TM) proteins were predicted in the soybean genome; out of these, 3306 non-redundant transporter genes carrying two or more transmembrane domains were selected for further analysis. The identified transporter genes were classified according to a standard transporter classification (TC) system. Comparative analysis of transporter genes among 47 plant genomes provided insights into expansion and duplication of transporter genes in land plants. The whole genome resequencing (WGRS) and tissue-specific transcriptome datasets of soybean were integrated to investigate the natural variants and expression profile associated with transporter(s) of interest. Overall, SoyTD provides a comprehensive interface to study genetic and molecular function of soybean transporters. SoyTD is publicly available at http://artemis.cyverse.org/soykb_dev/SoyTD/.
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http://dx.doi.org/10.1111/ppl.13287DOI Listing
April 2021

Circulating free DNA as a marker of response to chemoradiation in locally advanced head and neck squamous cell carcinoma.

Indian J Pathol Microbiol 2020 Oct-Dec;63(4):521-526

Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Vibhuti Khand, Gomti Nagar, Lucknow, Uttar Pradesh, India.

Context: Liquid biopsy has moved from bench to bedside as a non-invasive biomarker for early diagnosis and monitoring treatment response.

Objective: This study investigated the role of circulating free DNA (cfDNA) as a diagnostic marker in locally advanced head and neck squamous cell carcinoma (HNSCC) and in monitoring response to chemoradiation therapy.

Materials And Methods: Serum was collected from treatment naïve, histopathologically diagnosed tumors in 24 HNSCC cases and 16 normal controls. CfDNA levels were quantified using β globin gene amplification.

Results: The cfDNA level was significantly elevated in HNSCC (992.67 ± 657.43 ng/mL) as compared to healthy controls (60.65 ± 30.42 ng/mL, P = <0.001). The levels of cfDNA did not significantly correlate with TNM stage, lymph node involvement and grade. In responders, percentage decrease in cfDNA levels was 9.57% and 29.66%, whereas in nonresponders percentage increase was 13.28% and 24.52% at the end of three months of follow-up.

Conclusion: Our study adds to the evidence that cfDNA levels are significantly higher in HNSCC cases and provides some evidence that levels increase with tumor progression. CfDNA may be a promising prospective non-invasive marker to predict response in patients undergoing chemo-radiotherapy.
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http://dx.doi.org/10.4103/IJPM.IJPM_28_20DOI Listing
July 2021

Epigenetics and epigenomics: underlying mechanisms, relevance, and implications in crop improvement.

Funct Integr Genomics 2020 Nov 21;20(6):739-761. Epub 2020 Oct 21.

Center of Excellence in Genomics & Systems Biology (CEGSB), International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Hyderabad, Telangana, India.

Epigenetics is defined as changes in gene expression that are not associated with changes in DNA sequence but due to the result of methylation of DNA and post-translational modifications to the histones. These epigenetic modifications are known to regulate gene expression by bringing changes in the chromatin state, which underlies plant development and shapes phenotypic plasticity in responses to the environment and internal cues. This review articulates the role of histone modifications and DNA methylation in modulating biotic and abiotic stresses, as well as crop improvement. It also highlights the possibility of engineering epigenomes and epigenome-based predictive models for improving agronomic traits.
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http://dx.doi.org/10.1007/s10142-020-00756-7DOI Listing
November 2020

Pediatric Primary Hyperparathyroidism: Experience in a Tertiary Care Referral Center in a Developing Country Over Three Decades.

World J Surg 2021 Feb 12;45(2):488-495. Epub 2020 Oct 12.

Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India.

Background: There is limited experience in managing pediatric primary hyperparathyroidism (PHPT). The aim of this study was to analyze the clinical presentation and outcome of surgery in children with PHPT managed at a tertiary referral center.

Methods: This retrospective study (September 1989-August 2019) consisted of 35 pediatric PHPT patients (< 18 years) who underwent parathyroidectomy. Clinico-pathologic profile and outcome were noted.

Results: The mean age of cohort was 15.2±2.9 years and girls outnumbered boys (M:F = 1:1.9). Familial and symptomatic disease was noted in 8.5 and 94.3% cases, respectively. Skeletal manifestations (83%) were the commonest followed by renal (29%). Fifty-four percent children had skeletal fractures, and 23% were bed-ridden. Among rare manifestations, hypercalcemic crisis, recurrent pancreatitis and stigmata of rickets were observed in 2.8, 11.4 and 14.2% children, respectively. Mean calcium concentration was 12.1 ± 2.0 mg/dl and PTH 91.8 ± 66.5 pmol/L. The sensitivity of preoperative imaging in parathyroid localization was 91.4%. Minimally invasive parathyroidectomy (MIP) was performed in 40% cases. Parathyroid adenoma was observed in 91.4% patients, whereas remaining had hyperplasia. Thirty-four percent suffered from Hungry bone syndrome in postoperative period. The cure rate following primary surgery was 97%. One child with persistent PHPT had successful re-operation. Median follow-up was 5 (1-17) years, and no recurrence or familial disease was revealed during this period.

Conclusion: Majority of pediatric patients present with symptomatic PHPT. Despite relatively high incidence of familial disease select pediatric patients can undergo successful MIP.
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http://dx.doi.org/10.1007/s00268-020-05816-4DOI Listing
February 2021

Total postoperative analgesia for total knee arthroplasty: Ultrasound guided single injection modified 4 in 1 block.

J Anaesthesiol Clin Pharmacol 2020 Apr-Jun;36(2):261-264. Epub 2020 Jun 15.

Department of Anaesthesia and Pain Management, CARE Hospitals, Bhubaneswar, Odisha, India.

Background And Aims: Total pain free outcome following total knee arthroplasty has led to the evolution of regional blocks. In this series, the authors have revisited and modified Roy . 's technique of Ultrasound guided 4 in 1 block for knee and below knee surgeries, to provide a complete comprehensive yet simple single injection technique for postoperative analgesia for Total Knee Arthroplasty (TKA).

Material And Methods: After Instituional ethics approval, we performed the modified 4 in 1 block on 10 consenting patients scheduled to undergo total knee arthroplasty. A linear USG-probe was used to identify medial femoral condyle, then vastus and sartorius intersection was identified. The probe was slid till the descending genicular artery branching from superficial femoral artery was visualized proximal to hiatus. At this point the needle with PNS attached, was guided into the Vastus medialis muscle till the stimulation of the nerve to Vastus medialis (0.4-0.5 mA). At this point 5-7 mL of 0.2% Ropivacaine was injected. The needle was guided in plane to perivascular region and after negative aspiration 0.2%ropivacaine 20-25 ml was injected, visualised to push the femoral artery.

Results: All ten patients considered in this study had an optimum pain score of <5 and were comfortable along with no quadriceps weakness, except one patient had a pain score of more than 5 after 36 hr post-operatively and required rescue analgesia.

Conclusion: The addition of USG and PNS guided Vastus medialis nerve block to USG 4-in-1 block in the technique gives good post-operative analgesia for TKA.
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http://dx.doi.org/10.4103/joacp.JOACP_260_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480285PMC
June 2020

Sacral multifidus plane block for post-operative analgesia in perianal procedures.

J Clin Anesth 2021 Feb 30;68:110060. Epub 2020 Sep 30.

Department of Anaesthesia & Pain Management, CARE Hospitals, Bhubaneswar, Odisha, India.

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http://dx.doi.org/10.1016/j.jclinane.2020.110060DOI Listing
February 2021

Two New Reference Genomes Reveal a Large Insertion Potentially Contributing to Isolate Stress Tolerance and Aflatoxin Production.

G3 (Bethesda) 2020 10 5;10(10):3515-3531. Epub 2020 Oct 5.

USDA-ARS, Crop Protection and Management Research Unit, Tifton, GA 31793

Efforts in genome sequencing in the genus have led to the development of quality reference genomes for several important species including , , and However, less progress has been made for As part of the effort of the USDA-ARS Annual Aflatoxin Workshop Fungal Genome Project, the isolate NRRL3357 was sequenced and resulted in a scaffold-level genome released in 2005. Our goal has been biologically driven, focusing on two areas: isolate variation in aflatoxin production and drought stress exacerbating aflatoxin production by Therefore, we developed two reference pseudomolecule genome assemblies derived from chromosome arms for two isolates: AF13, a MAT1-2, highly stress tolerant, and highly aflatoxigenic isolate; and NRRL3357, a MAT1-1, less stress tolerant, and moderate aflatoxin producer in comparison to AF13. Here, we report these two reference-grade assemblies for these isolates through a combination of PacBio long-read sequencing and optical mapping, and coupled them with comparative, functional, and phylogenetic analyses. This analysis resulted in the identification of 153 and 45 unique genes in AF13 and NRRL3357, respectively. We also confirmed the presence of a unique 310 Kb insertion in AF13 containing 60 genes. Analysis of this insertion revealed the presence of a bZIP transcription factor, named , which may contribute to isolate pathogenicity and stress tolerance. Phylogenomic analyses comparing these and other available assemblies also suggest that the species complex of is polyphyletic.
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http://dx.doi.org/10.1534/g3.120.401405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534430PMC
October 2020

Endoscopic versus Conventional Thyroid Surgery: A Comparison of Quality of Life, Cosmetic Outcomes and Overall Patient Satisfaction with Treatment.

World J Surg 2020 Dec 13;44(12):4118-4126. Epub 2020 Aug 13.

Department of Endocrine Surgery, SGPGIMS, Lucknow, India.

Background: Our aim was to investigate whether the surgical approach, i.e. endoscopic (ET) versus conventional/open thyroidectomy (ConT), contributes towards the improvement in quality of life (QoL), cosmetic outcomes and overall patient satisfaction with treatment.

Methods: We conducted a prospective study (October 2016-August 2018) consisting of patients undergoing hemithyroidectomy for euthyroid, non-malignant solitary thyroid nodules (STNs). Patients were divided into two groups: Group I (ET)-41 patients and Group II (ConT)-52 patients. ET was performed via bilateral-axillo breast approach (BABA). A thyroid disease-specific questionnaire "ThyPRO-39hin" was used to evaluate pre- and post-operative QoL. Visual analogue scale (VAS) was used for post-operative pain. Cosmetic satisfaction, paraesthesia and overall satisfaction with treatment were evaluated using Likert-type verbal response scales. Pre- and post-operative scores (>6 months) were compared, and p value < 0.05 was considered significant.

Results: Mean age (p = 0.26), gender distribution (p = 0.07), mean tumour size (p = 0.74) and preoperative scores of QoL were comparable between the two groups. Post-operatively scores of symptom domain (p = 0.03), tiredness (p = 0.03), impaired social life (p = 0.03), cosmetic complaints (p =  < 0.001) and overall QoL (p =  < 0.001) were significantly better in Group I. Also, post-operative pain perception at first follow-up visit (p = 0.001) was lower in patients undergoing ET/Group I, with higher scar satisfaction scores (p =  < 0.001) and overall satisfaction with treatment (p =  < 0.001). Post-operative paraesthesia perception was comparable (p = 0.06) amongst the two groups.

Conclusion: In this cohort study, patients undergoing endoscopic thyroid surgery reported superior post-operative QoL, cosmetic and overall satisfaction with treatment as compared to conventional/open thyroidectomy.
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http://dx.doi.org/10.1007/s00268-020-05732-7DOI Listing
December 2020

Fungating Breast Cancer: Experience in Low and Middle Income Country.

Indian J Surg Oncol 2020 Jun 19;11(2):281-286. Epub 2020 Feb 19.

Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014 India.

Fungating breast cancer (FBC) is a rare entity in developed nations. But this occurrence is not uncommon in our country. The aim of this study was to review clinico-pathologic profile and outcomes of FBC in a developing country. This retrospective study consisted of patients with FBC managed at our institute (Jan 2005-Dec 2015). Clinico-pathologic profile, management details, and outcomes were analyzed. The Kaplan-Meier method was used to determine overall survival (OS). Log-rank test was performed to compare survival in various subgroups. Seventy-nine patients were detected to have FBC constituting 3.3% of all breast cancers and 24.8% of those having T4b lesions. Mean age of the patients was 55 + 11 years. Ninety-six percent were women and 67% belonged to rural areas. A total of 75% women were postmenopausal. Mean duration of lump was 16 + 11 months. The mean tumor size was 8+ 2 cm. Eighty-seven percent had axillary lymph node involvement and 42% distant metastases. Fifty-eight percent ( = 46) patients had stage III and 42% ( = 33) stage had IV tumors. Hormone receptor (HR) positivity was noted in 44% ( = 35) and HER2/neu overexpression in 39% ( = 31) tumors, whereas 32% ( = 25) were triple negative. Overall, 95% ( = 75) of patients received chemotherapy, 91% ( = 72) patients underwent mastectomy, and 76% ( = 60) loco-regional radiotherapy. Median duration of follow-up was 40 (2-93) months. Median survival was 36 months, and 5-year OS was 40%. Except for stage (53% vs 22%,  = 0.005), no other factor influenced OS. Multimodality therapy in FBS results in good symptom palliation and comparable survival to stage III and IV patients without fungating tumors.
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http://dx.doi.org/10.1007/s13193-020-01040-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260334PMC
June 2020

Low-cost Fluorescein as an Alternative to Radio-colloid for Sentinel Lymph Node Biopsy-a Prospective Validation Study in Early Breast Cancer.

World J Surg 2020 10;44(10):3417-3422

Department of Endocrine & Breast Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Raebareli Road, Lucknow, Uttar Pradesh, 226014, India.

Background: Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical (RP) and a blue dye is gold standard for axillary staging in clinically node-negative early breast cancer. High costs and limited availability of RP and/or gamma probe are major deterrents in performing SLNB in developing countries. Fluorescence-guided SLNB can obviate the need for RP and gamma probe. Fluorescein is an inexpensive fluorescent lymphatic tracer. In this study, we compared SLN identification rate (SLN-IR) and false negative rates (FNR) of fluorescein-guided SLNB and radio-guided SLNB using Tc-Sulfur-colloid, in isolation, or in combination with methylene blue dye (MBD).

Methods: Sixty-five cN0 early and large operable breast cancer patients underwent validation SLNB using fluorescein (and blue LED light), Tc-Sulfur-colloid (and gamma probe) and MBD. Inj Fluorescein 4% was injected, 1 ml each peri-tumoral and sub-areolar five minutes before axillary incision. Axillary dissection was performed irrespective of SLNB histology. The SLN-IR and FNR with various tracers and their combinations were compared.

Results: The mean number of SLNs identified was 3.5 ± 1.8 (range 1-6). The SLN-IR using RP alone was 94%, fluorescein alone was 92%, and MBD alone was 82%. The SLN-IR using fluorescein plus MBD combination was 95.4%, compared to 97% using MBD plus RP combination. FNR was 6.3% using fluorescein plus MBD, as well as RP plus MBD combinations.

Conclusions: SLN-IR of > 90% and SLN-FNR of < 10% using fluorescein plus MBD combination are in acceptable range, and are comparable to that of RP plus MBD combination. Fluorescein can replace RP for performing SLNB, in combination with MBD.
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http://dx.doi.org/10.1007/s00268-020-05631-xDOI Listing
October 2020

Breast cancer treatment: A phased approach to implementation.

Cancer 2020 05;126 Suppl 10:2365-2378

Hopital Riviera Chablais, Vaud-Valais, Rennaz, Switzerland.

Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana.
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http://dx.doi.org/10.1002/cncr.32910DOI Listing
May 2020

Artificial Intelligence-Based Differential Diagnosis: Development and Validation of a Probabilistic Model to Address Lack of Large-Scale Clinical Datasets.

J Med Internet Res 2020 04 28;22(4):e17550. Epub 2020 Apr 28.

1mg Technologies Pvt Ltd, Gurgaon, India.

Background: Machine-learning or deep-learning algorithms for clinical diagnosis are inherently dependent on the availability of large-scale clinical datasets. Lack of such datasets and inherent problems such as overfitting often necessitate the development of innovative solutions. Probabilistic modeling closely mimics the rationale behind clinical diagnosis and represents a unique solution.

Objective: The aim of this study was to develop and validate a probabilistic model for differential diagnosis in different medical domains.

Methods: Numerical values of symptom-disease associations were utilized to mathematically represent medical domain knowledge. These values served as the core engine for the probabilistic model. For the given set of symptoms, the model was utilized to produce a ranked list of differential diagnoses, which was compared to the differential diagnosis constructed by a physician in a consult. Practicing medical specialists were integral in the development and validation of this model. Clinical vignettes (patient case studies) were utilized to compare the accuracy of doctors and the model against the assumed gold standard. The accuracy analysis was carried out over the following metrics: top 3 accuracy, precision, and recall.

Results: The model demonstrated a statistically significant improvement (P=.002) in diagnostic accuracy (85%) as compared to the doctors' performance (67%). This advantage was retained across all three categories of clinical vignettes: 100% vs 82% (P<.001) for highly specific disease presentation, 83% vs 65% for moderately specific disease presentation (P=.005), and 72% vs 49% (P<.001) for nonspecific disease presentation. The model performed slightly better than the doctors' average in precision (62% vs 60%, P=.43) but there was no improvement with respect to recall (53% vs 56%, P=.27). However, neither difference was statistically significant.

Conclusions: The present study demonstrates a drastic improvement over previously reported results that can be attributed to the development of a stable probabilistic framework utilizing symptom-disease associations to mathematically represent medical domain knowledge. The current iteration relies on static, manually curated values for calculating the degree of association. Shifting to real-world data-derived values represents the next step in model development.
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http://dx.doi.org/10.2196/17550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218591PMC
April 2020
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