Brought about by necessity: how the pandemic accelerated a transformation of continuing professional development.

The COVID-19 pandemic has had a profound impact on medical education and accelerated an evolution in continuing professional development that was already underway. Physicians around the world have had to quickly learn a new evolving clinical entity and do so in a virtual manner. As local and international travel ceased, academic and practice deliberations on diagnosis and treatment of novel diseases which historically have occurred during in-person conferences have shifted to virtual forums enabled with technology and social media. Medical educators have the added complexity of learning to teach and assess trainees virtually as remote learning has become a necessity. National and international organisations have increased collaborative efforts to ensure the latest clinical information is disseminated promptly to front-line physicians. The shift to virtual learning has democratised clinical information, allowing for wider global participation and transforming how we approach continuing professional development.

The need for pragmatic clinical trials in low and middle income settings - taking essential neonatal interventions delivered as part of inpatient care as an illustrative example.

BACKGROUND: Pragmatic randomized trials aim to examine the effects of interventions in the full spectrum of patients seen by clinicians who receive routine care. Such trials should be employed in parallel with efforts to implement many interventions which appear promising but where evidence of effectiveness is limited. We illustrate this need taking the case of essential interventions to reduce inpatient neonatal mortality in low and middle income countries (LMIC) but suggest the arguments are applicable in most clinical areas. DISCUSSION: A set of basic interventions have been defined, based on available evidence, that could substantially reduce early neonatal deaths if successfully implemented at scale within district and sub-district hospitals in LMIC. However, we illustrate that there remain many gaps in the evidence available to guide delivery of many inpatient neonatal interventions, that existing evidence is often from high income settings and that it frequently indicates uncertainty in the magnitude or even direction of estimates of effect. Furthermore generalizing results to LMIC where conditions include very high patient staff ratios, absence of even basic technologies, and a reliance on largely empiric management is problematic. Where there is such uncertainty over the effectiveness of interventions in different contexts or in the broad populations who might receive the intervention in routine care settings pragmatic trials that preserve internal validity while promoting external validity should be increasingly employed. Many interventions are introduced without adequate evidence of their effectiveness in the routine settings to which they are introduced. Global efforts are needed to support pragmatic research to establish the effectiveness in routine care of many interventions intended to reduce mortality or morbidity in LMIC. Such research should be seen as complementary to efforts to optimize implementation.

Transcriptional variation in the malaria parasite Plasmodium falciparum.

Malaria genetic variation has been extensively characterized, but the level of epigenetic plasticity remains largely unexplored. Here we provide a comprehensive characterization of transcriptional variation in the most lethal malaria parasite, Plasmodium falciparum, based on highly accurate transcriptional analysis of isogenic parasite lines grown under homogeneous conditions. This analysis revealed extensive transcriptional heterogeneity within genetically homogeneous clonal parasite populations. We show that clonally variant expression controlled at the epigenetic level is an intrinsic property of specific genes and gene families, the majority of which participate in host-parasite interactions. Intrinsic transcriptional variability is not restricted to genes involved in immune evasion, but also affects genes linked to lipid metabolism, protein folding, erythrocyte remodeling, or transcriptional regulation, among others, indicating that epigenetic variation results in both antigenic and functional variation. We observed a general association between heterochromatin marks and clonally variant expression, extending previous observations for specific genes to essentially all variantly expressed gene families. These results suggest that phenotypic variation of functionally unrelated P. falciparum gene families is mediated by a common mechanism based on reversible formation of H3K9me3-based heterochromatin. In changing environments, diversity confers fitness to a population. Our results support the idea that P. falciparum uses a bet-hedging strategy, as an alternative to directed transcriptional responses, to adapt to common fluctuations in its environment. Consistent with this idea, we found that transcriptionally different isogenic parasite lines markedly differed in their survival to heat-shock mimicking febrile episodes and adapted to periodic heat-shock with a pattern consistent with natural selection of pre-existing parasites.

Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum.

Epigenetic mechanisms are emerging as one of the major factors of the dynamics of gene expression in the human malaria parasite, Plasmodium falciparum. To elucidate the role of chromatin remodeling in transcriptional regulation associated with the progression of the P. falciparum intraerythrocytic development cycle (IDC), we mapped the temporal pattern of chromosomal association with histone H3 and H4 modifications using ChIP-on-chip. Here, we have generated a broad integrative epigenomic map of twelve histone modifications during the P. falciparum IDC including H4K5ac, H4K8ac, H4K12ac, H4K16ac, H3K9ac, H3K14ac, H3K56ac, H4K20me1, H4K20me3, H3K4me3, H3K79me3 and H4R3me2. While some modifications were found to be associated with the vast majority of the genome and their occupancy was constant, others showed more specific and highly dynamic distribution. Importantly, eight modifications displaying tight correlations with transcript levels showed differential affinity to distinct genomic regions with H4K8ac occupying predominantly promoter regions while others occurred at the 5' ends of coding sequences. The promoter occupancy of H4K8ac remained unchanged when ectopically inserted at a different locus, indicating the presence of specific DNA elements that recruit histone modifying enzymes regardless of their broad chromatin environment. In addition, we showed the presence of multivalent domains on the genome carrying more than one histone mark, highlighting the importance of combinatorial effects on transcription. Overall, our work portrays a substantial association between chromosomal locations of various epigenetic markers, transcriptional activity and global stage-specific transitions in the epigenome.

A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells.

Cerebral malaria is the most deadly manifestation of infection with Plasmodium falciparum. The pathology of cerebral malaria is characterized by the accumulation of infected erythrocytes (IEs) in the microvasculature of the brain caused by parasite adhesins on the surface of IEs binding to human receptors on microvascular endothelial cells. The parasite and host molecules involved in this interaction are unknown. We selected three P. falciparum strains (HB3, 3D7, and IT/FCR3) for binding to a human brain endothelial cell line (HBEC-5i). The whole transcriptome of isogenic pairs of selected and unselected parasites was analyzed using a variant surface antigen-supplemented microarray chip. After selection, the most highly and consistently up-regulated genes were a subset of group A-like var genes (HB3var3, 3D7_PFD0020c, ITvar7, and ITvar19) that showed 11- to >100-fold increased transcription levels. These var genes encode P. falciparum erythrocyte membrane protein (PfEMP)1 variants with distinct N-terminal domain types (domain cassette 8 or domain cassette 13). Antibodies to HB3var3 and PFD0020c recognized the surface of live IEs and blocked binding to HBEC-5i, thereby confirming the adhesive function of these variants. The clinical in vivo relevance of the HBEC-selected parasites was supported by significantly higher surface recognition of HBEC-selected parasites compared with unselected parasites by antibodies from young African children suffering cerebral malaria (Mann-Whitney test, P = 0.029) but not by antibodies from controls with uncomplicated malaria (Mann-Whitney test, P = 0.58). This work describes a binding phenotype for virulence-associated group A P. falciparum erythrocyte membrane protein 1 variants and identifies targets for interventions to treat or prevent cerebral malaria.

H2A.Z and H2B.Z double-variant nucleosomes define intergenic regions and dynamically occupy var gene promoters in the malaria parasite Plasmodium falciparum.

Histone variants are important components of eukaryotic chromatin and can alter chromatin structure to confer specialized functions. H2B variant histones are rare in nature but have evolved independently in the phyla Apicomplexa and Trypanasomatida. Here, we investigate the apicomplexan-specific Plasmodium falciparum histone variant Pf H2B.Z and show that within nucleosomes Pf H2B.Z dimerizes with the H2A variant Pf H2A.Z and that Pf H2B.Z and Pf H2A.Z occupancy correlates in the subset of genes examined. These double-variant nucleosomes also carry common markers of euchromatin like H3K4me3 and histone acetylation. Pf H2B.Z levels are elevated in intergenic regions across the genome, except in the var multigene family, where Pf H2A.Z/Pf H2B.Z double-variant nucleosomes are only enriched in the promoter of the single active var copy and this enrichment is developmentally regulated. Importantly, this pattern seems to be specific for var genes and does not apply to other heterochromatic gene families involved in red blood cell invasion which are also subject to clonal expression. Thus, Pf H2A.Z/Pf H2B.Z double-variant nucleosomes appear to have a highly specific function in the regulation of P. falciparum virulence.

3D Virtual Bronchoscopy as an Aid to Airway Management in a Patient with Anterior Mediastinal Mass.

ABSTRACT: Mediastinal masses pose one of the great challenges for any anesthesiologist during airway maintenance, underlining the need to devise a well-formulated plan to avoid perioperative complications. As a general rule, such patients are managed with spontaneous ventilation without the use of muscle relaxants and awake intubation. We report a case of a 66-year-old male with severe dyspnea, having a very large invasive anterior mediastinal mass, causing left lung collapse for urgent debulking surgery. The tracheobronchial compromise was ruled out using three-dimensional reconstruction on computed tomography imaging (virtual bronchoscopy) and that helped in using general anesthesia with muscle relaxation for subsequent endotracheal intubation and surgery.

Mitochondrial ß-oxidation regulates organellar integrity and is necessary for conidial germination and invasive growth in Magnaporthe oryzae.

Fatty acids stored as triglycerides, an important source of cellular energy, are catabolized through ß-oxidation pathways predicted to occur both in peroxisomes and mitochondria in filamentous fungi. Here, we characterize the function of Enoyl-CoA hydratase Ech1, a mitochondrial ß-oxidation enzyme, in the model phytopathogen Magnaporthe oryzae. Ech1 was found to be essential for conidial germination and viability of older hyphae. Unlike wild-type Magnaporthe, the ech1Δ failed to utilize C14 fatty acid and was partially impeded in growth on C16 and C18 fatty acids. Surprisingly, loss of ß-oxidation led to significantly altered mitochondrial morphology and integrity with ech1Δ showing predominantly vesicular/punctate mitochondria in contrast to the fused tubular network in wild-type Magnaporthe. The ech1Δ appressoria were aberrant and displayed reduced melanization. Importantly, we show that the significantly reduced ability of ech1Δ to penetrate the host and establish therein is a direct consequence of enhanced sensitivity of the mutant to oxidative stress, as the defects could be remarkably reversed through exogenous antioxidants. Overall, our comparative analyses reveal that peroxisomal lipid catabolism is essential for appressorial function of host penetration, whereas mitochondrial ß-oxidation primarily contributes to conidial viability and maintenance of redox homeostasis during host colonization by Magnaporthe.

Pioneering family physicians and the mechanisms for strengthening primary health care in India-A qualitative descriptive study.

India has one of the most unequal healthcare systems globally, lagging behind its economic development. Improved primary care and primary health care play an integral role in overcoming health disparities. Family medicine is a subset of primary care-delivered by family physicians, characterized by comprehensive, continuous, coordinated, collaborative, personal, family and community-oriented services-and may be able to fill these gaps. This research aims to understand the potential mechanisms by which family physicians can strengthen primary health care. In this qualitative descriptive study, we interviewed twenty family physicians, identified by purposeful and snowball sampling, who are among the first family physicians in India who received accredited certification in FM and were identified as pioneers of family medicine. We used the Contribution of Family Medicine to Strengthening Primary Health Care Framework to understand the potential mechanisms by which family medicine strengthens primary health care. Iterative inductive techniques were used for analysis. This research identifies multiple ways family physicians can strengthen primary health care in India. They are skilled primary care providers and support mid and low-level health care providers' ongoing training and capacity building. They develop relationships with specialists, ensure appropriate referral systems are in place, and, when necessary, work with governments and organizations to access the essential resources needed to deliver care. They motivate the workforce and change how care is delivered by ensuring providers' skills match the needs of communities and engage communities as partners in healthcare delivery. These findings highlight multiple mechanisms by which family physicians strengthen primary health care. Investments in postgraduate training in family medicine and integrating family physicians into the primary care sector, particularly the public sector, could address health disparities.

Shear Wave Elastography: A Reliable Secondary Parameter for Diagnosing Biliary Atresia in Infants With Neonatal Cholestasis.

Objective In this study, we aimed to optimize various grayscale, Doppler, and elastography parameters and evaluate their diagnostic performance in the preoperative diagnosis of biliary atresia (BA). Materials and methods A total of 158 infants aged <6 months with neonatal cholestasis (NC) were enrolled in the study and sonography was performed after four hours of fasting. For comparison of elastography, 31 exclusively age-matched controls, not suffering from liver disease, were included separately. Triangular cord and gallbladder (GB) parameters were considered as primary parameters, while right hepatic artery (RHA) caliber, RHA-to-right portal vein (RPV) ratio, hepatic subcapsular flow (HSF), and shear wave elastography (SWE) were considered as secondary parameters. Diagnosis of infants with BA was confirmed on histopathology. Data were presented as mean ±standard deviation (SD) and frequency. Differences between groups were compared using the Chi-square test and the unpaired student t-test. Receiver operating characteristic (ROC) curve analysis was done for individual ultrasound/Doppler/SWE parameters to calculate the optimal cutoff value. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for each parameter and their combinations. Results Of the primary parameters, GB contractility index (CI) and length showed the highest sensitivity and specificity respectively. A cutoff of 14 kPA was derived for SWE for the diagnosis of BA. Among secondary parameters, SWE had the best diagnostic performance, better than even the individual primary parameters. A combination of primary parameters with SWE in series showed the highest accuracy. Conclusion Among secondary parameters, elastography can prove to be highly useful. The highest accuracy in diagnosing BA can be obtained by combining primary parameters with SWE.

The emergence of family medicine in India-A qualitative descriptive study.

Countries globally are introducing family medicine to strengthen primary health care; however, for many, that process has been slow. Understanding the implementation of family medicine in a national context is complex but critical to uncovering what worked, the challenges faced, and how the process can be improved. This study explores how family medicine was implemented in India and how early cohort family physicians supported the field's emergence. In this qualitative descriptive study, we interviewed twenty family physicians who were among the first in India and recognized as pioneers. We used Rogers's Diffusion of Innovation Theory to describe and understand the roles of family physicians, as innovators and early adopters, in the process of implementation. Greenhalgh's Model of Diffusion in Service Organizations is applied to identify barriers and enablers to family medicine implementation. This research identifies multiple mechanisms by which pioneering family physicians supported the implementation of family medicine in India. They were innovators who developed the first family medicine training programs. They were early adopters willing to enter a new field and support spread as educators and mentors for future cohorts of family physicians. They were champions who developed professional organizations to bring together family physicians to learn from one another. They were advocates who pushed the medical community, governments, and policymakers to recognize family medicine's role in healthcare. Facilitators for implementation included the supportive environment of academic institutions and the development of family medicine professional organizations. Barriers to implementation included the lack of government support and awareness of the field by society, and tension with subspecialties. In India, the implementation of family medicine has primarily occurred through pioneering family physicians and supportive educational institutions. For family medicine to continue to grow and have the intended impacts on primary care, government and policymaker support are needed.

Histone deacetylases play a major role in the transcriptional regulation of the Plasmodium falciparum life cycle.

The apparent paucity of molecular factors of transcriptional control in the genomes of Plasmodium parasites raises many questions about the mechanisms of life cycle regulation in these malaria parasites. Epigenetic regulation has been suggested to play a major role in the stage specific gene expression during the Plasmodium life cycle. To address some of these questions, we analyzed global transcriptional responses of Plasmodium falciparum to a potent inhibitor of histone deacetylase activities (HDAC). The inhibitor apicidin induced profound transcriptional changes in multiple stages of the P. falciparum intraerythrocytic developmental cycle (IDC) that were characterized by rapid activation and repression of a large percentage of the genome. A major component of this response was induction of genes that are otherwise suppressed during that particular stage of the IDC or specific for the exo-erythrocytic stages. In the schizont stage, apicidin induced hyperacetylation of histone lysine residues H3K9, H4K8 and the tetra-acetyl H4 (H4Ac4) and demethylation of H3K4me3. Interestingly, we observed overlapping patterns of chromosomal distributions between H4K8Ac and H3K4me3 and between H3K9Ac and H4Ac4. There was a significant but partial association between the apicidin-induced gene expression and histone modifications, which included a number of stage specific transcription factors. Taken together, inhibition of HDAC activities leads to dramatic de-regulation of the IDC transcriptional cascade, which is a result of both disruption of histone modifications and up-regulation of stage specific transcription factors. These findings suggest an important role of histone modification and chromatin remodeling in transcriptional regulation of the Plasmodium life cycle. This also emphasizes the potential of P. falciparum HDACs as drug targets for malaria chemotherapy.

Late presentation of lane-hamilton syndrome in a 33 year old female: A case report.

Lane-Hamilton syndrome (LHS) is a rare syndromic association between idiopathic pulmonary hemosiderosis and celiac disease (CD). It is usually seen in children below 15 years of age. It can occasionally be seen in adults. We present the case of a 33-year-old female patient who presented with recurrent episodes of hemoptysis to the pulmonary outpatient department. She also gave a history of having frequent loose stools. She was admitted and investigated thoroughly and was found to be suffering from LHS which is a rare disease. High-resolution computed tomography (HRCT) of the chest and duodenal biopsy helped in concluding the diagnosis. She was started on gluten-free diet (GFD) and has responded well with no episodes of hemoptysis on 9-month follow-up and is in good general condition. This case highlights the importance of keeping a high index of suspicion of LHS in a young patient presenting with unexplained hemoptysis and diarrhea. In a known case of CD presenting with hemoptysis, a HRCT chest aids in the diagnosis of LHS. A GFD is the mainstay of long-term treatment, and adherence to this diet shows remarkable improvement in the symptoms of the patient and their overall general condition.

Primary care for the urban poor in India during the pandemic: Uninterrupted management of non-communicable diseases and home-based care of patients with COVID-19 infection.

Problem: The two waves of COVID-19 severely affected the healthcare system in India. The government responded to the first wave with a strict nationwide lockdown which disrupted primary care, including the management of non-communicable diseases (NCDs). The second wave overwhelmed healthcare facilities leading to inadequate access to hospital services. Collectively, these issues required urgent responses, including the adaptation of primary care. Approach: The Low-Cost Effective Care Unit (LCECU) of Christian Medical College, Vellore (CMC) has a network of community volunteers, community health workers, an outreach nurse, social workers and doctors who operate clinics in six poorer areas of Vellore. The network adapted quickly, responding to the lockdown during the first wave and ensuring ongoing primary care for patients with non-communicable diseases. During the second wave, the team developed a system in collaboration with other CMC departments to provide home-based care for patients with COVID-19. Local setting: The LCECU is a 48-bed unit of the Department of Family Medicine, part of the 3,000-bed CMC. It originated in 1982, aiming to care for the poor populations of Vellore town. It has been actively working among urban communities since 2002, with a focus on delivering Community Oriented Primary Care (COPC), for six poor urban communities since 2016. Relevant changes: During the first wave of COVID the LCECU team ensured patients with NCDs had uninterrupted primary care and medications by visiting them in their homes. The team also addressed food insecurity by organizing a daily lunch service for 600 people for over 2 months. In the second wave, the team responded to community needs by organizing and delivering home-based care to monitor patients affected by COVID-19. Lessons learned: The COVID-19 pandemic raises many questions about the preparedness of health systems for disasters that disproportionately affect marginalized populations globally. COVID-19 is only one of the many potential disasters, including non-communicable diseases, mental health problems, pollution, climate change, and lifestyle illness. There is an urgent need to study models of care that support vulnerable communities in an accessible, cost-effective, and patient-oriented way, particularly in low- and middle-income countries. This paper outlines lessons on how the LCECU team addressed disaster management:1. The COVID-19 pandemic has highlighted the importance of primary care-based rapid response interventions in disaster management.2. The LCECU model demonstrated the effectiveness of a primary care intervention based on pre-existing networks and familiarity between primary care teams and the community.3. Establishing community-based health care via interdisciplinary teams, including community health workers, community volunteers, outreach nurses, and doctors, is key.4. Addressing other social determinants of health, such as food insecurity, is an important component of care delivery.

The Utility of Biliary Manometry in Assessing Early Catheter Removal After Percutaneous Balloon Dilatation of Hepaticojejunostomy Strictures.

Background and objective Percutaneous balloon dilatation followed by long-term internal-external biliary catheter (IEBC) placement is the standard radiological management for postoperative hepaticojejunostomy (HJ) strictures. The treatment is considered successful when cholangiography shows a free flow of contrast across the anastomosis and the patient passes a "clinical test". However, these tests may not be suitable predictors of long-term successful treatment outcomes. The purpose of this study was to assess the utility of biliary manometry in the evaluation of successful treatment outcomes after HJ stricture dilatation and IEBC placement and its efficacy as a tool for early catheter removal. Patients and methods A total of 14 patients underwent percutaneous balloon dilatation of HJ strictures with IEBC placement. A two-to-three-month interval was maintained between sessions of exchanging or upsizing IEBCs. Biliary manometry was performed after a mean duration of 6.3 months. Intra-biliary pressure of <15 mmHg was considered as the success threshold. Results Among the 14 patients, 11 patients passed initial manometry and had their IEBCs removed and were followed up for a mean duration of 47.8 months. Of these, one patient developed biliary obstruction after six months and underwent repeat HJ stricture dilatation and long-term IEBC placement. Three patients failed manometry and underwent re-dilatation of HJ strictures with IEBC placement. Using Kaplan-Meier survival analysis, the probability of patients remaining stricture-free after HJ stricture dilatation was found to be 100% at three months and 91% at six, 12, 18, 24, 36, and 47.8 months. Conclusion Biliary manometry prevents subjective variations in determining treatment endpoints and helps to assess early catheter removal after percutaneous balloon dilatation of HJ strictures.

Design of a variant surface antigen-supplemented microarray chip for whole transcriptome analysis of multiple Plasmodium falciparum cytoadherent strains, and identification of strain-transcendent rif and stevor genes.

BACKGROUND: The cytoadherence of Plasmodium falciparum is thought to be mediated by variant surface antigens (VSA), encoded by var, rif, stevor and pfmc-2tm genes. The last three families have rarely been studied in the context of cytoadherence. As most VSA genes are unique, the variability among sequences has impeded the functional study of VSA across different P. falciparum strains. However, many P. falciparum genomes have recently been sequenced, allowing the development of specific microarray probes for each VSA gene. METHODS: All VSA sequences from the HB3, Dd2 and IT/FCR3 genomes were extracted using HMMer software. Oligonucleotide probes were designed with OligoRankPick and added to the 3D7-based microarray chip. As a proof of concept, IT/R29 parasites were selected for and against rosette formation and the transcriptomes of isogenic rosetting and non-rosetting parasites were compared by microarray. RESULTS: From each parasite strain 50-56 var genes, 125-132 rif genes, 26-33 stevor genes and 3-8 pfmc-2tm genes were identified. Bioinformatic analysis of the new VSA sequences showed that 13 rif genes and five stevor genes were well-conserved across at least three strains (83-100% amino acid identity). The ability of the VSA-supplemented microarray chip to detect cytoadherence-related genes was assessed using P. falciparum clone IT/R29, in which rosetting is known to be mediated by PfEMP1 encoded by ITvar9. Whole transcriptome analysis showed that the most highly up-regulated gene in rosetting parasites was ITvar9 (19 to 429-fold up-regulated over six time points). Only one rif gene (IT4rifA_042) was up-regulated by more than four fold (five fold at 12 hours post-invasion), and no stevor or pfmc-2tm genes were up-regulated by more than two fold. 377 non-VSA genes were differentially expressed by three fold or more in rosetting parasites, although none was as markedly or consistently up-regulated as ITvar9. CONCLUSIONS: Probes for the VSA of newly sequenced P. falciparum strains can be added to the 3D7-based microarray chip, allowing the analysis of the entire transcriptome of multiple strains. For the rosetting clone IT/R29, the striking transcriptional upregulation of ITvar9 was confirmed, and the data did not support the involvement of other VSA families in rosette formation.

Systematic reporting of computed tomography enterography/enteroclysis as an aid to reduce diagnostic dilemma when differentiating between intestinal tuberculosis and Crohn's disease: A prospective study at a tertiary care hospital.

BACKGROUND AND AIM: Crohn's disease (CD) and intestinal tuberculosis (ITB) have similar symptomatology and overlapping features on imaging, endoscopy, and histopathology. It is important to differentiate ITB from CD to initiate correct medical management. This prospective study aimed to characterize imaging features on computed tomography enteroclysis/enterography (CTE) that help in differentiating ITB from CD. METHODS: A total of 300 consecutive patients who underwent CTE with the suspicion of small bowel diseases were evaluated. CTE findings were documented on a detailed "CTE case record form" and were correlated with other investigations like endoscopy, histopathological and microbiological examination, and improvement on empirical therapy to arrive at a final diagnosis. Only confirmed cases of ITB/CD were included for further analysis. RESULTS: Final diagnoses revealed that 61 patients had ITB, 24 had CD, 90 patients had a final diagnosis not related to ITB/CD, and 125 had no bowel-related diseases. The sensitivity of CTE (ITB vs CD, 90.2 vs 91.6%) was higher than the sensitivity of ileocolonoscopy (ITB vs CD, 87 vs 83.3%). A homogenous pattern of bowel wall thickening and confluent bowel involvement were significantly more common in ITB. Stratified bowel wall thickening with mucosal hyperenhancement, skip lesions in the bowel, and a comb sign were significantly more common in CD. Stratified bowel wall enhancement with an intervening layer of fat was specifically (P < 0.001) seen in patients with CD, and necrotic (P = 0.002) and calcified (P = 0.055) lymph nodes were specifically seen in patients with ITB. CONCLUSION: We propose a systematic approach to the radiological differentiation of ITB from CD.

Inter-Variability Study of COVLIAS 1.0: Hybrid Deep Learning Models for COVID-19 Lung Segmentation in Computed Tomography.

Background: For COVID-19 lung severity, segmentation of lungs on computed tomography (CT) is the first crucial step. Current deep learning (DL)-based Artificial Intelligence (AI) models have a bias in the training stage of segmentation because only one set of ground truth (GT) annotations are evaluated. We propose a robust and stable inter-variability analysis of CT lung segmentation in COVID-19 to avoid the effect of bias. Methodology: The proposed inter-variability study consists of two GT tracers for lung segmentation on chest CT. Three AI models, PSP Net, VGG-SegNet, and ResNet-SegNet, were trained using GT annotations. We hypothesized that if AI models are trained on the GT tracings from multiple experience levels, and if the AI performance on the test data between these AI models is within the 5% range, one can consider such an AI model robust and unbiased. The K5 protocol (training to testing: 80%:20%) was adapted. Ten kinds of metrics were used for performance evaluation. Results: The database consisted of 5000 CT chest images from 72 COVID-19-infected patients. By computing the coefficient of correlations (CC) between the output of the two AI models trained corresponding to the two GT tracers, computing their differences in their CC, and repeating the process for all three AI-models, we show the differences as 0%, 0.51%, and 2.04% (all < 5%), thereby validating the hypothesis. The performance was comparable; however, it had the following order: ResNet-SegNet > PSP Net > VGG-SegNet. Conclusions: The AI models were clinically robust and stable during the inter-variability analysis on the CT lung segmentation on COVID-19 patients.