FDG PET in Neurological Manifestations of COVID-19.

ABSTRACT: Both the central and peripheral nervous systems can be affected in COVID-19. Although MRI is the primary investigative tool for neurological imaging, FDG PET may show additional areas of involvement in the brain in the form of regional hypometabolism or hypermetabolism, secondary to synaptic dysfunction and electrical or glial activation. We present a case series of 4 patients who had neurological symptoms attributable to COVID-19 infection with abnormalities in the brain FDG PET scan.

Disseminated multiloculated peritoneal inclusion cysts: Bubble trouble in belly.

ABSTRACT: Multiloculated peritoneal inclusion cysts, usually arise from peritoneal mesothelium lining the serous cavity of the abdomen, pelvis and retroperitoneum. These lesions can be incidentally found on imaging or during surgery, and confirmation of the diagnosis is done by radiological imaging, histomorphology and immunohistochemical findings. Although fewer than 200 cases of solitary peritoneal inclusion cysts have been reported, their occurrence in a disseminated fashion has hardly ever been described in literature. Herein, we report a case of multiloculated peritoneal inclusion cysts that involved the whole abdominal and pelvic cavity and were successfully treated with surgery.

Multilocular cystic nephroma in an adult: a diagnostic quandary.

Multilocular cystic nephroma (MLCN) is an unusual, benign slow-growing renal cystic neoplasm which mimics other cystic renal lesions and has such clinical, radiological, and morphological features that causes diagnostic dilemma. MLCN lies in the spectrum of mixed epithelial and stromal tumor (MEST) family of kidney. According to World Health Organization (WHO 2016 classification), MEST encompasses spectrum of tumors ranging from predominantly cystic tumors, adult cystic nephroma (ACN) to tumors that are variably solid (MEST), thus creating diagnostic dilemma. Moreover, it has several benign and malignant differentials due to its several overlapping histomorphological features which when not cautiously dealt with may result in misdiagnosing it as malignant lesion. We hereby present a case of a woman in late twenties who presented with left flank swelling and pain since 6 months which was misdiagnosed as renal cell carcinoma on radiology which turned out to be ACN on histology and further verified on immunohistochemistry.

A Look Into the Future: Are We Ready for an Approved Therapy in Celiac Disease?

As it appears that we are currently at the cusp of an era in which drugs that are new, re-purposed, or "supplements" will be introduced to the management of celiac disease, we need to reflect on whether the framework is set for celiac disease to be treated increasingly with pharmaceuticals as well as diet. This refers to reflecting on the rigor of current diagnostic practices; the limitations of the current standard of care, which is a gluten-free diet; and that we lack objective markers of disease severity. Investigating these issues will help us to identify gaps in technology and practices that could be critical for selecting patients with a well-defined need for an improved or alternative treatment. Both aspects, circumscribed limitations of the gluten-free diet and diagnostics helping to define celiac disease target groups, together with the guiding requirements by the responsible regulatory authorities, will contribute to defining the subgroups of patients with confirmed celiac disease eligible for distinct pharmacologic strategies. Because many patients with celiac disease are diagnosed in childhood, these aspects need to be differentially discussed for the pediatric setting. In this perspective, we aimed to describe these contextual issues and then looked ahead to the future. What might be the major challenges in celiac disease clinics in the coming years once drugs are an option alongside diet? And what will be the future objectives for researchers who further decipher the mucosal immunology of celiac disease? Speculating on the answers to these questions is as stimulating as it is fascinating to be part of this turning point.

Standardizing Randomized Controlled Trials in Celiac Disease: An International Multidisciplinary Appropriateness Study.

BACKGROUND & AIMS: There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. METHODS: A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale. RESULTS: For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal-sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points. CONCLUSIONS: We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.

Incidental Identification of Osteoid Osteoma of Skull Bone on 68 Ga-PSMA PET/CT.

ABSTRACT: An osteoid osteoma (OO) is a benign bone neoplasm, characterized by significant nocturnal pain that usually responds to nonsteroidal anti-inflammatory drugs. It occurs most commonly in the lower extremities and vertebrae. Here, we present a case of carcinoma prostate, who was referred to our department for 68 Ga-PSMA PET/CT scan, and we incidentally found out PSMA-avid OO involving frontal bone of skull, which is a rare finding. To the best of our knowledge, this is the second case in which high PSMA uptake is found in the OO, suggesting a possible PSMA expression related to osteoblastic activity.

A Clinician's Guide to Gluten Challenge.

Gluten challenge is an essential clinical tool that involves reintroducing or increasing the amount of gluten in the diet to facilitate diagnostic testing in celiac disease (CD). Nevertheless, there is no consensus regarding the applications of gluten timing, dosing, and duration in children. This review aims to summarize the current evidence, discuss practical considerations, and proposes a clinical algorithm to help guide testing in pediatric patients. Childhood development, social circumstances, and long-term health concerns must be considered when identifying a candidate for gluten challenge. Based on previous studies, the authors suggest baseline serology followed by a minimum of 3-6 grams of gluten per day for over 12 weeks to optimize diagnostic accuracy for evaluation of CD. A formal provider check-in at 4-6 weeks is essential so the provider and family can adjust dosing or duration as needed. Increasing the dose of gluten further may improve diagnostic yield if tolerated, although in select cases a lower dose and shorter course (6-12 weeks) may be sufficient. There is consensus that mild elevations in celiac serology (<10 times the upper limit of normal) or symptoms, while supportive are not diagnostic for CD. Current North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend histologic findings of intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy as the accurate and most appropriate endpoint for gluten challenge.

Are non-lactose-fermenting Escherichia coli important diarrhoeal pathogens in children and adults?

Introduction: Diarrhoeagenic Escherichia coli (DEC) remains one of the major causes of acute diarrhoea episodes in developing countries. The percentage of acute diarrhoea cases caused by DEC is 30-40 % in these countries. Approximately 10% of E. coli isolates obtained from stool specimens have been reported to be non-lactose-fermenting (NLF). The available literature is sparse regarding the pathogenicity of NLF E. coli causing infectious diarrhoea. Aim: We aimed to elucidate the importance of NLF E. coli in causing diarrhoea in both adults and children by detecting various DEC pathotypes among NLF E. coli in stool samples taken from gastroenteritis cases. Material and Methods: A total of 376 NLF E. coli isolates from 3110 stool samples from diarrhoea/gastroenteritis patients were included in the study. Up to three NLF colonies that were not confirmed as Vibrio cholerae , Aeromonas spp., Salmonella spp. or Shigella spp., but were identified as E. coli using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), were carefully picked up from each MacConkey agar plate and then meticulously streaked onto freshly prepared, sterilized nutrient agar plates, and biochemical reactions were conducted. Multiplex PCR was conducted for the EAEC, EPEC, ETEC and EHEC pathotypes and PCR for the ipaH gene was conducted for EIEC. The disc diffusion method was used for antibiotic sensitivity testing. Results: Using multiplex PCR and ipaH PCR, a total of 63 pathotypes of DEC were obtained, with EAEC being the most predominant (n=31) followed by EIEC (n=22), EPEC (n=8) and ETEC (n=2). To further differentiate EIEC from Shigella , additional biochemical tests were performed, including acetate utilization, mucate and salicin fermentation, and aesculin hydrolysis. Antimicrobial susceptibility testing (AST) showed that maximum resistance was seen against ciprofloxacin (82.5 %) followed by ampicillin (77.8 %) and cotrimoxazole (68.2 %), and minimum resistance was seen against ertapenem (4.8 %). Conclusion: In our study two pathotypes (EAEC, EIEC) were predominant among NLF E. coli and these were not only important aetiological agents in children, but also in adults. Our study also sheds light on the epidemiology of EIEC, which is one of the most neglected DEC pathotypes, as hardly any microbiological laboratories process NLF E. coli for EIEC.

Transient Suppression of Bacterial Populations Associated with Gut Health is Critical in Success of Exclusive Enteral Nutrition for Children with Crohn's Disease.

BACKGROUND AND AIMS: Exclusive enteral nutrition [EEN] is a dietary intervention to induce clinical remission in children with active luminal Crohn's disease [CD]. While changes in the gut microbial communities have been implicated in achieving this remission, a precise understanding of the role of microbial ecology in the restoration of gut homeostasis is lacking. METHODS: Here we reconstructed genomes from the gut metagenomes of 12 paediatric subjects who were sampled before, during and after EEN. We then classified each microbial population into distinct 'phenotypes' or patterns of response based on changes in their relative abundances throughout the therapy on a per-individual basis. RESULTS: Our data show that children achieving clinical remission during therapy were enriched with microbial populations that were either suppressed or that demonstrated a transient bloom as a function of EEN. In contrast, this ecosystem-level response was not observed in cases of EEN failure. Further analysis revealed that populations that were suppressed during EEN were significantly more prevalent in healthy children and adults across the globe compared with those that bloomed ephemerally during the therapy. CONCLUSIONS: These observations taken together suggest that successful outcomes of EEN are marked by a temporary emergence of microbial populations that are rare in healthy individuals, and a concomitant reduction in microbes that are commonly associated with gut homeostasis. Our work is a first attempt to highlight individual-specific, complex environmental factors that influence microbial response in EEN. This model offers a novel, alternative viewpoint to traditional taxonomic strategies used to characterize associations with health and disease states.

Isolated Urinary Bladder Metastasis in Renal Cell Carcinoma Detected on 18F-FDG PET/CT Scan.

ABSTRACT: Renal cell carcinoma (RCC) is an aggressive carcinoma with hematogenous spread commonly to lungs, liver, and bones. However, few cases of isolated urinary bladder metastasis have also been reported. Here we report a case of 63-year-old man, a known case of left RCC (clear cell type), post left nephrectomy, who was on regular clinicoradiological follow-up. He presented with complaints of painless hematuria; on further evaluation, 18F-FDG PET/CT revealed few FDG-avid intramural nodular lesions along the walls of urinary bladder. He underwent TURBT, and the tissue was sent for histopathological examination, which was diagnostic of metastatic RCC.

The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position on the Role of the Registered Dietitian Nutritionist in the Care of the Pediatric Patient With Chronic Gastrointestinal Diseases.

The optimization of nutrition is essential for the growth and development of all children, including those with gastrointestinal (GI) conditions that can variably affect nutrient intake, absorption, or metabolism. Registered Dietitian Nutritionists (RDNs) are essential partners in delivering high quality care for pediatric GI disorders, but limited evidence is available to support the role of the RDN in the care of these patients. This position paper outlines the evidence supporting the role of the RDN in the management of chronic pediatric GI issues in both inpatient and outpatient settings. Gaps in the literature, opportunities for future research, and barriers to RDN access are discussed.

Primary Renal Well-Differentiated Neuroendocrine Tumors: Analyis of Six Cases from a Tertiary Care Center in North India with Review of Literature.

Well-differentiated renal neuroendocrine tumors are rare tumors. As their biologic behavior is not fully known, there is a need to know more about these cases. We performed a retrospective chart review of all the cases diagnosed with renal neuroendocrine tumors from January 2016 to December 2020 (five years) in order to understand their clinical features, morphological characteristics and outcome. We included six cases with mean age of 46.2 years (4 males) in our study. All patients underwent radical nephrectomy. Histologically all showed tumor disposed in nests and trabeculae and majority of the tumors belonged to well-differentiated neuroendocrine tumor Grade 1 (WHO criteria of gastoroenteropancreatic neuroendocrine neoplasms). Lymph node metastasis was seen in two cases at the time of clinical presentation. All the tumors were diffusely positive for neuroendocrine tumor markers (synaptophysin, chromogranin, NSE, CD56). Follow-up data was available in all cases with an average follow-up of two years and neither has shown evidence of metastasis or relapse till last follow-up. Role of morphological patterns and immunohistochemical markers is highlighted with the importance of including Ki-67 index in grading them to better understand their outcome.

Histopathological spectrum of duodenal polyps in a retrospective ten-year study.

INTRODUCTION AND AIMS:  Duodenal polyps are rare in patients undergoing upper gastrointestinal endoscopy. The present study is an experience of the histopathological spectrum of the duodenal polyps and its correlation with the clinical and endoscopic findings in a tertiary care centre. MATERIALS AND METHODS: The present study is a 10-year retrospective study from the year 2011 to 2020. All the relevant clinical, endoscopic and radiologic findings were retrieved from the hospital medical records. Old histopathology slides were restained, and wherever required, special stains and immunohistochemistry (IHC) were performed. All the cases were reviewed. The present study mainly included descriptive statistics with categorical and continuous variables. RESULTS: Total 81 cases of duodenal polyps were studied in the period of 10 years. The median age was 48 years. Male: female ratio was 2.2:1. The most common presenting system was abdominal pain. We experienced both solitary and multiple polyps. The majority of the duodenal polyps were non-neoplastic, with unremarkable mucosa or inflammatory type. Unlike previous studies the most common site for the hyperplastic polyp in the present study was the first part of the duodenum. Among the neoplastic polyps, adenomatous polyp was the most common type. Contrary to the previous studies, our study showed the first part of the duodenum as the most common site for the sporadic nonampullary adenomatous duodenal polyps. Of the rare entities, we encountered a single case each of lipomatous polyp and gangliocytic paraganglioma. Among the syndromes we encountered two cases of Peutz-Jeghers syndrome and one case of familial adenomatous polyp in our study population.CONCLUSION Duodenal polyps are a rare finding on endoscopic examinations, though most of them are non-neoplastic in nature, vigilant examination under the microcope is required to rule out any neoplastic pathology and identify the risk of malignancy.

18F-FDG PET/CT and 99mTc-TRODAT Scan Findings in the Variants of Progressive Supranuclear Palsy and Correlation With Clinical Findings.

Aim: The aim of this study is to elucidate the patterns of characteristic hypometabolism on 18F-Fluoro Deoxy-glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) in the variants of Progressive supranuclear palsy (PSP) and its correlation with their core clinical features. Material and Methods: A retrospective analysis of 88 subjects with clinically suspected PSP was done. An institutional informed consent to participate in the study was taken from all the subjects. All the subjects had undergone a prior 99mTechnetium labeled Tropane derivative of dopamine transporter Single Photon Emission Computed Tomography (99mTc TRODAT-1 SPECT) study and had abnormal scans to confirm degenerative parkinsonism. The subjects were clinically examined by the neurologists using the Progressive Supranuclear Palsy Rating Scale proposed by the Movement Disorder Society and were further clinically segregated into eight subtypes. All the included subjects further underwent a detailed clinical analysis to obtain their individual Schwab and England activities of daily living scale and Modified Hoehn and Yahr staging by a neurologist. All the subjects underwent 18F-FDG PET/CT scan after adequate preparation. The scans were analyzed both qualitatively (visually) and quantitatively using Statistical Parametric Mapping. Results: The frontal, limbic, and sensorimotor cortices represented the common areas of hypometabolism among all the subtypes of PSP. The subcortical regions showing the most significant hypometabolism were the thalami, mid-brain, nucleus accumbens, caudate, globus pallidus, and putamen in descending order. Multiple cortical and subcortical regions of hypometabolism were identified in different subtypes of PSP. Conclusion: The characteristic patterns of hypometabolism observed in the different subgroups were more apparent on quantification and based on visual analysis alone, it may not be possible to differentiate the different subtypes of PSP. A good correlation was seen between some of the core clinical features and hypometabolic clusters.

Post-CMV Organizing Pneumonia - An Unusual Presentation 10 years after Kidney Transplantation.

A 45-year-old gentleman underwent kidney transplantation in March 2010. He remained apparently healthy for the next 10 years when he developed anorexia and weight loss. Diagnostic workup revealed cytomegalovirus (CMV) pneumonia. While viremia resolved within 3 weeks of initiation of valganciclovir, he developed progressive breathlessness and hypoxia on exertion. Imaging of thorax revealed central peri-bronchovascular consolidation and fine reticulations with peripheral sparing. Computed tomography (CT)-guided percutaneous lung biopsy revealed organizing intra-alveolar exudates, suggestive of organizing pneumonia, with no evidence of active infection on biopsy as well as bronchoalveolar lavage (BAL) cytology. This atypical pattern of central distribution of opacities is not typical of organizing pneumonia where peripheral subpleural distribution is more common. Patient responded dramatically following escalation of steroids, with complete resolution of infiltrates on follow-up imaging.

Obstacles for T-lymphocytes in the tumour microenvironment: Therapeutic challenges, advances and opportunities beyond immune checkpoint.

The tumour microenvironment (TME) imposes a major obstacle to infiltrating T-lymphocytes and suppresses their function. Several immune checkpoint proteins that interfere with ligand/receptor interactions and impede T-cell anti-tumour responses have been identified. Immunotherapies that block immune checkpoints have revolutionized the treatment paradigm for many patients with advanced-stage tumours. However, metabolic constraints and soluble factors that exist within the TME exacerbate the functional exhaustion of tumour-infiltrating T-cells. Here we review these multifactorial constraints and mechanisms - elevated immunosuppressive metabolites and enzymes, nutrient insufficiency, hypoxia, increased acidity, immense amounts of extracellular ATP and adenosine, dysregulated bioenergetic and purinergic signalling, and ionic imbalance - that operate in the TME and collectively suppress T-cell function. We discuss how scientific advances could help overcome the complex TME obstacles for tumour-infiltrating T-lymphocytes, aiming to stimulate further research for developing new therapeutic strategies by harnessing the full potential of the immune system in combating cancer.

Lewy Body Dementia Associated with Anti-IgLON 5 Encephalitis Detected on 18F Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography and 99mTc-TRODAT Single-Photon Emission Computed Tomography/Computed Tomography.

We present a case of Anti-IgLON 5 encephalitis with Lewy body dementia. 18F fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan and 99 mTc-TRODAT-1 SPECT/CT scan were done. 99 mTc-TRODAT-1 scan findings revealed severely reduced concentration of dopamine transporter in bilateral basal ganglia, suggestive of a degenerative parkinsonian disorder. 18F-FDG PET scan findings were suggestive of moderate-to-severe hypometabolism in the bilateral parieto-temporal and bilateral occipital cortices including the primary visual cortices, supporting Lewy body spectrum disease with associated hypermetabolism in the bilateral sensorimotor cortices, bilateral basal ganglia, thalami, brain stem, and bilateral cerebellar hemispheres suggestive of inflammatory pathology.

The prevalence and clinical characteristics of anti-HMGCR (anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) antibodies in idiopathic inflammatory myopathy: an analysis from the MyoCite registry.

This study aimed to determine the prevalence and clinical characteristics of anti-HMGCR antibodies in idiopathic inflammatory myositis (IIM) at a tertiary care centre in northern India. Data (adult and children) were retrieved from the MyoCite dataset, identifying patients with polymyositis, dermatomyositis, and antibody-negative IIM whilst fulfilling the ACR/EULAR criteria. SLE, sarcoidosis, and systemic sclerosis were included for comparison as disease controls. The baseline clinical profile, laboratory tests, and muscle biopsies were retrieved and analysed. Descriptive statistics and non-parametric statistics were used for comparison. Among 128 IIM (112 adults, 16 children, M:F 1:2.8) of age 37 (24-47) years and 6 (3-17) months disease duration, 4 (3.6%) young adults tested positive for anti-HMGCR antibodies. All children and disease control tested negative for the antibody. Anti-HMGCR + IIM exhibited higher muscle enzymes [AST (367 vs 104 IU/L, p = 0.045), ALT (502 vs 78 IU/L, p = 0.004), and CPK (12,242 vs 699 IU/L, p = 0.001] except lactate dehydrogenase with less frequent systemic features such as fatigue than antibody-negative IIM. One young girl presented with a Limb-girdle muscular dystrophy (LGMD) with chronic pattern. None of the patients exhibited rashes, statin exposure, or cancer, though one had anti-Ro52 and mild disease. Our observations depict a younger population while affirming previous literature, including NM-like presentation, and chronic LGMD-like pattern of weakness in one case. Although a small number of children were included, ours is one of the few paediatric studies that evaluated HMGCR antibodies thus far. Further investigations in a larger Indian cohort are warranted to substantiate our findings.