Diffuse Gastric Ganglioneuromatosis: Novel Presentation of PTEN

Gastrointestinal ganglioneuromatous proliferations are rare, most often found in the colon, and are three types: polypoid ganglioneuromas, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. We present a case of diffuse ganglioneuromatosis in the posterior gastric wall in a nine-year-old female. To our knowledge, this is the first reported case of diffuse ganglioneuromatosis located in the stomach. Only six cases of gastric ganglioneuromatous proliferations have previously been reported, two in English and none were diffuse ganglioneuromatosis. A diagnosis of diffuse ganglioneuromatosis is relevant for patient care because, unlike sporadic polypoid ganglioneuromas or ganglioneuromatous polyposis, most are syndromic. Diffuse ganglioneuromatosis is commonly associated with neurofibromatosis type 1, multiple endocrine neoplasia type 2b, and Cowden Syndrome, one of the phenotypes of PTEN hamartoma tumor syndrome. The patient had the noted gastric diffuse ganglioneuromatosis, as well as other major and minor criteria for Cowden syndrome. Genetic testing revealed a novel frameshift mutation in the PTEN gene in the patient, her father, paternal aunt, and the aunt’s son who is a paternal first cousin of the patient

Gallbladder Metastases: A Report of Two Cases

Introduction: Metastasis to the gallbladder is not common and usually manifests an advanced stage of malignancy. Herein, we report a case of triple negative high grade invasive ductal carcinoma of breast with a metastatic lesion to the gallbladder. Case Presentation: The patient is a 52-year-old female diagnosed with invasive ductal carcinoma treated with mastectomy and chemotherapy. After 12 months, she presented to the emergency department with right upper quadrant pain and elevated liver chemistries. Abdominal enhanced computed tomography showed periportal and gallbladder wall edema. After cholecystectomy, the resected gallbladder was histologically considered to be a metastatic lesion arising from the primary lung cancer. The second case describes a case of a 77-year-old woman with multiple co-morbidities who presented to the hospital with sepsis secondary to biliary source. Abdominal enhanced computed tomography findings were concerning for acute cholecystitis. After cholecystectomy, the pathology of the resected gallbladder demonstrated cholecystitis and plasmacytoma. Conclusion: The atypical presentation of gallbladder metastases could mislead treating providers. The diagnosis might alter management decisions and prognosis

Tuberculous Enteritis Presenting as Acute Appendicitis and Perirectal Abscess

Mycobacterium tuberculosis has a wide variety of presentations. A rare occurrence is gastrointestinal tuberculosis. It may occur anywhere along the alimentary canal but usually occurs in the ileocecum with rare involvement of the appendix

Noncanonical NF-κB Signaling Upregulation in Inflammatory Bowel Disease Patients is Associated With Loss of Response to Anti-TNF Agents

Objectives: Targeting tumor necrosis factor (TNF) with biologic agents, such as infliximab and adalimumab, is a widely used and effective therapeutic strategy in inflammatory bowel disease (IBD). Unfortunately, a significant number of patients fail to respond or lose response over time to these agents. Previous studies have defined multiple complex roles for canonical NF-κB signaling in the pathogenesis of IBD. However, preliminary evidence suggests that the lesser defined noncanonical NF-κB signaling pathway also contributes to disease pathogenesis and response to anti-TNF agents. The objective of this study was to evaluate this hypothesis in Crohn’s disease (CD) and ulcerative colitis (UC) patients.Design: A total of 27 subjects with IBD (19 with CD and 8 with UC) and 15 control subjects were tested. Clinical criteria, patient history, and endoscopic disease activity were factors used to categorize patients and define therapeutic response. Biopsy specimens were collected during colonoscopy and expression was determined for 88 target genes known to be associated with noncanonical NF-κB signaling and IBD.Results: Noncanonical NF-κB signaling was significantly upregulated in IBD patients and was associated with increased gastrointestinal inflammation, epithelial cell death, lymphocyte migration, and Nod-like receptor signaling. Furthermore, noncanonical NF-κB signaling was further upregulated in patients unresponsive to anti-TNF agents and was suppressed in responsive patients. MAP3K14, NFKB2, CCL19, CXCL12, and CXCL13 were significantly dysregulated, as were genes that encode pathway regulators, such as CYLD, NLRP12, and BIRC2/3.Conclusion: Our study identifies a previously uncharacterized role for the understudied noncanonical NF-κB signaling pathway in the pathogenesis of IBD and anti-TNF therapy responsiveness. The genes and pathways identified may ultimately prove useful in IBD management and could potentially be used as biomarkers of drug response

Epidural Interventions in the Management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) Comprehensive Evidence-Based Guidelines.

BACKGROUND: Chronic spinal pain is the most prevalent chronic disease with employment of multiple modes of interventional techniques including epidural interventions. Multiple randomized controlled trials (RCTs), observational studies, systematic reviews, and guidelines have been published. The recent review of the utilization patterns and expenditures show that there has been a decline in utilization of epidural injections with decrease in inflation adjusted costs from 2009 to 2018. The American Society of Interventional Pain Physicians (ASIPP) published guidelines for interventional techniques in 2013, and guidelines for facet joint interventions in 2020. Consequently, these guidelines have been prepared to update previously existing guidelines. OBJECTIVE: To provide evidence-based guidance in performing therapeutic epidural procedures, including caudal, interlaminar in lumbar, cervical, and thoracic spinal regions, transforaminal in lumbar spine, and percutaneous adhesiolysis in the lumbar spine. METHODS: The methodology utilized included the development of objective and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of epidural interventions was viewed with best evidence synthesis of available literature and recommendations were provided. RESULTS: In preparation of the guidelines, extensive literature review was performed. In addition to review of multiple manuscripts in reference to utilization, expenditures, anatomical and pathophysiological considerations, pharmacological and harmful effects of drugs and procedures, for evidence synthesis we have included 47 systematic reviews and 43 RCTs covering all epidural interventions to meet the objectives.The evidence recommendations are as follows: Disc herniation: Based on relevant, high-quality fluoroscopically guided epidural injections, with or without steroids, and results of previous systematic reviews, the evidence is Level I for caudal epidural injections, lumbar interlaminar epidural injections, lumbar transforaminal epidural injections, and cervical interlaminar epidural injections with strong recommendation for long-term effectiveness.The evidence for percutaneous adhesiolysis in managing disc herniation based on one high-quality, placebo-controlled RCT is Level II with moderate to strong recommendation for long-term improvement in patients nonresponsive to conservative management and fluoroscopically guided epidural injections. For thoracic disc herniation, based on one relevant, high-quality RCT of thoracic epidural with fluoroscopic guidance, with or without steroids, the evidence is Level II with moderate to strong recommendation for long-term effectiveness.Spinal stenosis: The evidence based on one high-quality RCT in each category the evidence is Level III to II for fluoroscopically guided caudal epidural injections with moderate to strong recommendation and Level II for fluoroscopically guided lumbar and cervical interlaminar epidural injections with moderate to strong recommendation for long-term effectiveness.The evidence for lumbar transforaminal epidural injections is Level IV to III with moderate recommendation with fluoroscopically guided lumbar transforaminal epidural injections for long-term improvement. The evidence for percutaneous adhesiolysis in lumbar stenosis based on relevant, moderate to high quality RCTs, observational studies, and systematic reviews is Level II with moderate to strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. Axial discogenic pain: The evidence for axial discogenic pain without facet joint pain or sacroiliac joint pain in the lumbar and cervical spine with fluoroscopically guided caudal, lumbar and cervical interlaminar epidural injections, based on one relevant high quality RCT in each category is Level II with moderate to strong recommendation for long-term improvement, with or without steroids. Post-surgery syndrome: The evidence for lumbar and cervical post-surgery syndrome based on one relevant, high-quality RCT with fluoroscopic guidance for caudal and cervical interlaminar epidural injections, with or without steroids, is Level II with moderate to strong recommendation for long-term improvement. For percutaneous adhesiolysis, based on multiple moderate to high-quality RCTs and systematic reviews, the evidence is Level I with strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. LIMITATIONS: The limitations of these guidelines include a continued paucity of high-quality studies for some techniques and various conditions including spinal stenosis, post-surgery syndrome, and discogenic pain. CONCLUSIONS: These epidural intervention guidelines including percutaneous adhesiolysis were prepared with a comprehensive review of the literature with methodologic quality assessment and determination of level of evidence with strength of recommendations

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome

Novel teprotumumab treatment of severe thyroid dermopathy; ototoxicity as an adverse side effect

Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy

Hidradenitis suppurativa at the knees

Hidradenitis suppurativa is a poorly understood, destructive disease centered on pilosebaceous units and characterized by inflammatory nodules that progress to abscesses, sinus tracts, and scars. The typical patient is a young woman with involvement of the axillae, breasts, and groin. Presented is a 60-year-old man with poorly controlled diabetes, who initially developed pink-to-yellowish plaques with punched out ulcers on his knees that evolved to scars and draining sinus tracts. Draining sinus tracts were also noted under the left axilla. Histopathology revealed suppurative granulomatous inflammation centered on hair follicles as well as sinus tracts. Special stains for fungus and mycobacterial bacilli were negative. Cultures and PCR for mycobacterial tuberculosis were negative. The patient was diagnosed with hidradenitis suppurativa. A treatment trial of topical corticosteroids and antibiotics was given, but this regimen failed to improve his lesions. The patient was then started on adalimumab, which yielded marked improvement within three months. This case is reported because of the unusual clinical presentation and to highlight the spectrum of atypical hidradenitis suppurativa