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Objective: Unusual clinical course. Background: Endometriosis is a common cause of chronic pelvic pain among women globally. Pharmacological therapy for endometriosis includes non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal contraceptives, while surgical therapy often involves either laparoscopic excision and ablation of endometriosis implants or open surgery. Surgical therapy is one of the mainstays of treatment especially for extrapelvic endometriomas. However, little guidance exists for the treatment of non-palpable or intermittently palpable lesions of this nature. Case Report: A 33-year-old woman with a previous cesarean section presented with complaints of intermittent discomfort in the area between her umbilicus and the surgical incision, for the previous 7 years, that worsened during her menstrual cycle. A 3×3-cm area of fullness was only intermittently palpable during various clinic visits, but was visualizable on computed tomography and magnetic resonance imaging. Given the lesion's varying palpability, a Savi Scout radar localization device was placed into the lesion pre-operatively to aid with surgical resection. The mass was excised, pathologic examination revealed endometrial tissue, and the patient had an uncomplicated postoperative course with resolution of her symptoms. Conclusions: Surgical removal of extrapelvic endometrioma lesions can be made difficult by varying levels of palpability or localizability due to a patient's menstrual cycle. The Savi Scout, most commonly used in breast mass localization, is a useful tool in guiding surgical excision of non-palpable or intermittently palpable extrapelvic endometrioma lesions. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Patients with advanced stage ovarian cancer typically have vague non-specific abdominal symptoms related to pelvic tumor, metastasis, and ascites. When these patients present with more acute abdominal pain, appendicitis is rarely considered. Acute appendicitis due to metastatic ovarian cancer has been sparsely documented in the medical literature; only twice, to our knowledge. Case Report: A 61-year-old woman with a 3-week history of abdominal pain, shortness of breath, and bloating was diagnosed with ovarian cancer after computed tomography (CT) demonstrated a large pelvic cystic and solid mass. Five weeks later she underwent an omental biopsy to determine cell type and potential upstaging of the ovarian cancer to stage IV, as other aggressive cancers such as breast cancer can also involve the pelvis/omentum. Seven hours after her biopsy, she presented with increasing abdominal pain. Post-biopsy complications such as hemorrhage or bowel perforation were initially suspected to be the cause of her abdominal pain. However, CT demonstrated ruptured appendicitis. The patient underwent an appendectomy and histopathologic examination of the specimen revealed infiltration by low-grade ovarian serous carcinoma. Conclusions: Given the low incidence of spontaneous acute appendicitis in this patient’s age group, and the lack of any other clinical, surgical, or histopathological evidence to suggest another cause, metastatic disease was ruled to be the likely source of her acute appendicitis. Providers should be aware of appendicitis in a broad differential diagnosis and have a low threshold for ordering abdominal pelvis CT when advanced stage ovarian cancer patients present with acute abdominal pain. [ABSTRACT FROM AUTHOR]

Context.--Acquired thrombotic thrombocytopenic purpura (A-TTP) is a rare but significant disease requiring rapid diagnosis and treatment. The diagnosis is often difficult because of variability in the presence of specific clinical criteria. The primary etiology of A-TTP involves inhibitors directed against ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Literature has shown that the ADAMTS13 activity assay is sensitive and specific for identifying cases of A-TTP, and application of this test as an on-site screening method has not been fully explored. Objective.--Our objective is to determine if the ADAMTS13 activity assay can be used as a successful, on-site diagnostic modality to rapidly identify cases of ATTP and prevent unnecessary use of prophylactic therapeutic plasma exchange. Design.--A retrospective analysis was performed including 152 patients with clinically suspected A-TTP, screened using the ADAMTS13 activity assay. Results were correlated with potential therapeutic plasma exchange treatment for all cases highly suspicious for A-TTP and evaluated for unnecessary patient morbidity and financial cost. Results.--The ADAMTS13 activity assay had an overall sensitivity and specificity of 100% and 99%, respectively. The positive predictive value was 91% and the negative predictive value was 100%. In 95% of the studies ordered, A-TTP was ruled out, leading to decreased patient morbidity and $1.7 million of potential treatment costs avoided. Conclusion.--Implementation of the fluorescence energy transfer-based ADAMTS13 activity assay as a point-ofcare laboratory study decreased patient morbidity while also directing more efficient employment of therapeutic plasma exchange in cases of suspected A-TTP. (Arch Pathol Lab Med. 2014; 138:546-549; doi: 10.5858/arpa.2013-0170-0A), Thrombotic thrombocytopenic purpura (TTP) is a rare disease that was first described in 1925 by Moschcowitz (1) in his report of a young girl with hemolytic anemia, thrombocytopenia, and coma [...]

Patient: Female, 74-year-old. Final Diagnosis: Giant diverticulum. Symptoms: Abdominal discomfort • bloating and constipation. Medication: --. Clinical Procedure: Laparoscopic washout • open sigmoidectomy. Specialty: Surgery. Objective: Rare disease. Background: Diverticulosis and its complication of diverticulitis is a common condition that can be found in up to 35% of the population. Giant colonic diverticulum is a rare entity with fewer than 200 cases reported in the scientific literature. Development of a giant diverticulum as a sequelae of laparoscopic washout is an unreported event in current literature. Case Report: The patient was a 74-year-old female who had a well-known history of diverticulosis and diverticulitis. She developed perforated sigmoid diverticulitis, underwent laparoscopic washout and recovered without colon resection. Within a year after washout, she developed abdominal distention and bloating, and computed tomography (CT) imaging revealed a giant diverticulum. She went on to undergo surgery for resection of her sigmoid colon, which contained the giant diverticulum. Her recovery was otherwise uneventful. Conclusions: To our knowledge, this is the first case report of giant diverticulum presenting as a complication of abdominal washout for management of acute diverticulitis. Initial CT scan performed at the time of perforation did not demonstrate this diverticulum, indicating that it developed within the year after abdominal washout for sepsis and acute rupture, likely due to weakening of the colonic wall secondary to ongoing inflammation. The very rare presentation of giant diverticulum makes it difficult to establish a clear link to washout, however, this case establishes a groundwork for further investigation as our fund of knowledge on the subject continues to grow. [ABSTRACT FROM AUTHOR]

A mutation in the Caenorhabditis elegans bre-1 gene was isolated in a screen for Bacillus thuringiensis toxin-resistant (bre) mutants to the Cry5B crystal toxin made by B. thuringiensis. bre-1 mutant animals are different from the four other cloned bre mutants in that their level of resistance is noticeably lower. bre-1 animals also display a significantly reduced brood size at 25 °C. Here we cloned the bre-1 gene and characterized the bre-1 mutant phenotype. bre-1 encodes a protein with significant homology to a GDP-mannose 4,6-dehydratase, which catalyzes the first step in the biosynthesis of GDP-fucose from GDP-mannose. Injection of GDP-fucose but not fucose into C. elegans intestinal cells rescues bre-1 mutant phenotypes. Thus, C. elegans lacks a functional fucose salvage pathway. Furthermore, we demonstrate that bre-1 mutant animals are defective in production of fucosylated glycolipids and that bre-1 mutant animals make quantitatively reduced levels of glycolipid receptors for Cry5B. We finally show that bre-1 mutant animals, although viable, show a lack of fucosylated N- and O-glycans, based on mass spectrometric evidence. Thus, C. elegans can survive with little fucose and can develop resistance to crystal toxin by loss of a monosaccharide biosynthetic pathway. [ABSTRACT FROM AUTHOR]

A response from the author of the article "Use of the ADAMTS13 activity assay improved the accuracy and efficiency of the diagnosis and treatment of suspected acquired thrombotic thrombocytopenic purpura" by Brad D. Barrows and Jun Teruya in the 2014 issue is presented.

Crystal (Cry) proteins made by the bacterium Bacillus thuringiensis are pore-forming toxins that specifically target insects and nematodes and are used around the world to kill insect pests. To better understand how pore-forming toxins interact with their host, we have screened for Caenorhabditis elegans mutants that resist Cry protein intoxication. We find that Cry toxin resistance involves the loss of two glycosyltransferase genes, bre-2 and bre-4. These glycosyltransferases function in the intestine to confer susceptibility to toxin. Furthermore, they are required for the interaction of active toxin with intestinal cells, suggesting they make an oligosaccharide receptor for toxin. Similarly, the bre-3 resistance gene is also required for toxin interaction with intestinal cells. Cloning of the bre-3 gene indicates it is the C. elegans homologue of the Drosophila egghead (egh) gene. This identification is striking given that the previously identified bre-5 has homology to Drosophila brainiac (brn) and that egh-brn likely function as consecutive glycosyltransferases in Drosophila epithelial cells. We find that, like in Drosophila, bre-3 and bre-5 act in a single pathway in C. elegans, bre-2 and bre-4 are also part of this pathway, thereby extending it. Consistent with its homology to brn, we demonstrate that C. elegans bre-5 rescues the Drosophila brn mutant and that BRE-5 encodes the dominant UDP-GlcNAc:Man GlcNAc transferase activity in C. elegans. Resistance to Cry toxins has uncovered a four component giycosylation pathway that is functionally conserved between nematodes and insects and that provides the basis of the dominant mechanism of resistance in C. elegans. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls., Design: Using a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels., Results: Compared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (p<0.0001), Faecalibacterium (p=0.0077) and Roseburium (p=0.0327), while having increased Bacteroides (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria., Conclusion: We hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention., Trial Registration Number: NCT04031469 (PCR-) and 04359836 (PCR+)., Competing Interests: Competing interests: SH declares that she has pecuniary interest in Topelia Pty Ltd in Australia, and Topelia Pty Ltd in USA where development of COVID-19 preventative/treatment options is being pursued. She has also filed patents relevant to Coronavirus treatments. She is the founder and owner of Microbiome research foundation, Progenabiome and Ventura Clinical Trials. TJB declares that he has pecuniary interest in Topelia Pty Ltd in Australia, and Topelia Therapeutics Inc. in USA developing COVID-19 preventative/treatment medications. He has also filed patents relevant to COVID-19 treatments. SD declares she has corporate affiliation to McKesson Specialty Health/Ontada and North End Advisory, LLC. SD is unaware of SARS-CoV-2 and microbiome projects and not directly involved in COVID-19 relevant projects at McKesson, but they may exist. AJP and BDB have corporate affiliations to Progenabiome. EMMQ serves as a consultant to Precisionbiotics, Novazymes, Salix, Biocodex and Axon Pharma and has received research support from 4D Pharma., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The effectiveness of fecal microbiota transplantation (FMT), a treatment for Clostridioides difficile infection (CDI), is dependent on successful engraftment (incorporation) of donor stool. We present a method for evaluating engraftment success based on next-generation sequencing (NGS)-based profiling of bacterial strains present in donor and recipient stool, and we suggest its potential to guide treatment decisions., Methods: Bacterial strains in stool samples from three patients from the clinic and one donor were analyzed via NGS and metagenomic sequencing, before and 1 month after FMT for CDI. The similarity of strains present was assessed via relative abundance, principal component analysis, Shannon and Simpson diversity indexes, and Bray-Curtis dissimilarity matrix. A positive outcome was successful engraftment, where the post-FMT sample closely resembled that of the donor and CDI was cured., Results: Patients (Pts.) 1 and 2, but not Pt. 3's stool samples closely resembled the donor specimen post-FMT. Noteworthy, Pt. 3 pre-FMT sample was less similar to the donor than that of Pts. 1 and 2. All methods of assessing similarity and dissimilarity used yielded virtually identical conclusions. Pts. 1 and 2 which closely resembled donor specimen, eradicated CDI giving a surrogate objective measure of engraftment., Conclusions: Success of engraftment in FMT can be assessed using NGS and metagenomic analysis and parallels success in curing CDI of the microbiome. The statistical methods we present here are reliable and consistent for such purposes. The dissimilarity of Pt. 3 to the donor combined with the failure of engraftment and failure to cure CDI in Pt. 3 suggests that FMT success may be predictable by comparing pre-FMT samples to donor. There is no clinical trial registry listing this study., Competing Interests: Drs. S. Hazan, B. Barrows, A.J. Papoutsis and T. Borody have corporate affiliation to ProgenaBiome™. Dr. S. Hazan has additional corporate affiliation to Ventura Clinical Trials and Topelia Therapeutics Inc. Dr. T. Borody has additional corporate affiliation to Topelia Therapeutics Inc. Dr. S. Dave has corporate affiliation to North End Advisory, LLC and McKesson Specialty Health. No products of these affiliated companies were used in this study., (Copyright 2021, Hazan et al.)