Lower Gastrointestinal Tract Research Articles

Analysing Immunohistochemical Co-expression of CDH17, CK7 and CK20 in Lower Gastrointestinal Tumours: A Cross-sectional Study

Introduction: Lower gastrointestinal tract malignancies, especially colorectal malignancy constitute one of the most common malignancies worldwide and most common cause of cancer-related deaths in developed countries. It accounts for third most common malignancy in men and the second most common in women worldwide. In this context, CDH17 and CK20 are emerging markers for diagnosis, prognosis, and for targeted therapy in the future. Aim: To assess the expression of immunohistochemical markers like CDH17, CK7 and CK20 in lower gastrointestinal tumours. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology, Chengalpattu Medical College, Chengalpattu, Tamil Nadu, India, for the duration one year six months, April 2020-October 2021. All cases of lower gastrointestinal tract malignancies obtained as small biopsies or resected specimens of about 40 cases were included in this study. For all cases, four sections were taken: one for Haematoxylin and Eosin (H&E) stain and the other three for immunohistochemical stains for CDH17, CK7, and CK20, respectively. The sections were stained using a standard protocol. Histopathological categorisation, pathological staging, and grading of lower gastrointestinal carcinomas were conducted in conjunction with the immunohistochemical markers CDH17, CK7, and CK20. Descriptive statistics, including frequency and percentages, were calculated. The association between categorical variables was analysed by Kruskal-Wallis test. Results: Among the 40 cases, the expression of the CDH17, CK20, and CK7 markers showed 95.00% positivity (38 cases) for CDH17 and 92.50% positivity (37 cases) for CK20, whereas CK7 was found to be negative in 95.00% (38 cases) of the cases. Conclusion: The expression of CDH17 and CK20 in lower gastrointestinal malignancies, especially in the colorectum, was strong and diffuse. In contrast, the CK7 marker was not expressed in lower gastrointestinal malignancies. Thus, the IHC markers CDH17 and CK20 can be routinely employed as cocktail markers in lower gastrointestinal malignancies, especially in colorectal carcinoma of unknown primary origin.

Use of Endoscopy to Remove Fish Bone That Caused Sigmoid Colon Perforation.

An 87-year-old man experiencing lower abdominal discomfort resulting from the ingestion of a fish bone underwent conservative management involving endoscopic extraction of the fish bone lodged in the sigmoid colon. Most patients with lower gastrointestinal tract perforations typically develop peritonitis or abscesses, necessitating surgical intervention. Notably, endoscopic management of lower gastrointestinal tract perforations is infrequently employed. Patients presenting with localized abdominal symptoms along with a stable overall health condition may benefit from conservative therapeutic approaches that utilize endoscopic methods. Notably, the transition from endoscopic procedures for foreign body removal to surgical intervention requires close collaboration with a surgeon and must be executed judiciously.

Hypovolemic Shock Due to Lower Gastrointestinal Tract Bleeding Secondary to Primary Rectal Syphilitic Ulcer. Case Report and Literature Review

Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum, it has a well-defined course with several stages throughout its natural history ranging from primary to tertiary. Rectal syphilis is a rare syphilis presentation and can occur in both primary and secondary syphilis, either in a syphilitic ulcer or proctitis. It's generally doesn't have symptoms, however it can cause rectal bleeding that in most cases tends to be self-limiting. The diagnosis is established when it's possible with direct observation studies; However, in cases of concomitant contamination by spirochetes of the usual rectal flora, the sensibility and specificity of direct observation tests decreases, so the diagnosis requires an adequate clinical, serological and, if necessary, histopathological correlation. The treatment and follow-up is the same as in other syphilis types and depends on the time of evolution and specific conditions of the patient in question. We present the case of a male patient with primary rectal syphilis that during his course triggered a state of hypovolemic shock secondary to massive rectal bleeding.

Diagnosis by Endoscopic Ultrasonography-Guided Sampling through the Lower Gastrointestinal Tract.

Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) is very safe and has a high diagnostic rate for upper gastrointestinal lesions, especially pancreatic lesions, but its application in the lower gastrointestinal tract has rarely been reported. Due to the tortuous course of the colorectum, with the sigmoid colon particularly prone to perforation, most endoscopists are reluctant to perform lateral-sector endoscopic ultrasound scanning without a water-bag protection for the puncture. The ultrasonic endoscopy and flexible puncture needle techniques recently introduced into clinical practice have made ultrasound-guided puncture safer and more convenient. In addition, endoscopists have carefully tested various protective measures to improve the safety of the lower gastrointestinal puncture, substantially increasing its clinical feasibility. In this article, we review the iterations of endoscopic ultrasound equipment introduced in recent years and the many ingenious ideas proposed by endoscopists regarding lower gastrointestinal puncture.

CRPU-NET: a deep learning model based semantic segmentation for the detection of colorectal polyp in lower gastrointestinal tract

Purpose. The objectives of the proposed work are twofold. Firstly, to develop a specialized light weight CRPU-Net for the segmentation of polyps in colonoscopy images. Secondly, to conduct a comparative analysis of the performance of CRPU-Net with implemented state-of-the-art models. Methods. We have utilized two distinct colonoscopy image datasets such as CVC-ColonDB and CVC-ClinicDB. This paper introduces the CRPU-Net, a novel approach for the automated segmentation of polyps in colorectal regions. A comprehensive series of experiments was conducted using the CRPU-Net, and its performance was compared with that of state-of-the-art models such as VGG16, VGG19, U-Net and ResUnet++. Additional analysis such as ablation study, generalizability test and 5-fold cross validation were performed. Results. The CRPU-Net achieved the segmentation accuracy of 96.42% compared to state-of-the-art model like ResUnet++ (90.91%). The Jaccard coefficient of 93.96% and Dice coefficient of 95.77% was obtained by comparing the segmentation performance of the CRPU-Net with ground truth. Conclusion. The CRPU-Net exhibits outstanding performance in Segmentation of polyp and holds promise for integration into colonoscopy devices enabling efficient operation.

Peitz–Jaegers syndrome as a cause of intussusception in children

BACKGROUND: Intestinal intussusception is a common cause of acute intestinal pathology in children. Peitz–Jaegers syndrome is a rare disease with an autosomal dominant type of inheritance characterized by the development of hamartomic polyps in the gastrointestinal tract and pigmented spots on the skin and mucous membranes. It is a “precancerous” state which increases the risk of oncologic formations in the gastrointestinal tract and in genital glands. Peitz–Jaegers syndrome is associated with mutations in STK11 or LKB1 genes.
 CLINICAL CASE DESCRIPTION: The article describes the authors’ experience in surgical resolution of the intestinal intussusception with atypical course in a 6-year-old child. Diagnostic laparoscopy detected intussusceptions in the small intestine, one of which was immediately desinvaginated with instruments and the other one required conversion. During the surgery, dense tumor-like formations were identified; therefore, jejunum loop with revealed formations was resected. Further histological and other testings showed that these formations were hamartomic polyps. The patient had been preliminary diagnosed with Peitz–Jaegers syndrome which further was confirmed by genetic and histological analyses and gastroscopic examination. The postoperative period was uneventful; the child was discharged in the satisfactory condition on day 7 after the surgery.
 CONCLUSION: Consultations with a pediatric surgeon and gastroenterologist, examination of the upper and lower gastrointestinal tract, monitoring polyps’ onset or growth are stages of key importance in children with Peitz–Jaegers syndrome. Such an approach promotes minimization of risks associated with the course of this disease. To prevent emergency surgical situations, it is important to make genetic analyses for children with the family history of polypous syndrome in the gastrointestinal tract.

Investigations into Increased Incidence of Severe Gizzard Erosions and Ulcerations in U.S. Commercial Broilers.

During a series of pathology surveys in four production complexes of a U.S. broiler integrator, the technical services veterinarians of an animal health company noted a high incidence of severe gizzard erosions and ulcerations (GEU), prompting further clinical investigation and a battery trial. No growth-promoting antibiotics or ionophore coccidiostats were used during the period of these surveys. All used tribasic copper chloride (TBCC) at ≤120 ppm added copper in broiler rations. Clostridium perfringens was isolated from 83% and 67% of gizzard lesions cultured in two complexes, and cecal C. perfringens most probable number determinations were higher in severely affected than in mildly affected or unaffected birds. Histopathology revealed both acellular koilin fusion defects characteristic of copper toxicity, as well as inflammatory cell infiltrates. Intralesional bacilli suggestive of C. perfringens were noted in 78% of affected flocks examined. Species E Aviadenovirus was isolated from one bird in one complex, and that bird had a single intranuclear inclusion body; no other flocks had Adenoviruses isolated or detected on PCR, nor any inclusion bodies. Other viruses detected were thought to be incidental. A pilot study using feed with supplemental copper from TBCC or copper sulfate and challenge with one of the isolated C. perfringens strains reproduced the lesions. A battery study was conducted with an unchallenged negative control group fed a diet with 16 ppm added copper, a group fed the control diet and orally challenged with 108 organisms of a field strain of C. perfringens at 21 and 22 days, and a group treated with the same diet containing 250 ppm added copper from TBCC and orally challenged with C. perfringens. Birds were necropsied at 23 and 28 days. All challenged groups developed lesions, with those receiving both TBCC and C. perfringens having significantly higher gross and histopathological lesion scores than the unchallenged negative controls. Lesions were qualitatively similar to those in the field and contained suspected C. perfringens bacilli. Because the levels of TBCC used in the commercial birds and in the battery trial generally have been considered safe, and because C. perfringens is usually regarded as a pathogen of the lower GI tract, the possible association of these two agents with GEU is a novel observation and warrants further investigation.

Reduced risk of gastrointestinal bleeding associated with eupatilin in aspirin plus acid suppressant users: nationwide population-based study.

Mucoprotective agents, such as eupatilin, are often prescribed to prevent gastrointestinal (GI) bleeding in addition to an acid suppressant despite the absence of a large-scale study. We evaluated the additional effect of eupatilin on the prevention of GI bleeding in both the upper and lower GI tract in concomitant aspirin and acid suppressant users using the nationwide database of national claims data from the Korean National Health Insurance Service (NHIS). An aspirin cohort was constructed using the NHIS claims data from 2013 to 2020. Patients who manifested with hematemesis, melena, or hematochezia were considered to have GI bleeding. A Cox proportional hazards regression model was used to determine the risk factors for GI bleeding associated with the concomitant use of GI drugs and other covariates among aspirin users. Overall, a total of 432,208 aspirin users were included. The concurrent use of an acid suppressant and eupatilin (hazard ratio [HR] = 0.85, p = 0.016, vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Moreover, a more than 3-month duration (HR = 0.88, p = 0.030) of acid suppressant and eupatilin prescription (vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Eupatilin administration for ≥ 3 months showed additional preventive effect on GI bleeding in concomitant aspirin and acid suppressant users. Thus, cotreatment with eupatilin with a duration of 3 months or longer is recommended for reducing GI bleeding among aspirin plus acid suppressant users.

From Selye's and Szabo's Cysteamine-Duodenal Ulcer in Rats to Dopamine in the Stomach: Therapy Significance and Possibilities.

We reviewed gastric ulcer healing by dopamine considering several distinctive duodenal key points. Selye and Szabo describe the cysteamine-induced duodenal ulcer in rats as a duodenal stress ulcer in patients. Szabo's cysteamine duodenal ulcer as the dopamine duodenal healing and cysteamine as a dopamine antagonist signifies the dopamine agonists anti-ulcer effect and dopamine antagonists ulcerogenic effect. From these viewpoints, we focused on dopamine and gastric ulcer healing. We mentioned antecedent studies on the dopamine presence in the stomach and gastric juice. Then we reviewed, in the timeline, therapy significance arising from the anti-ulcer potency of the various dopamine agonists, which is highly prevailing over the quite persistent beneficial evidence arising from the various dopamine antagonists. Meanwhile, the beneficial effects of several peptides (i.e., amylin, cholecystokinin, leptin, and stable gastric pentadecapeptide BPC 157, suggested as an acting mediator of the dopamine brain-gut axis) were included in the dopamine gastric ulcer story. We attempt to resolve dopamine agonists/antagonists issue with the dopamine significance in the stress (cysteamine as a prototype of the duodenal stress ulcer), and cytoprotection (cysteamine in small dose as a prototype of the cytoprotective agents; cysteamine duodenal ulcer in gastrectomized rats). Thereby, along with dopamine agonists' beneficial effects, in special circumstances, dopamine antagonists having their own ulcerogenic effect may act as "mild stress (or)" or "small irritant" counteracting subsequent strong alcohol or stress procedure-induced severe lesions in this particular tissue. Finally, in the conclusion, as a new improvement in further therapy, we emphasized the advantages of the dopamine agents' application in lower gastrointestinal tract therapy.

An injectable subcutaneous colon-specific immune niche for the treatment of ulcerative colitis.

As a chronic autoinflammatory condition, ulcerative colitis is often managed via systemic immunosuppressants. Here we show, in three mouse models of established ulcerative colitis, that a subcutaneously injected colon-specific immunosuppressive niche consisting of colon epithelial cells, decellularized colon extracellular matrix and nanofibres functionalized with programmed death-ligand 1, CD86, a peptide mimic of transforming growth factor-beta 1, and the immunosuppressive small-molecule leflunomide, induced intestinal immunotolerance and reduced inflammation in the animals' lower gastrointestinal tract. The bioengineered colon-specific niche triggered autoreactive T cell anergy and polarized pro-inflammatory macrophages via multiple immunosuppressive pathways, and prevented the infiltration of immune cells into the colon's lamina propria, promoting the recovery of epithelial damage. The bioengineered niche also prevented colitis-associated colorectal cancer and eliminated immune-related colitis triggered by kinase inhibitors and immune checkpoint blockade.

ADENOVIRUS: EPIDEMIOLOGY, SPREAD OF NOVEL SEROTYPES AND IN ROLE WITH RESPIRATORY TRACT INFECTIONS

Adenoviruses (AdVs) are the DNA viruses that can cause mild infections involving both upper or lower respiratory tract,gastrointestinal tract, or conjunctiva. Adenovirus plays a very notable role in respiratory tract disease in both pediatric and adult patients. It has been linked with outbreaks and epidemics in various patient populations, resulting in considerable morbidity and mortality. Fatality rates for severe untreated AdV pneumonia may exceed 50%. More than 50 serotypes of the AdV have been recognised. Different serotypes display different tissue tropisms that can correlate with the clinical manifestations of infection. In this paper, we discuss the epidemiology, pathogenesis,clinical presentation, respiratory tract illnesses and complications, and roles of diagnosis and potential treatment options. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been conducted. Cidofovir is the drug of choice for severe AdV infections, but not all patients require treatment.The role of the past oral adenovirus vaccine and the military implications of its withdrawal from routine use in military recruits is discussed as well.

Bleeding and Thrombosis in Patients with Cancer and Acute Venous Thromboembolism Requiring Urgent Procedures

BACKGROUND There are limited data of outcomes in patients who require anticoagulation interruption for a surgical procedure shortly after an acute VTE, especially in patients with cancer who are at higher risk for both hemorrhage and recurrent thrombosis. Our goal was to assess the incidence of recurrent thrombosis or major hemorrhage at 60-days following an urgent surgical procedure in patients with acute VTE (within one month prior to surgery). METHODS We performed a retrospective cohort study of patients with cancer at Memorial Sloan Kettering Cancer Center (from January 1 st 2021 to December 31 st 2022). Patients were eligible for inclusion if they were diagnosed with a new acute deep vein thrombosis or pulmonary embolism and underwent surgical procedure within 30-days following the acute VTE diagnosis. Recurrent VTE was defined as symptomatic new deep-vein thrombosis or pulmonary embolism, incidental new deep-vein thrombosis or pulmonary embolism involving segmental or more proximal pulmonary arteries, or fatal pulmonary embolism or unexplained death for which pulmonary embolism could not be ruled out as the cause. Major hemorrhage was characterized according to ISTH definition. Competing risk framework was used to estimate cumulative incidences of major hemorrhage, VTE and death at 30 and 60-days. RESULTS A total of 90 patients were included in this analysis. The median age was 73 years and 62% were female (Table 1). Surgical procedures were classified by their risk of bleeding with 64 patients undergoing lower bleeding risk procedures and 26 high-risk procedures (Table 1). There were 10 recurrent or new VTE within 60-days of surgery (60-day cumulative incidence of 8.9%, 95% CI 4.1-16%). The recurrent sites were deep venous (N=7) and new PE (N=3). There were 12 major hemorrhagic events within 60 days (cumulative incidence of 12%, 95% CI 6.5-20%). The most common sites of hemorrhage were the lower gastrointestinal tract and genitourinary system. The competing risk framework is shown graphically in Figure 1. Among patients who received IVC filters the incidence of recurrent VTE was 1.1% and major hemorrhage was 2.2%. The 60-day cumulative incidence of death following surgical procedure was 19% (95% 12-28%). There were no fatal VTE and 3 fatal hemorrhagic events. CONCLUSION Among patients with cancer undergoing surgical procedures within 30-days of an acute VTE, the rates of recurrent VTE and major hemorrhage are substantively higher than reported in non-surgical acute VTE cohorts. Placement of temporary IVC filters may improve short-term bleeding and thrombotic outcomes.

EPCO-01. THE GENOMIC LANDSCAPE OF BRAIN METASTASIS

Abstract BACKGROUND The prognosis for patients with brain metastasis (BM) is devastating, while the underlying biology of BM development remains poorly understood. Identification of genomic biomarkers can offer promising opportunities for prediction of BM development and guidance in personalized treatment. In this study we evaluate the genomic alterations present in a large cohort of resected BM. METHODS Upon retrospective review, we identified 868 patients with diagnosis of solid primary cancers who had undergone a standard of care craniotomy at Memorial Sloan Kettering Cancer Center (MSKCC). BM samples were profiled by MSK-IMPACT, a next-generation sequencing (NGS) assay designed to detect a wide range of genetic alterations in 341-505 cancer genes. Genomic alterations were filtered for driver variants using OncoKB. Disease sites included cancers of head and neck, breast, lung, lower and upper gastrointestinal tract, kidney, ovary, uterus, prostate, skin, soft tissues, and others. RESULTS More than half (57%; 493/868) of patients were female and the median age was 63 (range 22-93). Foreseeably, the most common histology was non-small cell lung cancer (NSCLC; 38%), followed by invasive carcinoma of the breast and melanoma (16% and 13%, respectively). The most frequently encountered alterations were inTP53 (60%), CDKN2A (25%), TERT (23%), KRAS (18%), and PTEN (12%) across all BM samples. The median fraction of genome altered was 0.41 [range: 0-0.99] and the median tumor mutational burden was 6.6 muts/Mb [range: 0-395]. Additionally, TP53 was the most frequently altered gene after stratifying by primary histology in most cancer types, except for melanoma, renal, and thyroid, which were enriched for alterations in TERT, CDKN2A, and TERT, respectively. CONCLUSION The landscape of genomic alterations present in BM is distinct and varies by primary histologic diagnosis. Ongoing analyses of matched primary-BM pairs and clinicogenomic correlation will identify factors predisposing patients to BM development and progression.

103 Development of a Novel, Experimental, Minimally Invasive Model to Investigate the Genesis and Etiology of Liver Abscesses in Cattle

Abstract Most research surrounding liver abscesses involves post-hoc evaluation of naturally occurring abscesses in production settings. Few studies have been designed to experimentally induce abscesses with the purpose of identifying a time course, causality, and associated physiological implications. Therefore, we set out to develop a minimally invasive, reliable, and repeatable model to induce liver abscesses in calves in a controlled research environment to elucidate the genesis and etiology of the disease, with the ultimate goal of developing abscess reduction strategies. Experiment 1 was an attempt to induce abscesses by intraruminal inoculation with Fusobacterium necrophorum, Salmonella lubbock, and Truperella pyogenes (FST) following an intravenous lipopolysaccharide challenge. Holstein steers were harvested 3- and 10-d after inoculation, but no abscesses were detected. Experiments 2 and 3 involved diet manipulation by cycling calves on and off a high-starch, acidotic diet followed by intraruminal inoculation of microbes. In Experiment 2, Holstein calves were fed a negative control diet, an acidotic diet, and an acidotic diet plus bacterial inoculation with FST. No abscesses formed in the control or acidotic diet calves, but 43% of calves fed the acidotic diet with FST inoculation formed liver abscesses, suggesting that acidosis alone is insufficient to produce abscesses. In Experiment 3, treatments consisted of Holstein steers fed a negative control, an acidotic diet, an acidotic diet plus ruminal Fusobacterium necrophorum (F), and an acidotic diet plus Fusobacterium and Salmonella (FS). Again, there were no abscesses in the control or calves fed an acidotic diet alone; however, 40% of calves receiving F presented with an abscess, and 50% of the calves that received FS presented with abscesses. These data suggest that ruminal acidosis in conjunction with a ruminal load of pathogens commonly associated with liver abscesses provides a model that will induce liver abscesses. While the role of barrier dysfunction in the rumen and the lower gastrointestinal tract in formation of abscesses is not fully understood, this work provides a foundation to further explore the etiology of this disease and potential mitigation strategies.

18 Role of the Rumen Microbiome in Beef Cattle Gut Physiology and Performance

Abstract The diverse rumen microbiome converts low-quality feedstuffs into usable energy and provides approximately 70% of the energy required by its ruminant host through fermentation byproducts. Due to microbial impacts on host health and productivity, numerous studies have associated rumen microbiome variation with important sustainability phenotypes, such as feed efficiency and methane emissions. Although diet, genetics, and environment contribute to variation in feed efficiency, selection for feed-efficient beef cattle using genetic improvement technologies has helped to understand and improve the persistence and longevity of such phenotypes within the herd. While diet has been considered to be the primary driver for the composition and structure of the rumen microbiome, recent studies have indicated the microbial communities present in the rumen are under low-to-moderate host genetic control. The mutualistic, commensal, and parasitic microorganisms that reside in the rumen and lower gastrointestinal tract of cattle and other ruminants exert enormous influence over animal physiology and performance. The ability to interrogate these systems at great depth has permitted a greater understanding of the microbiological and molecular mechanisms involved in ruminant nutrition and health. The work in our group in the field of beef cattle gut microbiology, as it relates to feed efficiency, permits the exploration of these critical microbial community networks. This knowledge will aid researchers seeking to address the grand challenge of maintaining host-efficient gut microbiomes throughout cattle production operations. This work is supported by the Agriculture and Food Research Initiative grant no. 2020-67015-30832 from the USDA National Institute of Food and Agriculture.

Understanding endoscopic and clinicopathological features of patients with very early onset inflammatory bowel disease: Results from a decade of study

BackgroundVery early onset inflammatory bowel disease (VEOIBD) is associated with a unique disease course and distinct endoscopic features. AimsThis study aims to provide a comprehensive description of the endoscopic and histologic features observed in a large cohort of patients with VEOIBD from a tertiary medical center. MethodsA retrospective review of medical records from 2011 to 2021 was conducted to analyze clinical data, including disease phenotypes, endoscopic and histologic findings. Next generation sequencing was performed. ResultsA total of 225 VEOIBD subjects were included in this study. Monogenic defects were identified in 161 patients. Monogenic IBD patients more commonly had CD-like disease. Colonic involvement was more prevalent among those with monogenic IBD (P<0.001). Pseudo-polyps were significantly more common in the monogenic IBD group (P<0.001), while ileal edema and ulcers were significantly more prevalent in non-monogenic IBD cases. IL10RA deficiency were characterized by colonic ulcers and pseudo-polyps without upper gastrointestinal tract lesions, while patients with TNFAIP3 mutations demonstrated both upper and lower gastrointestinal tract involvement. The non-monogenic IBD patients showed a higher incidence of chronic architectural changes of crypt, increased apoptosis and eosinophils infiltration. ConclusionsEndoscopic and histologic analysis of children with VEOIBD plays a crucial role in facilitating accurate diagnosis. Various forms of monogenic IBD exhibit distinct endoscopic and pathologic changes.

Patterns of Graft-Versus-Host Disease (GvHD) Prevention and Management in the Eastern Mediterranean (EM) Region: A Worldwide Network for Blood & Marrow Transplantation (WBMT) Survey

Introduction: GvHD is a significant cause of morbidity and mortality in recipients of allogeneic hematopoietic cell transplant (HCT). The prevention, management, and treatment of GvHD vary in different regions worldwide. This WBMT study aims to better understand the current clinical practices of GvHD prevention and management around the globe. This study presents our survey results in the Eastern Mediterranean Region. Methodology: This is a cross-sectional survey-based study involving hematopoietic cell transplant (HCT) centers in the EM region. Participants of the survey were programs' directors or their designees. The survey comprised two parts; the first part aimed to study the practices of GvHD prevention, whereas the second part aimed to study GvHD management and treatment. The survey was distributed and filled out between December 2022 and May 2023. Results: Thirty participants from 28 institutions responded. Participants were from eleven different countries in the EM region. Fourteen participants (50%) filled it for combined pediatrics and adult HCT programs. The remaining participants filled it for programs performing HCT, either only in adult (27%) or pediatrics (23%) patients. The majority of participants indicated that cyclosporine and methotrexate combination is the most used GvHD prophylaxis therapy in both myeloablative and reduced intensity HCT in their centers. Cyclosporine was the predominantly used calcineurin inhibitor (CNI), followed by tacrolimus. All centers using cyclosporine indicated that they monitor its level, with 200-300 mcg/L being the target in 66% of the survey. Cyclosporine was typically given for 2-12 months after HCT, with around 80% of centers stopping it at 3-4 months post-HCT in recipients with malignant indications and around 90% of centers stopping it around 6-12 months post-HCT in recipients with non-malignant indications. When tacrolimus is used, results showed that it is typically used for similar duration to cyclosporine. Twenty-nine participants reported using post-transplant cyclophosphamide (PTCy) in their centers, with seven centers (24%) reporting its use in indications other than haploidentical transplants. Additionally, the results show that PTCy is typically used in combination with other medications, with 53% of participants reporting that it is used along with mycophenolate mofetil and cyclosporine and only one participant reported its use as a single agent. Seven participants (23%) reported that PTCy is typically used in doses less than 50 mg/kg. In patients with established GvHD, steroids were most commonly used alone as a first-line therapy in acute and chronic GvHD. The majority of centers report re-introducing or continuing the immunosuppressive agent used in GvHD prevention, with few centers indicating that they switched to another CNI. 64% and 55% of centers indicated that they have a standard-operating procedure (SOP) for steroid-refractory acute GvHD (aGvHD) and chronic GvHD (cGvHD), respectively. Only two centers reported involving steroid-refractory GvHD patients in clinical trials. Second-line therapy for steroid-refractory aGvHD and cGvHD varies significantly between centers depending on the type of GvHD and organ involved. In steroid-refractory aGvHD, ruxolitinib was the most frequently listed agent to be considered in the second line, regardless of the involved organ. Ruxolitinib was followed by Extracorporeal photopheresis in Skin aGvHD, Budesonide in lower GI tract aGVHD, and Mycophenolate Mofetil in liver aGvHD. In cGvHD, ruxolitinib was also the most frequently listed medication. However, more significant variability between centers was noted in treating organ-specific cGvHD. Conclusion: GvHD prevention and management practices vary between the different EM region centers. Some variations could be related to access to some medications. This might indicate the need for more evidence-based practices in preventing and managing GvHD and possibly adjusting the guidelines according to access and availability of some medications. WBMT is currently working on understanding the global patterns of GvHD practices in other regions and, ultimately, a global comparative study of all data combined.

Abstract 17 — Overall Infection Risks of Tofacitinib in Patient with Rheumatoid Arthritis: A Meta-Analysis of Randomized Clinical Trials

Background There is an ongoing controversy surrounding whether tofacitinib increases the risk of infections in patients with rheumatoid arthritis (RA). To address this issue, we conducted a meta-analysis using data from randomized clinical trials (RCTs) to assess the overall risk of infection in these patients. Methods We conducted a comprehensive systematic search in EMBASE, MEDLINE, and CENTRAL from their inception until December 2022 to identify relevant RCTs reporting the occurrence of infections in patients with RA who were treated with the standard clinical therapeutic dosage of tofacitinib (5mg twice daily orally). The primary outcomes of the included studies in this review focused on the incidence of total infections, serious infections, non-serious infections, and opportunistic infections (including herpes zoster and tuberculosis). Additionally, we examined secondary outcomes related to the incidence of various sites of infections, including the upper respiratory tract, lower respiratory tract, gastrointestinal tract, hepatobiliary system, urinary tract, skin and soft tissue, blood, dental and oral soft tissue, genital, reproductive tract, bone and joint, and central nervous system infections. Due to the expected anticipation of clinical and methodological heterogeneity across studies, the effect estimate was pooled with a random-effects model, to obtain the RRs and 95% CIs, using Mantel-Haenszel statistical method. Results Twelve eligible RCTs, involving a total of 6,056 patients, were included in the analysis. In comparison to the control group (placebo and other active treatments), tofacitinib exhibited a significant increase in the risk of total infections (RR, 1.21; 95% CI, 1.07-1.37; I2, 28%), serious infections (RR, 1.23; 95% CI, 1.02-1.48; I2, 0%), non-serious infections (RR, 1.20; 95% CI, 1.05-1.36; I2, 29%), and opportunistic infections (RR, 1.66; 95% CI, 1.40-1.97; I2, 0%). Secondary outcomes analyses revealed a significant increase in the risk of lower respiratory infections with tofacitinib (RR, 1.27; 95% CI, 1.10–1.47; I2, 0%). Conclusion Compared with placebo and other active treatments, tofacitinib significantly increased the overall risk of infections (total infections, serious infections, non-serious infections, and opportunistic infections). These findings can help clinicians assess the risk of infections in RA patients treated with tofacitinib.

Near-infrared fluorescence tattooing: a new approach for endoscopic marking of tumors in minimally invasive colorectal surgery using a persistent near-infrared marker

IntroductionIntraoperative accurate localization of tumors in the lower gastrointestinal tract is essential to ensure oncologic radicality. In minimally invasive colon surgery, tactile identification of tumors is challenging due to diminished or absent haptics. In clinical practice, preoperative endoscopic application of a blue dye (ink) to the tumor site has become the standard for marking and identification of tumors in the colon. However, this method has the major limitation that accidental intraperitoneal spillage of the dye can significantly complicate the identification of anatomical structures and surgical planes. In this work, we describe a new approach of NIR fluorescent tattooing using a near-infrared (NIR) fluorescent marker instead of a blue dye (ink) for endoscopic tattooing.MethodsAFS81x is a newly developed NIR fluorescent marker. In an experimental study with four domestic pigs, the newly developed NIR fluorescent marker (AFS81x) was used for endoscopic tattooing of the colon. 7–12 endoscopic submucosal injections of AFS81x were placed per animal in the colon. On day 0, day 1, and day 10 after endoscopic tattooing with AFS81x, the visualization of the fluorescent markings in the colon was evaluated during laparoscopic surgery by two surgeons and photographically documented.ResultsThe detection rate of the NIR fluorescent tattoos at day 0, day 1, and day 10 after endoscopic tattooing was 100%. Recognizability of anatomical structures during laparoscopy was not affected in any of the markings, as the markings were not visible in the white light channel of the laparoscope, but only in the NIR channel or in the overlay of the white light and the NIR channel of the laparoscope. The brightness, the sharpness, and size of the endoscopic tattoos did not change significantly on day 1 and day 10, but remained almost identical compared to day 0.ConclusionThe new approach of endoscopic NIR fluorescence tattooing using the newly developed NIR fluorescence marker AFS81x enables stable marking of colonic sites over a long period of at least 10 days without compromising the recognizability of anatomical structures and surgical planes in any way.

Management of a Female Patient with Fournier’s Gangrene Complicated by Hyperglycemic Hyperosmolar State and Multi-Organ Dysfunction: A Case Report

Fournier's gangrene is a rare but deadly condition, with propensity for people with diabetes and long-term alcohol abuse, although it can also afflict patients with non-obvious immunological impairment. The nidus might be found in the genitourinary tract, lower gastrointestinal tract or the skin and is a mixed aerobic and anaerobic infection. The gangrene's development and spread is often fulminating resulting in multiple organ failure and death. Fournier’s gangrene in female patients has been reported to be associated with infection from episiotomy wounds and Bartholin’s abscess. But despite advanced management, mortality is still high and averages 20-30% .The current article discusses a case of Fournier’s gangrene in a female patient that was further complicated by a hyperglycemic hyperosmolar condition with approaching multi-organ dysfunction, as well as the successful medical and surgical therapy of the patient.