Single cell analysis via mass cytometry of spontaneous intestinal perforation reveals alterations in small intestinal innate and adaptive mucosal immunity.

Introduction: Spontaneous intestinal perforation (SIP) is a poorly understood severe gastrointestinal complications of prematurity which is poorly understood. Extremely premature infants born prior to 28 weeks' gestation develop a localized perforation of the terminal ileum during the first week of life and therapy involves surgery and cessation of enteral feeds. Little is known regardj g the impact of mucosal immune dysfunction on disease pathogenesis. Methods: We performed mass cytometry time of flight (CyTOF) of small intestinal mucosa of patients with SIP (Gestational age (GA) 24 - 27 weeks, n=8) compared to patients who had surgery for non-SIP conditions (neonatal (GA >36 weeks, n=5 ) and fetal intestine from elective terminations (GA 18-21 weeks, n=4). CyTOF analysis after stimulation of T cells with PMA/Ionomycin was also performed. Results: We noted changes in innate and adaptive mucosal immunity in SIP. SIP mucosa had an expansion of ckit+ neutrophils, an influx of naïve CD4 and CD8 T cells and a reduction of effector memory T cells. SIP T cells were characterized by reduced CCR6 and CXCR3 expression and increased interferon gamma expression after stimulation. Discussion: These findings suggest that previously unrecognized immune dysregulation is associated with SIP and should be explored in future studies.

Blood group AB increases risk for surgical necrotizing enterocolitis and focal intestinal perforation in preterm infants with very low birth weight.

Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are two of the most common emergencies of the gastrointestinal tract in preterm infants with very low birth weight (VLBW, birth weight < 1500 g). Identification of risk factors among these children is crucial for earlier diagnosis and prompt intervention. In this study, we investigated a relationship between ABO blood groups and the risk for surgical NEC/FIP. We genotyped the ABO locus (rs8176746 and rs8176719) in VLBW infants enrolled in a prospective, population-based cohort study of the German Neonatal Network (GNN). Of the 10,257 VLBW infants, 441 (4.3%) had surgical NEC/FIP. In univariate analyses, the blood group AB was more prevalent in VLBW infants with surgical NEC/FIP compared to non-AB blood groups (OR 1.51, 95% CI 1.07-2.13, p = 0.017; absolute risk difference 2.01%, 95% CI 0.06-3.96%). The association between blood group AB and surgical NEC/FIP was observed in a multivariable logistic regression model (OR of 1.58, 95% CI 1.10-2.26, p = 0.013) as well. In summary, our study suggests that the risk of surgical NEC and FIP is higher in patients with blood group AB and lower in those having non-AB blood groups.

Delayed bowel perforation after instilling over warmed peritoneal dialysate.

BACKGROUND: Peritoneal dialysis (PD) is a safe and home-based treatment for end-stage renal disease (ESRD) patients. The direct thermal damage of abdominal organs is very rare. CASE PRESENTATION: We report a peritoneal dialysis patient presented abdominal pain and feculent effluent 3 weeks after he instilled hot dialysis solution. In spite of emergency exploratory laparotomy and active treatment, the patient died of septic shock. Biopsy revealed necrosis and perforation of the intestines. CONCLUSIONS: Delayed bowel perforation by hot fluid is very rare. Standardized performance is of the first importance for peritoneal dialysis patients.

Bowel perforation due to methotrexate therapeutic error: an insidious adverse reaction.

OBJECTIVE: Methotrexate (MTX) is widely used in the treatment of rheumatic and non-rheumatic disorders. Severe adverse effects are often associated with therapeutic errors, such as daily intake rather than weekly intake. Among them, the risk of bowel perforation is extremely rare (0.1%). We describe a case of bowel perforation, occurred following daily intake of MTX. CASE REPORT: A 68-year-old man was prescribed to take MTX 7,5 mg orally once a week, while waiting for switch to abatacept for a recent reactivation of rheumatoid arthritis. After 10 days he started having pharyngodynia, hematochezia and general malaise. At medical examination he presented oral and nasal mucositis; moreover, blood exams showed thrombocytopenia. The anamnesis revealed that he had been taken the prescribed dosage of MTX daily, instead of weekly. Therapy with Lederfolin 1000 mg (mg/m²/die) and urine alkalinization started. After 7 days of hospitalization, there was an abrupt worsening of clinical conditions and an emergency CT scan revealed millimetric gas bubbles indicating bowel perforation. The patient underwent an emergency exploratory laparotomy that resulted in peritoneal toilette and sigma resections. Anatomopathological findings were suggestive of MTX poisoning. CONCLUSIONS: The patient was discharged on the 17th day in good clinical condition.

A Novel Presentation of Tuberculosis with Intestinal Perforation in a Free-Ranging Australian Sea Lion (Neophoca cinerea).

We detail a novel presentation of tuberculosis associated with intestinal perforation in an endangered Australian sea lion (Neophoca cinerea) from South Australian waters and confirm the presence of this disease in the region of highest pup production. In February 2017, a 3-yr-old juvenile male died shortly after hauling out at the Kingscote beach on Kangaroo Island. On postmortem examination, we found a mid-jejunal intestinal perforation and partial obstruction (from a strangulating fibrous and granulomatous mesenteric mass), a marked multicentric abdominal fibrosing granulomatous lymphadenitis, and a large volume serosanguinous peritoneal effusion. Acid-fast bacteria were detected postmortem in cytologic preparations of the mesenteric lymph node and in histologic sections of jejunum and the encircling mass. Mycobacterial infection was confirmed by positive culture after 3 wk. Molecular typing using mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing with 12-locus analysis identified Mycobacterium pinnipedii. This case highlights the need for vigilance of zoonotic disease risk when handling pinnipeds, including in the absence of specific respiratory signs or grossly apparent pulmonary pathology. Increased serologic population surveillance is recommended to assess the species' risk from this and other endemic diseases, especially given its endangered status.

Gastrointestinal perforation in anti-NXP2 antibody-associated juvenile dermatomyositis: case reports and a review of the literature.

BACKGROUND: To summarize the characteristics of gastrointestinal (GI) perforation in anti-nuclear matrix protein 2 (NXP2) antibody-associated juvenile dermatomyositis (JDM). METHODS: Five patients with GI perforation from a JDM cohort of 120 cases are described. Relevant literature was reviewed. RESULTS: Five patients, including four females and one male, were included in the study. The age of onset of these patients ranged from 3.3 to 9.5 years with the median age of 5.0 years. When these patients were complicated by GI perforation, childhood myositis assessment score (CMAS) ranged from 1 to 5 with the median score of 2. Myositis-specific antibody (MSA) spectrum analysis indicated that the five patients were anti-NXP2 antibody positive. The initial symptoms of GI perforation were progressive abdominal pain and intermittent fever. Two patients also presented with ureteral calculus with hydronephrosis and ureteral stricture. Surgery was performed in four patients. One patient failed to undergo a repair as the perforation was high in position. For the other three patients, perforation repair was successful, of which two patients failed due to recurrent perforation. At 24 months postoperative follow-up, one patient was in complete remission on prednisone (Pred) and methotrexate (MTX) treatment, and her ureteral stricture had disappeared. The other four patients died. Adding these cases with 16 other patients described in the literature, the symptom at onset was progressive abdominal pain, which often occurred within 10 months after JDM was diagnosed. Perforation most commonly occurred in the duodenum, although it also occurred at multiple sites or was recurrent. The mortality rate of GI perforation in JDM was 38% (8/21). CONCLUSIONS: All the five perforation cases in our study subjected to MSA analysis were anti-NXP2 antibody positive. The symptom at onset was abdominal pain. The most common site of perforation was the duodenum in the retroperitoneum, and the lack of acute abdominal manifestations prevented early diagnosis. GI perforation may be a fatal complication in JDM, and early diagnosis is very important. More research is needed to determine the pathogenesis and predictive factors of GI perforation in JDM.

HARTMANN PROCEDURE OR RESECTION WITH PRIMARY ANASTOMOSIS FOR TREATMENT OF PERFORATED DIVERTICULITIS? SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Mortality after emergency surgery in randomized controlled trials. The Hartmann procedure remains the treatment of choice for most surgeons for the urgent surgical treatment of perforated diverticulitis; however, it is associated with high rates of ostomy non-reversion and postoperative morbidity. AIM: To study the results after the Hartmann vs. resection with primary anastomosis, with or without ileostomy, for the treatment of perforated diverticulitis with purulent or fecal peritonitis (Hinchey grade III or IV), and to compare the advantages between the two forms of treatment. METHOD: Systematic search in the literature of observational and randomized articles comparing resection with primary anastomosis vs. Hartmann's procedure in the emergency treatment of perforated diverticulitis. Analyze as primary outcomes the mortality after the emergency operation and the general morbidity after it. As secondary outcomes, severe morbidity after emergency surgery, rates of non-reversion of the ostomy, general and severe morbidity after reversion. RESULTS: There were no significant differences between surgical procedures for mortality, general morbidity and severe morbidity. However, the differences were statistically significant, favoring primary anastomosis in comparison with the Hartmann procedure in the outcome rates of stoma non-reversion, general morbidity and severe morbidity after reversion. CONCLUSION: Primary anastomosis is a good alternative to the Hartmann procedure, with no increase in mortality and morbidity, and with better results in the operation for intestinal transit reconstruction.

Prevalence and Clinicopathologic Features of Intestinal Perforation Caused by Segmental Absence of the Intestinal Musculature in Adults.

Segmental absence of the intestinal musculature (SAIM) can cause intestinal perforation in adults. However, its prevalence and clinicopathologic features have not been well-described. This study aimed to determine the prevalence of SAIM-associated perforation and characterize its clinicopathologic features. We retrospectively examined 109 cases of intestinal perforation that underwent surgical resection from January 2009 to December 2019. SAIM was defined as the complete absence of the muscularis propria without extensive inflammation and fibrinous exudation around the perforation. SAIM was the second most frequent cause of perforation (26 cases: 24%), the most frequent cause being related to diverticulitis (39 cases: 36%). The most common site was the sigmoid colon (12 cases: 46.2%). The younger group (aged below 65 y) exhibited more frequent perforation of the upper segments of the gastrointestinal tract (from the duodenum to the descending colon) than the older group (65 y and above) (P=0.0018). No patients developed recurrence. The most common gross features were well-defined circular or small punched-out lesions, and the histologic features were complete absence of the muscularis propria and absence of hemorrhage and necrosis around the area of perforation. The characteristic features of SAIM were unique and their prevalence was higher than previously reported. The precise recognition of SAIM can aid in understanding the cause of perforation and avoiding further unnecessary examinations.

The Importance of Autopsy in a Case of Digestive Perforation Undetected by Postmortem Computed Tomography.

ABSTRACT: Cases of foreign body ingestion in the forensic literature are mainly described in children or psychiatric patients. Postmortem imaging can detect most foreign bodies, but its sensitivity depends, among other things, on the type of item and its location. In some cases, the ingestion of foreign bodies can remain unnoticed and have serious consequences for the patient. We describe the case of a patient who died in a psychiatric seclusion room with no obvious cause and for whom a forensic autopsy was requested. Further investigations showed the existence of a subdural hematoma associated with a midline shift, secondary to a skull fracture that was considered to be the cause of death. Toxicological analyses identified in blood several drugs, including diazepam (24 ng/mL) and its major metabolite nordazepam (24 ng/mL), propranolol (57 ng/mL), paliperidone (9 ng/mL), and loxapine (620 ng/mL). The forensic autopsy revealed the existence of a gastrointestinal perforation after the ingestion of a plastic teaspoon, which the postmortem CT scan had failed to detect. Although technological advances continue to assist the forensic pathologist in his diagnosis, autopsy still has a leading role in forensic investigations and does not yet seem to be replaceable by imaging techniques alone.

Case report: Intestinal perforation and secondary peritonitis due to Acanthocephala infection in a black-bellied pangolin (Phataginus tetradactyla).

A case of Acanthocephala infection in a 5-year-old female rehabilitated and released black-bellied pangolin (Phataginus tetradactyla), which was part of a post-release monitoring program of a pangolin research operation in the Central African Republic, is described. This represents the first report of Acanthocephala infection in this species, which lead to intestinal perforation, secondary peritonitis and ultimately to the death of the animal concerned. It is of relevance to alert the pangolin conservation and research community to a so far unreported cause of death. A case history and necropsy findings, as well as preliminary parasite identification and genetic characterization which potentially revealed a new gigantorhynchid taxon are presented.

Characterization of the cortisol response to traumatic hemorrhage and intra-abdominal contamination models in Cynomologus Macaques.

INTRODUCTION: Trauma, hemorrhage, and peritonitis have widely varying impacts on endocrine response in the injured patient. We sought to examine cortisol response in established non-human primate models of traumatic hemorrhage and intra-abdominal contamination. METHODS: Cynomologus Macaques were separated into two experimental groups, the polytrauma and hemorrhage model, involving a laparoscopic liver resection with uncontrolled hemorrhage, cecal perforation, and soft tissue excision; and the traumatic hemorrhage model, involving only liver resection and uncontrolled hemorrhage. Cortisol levels were measured pre-operatively, at the time of injury, and at regular intervals until post-operative day 1. RESULTS: Cortisol levels increased 600% from the pre-operative value in the polytrauma and hemorrhage model, with minimal changes (20%) in the hemorrhage only model. CONCLUSION: Cortisol levels increase dramatically in response to polytrauma and intra-abdominal contamination as compared to hemorrhage only. The lack of response in the hemorrhage only group may be due to relative adrenal insufficiency caused by the shock state or lack of enticing stimuli from fecal peritonitis.

A fatal case of cannabis body-packing: About an autopsy case report.

The body packing represents an illegal drug trafficking practice across the borders of certain countries. It has experienced enormous growth in recent years. The medical literature is rich in publications interested in body packaging of cocaine or heroin with sometimes lethal consequences. However, reported cases of cannabis body packing appear to be rare, sometimes underestimated, despite the notoriety of cannabis in the illegal drug market and its wide consumption around the world. We report in this work a forensic case of a cannabis body packer deceased due toa stercoral peritonitis secondary to a double perforation of thesigmoid and rectal colon.

Over-the-scope clip closure indicated as first- line therapy for iatrogenic rectal perforation.

n/a.

Impact of rectal perforation on recurrence during rectal cancer surgery in a national population registry.

BACKGROUND: Incidental perforation in rectal cancer surgery is considered a risk factor for poorer oncological outcome. Most studies emanate from the era before total mesorectal excision when staging, neoadjuvant treatment and surgical technique were suboptimal. This study assessed the impact of incidental perforation on oncological outcome in a cohort of patients with optimized management. METHODS: Data from the Swedish Colorectal Cancer Registry for patients undergoing R0 abdominal surgery for TNM stage I-III rectal cancer between 2007 and 2012, with 5-year follow-up, were analysed. Multivariable analysis was performed. RESULTS: In total, 6176 patients were analysed (208 with and 5968 without perforation). The local recurrence rate was increased after perforation (7·2 per cent (15 of 208) versus 3·2 per cent (188 of 5968); P = 0·001), but there were no differences in rates of distant metastasis (16·3 per cent (34 of 208) versus 19·8 per cent (1183 of 5968); P = 0·215) and overall recurrence (20·7 per cent (43 of 208) versus 21·0 per cent (1256 of 5968); P = 0·897). The 5-year overall survival rate was lower after perforation (66·4 versus 75·5 per cent; P = 0·002), but the 5-year relative survival rate was no different (79·9 versus 88·2 per cent; P = 0·083). In multivariable analysis, perforation was a risk factor for local recurrence (hazard ratio 2·10, 95 per cent c.i. 1·19 to 3·72; P = 0·011), but not for the other outcomes. CONCLUSION: Incidental perforation remains a significant risk factor for LR, even with optimized management of rectal cancer. This must be considered when discussing adjuvant treatment and follow-up.

ANTECEDENTES: La perforación incidental durante la cirugía de cáncer de recto se considera un factor de riesgo de un peor resultado oncológico. La mayoría de los estudios proceden de la era previa a la exéresis total del mesorrecto cuando la estadificación, el tratamiento neoadyuvante y la técnica quirúrgica eran subóptimos. En este estudio se evalúa el impacto de la perforación incidental en el resultado oncológico en una cohorte de pacientes con un tratamiento óptimo. MÉTODOS: Se analizaron los datos del Registro Sueco de Cáncer Colorrectal para pacientes sometidos a cirugía abdominal R0 en estadios TNM I-III entre 2007-2012 con un seguimiento de 5 años. Se realizó un análisis multivariable. RESULTADOS: En total, se analizaron 6.176 pacientes (208 con perforación, 5.968 sin perforación). La tasa de recidiva local (local recurrence, LR) aumentó después de la perforación (7,2% (15/208) versus 3,2% (188/5.968); P = 0,001)), pero no se detectaron diferencias con respecto a las tasas de metástasis a distancia (16,3% (34/208) versus 19,8% (1.183/5.968); P = 0,215)) ni de recidiva global (20,7% (43/208) versus 21,0% (1.256/5.968); P = 0,897)). La tasa de supervivencia global a los 5 años fue menor después de la perforación (66,4% versus 75,5%; P = 0,002), pero la tasa de supervivencia relativa a los 5 años fue similar (79,9% versus 88,2%; P = 0,083). En el análisis multivariable, la perforación fue un factor de riesgo para la LR (cociente de riesgos instantáneos, hazard ratio, HR 2,10 (i.c. del 95% 1,19-3,72); P = 0,011], pero no fue un factor de riesgo para los otros resultados. CONCLUSIÓN: La perforación incidental sigue siendo un factor de riesgo significativo para la LR incluso con el tratamiento optimizado del cáncer de recto, lo que debe tenerse en cuenta al discutir la indicación de tratamiento adyuvante y el tipo de seguimiento.

Case of Gut Necrosis in Adult-Onset Immunoglobulin A Vasculitis (Henoch-Schönlein Purpura).

Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is an immune-mediated small vessel vasculitis characterized by palpable purpura, arthralgia, abdominal pain, and renal disease. It is primarily a childhood disease and usually resolves spontaneously with supportive therapy. Treatment of IgAV in adults is controversial with no clearly established guidelines. We report a rare case of IgAV in an adult male who developed gut necrosis and perforation while receiving glucocorticoid therapy for treatment of acute glomerulonephritis. A 44-year-old male was admitted with joint pain, leg swelling, mild abdominal pain, and a diffuse rash. Laboratory values revealed acute kidney injury with significant proteinuria and hematuria. The patient was started on glucocorticoid therapy for suspected IgAV nephritis, which was confirmed by kidney biopsy. Several days later, he complained of worsening abdominal pain. Imaging demonstrated bowel ischemia and perforation requiring multiple abdominal surgeries. The patient was critically ill in the intensive care unit with worsening renal failure requiring dialysis. He was discharged a month later after gradual recovery with stable but moderately impaired kidney function. IgAV is less common in adults; however, the disease is more severe with a higher risk of long-term complications. Adult patients with renal involvement may benefit from glucocorticoid therapy in preventing progression to end-stage renal disease. However, glucocorticoids may mask the symptoms of abdominal complications like gut necrosis and perforation causing delay in diagnosis and treatment. Therefore, vigilance to detect early signs of gut ischemia is imperative when treating an adult case of IgAV nephritis with glucocorticoids.