CD5L as a promising biological therapeutic for treating sepsis.

Sepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for treating experimental sepsis caused by cecal ligation and puncture (CLP). We show that CD5L's important features include its ability to enhance neutrophil recruitment and activation by increasing circulating levels of CXCL1, and to promote neutrophil phagocytosis. CD5L-deficient mice exhibit impaired neutrophil recruitment and compromised bacterial control, rendering them susceptible to attenuated CLP. CD5L-/- peritoneal cells from mice subjected to medium-grade CLP exhibit a heightened pro-inflammatory transcriptional profile, reflecting a loss of control of the immune response to the infection. Intravenous administration of recombinant CD5L (rCD5L) in immunocompetent C57BL/6 wild-type (WT) mice significantly ameliorates measures of disease in the setting of high-grade CLP-induced sepsis. Furthermore, rCD5L lowers endotoxin and damage-associated molecular pattern (DAMP) levels, and protects WT mice from LPS-induced endotoxic shock. These findings warrant the investigation of rCD5L as a possible treatment for sepsis in humans.

Spontaneous cecal perforation in a cat diagnosed with ultrasonography.

An 8-year-old cat was presented for an acute history of anorexia, marked abdominal pain, and hyperthermia. Ultrasonography showed a cecal perforation with focal steatitis and adjacent free gas bubbles, consistent with focal peritonitis. Surgery confirmed the imaging findings. An enterectomy was performed with the removal of the cecum and ileocolic valve, and anastomosis between the ileum and colon was performed. Histology revealed transmural enteritis and chronic severe pyogranulomatous peritonitis with intralesional plant fragments.

Sepsis-Induced Inhibition of Contractile Function of Lymphatic Nodes.

Inflammation accompanies most pathological processes, while the lymphatic system takes part in both the development and resolution of inflammation. We studied the contractile function of rat lymph nodes after cecal ligation and puncture (CLP). In 24 h after CLP, the mesenteric lymph nodes were removed and placed in the myograph chamber. After CLP, the lymph nodes showed lower tension than lymph nodes from sham-operated animals (control). The expression of inducible NO synthase, cyclooxygenase-2, and cystathionine-γ-lyase was observed in the lymph nodes of CLP rats. NO, prostaglandins, and H2S formed during inflammation inhibited contractile activity of smooth muscle cells in the capsule of the lymph nodes, which manifested itself in inhibition of phase contractions and a decrease in the tone of their capsule.

EARLY BLOOD LACTATE AS A BIOMARKER FOR CARDIOVASCULAR COLLAPSE IN EXPERIMENTAL SEPSIS.

ABSTRACT: Cecal ligation and puncture (CLP) is the gold standard model for studying septic shock, which is characterized by hypotension and hyporeactivity to vasoconstrictors. However, approximately 30% of CLP animals do not exhibit cardiovascular changes, requiring more replicates because of the high variability of the model. Therefore, biomarkers enabling the early prediction of cardiovascular collapse in sepsis would greatly benefit sepsis nonclinical studies, refining experimental models and improving clinical translation. Thus, this study aimed to test whether the early increase in lactate levels could predict hypotension and hyporesponsiveness to vasoconstrictors in a rat model of sepsis. Male and female Wistar rats were subjected to CLP or sham procedure. Tail blood lactate was measured 6, 12, and 24 h after surgery. Then, inflammatory, biochemical, and hemodynamic parameters were evaluated. Rats subjected to CLP developed hypotension, hyporesponsiveness to vasoconstrictors, an intense inflammatory process, and increased plasma markers of organ dysfunction. By using receiver operating characteristics curve analysis, we have established that a lactate value of 2.45 mmol/L can accurately discriminate between a rat exhibiting a normal vasoconstrictive response and a vasoplegic rat with 84% accuracy (area under the curve: 0.84; confidence interval [CI]: 0.67-1.00). The sensitivity, which is the ability to identify a diseased rat (true positive), was 75% (CI: 41-95), and the true negative rate was 81% (CI: 57-93). Therefore, early measurement of lactate levels in sepsis could serve as a valuable biomarker for distinguishing vasoplegic rats from those exhibiting normal vasoconstrictive responses.

Outcomes Among Malnourished Patients With Crohn's Disease Undergoing Elective Ileocecectomy: A Nationwide Analysis.

BACKGROUND: Crohn's patients' nutritional status can be suboptimal given disease pathophysiology; the effect of a malnourished state prior to elective surgery on post-operative outcomes remains to be more clearly elucidated. This study aims to characterize the effect of malnutrition on post-operative outcomes and readmission patterns for Crohn's patients undergoing elective ileocecectomy using a nationally representative cohort. METHODS: The colectomy-targeted National Surgical Quality Improvement Program Database (2016-2020) was used to identify patients with Crohn's disease without systemic complications who underwent elective ileocecectomy; emergency surgeries were excluded. Malnourished status was defined as pre-operative hypoalbuminemia <3.5 g/dL, weight loss >10% in 6 months, or body mass index <18.5 kg/m2 prior to surgery. RESULTS: Of 1464 patients (56% female) who met inclusion criteria, 1137 (78%) were well-nourished and 327 (22%) were malnourished. Post-operatively, malnourished patients had more organ space surgical site infections (SSI) (9% vs 4% nourished groups, P < .001) and more bleeding events requiring transfusion (9% vs 3% nourished, P < .001). 30-day unplanned readmission was higher in the malnourished group (14% vs 9% nourished, P = .032). Index admission length of stay was significantly longer in the malnourished group (4 days [3-7 days] vs the nourished cohort: 4 days [3-5 days], P < .001). DISCUSSION: Poor nutritional status is associated with organ space infections and bleeding as well as longer hospitalizations and more readmissions in Crohn's patients undergoing elective ileocecectomy. A detailed nutritional risk profile and nutritional optimization is important prior to elective surgery.

Laparoscopic cecectomy for diseases of the appendix and cecum

Introduction: The cecum is the first part of the large bowel. Cecectomy is a sufficient treatment for some patients, avoiding overtreatment by ileocolic resection. Purpose:The goal of this study was to review a surgeon's experience with laparoscopic cecectomy and provide a technical video demonstration of this uncommon operation. Methods: A retrospective chart review was conducted of all consecutive patients treated with laparoscopic cecectomy over a 16-year period. All operations were performed using a 3-trocar technique. The cecum was transected with 1 to 2 firings of a 60 millimeters linear stapler, preserving the ileocecal valve and ascending colon. Results: 19 patients were identified including 12 females (63.2%). Median age was 42 years (range 16-84). Indication for surgery included appendiceal pathology in 12 patients (63.2%) and cecal abnormality in 7 (38.9%). There was no conversion to open surgery. Median intraoperative blood loss was 25 ml (range 0-150 ml) and no patient received a blood transfusion. No intraoperative or postoperative complication was noted. The median length stay was 1 day (range 0-6). Readmission rate was 0%. Final appendiceal histopathology revealed acute/chronic appendicitis in 5 patients, mucinous cystadenoma in 4 patients. Cecal histopathology revealed adenoma in 4 patients. Median follow-up was 16 months (range 4-53). Conclusions: Laparoscopic cecectomy is a sufficient treatment for some patients with benign conditions of the appendix and cecum. It carries minimal morbidity. It should be considered as an alternative to segmental bowel resection in a select group of patients. (AU)

Internal hernia through the foramen of Winslow: a rare cause of intestinal obstruction with imminent ischaemia of the caecum.

An internal hernia through the foramen of Winslow represents a rare surgical pathology. This report describes a case with incipient caecal ischaemia and discusses current diagnostic and therapeutic approaches. A patient in his early 60s presented at the emergency department with abdominal pain and last bowel movement three days prior. A CT scan of the abdomen suggested an internal hernia into the lesser sac. Intraoperatively, the suspected diagnosis could be confirmed laparoscopically with a twisted mobile caecum herniating through the foramen of Winslow. Due to a suspected ischaemia and laparoscopic frustrated reduction, a right open hemicolectomy was performed. The hernia gap was closed. The postoperative course was uneventful. Despite the rarity of internal hernias in patients without prior abdominal surgery, surgeons should be aware of this entity. The diagnosis can be difficult and sometimes only established intraoperatively. Open surgery is usually required. If the gap is clearly identified, the recommendations tend towards its closure.

Impact of timing of primary ileocecal resection on prognosis in patients with Crohn's disease.

BACKGROUND: The advantage of early ileocecal resection after Crohn's disease diagnosis is a matter of debate. This study aims to assess the timing of ileocecal resection on prognosis, after correction for possible confounders. METHODS: Patients with Crohn's disease with primary ileocecal resection between 2000 and 2019 were included in a retrospective multicentre cohort. The primary endpoint was endoscopic recurrence (Rutgeerts score ≥i2b) within 18 months. Secondary endpoints were escalation of inflammatory bowel disease medication within 18 months and re-resection during follow-up. The association between timing of ileocecal resection and these endpoints was investigated using multivariable proportional hazard models, corrected for covariates including Montreal classification, postoperative prophylaxis, smoking, indication for surgery, medication before ileocecal resection, perianal fistulas, surgical approach, histology, length of resected segment and calendar year. RESULTS: In 822 patients ileocecal resection was performed after a median of 3.1 years (i.q.r. 0.7-8.0) after Crohn's disease diagnosis. The lowest incidence of endoscopic recurrence, escalation of inflammatory bowel disease medication and re-resection was observed for patients undergoing ileocecal resection shortly after diagnosis (0-1 months). After correction for covariates, patients with ileocecal resection at 0, 4 and 12 months after diagnosis had a cumulative incidence of 35 per cent, 48 per cent and 39 per cent for endoscopic recurrence, 20 per cent, 29 per cent and 28 per cent for escalation of inflammatory bowel disease medication and 20 per cent, 30 per cent and 34 per cent for re-resection, respectively. In the multivariable model ileocolonic disease (HR 1.39 (95 per cent c.i. 1.05 to 1.86)), microscopic inflammation of proximal and distal resection margins (HR 2.20 (95 per cent c.i. 1.21 to 3.87)) and postoperative prophylactic biological and immunomodulator (HR 0.16 (95 per cent c.i. 0.05 to 0.43)) were associated with endoscopic recurrence. CONCLUSION: The timing of ileocecal resection was not associated with a change of disease course; in the multivariable model, the postoperative recurrence was not affected by timing of ileocecal resection.

Stattic ameliorates the cecal ligation and puncture-induced cardiac injury in septic mice via IL-6-gp130-STAT3 signaling pathway.

AIM: Sepsis-induced cardiac dysfunction is the leading cause of higher morbidity and mortality with poor prognosis in septic patients. Our recent previous investigation provides evidence of the hallmarks of signal transducer and activator of transcription3 (STAT3) activation in sepsis and targeting of STAT3 with Stattic, a small-molecule inhibitor of STAT3, has beneficial effects in various septic tissues. We investigated the possible cardioprotective effects of Stattic on cardiac inflammation and dysfunction in mice with cecal ligation and puncture (CLP)-induced sepsis. MAIN METHODS: A polymicrobial sepsis model was induced by CLP in mice and Stattic (25 mg/kg) was intraperitoneally given at one and twelve hours after CLP operation. The cecum was exposed in sham-control mice without CLP. After 18 h of surgery, electrocardiogram (ECG) for anaesthized mice was registered followed by collecting of samples of blood and tissues for bimolecular and histopathological assessments. Myeloperoxidase, a marker of neutrophil infiltration, was assessed immunohistochemically. KEY FINDINGS: CLP profoundly impaired cardiac functions as evidenced by ECG changes in septic mice as well as elevation of cardiac enzymes, and inflammatory markers with myocardial histopathological and immunohistochemical alterations. While, Stattic markedly reversed the CLP-induced cardiac abnormalities and restored the cardiac function by its anti-inflammatory activities. SIGNIFICANCE: Stattic treatment had potential beneficial effects against sepsis-induced cardiac inflammation, dysfunction and damage. Its cardioprotective effects were possibly attributed to its anti-inflammatory activities by targeting STAT3 and downregulation of IL-6 and gp130. Our investigations suggest that Stattic could be a promising target for management of cardiac sepsis and inflammation-related cardiac damage.

[Caecum hernia of foramen of Winslow]. / Hernie caecale du foramen de Winslow.

Winslow's foramen hernia, or Blandin's hernia, is a rare internal hernia with a non-specific clinical presentation and its diagnosis may be difficult. The hernia occurs across the omental hiatus, bounded by the inferior vena cava posteriorly and the portal triad anteriorly. CT imaging provides several diagnostic clues in this condition. Prompt surgical management allows reduction before complications arise. We present a case of caecal internal herniation through Winslow's foramen in a patient who underwent gastrojejunal bypass about ten years ago. Laparoscopy with reduction of the caecal bascule and closure of the foramen is performed successfully.

La hernie du foramen de Winslow, ou hernie de Blandin, est une hernie interne rare, avec une présentation clinique non spécifique et son diagnostic peut être difficile. La hernie se produit au travers de l'hiatus omental, limité par la veine cave inférieure en arrière et la triade portale en avant. L'imagerie médicale par tomodensitométrie nous fournit plusieurs indices diagnostiques dans cette pathologie. La prise en charge chirurgicale rapide permet une réduction avant la survenue de complications. Nous présentons un cas de hernie interne caecale par le foramen de Winslow chez un patient ayant bénéficié d'un bypass gastro-jéjunal une dizaine d'années auparavant. Une laparoscopie avec réduction de la bascule caecale et fermeture du foramen est réalisée avec succès.

Targeting sting to reduce sepsis-induced acute intestinal injury.

BACKGROUND: Sepsis is a dysregulated host response to infection syndrome leading to life-threatening organ dysfunction. Sepsis-induced intestinal dysfunction is a key element in the progression to multisystem organ failure. The stimulator of interferon genes is an intracellular protein implicated in intestinal injury in sepsis. H151, a small molecule inhibitor of stimulator of interferon genes, has not yet been studied as a potential therapeutic in sepsis. We hypothesize that H151 therapeutically reduces sepsis-induced acute intestinal injury. METHODS: Male mice underwent cecal ligation and puncture and were treated with intraperitoneal H151 (10 mg/kg body weight) or vehicle. Intestines and serum were collected for analysis 20 hours after cecal ligation and puncture. Oral gavage of mice with FITC-dextran was performed 15 hours after cecal ligation and puncture. Five hours after gavage, serum was collected, and intestinal permeability was assessed. Mice were monitored for 10 days after cecal ligation and puncture to assess survival. RESULTS: Zonula occludens 1 tight junctional protein expression was reduced after cecal ligation and puncture and recovered with H151 treatment. This was associated with a 62.3% reduction in intestinal permeability as assessed by fluorimetry. After cecal ligation and puncture, treatment with H151 was associated with a 58.7% reduction in intestinal histopathologic injury (P < .05) and a 56.6% reduction in intestinal apoptosis (P < .05). Intestinal myeloperoxidase activity was decreased by 70.8% after H151 treatment (P < .05). Finally, H151 improved 10-day survival from 33% to 80% after cecal ligation and puncture (P = .011). CONCLUSION: H151, a novel stimulator of interferon genes inhibitor, reduces intestinal injury, inflammation, and permeability when administered as a treatment for cecal ligation and puncture-induced sepsis. Thus, targeting stimulator of interferon genes shows promise as a therapeutic strategy to ameliorate sepsis-induced acute intestinal injury.

Comparison of ileocecal resection and right hemicolectomy in the surgical treatment of complicated appendicitis.

BACKGROUND: Simple appendectomy with a complicated appendicitis diagnosis could prove difficult, sometimes requiring ex-tended resection. Hence, we aimed to compare two procedures that are preferred for extended resection, ileocecal resection, and right hemicolectomy, in terms of patients' demographic data, preoperative laboratory values (white blood cell [WBC], Neutrophil-to-lymphocyte ratio [N/L], C-reactive protein [CRP]), operation times, postoperative complications, length of hospital stay, and 1-month mortality rates. METHODS: We retrospectively reviewed patients who underwent extended resection with the diagnosis of complicated appen-dicitis in our clinic from February 2015 to December 2020. We divided the patients into two groups those who underwent right hemicolectomy and those who underwent ileocecal resection. RESULTS: Among the 55 patients who underwent extended resection with the diagnosis of complicated appendicitis, 32 (58.1%) underwent right hemicolectomy and 23 underwent ileocecal resection (41.8%). The groups did not differ statistically significantly in terms of demographic characteristics, preoperative laboratory values (WBC, N/L, CRP), Clavien-Dindo classification scores, mean hospital stay, or 1-month mortality rates (p>0.005). However, there was a statistically significant difference between the groups in terms of operation time (p<0.001). CONCLUSION: Ileocecal resection is a safe procedure for patients diagnosed with complicated appendicitis who are scheduled for extended resection.

[A Case of Inguinal Hernial Sac Metastasis of Cecal Cancer Resected with TAPP Approach].

Malignant tumor occurring in the inguinal region are relatively infrequent, and metastatic tumor is extremely rare. We report a case of inguinal hernial sac metastasis of cecal cancer resected with TAPP approach. The case is a 80's man. One year and 6 months after cecal cancer surgery, contrast-enhanced computer tomography(CT)examination revealed a solitary tumor in the right inguinal canal. We diagnosed inguinal hernia sac metastasis of cecal cancer and performed surgery. The mass in the hernia sac was resected with the TAPP approach. Histopathological findings were consistent with peritoneal metastasis directly to the inguinal hernia sac. The patient has been alive without 2 years after metastasectomy. It is necessary to treat patients with a history of malignant disease with keeping the possibility of inguinal hernia sac metastasis in mind.

Laparoscopic total colectomy with ileorectal anastomosis and subtotal colectomy with antiperistaltic cecorectal anastomosis for slow transit constipation.

To investigate the clinical efficacy of laparoscopic total colectomy with ileorectal anastomosis (TC-IRA) and laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis (SC-ACRA) on adults with slow transit constipation (STC). One hundred and three patients with STC were assigned to the TC-IRA group (n = 53) and the SC-ACRA group (n = 50). The clinical data were analyzed. The surgery was successful in all patients (100%). Significantly (P = 0.03) more patients took anti-laxatives during hospitalization in the TC-IRA than the SC-ACRA group (39.62% vs. 20.00%). Abdominal pain and distension was present in 33.96% and 32.00% patients in the TC-IRA and SC-ACRA group, respectively, which decreased insignificantly (P > 0.05) to 18.87% and 18.00% 24 months after surgery, respectively. The postoperative Wexner and gastrointestinal quality of life (GIQLI) scores were not significantly different (P > 0.05) at all times after surgery in both groups. The defecation frequency decreased in both groups, and the average defecation frequency was significantly (P < 0.05) higher in the TC-IRA than the SC-ACRA group (3.91 ± 1.23 vs. 3.14 ± 1.15 times/day) at 3 months. Three months after surgery, significantly (P < 0.05) fewer patients were satisfied with defecation frequency in the TC-IRA than the SC-ACRA group (29 vs. 37 patients), whereas the number of patients who were willing to choose the same procedure again was not significantly (P > 0.05) different between the two groups. The WIS score of patients was significantly (P = 0.035) higher in the TC-IRA than the SC-ACRA group (6 vs. 5) 3 months later. TC-IRA and SC-ACRA are both safe and effective for adult slow transit constipation, and can significantly improve the quality of life of patients. Even though SC-ACRA has better early defecation frequency, postoperative antidiarrheal application and satisfaction, the long-term follow-up effects are similar.

Positive margins and plexitis increase the risk of recurrence after ileocecal resection: A systematic review and meta-analysis.

INTRODUCTION: There is debate over the impact of residual microscopic disease after ileocecal resection in Crohn's disease (CD) to predict recurrence. We conducted a meta-analysis to evaluate the impact of positive histological margins and plexitis after ileocecal resection on the risk of postoperative recurrence. METHODS: Using a systematic search, we identified. 30 studies evaluating the impact of inflammatory margins on CD recurrence. The primary outcome was the postoperative clinical recurrence and secondary outcomes were surgical, and endoscopic recurrence. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs. RESULTS: Thirty studies were analyzed, seven focused on myenteric plexitis, six on submucosal plexitis and twenty-three on positive margins. Inflammatory margins were associated with a higher rate of clinical and surgical recurrences: respectively 14 studies - OR 2.38; 95% CI, 1.54 - 3.68- I2 = 68.2%, Q test-p = 0.0003 and 8 studies - OR, 1.52; 95% CI, 1.07-2.16 - I2 =0%; Q test-p = 0.43. The presence of myenteric plexitis was associated with a higher rate of clinical recurrence (4 studies- OR, 1.60; 95%CI, 1.12-2.29; I2= 0%, Q-test-p = 0.61), and of endoscopic recurrence (4 studies - OR, 4.25; 95%CI; 2.06-8.76; I2= 0%, Q test-p = 0.97). Submucosal plexitis was not associated with an increased risk of endoscopic recurrence (4 studies - OR, 0.94; 95%CI; 0.58-1.52; I2= 0%, Q test-p = 0.79). CONCLUSION: Inflammatory margins and/or plexitis were associated with postoperative recurrence after ileocecal resection for CD. These elements should be taken into account in future algorithm for prevention of postoperative recurrence.