Induction of IgG3 to LPS via Toll-Like Receptor 4 Co-Stimulation

B-cells integrate antigen-specific signals transduced via the B-cell receptor (BCR) and antigen non-specific co-stimulatory signals provided by cytokines and CD40 ligation in order to produce IgG antibodies. Toll-like receptors (TLRs) also provide co-stimulation, but the requirement for TLRs to generate T-cell independent and T-cell dependent antigen specific antibody responses is debated. Little is known about the role of B-cell expressed TLRs in inducing antigen-specific antibodies to antigens that also activate TLR signaling. We found that mice lacking functional TLR4 or its adaptor molecule MyD88 harbored significantly less IgG3 natural antibodies to LPS, and required higher amounts of LPS to induce anti-LPS IgG3. In vitro, BCR and TLR4 signaling synergized, lowering the threshold for production of T-cell independent IgG3 and IL-10. Moreover, BCR and TLR4 directly associate through the transmembrane domain of TLR4. Thus, in vivo, BCR/TLR synergism could facilitate the induction of IgG3 antibodies against microbial antigens that engage both innate and adaptive B-cell receptors. Vaccines might exploit BCR/TLR synergism to rapidly induce antigen-specific antibodies before significant T-cell responses arise

Elevated Platelet Count before Ileal Pouch–Anal Anastomosis for Ulcerative Colitis is Associated with the Development of Chronic Pouchitis

Acute pouchitis (AP) after ileal pouch–anal anastomosis (IPAA) is common and easily treated. However, chronic pouchitis (CP) remains a difficult management problem and may represent a form of Crohn disease (CD) of the ileal pouch. Because CD patients have higher platelet counts than ulcerative colotis (UC) patients, we prospectively evaluated the association between preoperative platelet count and pouchitis development in 159 patients undergoing IPAA. Reactive thrombocytosis (RT) was defined as a platelet count &gt;450 x 109/L. Median preoperative platelet count was 312 x 109/L (range, 103 x 109/L to 886 x 109/L). One hundred twenty-five patients (79%) had a normal (150 x 109/L to 450 x 109/L) platelet count (-RT patient group). Twenty-eight patients (18%) had RT. Six patients (3%) had a platelet count below 150 x 109/L. After a median follow-up of 13 months, 45 patients (28%) developed pouchitis. Pouchitis developed in 33 +RT patients (26%) versus 9 -RT patients (32%) ( P = NS). UC patients who had +RT had a 25 per cent incidence of CP compared to only 7 per cent of those UC patients who had -RT ( P = 0.03). The incidence of CP was significantly higher after IPAA in UC patients having thrombocytosis before surgery compared to UC patients having a normal platelet count before surgery. </jats:p

Evaluation of short-term risk factors associated with dehiscence and death following full-thickness incisions of the large intestine in cats: 84 cases (1993–2015)

Abstract OBJECTIVE To evaluate short-term risk factors associated with dehiscence and death in cats undergoing full-thickness large intestinal incisions. ANIMALS 84 client-owned cats that had undergone full-thickness large intestinal incisions and for which information regarding outcome through postoperative day 7 was available. PROCEDURES Medical records from 4 veterinary teaching hospitals were reviewed. For cats that met the inclusion criteria, signalment, history, laboratory test results, surgical and medical procedures, perioperative complications, and outcome were analyzed. A Fisher exact or Wilcoxon rank sum test was used to identify individual variables associated with dehiscence of intestinal incisions or patient nonsurvival to hospital discharge or both. RESULTS 84 cats met the inclusion criteria. The overall dehiscence and survival to hospital discharge rates were 8.3% (7/84 cats) and 94% (79/84 cats), respectively. Factors associated with dehiscence and nonsurvival to hospital discharge included presence of band neutrophils, performance of partial colectomy with colonic resection and anastomosis, administration of blood products, postoperative cardiopulmonary arrest, and incisional inflammation or infection. Factors associated with nonsurvival to hospital discharge only included low serum globulin concentration, repair of colonic trauma or dehiscence, and postoperative colonic dehiscence. Factors associated with dehiscence only included hypoalbuminemia, renal dysfunction, administration of blood products or &gt; 2 classes of antimicrobials, and intra-abdominal fecal contamination. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that intestinal dehiscence and mortality rates associated with large intestinal incisions in cats may be higher than previously proposed, although the risk of either outcome was still low. Factors suggestive of systemic illness were associated with colonic dehiscence or death, and focused prospective studies of risk factors are warranted. (J Am Vet Med Assoc 2021;259:162–171) </jats:sec

Evaluation of short-term outcomes and potential risk factors for death and intestinal dehiscence following full-thickness large intestinal incisions in dogs

Abstract OBJECTIVE To determine complication rates for dogs in which full-thickness large intestinal incisions were performed, assess potential risk factors for death during hospitalization and for intestinal dehiscence following these surgeries, and report short-term mortality rates for these patients. ANIMALS 90 dogs. PROCEDURES Medical records of 4 veterinary referral hospitals were reviewed to identify dogs that underwent large intestinal surgery requiring full-thickness incisions. Signalment, history, clinicopathologic data, medical treatments, surgical procedures, complications, and outcomes were recorded. Descriptive statistics were calculated; data were analyzed for association with survival to discharge (with logistic regression analysis) and postoperative intestinal dehiscence (with Fisher exact or Wilcoxon rank sum tests). RESULTS Overall 7-day postoperative intestinal dehiscence and mortality rates were 9 of 90 (10%) and 15 of 90 (17%). Dogs with preoperative anorexia, hypoglycemia, or neutrophils with toxic changes and those that received preoperative antimicrobial treatment had greater odds of death than did dogs without these findings. Preexisting colon trauma or dehiscence, preexisting peritonitis, administration of blood products, administration of &gt; 2 classes of antimicrobials, positive microbial culture results for a surgical sample, and open abdominal management of peritonitis after surgery were associated with development of intestinal dehiscence. Five of 9 dogs with intestinal dehiscence died or were euthanized. CONCLUSIONS AND CLINICAL RELEVANCE Factors associated with failure to survive to discharge were considered suggestive of sepsis. Results suggested the dehiscence rate for full-thickness large intestinal incisions may not be as high as previously reported, but several factors may influence this outcome and larger, longer-term studies are needed to confirm these findings. </jats:sec

Factors associated with postobstructive diuresis following decompressive surgery with placement of ureteral stents or subcutaneous ureteral bypass systems for treatment of ureteral obstruction in cats: 37 cases (2010–2014)

Abstract OBJECTIVE To describe postobstructive diuresis (POD) in cats undergoing surgical placement of ureteral stents or subcutaneous ureteral bypass systems for treatment of ureteral obstruction in cats and to identify factors associated with duration and maximum severity of POD. DESIGN Retrospective case series. ANIMALS 37 client-owned cats with ureteral obstruction treated between August 2010 and December 2014. PROCEDURES Medical records were reviewed, and data extracted included signalment, history, results from physical examinations and clinical laboratory analyses, treatment, urine output, and outcome. Data were evaluated to identify factors associated with POD duration and maximum severity, alone or in combination. RESULTS Serum concentrations of creatinine, potassium, phosphorus, and BUN before surgery positively correlated with duration and maximum severity of POD. Absolute changes in serum concentrations of creatinine, potassium, and BUN from before surgery to after surgery positively correlated with POD duration. Cats with anuria before surgery had longer POD than did other cats; however, there was no difference in POD duration or maximum severity with unilateral versus bilateral ureteral obstruction. Thirty-four of 37 (92%) cats survived to hospital discharge, which was not associated with whether ureteral obstruction was unilateral or bilateral. Azotemia resolved in 17 of the 34 (50%) cats that survived to hospital discharge. CONCLUSIONS AND CLINICAL RELEVANCE Results of the present study indicated that several factors were associated with POD duration and maximum severity, alone or in combination, and that with intensive management of fluid and electrolyte derangements, regardless of the extent of the original azotemia, a high percentage of cats survived to hospital discharge. </jats:sec