AA-amyloidosis in cats (Felis catus) housed in shelters.

Systemic AA-amyloidosis is a protein-misfolding disease characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. A high prevalence of AA-amyloidosis has been reported in captive cheetahs and a horizontal transmission has been proposed. In domestic cats, AA-amyloidosis has been mainly described in predisposed breeds but only rarely reported in domestic short-hair cats. Aims of the study were to determine AA-amyloidosis prevalence in dead shelter cats. Liver, kidney, spleen and bile were collected at death in cats from 3 shelters. AA-amyloidosis was scored. Shedding of amyloid fibrils was investigated with western blot in bile and scored. Descriptive statistics were calculated. In the three shelters investigated, prevalence of AA-amyloidosis was 57.1% (16/28 cats), 73.0% (19/26) and 52.0% (13/25), respectively. In 72.9% of cats (35 in total) three organs were affected concurrently. Histopathology and immunofluorescence of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B = 0.026, CI95% = 0.007-0.046; p = 0.010). AA-amyloidosis was very frequent in shelter cats. Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease. In conclusion, AA-amyloidosis was very frequent in shelter cats and those staying longer had more deposits. The cat may represent a natural model of AA-amyloidosis

Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis.

BACKGROUND Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low-flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA. AIM To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS. METHODS Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded. RESULTS At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month. CONCLUSIONS The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions. https://clinicaltrials.gov/ct2/show/NCT01532427

An unexpected protective role of low-affinity allergen-specific IgG through the inhibitory receptor FcγRIIb.

BACKGROUND Induction of allergen-specific IgG antibodies is a critical parameter for successful allergen-specific immunotherapy. IgG antibodies can inhibit IgE-mediated mast cell activation through direct allergen neutralization or through the inhibitory receptor FcγRIIb. The affinity of IgE antibodies to the allergen has been shown to be critical for cellular activation. OBJECTIVE Here we addressed the question of affinity thresholds of allergen-specific IgG antibodies for inhibition of mast cell activation using 2 different mAbs against the major cat allergen Fel d 1 both in vitro and in vivo in mice. METHODS Sequences of the 2 high-affinity mAbs were back-mutated to germline, resulting in low-affinity (10 mol/L) antibodies of the exact same specificity. RESULTS Using these newly generated recombinant antibodies, we demonstrate that low-affinity antibodies are still able to inhibit mast cell activation through FcγRIIb but do not neutralize the allergen. CONCLUSION Antibody affinity dictates the mechanism of mast cell inhibition, and IgG antibodies triggering the inhibitory FcγRIIb pathway can show a broader cross-reactivity pattern than previously thought. This indicates that allergen-specific immunotherapy generates a larger protective umbrella of inhibitory IgG antibodies than previously appreciated

Application of the 8th edition of the AJCC yTNM staging system shows improved prognostication in a single center cohort of esophageal carcinomas

Background The 8th edition of the AJCC TNM staging system presents for the first time a specific classification for esophageal carcinomas treated with neoadjuvant therapy (yTNM8). In this single center study, we applied the novel staging system in a “real life” case series and compared the prognostic value of yTNM8 with the preceding 7th edition (TNM7). Methods Out of 272 consecutive esophageal carcinomas that were treated during a 15-year period in one surgical center, all 198 cases that had undergone neoadjuvant therapy were reviewed and classified according to TNM7 and yTNM8. Results 50 ypT0 cases that had no specific staging in TNM7 were included into stages I (ypT0N0M0; n = 42), IIIA (ypT0N1M0; n = 6), IVA (ypT0N3M0; n = 1) and IVB (ypT0N0M1; n = 1) in yTNM8. Both systems showed significant prognostic impact (p < 0.0001 each). yTNM8 was superior regarding prognostication with lower values for goodness-of-fit criteria (Akaike Information Criterion 1589.331 vs 1593.239; and Schwarz Bayesian Criterion 1605.487 vs.1619.088). However, in TNM7, stage IIB tumors had better prognosis than stage IIA tumors, and likewise, stage IIIA tumors better compared to stage II in yTNM8. Conclusions yTNM8 allows accurate staging of esophageal carcinomas treated by neoadjuvant therapy, with slightly improved prognostication compared to TNM7. Additional data acquisition will be necessary for further improvement of staging for esophageal carcinomas after neoadjuvant treatment