Prospective evaluation of clinical characteristics and maternal outcomes of women with pathologically confirmed postpartum retained placental fragments.

OBJECTIVE: To determine the incidence, risk factors, and short-term maternal outcomes of women with pathologically confirmed retained products of conception (RPOC) following vaginal delivery. METHODS: Prospective cohort study of women with suspicion of RPOC following vaginal delivery, from March 2018 to April 2019. Women were followed for eight weeks postpartum. Women with complete retained placenta were excluded. Women with pathologically confirmed RPOC were compared to those without. Univariate analysis was conducted (ORs; [95% CI]) and was followed by multivariate analysis (aOR; [95% CI]). RESULTS: During the study period, there were 16,583 vaginal deliveries. A total of 96 women (0.58%) with a suspicion of RPOC were enrolled, of these, 53 women (55%) had pathologically confirmed RPOC. The most significant risk factors for pathologically confirmed RPOC were placental abruption (aOR 5.0 [2.29-11.13]) and Oxytocin augmentation of labor (aOR 1.7 [1.07-2.63]). Pathologically confirmed RPOC were associated with higher rates of prolonged hospitalization (OR 9.2 [2.83-30.05]), postpartum hemorrhage (PPH) (OR 6.6 [3.60-11.98]), hemoglobin drop > 3 g/dl (OR 11.4 [5.49-23.49]), and blood transfusion (OR 8.6 [2.07-38.18]). Women who had exploration of uterine cavity without pathological confirmation of RPOC, still had higher rates of perineal laceration (OR 17.6 [4.93-63.08]), PPH (OR 6.1 [3.05-12.21]), and a hemoglobin drop > 3 g/dl (OR 6.0 [2.13-16.95]). CONCLUSIONS: Pathologically confirmed RPOC following vaginal delivery has unique characteristics and is associated with significantly higher rates of PPH and blood transfusions. These findings may assist in the development of better criteria for selecting women for manual exploration and for preventive measures to reduce PPH and complications.

Recurrence of endometrial carcinoma presenting as vulvar lesions.

Vulvar metastasis is an unusual presentation of recurrent endometrial cancer and should be part of the differential diagnosis of vulvar lesion.

The Importance of Intestinal Eotaxin-1 in Inflammatory Bowel Disease: New Insights and Possible Therapeutic Implications.

BACKGROUND: Involvement of eotaxin-1 in inflammatory bowel disease has been previously suggested and increased levels of eotaxin-1 have been described in both ulcerative colitis and in Crohn's disease. The association between serum levels of eotaxin-1 and that within the colonic mucosa has not been well defined, as is the potential therapeutic value of targeting eotaxin-1. AIMS: To characterize serum and intestinal wall eotaxin-1 levels in various inflammatory bowel disease patients and to explore the effect of targeting eotaxin-1 by specific antibodies in dextran sodium sulfate-induced colitis model. METHODS: Eotaxin-1 levels were measured in colonic biopsies and in the sera of 60 ulcerative colitis patients, Crohn's disease patients and healthy controls. We also followed in experimental colitis the effect of targeting eotaxin-1 by a monoclonal antibody. RESULTS: Colon eotaxin-1 levels were significantly increased in active but not in quiescent ulcerative colitis and Crohn's disease patients compared to healthy controls. Levels of eotaxin-1 in the colon were correlated with eosinophilia only in tissues from active Crohn's disease patients. Our results did not show any statistically significant change in serum eotaxin-1 levels among ulcerative colitis, Crohn's disease and healthy controls. Moreover, we demonstrate that in dextran sodium sulfate-induced colitis, targeting of eotaxin-1 with 2 injections of anti eotaxin-1 monoclonal antibody ameliorates disease activity along with decreasing colon weight and improving histologic inflammation. CONCLUSION: Eotaxin-1 is increasingly recognized as a major mediator of intestinal inflammation. Our preliminary human and animal results further emphasize the value of targeting eotaxin-1 in inflammatory bowel disease.

Visceral cat scratch disease with endocarditis in an immunocompetent adult: a case report and review of the literature.

Infective endocarditis and hepatosplenic abscesses are rare manifestations of cat scratch disease (CSD), especially among immunocompetent adults. An otherwise healthy woman who presented with fever and abdominal pain was diagnosed with multiple abscesses in the spleen and the liver, as well as a mitral valve vegetation. PCR on spleen tissue was positive for Bartonella henselae. Prolonged treatment with doxycycline and gentamicin led to complete recovery. Review of the literature revealed 18 cases of hepatosplenic CSD in immunocompetent adults; the majority presented with fever of unknown origin and abdominal pain. In most cases the causative organism was B. henselae and the pathological findings were necrotizing granulomas, similar to the pathological features in classic CSD. Concomitant endocarditis was diagnosed in one case. Because Bartonella is one of the leading pathogens of culture-negative endocarditis, we raise the question of whether a comprehensive evaluation for endocarditis is needed in cases of systemic CSD.

Extra domain-A fibronectin is necessary for the development of nasal remodeling in chronic allergen-induced rhinitis.

BACKGROUND: Extra domain A-containing fibronectin (EDA-FN) is necessary for the development of allergen-induced lower airway fibrosis. The pathogenesis of fibrosis in allergic rhinitis has not been well studied. OBJECTIVES: To determine whether EDA-fibronectin is necessary for the development of nasal remodeling in a murine model of chronic allergic rhinitis and in human allergic rhinitis. METHODS: EDA(-/-) and wild-type (WT) C57Bl/6 mice were sensitized intraperitoneally and then challenged with inhaled ovalbumin (OVA) or saline for 2 and 5 weeks. Clinical signs of rhinitis and histological analysis of nasal tissue were evaluated. Immunohistological staining for EDA-FN was performed in human tissue of inferior nasal conchae from patients with allergic rhinitis and controls. RESULTS: After 2 weeks of allergen exposure, only goblet cell hyperplasia and perivascular eosinophilia were observed. After 5 weeks, goblet cell number, thickening of the subepithelial layer, and extent and area of collagen deposition were increased in the nasal tissue of WT OVA (ovalbumin)-challenged mice as compared with saline controls (P < .0001, P < .0001, P = .018, and P = .03, respectively). Clinical signs of rhinitis were observed only in WT OVA-challenged mice. In the EDA(-/-) mice exposed to OVA, collagen deposition, collagen area, and subepithelial thickness showed no increase and were similar to saline control mice, whereas goblet cell hyperplasia was similar to WT OVA-challenged mice. EDA-FN expression was prominent in inferior conchae from patients with allergic rhinitis but was absent in control patients. CONCLUSION: EDA-containing fibronectin is necessary for the development of nasal tissue fibrotic remodeling process in both murine and human allergic rhinitis.

Dietary copper supplementation restores ß-cell function of Cohen diabetic rats: a link between mitochondrial function and glucose-stimulated insulin secretion.

ß-Cell mitochondrial dysfunction as well as proinflammatory cytokines have been suggested to contribute to reduced glucose-stimulated insulin secretion (GSIS) in type 2 diabetes. We recently demonstrated that Cohen diabetic sensitive (CDs) rats fed a high-sucrose, low-copper diet (HSD) developed hyperglycemia and reduced GSIS in association with peri-islet infiltration of fat and interleukin (IL)-1ß-expressing macrophages, whereas CD resistant (CDr) rats remained normoglycemic on HSD. We examined: 1) the correlation between copper concentration in the HSD and progression, prevention, and reversion of hyperglycemia in CDs rats, 2) the relationship between activity of the copper-dependent, respiratory-chain enzyme cytochrome c oxidase (COX), infiltration of fat, IL-1ß-expressing macrophages, and defective GSIS in hyperglycemic CDs rats. CDs and CDr rats were fed HSD or copper-supplemented HSD before and during hyperglycemia development. Blood glucose and insulin concentrations were measured during glucose tolerance tests. Macrophage infiltration and IL-1ß expression were evaluated in pancreatic sections by electron-microscopy and immunostaining. COX activity was measured in pancreatic sections and isolated islets. In CDs rats fed HSD, GSIS and islet COX activity decreased, while blood glucose and infiltration of fat and IL-1ß-expressing macrophages increased with time on HSD (P < 0.01 vs. CDr-HSD rats, all parameters, respectively). CDs rats maintained on copper-supplemented HSD did not develop hyperglycemia, and in hyperglycemic CDs rats, copper supplementation restored GSIS and COX activity, reversed hyperglycemia and infiltration of fat and IL-1ß-expressing macrophages (P < 0.01 vs. hyperglycemic CDs-HSD rats, all parameters, respectively). We provide novel evidence for a critical role of low dietary copper in diminished GSIS of susceptible CDs rats involving the combined consequence of reduced islet COX activity and pancreatic low-grade inflammation.

Significance of bone marrow reticulin fibrosis in chronic lymphocytic leukemia at diagnosis: a study of 176 patients with prognostic implications.

BACKGROUND: Bone marrow (BM) biopsies from patients with chronic lymphocytic leukemia (CLL) may show reticulin fibrosis at diagnosis, but its significance remains unclear. This study sought to assess the prognostic impact of BM reticulin fibrosis in patients with previously untreated CLL. METHODS: Data was reviewed from untreated CLL patients in the national Israel CLL database, followed during 1987 to 2012. All bone marrow biopsies were graded for reticulin fibrosis using a modified scoring system containing 4 grades (0-3), based on the European consensus report. Grade of reticulin fibrosis was correlated with overall survival (OS), outcome, and a number of well-recognized prognostic factors for CLL. RESULTS: The final cohort included 176 patients (122 males and 51 females). Median age was 63 years (range, 32-86 years) and the 5-year OS was 77.1%. Grade of BM reticulin fibrosis correlated with OS (P < .0001) and mortality (P = .001), and separated patients into 2 groups with different survival curves. Advanced reticulin fibrosis (grades 2-3) was associated with thrombocytopenia (platelet counts of < 100,000/mm(3) ) (P = .025), anemia (P = .018), elevated ß2-microglobulin < 4000 µg/mL (P = .048), and the presence of 11q deletion (P = .0015). CONCLUSIONS: There was a significant correlation between poor survival and grade of BM reticulin fibrosis. This staining procedure is easy to perform and can readily be added routinely when examining BM biopsies in CLL, because the findings do have prognostic implications.

Involvement of CCR6/CCL20/IL-17 axis in NSCLC disease progression.

OBJECTIVES: Autocrine and paracrine chemokine/chemokine receptor-based interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis. CCL20/CCR6 interactions are involved in prostatic and colonic malignancy pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17 type immune response in NSCLC is not yet defined. We sought to characterize the role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. METHODS: A specialized histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue samples of NSCLC patients operated in our department. Results were correlated to disease progression. Colony assays, ERK signaling and chemokine production were measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation. RESULTS: CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression. High CCR6 expression was associated with a shorter disease-free survival (P = 0.008) and conferred a disease stage-independent 4.87-fold increased risk for disease recurrence (P = 0.0076, CI 95% 1.52-15.563). Cancerous cell colony-forming capacity was increased by CCL20 stimulation; this effect was dependent in part on ERK phosphorylation and signaling. IL-17 expression was detected in NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. CONCLUSION: Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression. CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17 axis as a potential new therapeutic target. Larger scale studies are required to consolidate these observations.

Perivascular epithelioid cell tumor of the ascending colon mesentery in a child: case report and review of the literature.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor. Perivascular epithelioid cell tumors of the gastrointestinal tract are very rare, with only about 20 previous reported cases. We present a 5.5-year-old boy with PEComa of the right colon. Treatment consisted of tumor resection only, without additional adjuvant therapy. Two years after surgery, he remains free of tumor. To the best of our knowledge, this is the youngest reported child with PEComa of the colon. We review the literature concerning PEComas in children, especially those of the gastrointestinal tract. We emphasize the importance of correct immunohistochemistry diagnosis, recommended treatment, and surveillance of this unique family of tumors.