Angiopoietin-Related/Angiopoietin-Like Proteins Regulate Angiogenesis

A general understanding of the molecular mechanisms underlying angiogenesis is emerging from the analysis of targeted mutations in vasculature-related genes. These analyses reveal that angiopoietin signaling through the TIE2 receptor is involved in regulating angiogenesis. Recently, we and several other groups have independently identified several molecules containing a coiled-coil domain and a fibrinogen-like domain, both of which are structurally conserved in angiopoietins. Because these molecules do not bind to the angiopoietin-specific receptor,TIE2, they have been named angiopoietin-related proteins (ARPs) or angiopoietin-like proteins (Angptls). ARPs/Angptls, which are all currently orphan ligands, also have potent activity for regulating angiogenesis as proangiogenic or antiangiogenic factors, suggesting that their receptors may be expressed on endothelial cells. In addition, ARPs/Angptls show pleiotropic effects not only on vascular cells but also on cells of other lineages, such as skin and chondrocyte cells. More recent studies have proposed that ARPs/Angptls are involved in various pathologies, such as tumor angiogenesis and metabolic diseases. To summarize the current findings relating to these proteins, we focus in this review on the functions of ARPs/Angptls as new angiogenic modulating factors in the vascular system and discuss the pleiotropic functions of ARPs/Angptls in nonvascular cell lineages.     

Stapled Mucosectomy for Rectocele Repair: A Preliminary Report

There is no optimum surgical method of repair for rectoceles; however, recent interest in the use of the circular hemorrhoidal stapler gun to treat rectoceles has stirred interest. We describe our early results using the circular hemorrhoidal stapler gun for repair of rectoceles. Seven patients (median age, 45 (range, 31–62) years; all females) have been treated. All seven patients presented with incomplete or difficult defecation, four patients required digital vaginal manipulation, and all patients had tried a variety of aperients to aid defecation. The procedure involved two pursestrings and one firing of the circular hemorrhoidal stapler gun. No perioperative complications were encountered. At a median of six (range, 1– 10) months follow-up, all patients were able to defecate without difficulty or manipulation. None of the patients required any medication to aid bowel evacuation after surgery. These promising early results support the use of stapled mucosectomy for the repair of rectoceles.     

Sclerosing Mesenteritis With Occult Ileal Perforation: Report of a Case Simulating Extensive Intra-Abdominal Malignancy

Sclerosing mesenteritis is a rare condition that is characterized by fibrosis affecting mainly small-bowel mesentery, which in extensive cases may mimic advanced intra-abdominal malignancy. Establishing the diagnosis in such cases is a clinical and histopathologic challenge. We report the successful management of a case of extensive sclerosing mesenteritis with occult ileal perforation, which was possibly the triggering cause. Severe complications occurred as a result of both the disease itself and its surgical treatment. Despite the complex course and life-threatening complications, a good prognosis can be expected. Although occasional recovery has been attributed to spontaneous regression and response to immunosuppressive therapy, a search for, and full eradication of, possible triggering focus is of paramount importance.Reprints are not available.     

Duloxetine for the long-term treatment of Major Depressive Disorder in patients aged 65 and older: an open-label study

Background  

Late-life depression is a common, chronic and recurring disorder for which guidelines recommend long-term therapy. The safety and efficacy of duloxetine for the treatment of major depressive disorder (MDD) were evaluated using data from elderly patients (age ≥ 65 years; n = 101) who participated in a large, multinational, open-label study.     

Kawasaki disease in an infant following immunisation with hepatitis B vaccine

The known association between hepatitis B and vasculitis has been reported in rare cases in adults after hepatitis B vaccination. We here describe a 35-day-old infant who developed Kawasaki disease 1 day after receiving his second dose of hepatitis B vaccine. Although extremely rare, this possible side effect should be noted and further investigated.Abbreviations AO Aorta - LCA Left coronary artery - RCA Right coronary artery - PAN Polyarteritis nodosa - KD Kawasaki disease - ESR Erythrocyte sedimentation rate - WBC White blood cell - LAD Left anterior descending - LC Left circumflex - IVIG Intravenous immunoglobulin - CT Computerized tomography     

Assessment of Mediastinal Lymph Node Size in Pneumococcal Pneumonia with Bacteremia

Introduction

The significance of mediastinal lymphadenopathy in bacterial pneumonia is unclear.

Methods

We performed a retrospective analysis of mediastinal lymph node size determined by chest CT in patients with bacteremic pneumococcal pneumonia. All patients who had positive blood cultures for streptococcus pneumonia over an 11-year period and had a chest CT scan (index CT) within 2 weeks of the positive blood culture were included in the study. Two thoracic radiologists and one pulmonologist independently examined the index CT plus any chest CT scans performed prior (pre-CT) or after (post-CT) the bacteremic episode.

Results

The study cohort of 49 patients was 57% male, 65% White, with mean age of 53 (SD = 20) years. Mediastinal lymphadenopathy was detected in 25/49 (51%) of the cases. The mean size of the largest mediastinal lymph node in short axis was 0.99 (SD = 0.71), ranging from 0.0 to 2.05 cm. There was no correlation noted between the number of lobes involved with pneumonia, and the size of the largest mediastinal lymph node (p = 0.33) or the number of pathologically enlarged mediastinal lymph nodes (p = 0.08). There was a statistically significant increase in the mean size of the largest lymph node between the pre-CT and index-CT group (p = 0.02), and decrease between the index-CT group and the post-CT (p = 0.03).

Conclusion

Pneumococcal pneumonia with bacteremia is associated with mild mediastinal lymph node enlargement. The presence of marked mediastinal lymphadenopathy (short axis LN size > 2 cm) should not be assumed from pneumococcal pneumonia.

     

Rhu-Epo down-regulates pro-tumorigenic activity of cancer-associated fibroblasts in multiple myeloma

We have previously demonstrated that recombinant human erythropoietin (rHuEpo) is involved in the regulation of the angiogenic response in multiple myeloma (MM) through a direct effect on macrophages and endothelial cells isolated from the bone marrow of patients with MM. The aim of the present study was designed to determine the effects of rHuEpo on cancer-associated fibroblasts (CAFs) from monoclonal gammopathy of undetermined significance (MGUS) and MM patients by means of in vitro and in vivo assays. rHuEpo treatment reduces the expression of mRNA levels of fibroblast activation markers, namely alpha smooth actin (αSMA) and fibroblast activation protein (FAP) in MGUS and MM CAFs, and of pro-inflammatory and pro-angiogenic cytokines, including interleukin (IL)-6 and IL-8, vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2), and hepatocyte growth factor (HGF) in MM CAFs. Moreover, rHuEpo inhibits the proliferative activity of MM CAFs and increased the apoptosis of MGUS and MM CAFs. Overall, these data suggest that rHu-Epo down-regulates CAFs pro-tumorigenic activity. Moreover, these results are not suggestive for a pro-angiogenic activity of rHuEpo on CAFs. In fact, rHuEpo pre-treatment induces a low angiogenic response in vivo in the chorioallantoic membrane (CAM) assay of MGUS and MM CAFs conditioned medium, not comparable to that of a well-known angiogenic cytokine, VEGF-A, tested in the same assay.     

Retromesenteric course of the middle colic artery—challenges and pitfalls in D3 right colectomy for cancer

Background

The middle colic artery (MCA) is of crucial importance in abdominal surgery, for laparoscopic or open right and transverse colectomies. Against this background, a high number of reports concerning anatomical variations of the MCA have been published intended to contribute to the improvement of operative techniques for the treatment of colon cancer. Despite this extensive literature, briefly reviewed in the present paper, a course of the MCA posterior to the superior mesenteric vein, called a retromesenteric trajectory, has been related to only once, to the best of our knowledge.

Methods

A total series of 507 patients included in two prospective trials concerning laparoscopic or open right colectomy for cancer between 2011 and 2017 are reported. The investigation included preoperative or postoperative multidetector-computed tomography angiography.

Results

We found four (0.79%) cases of retromesenteric MCA. They all underwent meticulous image analysis with mesenteric vessels’ road mapping, detailed morphometry, and surgical validation which revealed that, apart from their course, those cases did not differ significantly from the rest of the series.

Conclusion

This paper therefore documents the worth-knowing behavior causing considerable confusion for the operating surgeon unaware of the abnormality and shows its concrete impact on patient-tailored surgical practice, in particular for laparoscopic D3 colectomy (including the “uncinated process first” approach).

     

Late assessment of quality of life in patients with rectal carcinoma: comparison between sphincter preservation and definitive colostomy

Purpose

Patients with cancer of the lower and middle rectum who are candidates for curative surgery often have negative opinions on definitive colostomy. The purpose of this study is to compare the quality of life (QoL) of patients who undergo standard treatment for rectal cancer with sphincter preservation or definitive colostomy.

Methods

A total of 125 patients with adenocarcinoma of the lower or middle rectum who underwent radical surgery with curative intent with a follow-up ≥?1 year were recruited: 83 patients (group 1) were subjected to low anterior resection and low colorectal or coloanal anastomosis—thus preserving their sphincter—and 42 (group 2) were treated with abdominoperineal resection, followed by terminal definitive colostomy. QoL was assessed with the EORTC QLQ-C30 and QLQ-CR29 questionnaires.

Results

Health and global quality of life were similar between groups; however, patients who underwent definitive colostomy had higher scores on the emotional (p value?=?0.016) and cognitive function scales (p value?=?0.017). Patients with sphincter preservation presented with more symptoms that were related to stool frequency (p value <?0.001), intestinal constipation (p value?=?0.005), fecal incontinence (p value?=?0.001), buttock pain (p value?=?0.023), and nausea and vomiting (p value?=?0.036), whereas patients with permanent colostomy had higher scores for dysuria (p value?=?0.033).

Conclusion

Although global QoL scores did not differ between groups, patients who underwent definitive colostomy had significantly better functional and symptom scale scores, reflecting greater function with fewer symptoms.

     

Survey of alcohol-related cirrhosis at a tertiary care center in North East India

Background

Alcohol use is increasing in North East India and is important to estimate the influence of these changes in the epidemiology of alcohol related cirrhosis.

Methods

Among 1000 consecutive patients of cirrhosis, diagnosed by a combination of clinical, radiological and/or histopathological features, etiology was established by history of significant alcohol abuse, determining viral and autoimmune markers and by metabolic screening. Patients not confirmed to be cirrhotic were excluded from the study. All cases were studied to determine clinical features, complications, disease prognosis, and mortality. Alcoholic cirrhotics were then compared with nonalcohol etiology.

Results

72.2 % alcoholic cirrhosis were compared with 27.8 % patients of nonalcohol etiology and alcoholic cirrhotics were younger (45?+?9.4 years vs. 47.9?+?12.5 years), predominantly males (M/F ratio 37:1 vs. 1.8:1) with significantly high incidence of jaundice (38.5 % vs. 30.5 %), night blindness (14.4 % vs. 3.6 %), ascites (76.3 % vs. 69.1 %), upper gastrointestinal bleed (46.4 % vs. 34.5 %), and hepatic encephalopathy (24.1 % vs. 10.4 %). Biochemical parameters that were significantly higher in alcoholics were mean bilirubin (4.7?+?8.7 vs. 3.1?+?4.7 mg/dL), AST/ALT ratio (2.03 vs. 1.4), gamma-glutaryl transaminase levels (209.7?+?37.9 vs. 93.9?+?14 IU/mL), and serum ammonia (75.1?+?55.7 vs. 52.1?+?45.4 mg/dL). Mean model for end-stage liver disease, scores, and Child C disease was significantly higher in alcoholics (18.6?+?7.7 vs. 15.6?+?6.4) and (54.1 % vs. 37 %), respectively, representing advanced disease at presentation. Mortality within 1 month was significantly higher among alcoholic cirrhosis (9.8 % vs. 3.2 %).

Conclusion

Thus, alcoholic cirrhosis is of major concern in North East India as majority patients are in most productive age group and presented with advanced disease. Short-term mortality was high among alcoholic cirrhotics. Proper education and legislation are essential to mitigate the consequences of this disease.