Platelet formation is the consequence of caspase activation within megakaryocytes

Platelets are formed from mature megakaryocytes (MKs) and arise from the development of long and thin cytoplasmic extensions called proplatelets. After platelet release, the senescent MKs (nucleus surrounded by some cytoplasm) undergo cell death by apoptosis. To explore the precise role of apoptosis in proplatelet formation, we grew human MKs from CD34(+) cells and assessed the possible role of caspases. Proteolytic maturation of procaspase-3 and procaspase-9 was detected by immunoblots in maturing MKs as well as in proplatelet-bearing MKs and senescent MKs. Cleavage of caspase substrates such as gelsolin or poly adenosine diphosphate (ADP)-ribose polymerase (PARP) was also detected. Interestingly, activated forms of caspase-3 were detected in maturing MKs, before proplatelet formation, with a punctuate cytoplasmic distribution, whereas a diffuse staining pattern was seen in senescent and apoptotic MKs. This localized activation of caspase-3 was associated with a mitochondrial membrane permeabilization as assessed by the release of cytochrome c, suggesting an activation of the intrinsic pathway. Moreover, these MKs with localized activated caspase-3 had no detectable DNA fragmentation. In contrast, when apoptosis was induced by staurosporine, diffuse caspase activation was seen; these MKs had signs of DNA fragmentation, and no proplatelet formation occurred. The pan-caspase inhibitor z-VAD.fmk as well as more specific inhibitors of caspase-3 and caspase-9 blocked proplatelet formation, whereas an inhibitor of calpeptin had no effect. Overexpression of Bcl-2 also inhibited proplatelet formation in maturing MKs. Thus, localized caspase activation is causal to proplatelet formation. We conclude that proplatelet formation is regulated by a caspase activation limited to only some cellular compartments.     

Octreotide in Hennekam syndrome-associated intestinal lymphangiectasia

A number of disorders have been described to cause protein losing enteropathy (PLE) in children. Primary intestinal lymphangiectasia (PIL) is one mechanism leading to PLE. Few syndromes are associated with PIL; Hennekam syndrome (HS) is one of them. The principal treatment for PIL is a high protein, low fat diet with medium chain triglycerides supplementation. Supportive therapy includes albumin infusion. Few publications have supported the use of octreotide to diminish protein loss and minimize hypoalbuminemia seen in PIL. There are no publications on the treatment of PIL with octreotide in patients with HS. We report two children with HS and PLE in which we used octreotide to decrease intestinal protein loss. In one patient, octreotide increased serum albumin to an acceptable level without further need for albumin infusions. The other patient responded more dramatically with near normal serum albumin levels and cessation of albumin infusions. In achieving a good response to octreotide in both patients, we add to the publications supporting the use of octreotide in PIL and suggest that octreotide should be tried in patients with PIL secondary to HS. To the best of our knowledge, this is the first case report on the use of octreotide in HS-associated PIL.     

Anti-HCV-Positive Cirrhosis Associated with Schistosomiasis

Hepatosplenic schistosomiasis is occasionally associated with cirrhosis and progressive hepatic decompensation. The aim of the present study was to determine the prevalence of antibody to hepatitis C virus in patients with schistosomiasis and cirrhosis. The prevalence of anti-HCV was studied in 12 consecutive cases of schistosomiasis associated with biopsy proven cirrhosis. All patients had a past history of schistosomiasis and high liters of schistosomal antibodies in serum (1:32 to 1:4096). Five of the 12 patients had hepatic catheterization and were found to have sinusoidal involvement with corrected sinusoidal pressures ranging from 19 to 23 mm Hg. Four had ascites, six had pedal edema, and eight had peripheral signs of chronic liver disease in the form of palmar erythema, spider nevi, and/or gynecomastia. Ten of the 12 cases (83%) were repeatedly positive for anti-HCV/ELISA. These results suggest that when patients with schistosomiasis develop cirrhosis, associated hepatitis C virus infection should be suspected.     

Prediction of survival with multi-scale radiomic analysis in glioblastoma patients

We propose a multiscale texture features based on Laplacian-of Gaussian (LoG) filter to predict progression free (PFS) and overall survival (OS) in patients newly diagnosed with glioblastoma (GBM). Experiments use the extracted features derived from 40 patients of GBM with T1-weighted imaging (T1-WI) and Fluid-attenuated inversion recovery (FLAIR) images that were segmented manually into areas of active tumor, necrosis, and edema. Multiscale texture features were extracted locally from each of these areas of interest using a LoG filter and the relation between features to OS and PFS was investigated using univariate (i.e., Spearman’s rank correlation coefficient, log-rank test and Kaplan-Meier estimator) and multivariate analyses (i.e., Random Forest classifier). Three and seven features were statistically correlated with PFS and OS, respectively, with absolute correlation values between 0.32 and 0.36 and p?<?0.05. Three features derived from active tumor regions only were associated with OS (p?<?0.05) with hazard ratios (HR) of 2.9, 3, and 3.24, respectively. Combined features showed an AUC value of 85.37 and 85.54% for predicting the PFS and OS of GBM patients, respectively, using the random forest (RF) classifier. We presented a multiscale texture features to characterize the GBM regions and predict he PFS and OS. The efficiency achievable suggests that this technique can be developed into a GBM MR analysis system suitable for clinical use after a thorough validation involving more patients.

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Graphical abstract Scheme of the proposed model for characterizing the heterogeneity of GBM regions and predicting the overall survival and progression free survival of GBM patients. (1) Acquisition of pretreatment MRI images; (2) Affine registration of T1-WI image with its corresponding FLAIR images, and GBM subtype (phenotypes) labelling; (3) Extraction of nine texture features from the three texture scales fine, medium, and coarse derived from each of GBM regions; (4) Comparing heterogeneity between GBM regions by ANOVA test; Survival analysis using Univariate (Spearman rank correlation between features and survival (i.e., PFS and OS) based on each of the GBM regions, Kaplan-Meier estimator and log-rank test to predict the PFS and OS of patient groups that grouped based on median of feature), and multivariate (random forest model) for predicting the PFS and OS of patients groups that grouped based on median of PFS and OS.

     

Elevated ARG1 expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients

Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their “M1/M2” activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p = 0 .032), moist desquamation (p = 0 .027), and CTC grade (p = 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p = 0 .069), moist desquamation (p = 0 .037), and CTC grade (p = 0 .046). To conclude, our findings underline for the first time the biological significance of increased ARG1 mRNA levels as an early independent predictive biomarker of RT-induced acute skin toxicities.     

Giant aneurysmal bone cyst of the scapula: A case report

Aneurysmal bone cyst (ABC) is a benign bone tumor affecting mainly children and young adults. It occurs in the metaphysis of the long bones. The scapula is a very rare location. Imaging may be highly suggestive of ABC in cases of an osteolytic, expansive, and hemorrhagic lesion with fluid-fluid levels and thin septa. The diagnosis must systematically be confirmed by performing a biopsy, in order to adopt the best therapeutic strategy. There are several therapeutic means, but wide resection remains the gold standard. The evolution is very variable and can go from spontaneous healing to recurrence with the destruction of the bone. We report a rare case of aneurysmal bone cyst of the scapula in a young patient.     

Complete common mesentery revealed by acute perforated appendicitis: case report and review of the literature

Intestinal malrotation in children is a rare aberration, due to a halt in the rotation and attachment of the primitive gut, it can be asymptomatic if the rotation terminates at 90 degrees, which manifests itself in unusual forms of appendicitis as in our observation, or dangerous in cases of inadequate common mesentery and worsened by small intestine volvulus. This 12-year-old boy experienced abdominal discomfort in the hypogastrium and left iliac fossa 4 days before admission. The pain had been developing in a feverish setting, and the clinical examination had revealed abdominal sensitivity. A biological inflammatory syndrome was detected throughout the biological workup, the CT scan allowed the diagnosis of acute appendicitis on a complete common mesentery, and the patient underwent a laparotomy appendectomy. Even though children frequently experience acute appendicitis in its conventional form, it is nevertheless highly challenging to identify in its atypical forms when intestinal malrotation is involved. An abdominopelvic CT scan is used to make the diagnosis, and appendectomy, preferably with laparoscopy, is the recommended course of action.     

Patent omphalomesenteric duct (a case report).]

PURPOSE: To report a rare case of patent omphalo-mesenteric duct and discuss the pathogenesis, clinical and radiological findings of this pathology. CASE REPORT: A two-month-old infant presented with umbilical liquid production since birth. Local examination showed an inflammatory umbilical tumefaction. Catheterization and injection of contrast material through the canal evidenced a communication with the gut, consistent with a patent omphalo-mesenteric duct. DISCUSSION: Persistent omphalo-mesenteric duct is a rare affection. Diagnostis is based on clinical and radiological findings. Clinical findings may be atypical in some cases. Complications are severe and include prolapsus, occlusion, ulcus, haemorrhage and perforation. CONCLUSION: Diagnostis of patent omphalo-mesenteric duct must be precocious to avoid complications.