Colorectal adenocarcinoma with mucinous component: relation of MMP‐13, EGFR,and E‐cadherin expressions to clinicopathological features and prognosis

The aim of this study was to compare colorectal adenocarcinoma with mucinous component, ordinary adenocarcinoma (OA) and mucinous adenocarcinoma (MA) regarding clinicopathological parameters, survival, EGFR, MMP‐13, and E‐cadherin. We studied tumor tissue specimens from 28 patients with adenocarcinoma with mucinous component, 47 with OA, and 56 with MA, who underwent radical surgery from January 2007 to January 2012 at the Gastroenterology Centre, Mansoura University, Egypt. High density manual tissue microarrays were constructed and immunohistochemistry for EGFR, MMP‐13, and E‐cadherin was done. Colorectal adenocarcinoma with mucinous component (AWMC) was significantly associated with more perineural invasion, lower EGFR, and MMP‐13 expressions than OA, with no difference in E‐cadherin expression. Conversely, only microscopic abscess formation was significantly more with colorectal AWMC than MC with no difference in EGFR, MMP‐13 and E‐cadherin expression between both groups. Colorectal AWMC showed a better survival than MA with no difference with OA. In a univariate analysis, EGFR, MMP‐13, and E‐cadherin expressions did not show a significant impact on disease‐free or overall survival in patients with colorectal AWMC. Colorectal AWMC remains a vague entity that resembles OA in some clinicopathological and molecular respects as well as MA.     

Current updates in management of Clostridium difficile infection in cancer patients

Background: Clostridium difficile infection (CDI) is a significant health burden, now recognized as the leading cause of acquired diarrhea in patients receiving antibiotic therapy. Complications of infection with this pathogen include severe diarrhea, causing electrolyte imbalances, dehydration, hemodynamic instability, toxic megacolon, shock, and death. Hence it is extremely paramount to stay updated on management options for this infection, especially in cancer patients.

Review: This article presents an in-depth review of literature on the treatment modalities available for CDI in cancer patients. Relevant articles highlighting therapeutic and symptomatic management of CDI patients with underlying malignancy have been summarized.

Conclusions: Despite the current options available, more studies are needed to assess the newer therapeutic options that are being employed for populations other than cancer patients.     

Safety of pregabalin among hemodialysis patients suffering from uremic pruritus

Objectives: The aim of this study was to assess the safety and probability of adverse events associated with the use of 75 mg pregabalin post hemodialysis (pHD) among patients with UP. Methods: A cross-sectional study done among the hemodialysis patients suffering from uremic pruritus (UP) Aljaber Kidney Center (AJKC), Al-Ahsa, Eastern Province, Saudi Arabia. Assessment for the safety profile of pregabalin was done using Naranjo’s algorithm. A predictive model was developed using binary multiple logistic regression to explore association of patients’ demographics and risk factors with the occurrence of AEs. Throughout statistical significance level was considered significant at 0.05. Key findings: Assessment of safety of pregabalin revealed that somnolence and dizziness were the two frequent adverse events followed by constipation, weight gain and edema. However, it was noticed that female patients aged less than 50 years were found to be at a higher risk in comparison with men. Moreover, those patients having one comorbid complication (i.e. hypertension or diabetes mellitus alone) were at a higher risk of somnolence, weight gain and dry mouth. Conclusion: Naranjo’s quantification for the possibility and probability of adverse events reflect that all the events were probable. Age, gender and comorbid medical conditions are some of the factors that might have clinical association with the occurrence of the AEs.     

The effects of dynamic compressive loading on human mesenchymal stem cell osteogenesis in the stiff layer of a bilayer hydrogel

Bilayer hydrogels with a soft cartilage‐like layer and a stiff bone‐like layer embedded with human mesenchymal stem cells (hMSCs) are promising for osteochondral tissue engineering. The goals of this work were to evaluate the effects of dynamic compressive loading (2.5% applied strain, 1 Hz) on osteogenesis in the stiff layer and spatially map local mechanical responses (strain, stress, hydrostatic pressure, and fluid velocity). A bilayer hydrogel was fabricated from soft (24 kPa) and stiff (124 kPa) poly (ethylene glycol) hydrogels. With hMSCs embedded in the stiff layer, osteogenesis was delayed under loading evident by lower OSX and OPN expressions, alkaline phosphatase activity, and collagen content. At Day 28, mineral deposits were present throughout the stiff layer without loading but localized centrally and near the interface under loading. Local strains mapped by particle tracking showed substantial equivalent strain (~1.5%) transferring to the stiff layer. When hMSCs were cultured in stiff single‐layer hydrogels subjected to similar strains, mineralization was inhibited. Finite element analysis revealed that hydrostatic pressures ≥~600 Pa correlated to regions lacking mineralization in both hydrogels. Fluid velocities were low (~1–10 nm/s) in the hydrogels with no apparent correlation to mineralization. Mineralization was recovered by inhibiting ERK1/2, indicating cell‐mediated inhibition. These findings suggest that high strains (~1.5%) combined with higher hydrostatic pressures negatively impact osteogenesis, but in a manner that depends on the magnitude of each mechanical response. This work highlights the importance of local mechanical responses in mediating osteogenesis of hMSCs in bilayer hydrogels being studied for osteochondral tissue engineering.