Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype‐4 chronic hepatitis C patients

The therapeutic effect of pegylated interferon (peg‐IFN) alfa‐2a combined with ribavirin (RBV) on chronic hepatitis C Egyptian patients is low and further efforts are required to optimize this therapy for achievement of higher rates of virological response. This study aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) in combination with pegylated interferon plus ribavirin on early virological response (EVR) in chronic hepatitis C Egyptian patients. Naïve 120 Egyptian patients with chronic hepatitis C virus infection were divided into two groups. Group 1 have administered the standard of care therapy (pegylated interferon alfa‐2a plus ribavirin) for 12 weeks, (n = 60). Group 2 have administered hydroxychloroquine plus standard of care therapy for 12 weeks, (n = 60). Therapeutics included hydroxychloroquine (200 mg) oral twice daily, peginterferon alfa‐2a (160 μg) subcutaneous once weekly and oral weight‐based ribavirin (1000–1200 mg/day). Baseline characteristics were similar in the two groups. The percentage of early virological response was significantly more in patients given the triple therapy than in patients given the standard of care [54/60 (90%) vs. 43/60 (71.7%); P = 0.011; respectively]. Biochemical response at week 12 was also significantly higher in patients given the triple therapy compared with the standard of care [58/60 (96.7%) vs. 42/60 (70%); P < 0.001; respectively]. Along the study, the observed adverse events were mild and similar across treatment groups. Addition of hydroxychloroquine to pegylated interferon plus ribavirin improves the rate of early virological and biochemical responses in chronic hepatitis C Egyptian patients without an increase in adverse events. J. Med. Virol. 88:2170–2178, 2016. © 2016 Wiley Periodicals, Inc.

     

Synthesis,characterization, and biological activity of cross-linked chitosan biguanidine loaded with silver nanoparticles

Chitosan biguanidine hydrochloride (ChG) and glutaraldehyde cross-linked chitosan biguanidine (CChG) were synthesized and characterized by Fourier transform infrared spectroscopy, ¹H NMR and ¹³C NMR, X-ray diffraction, scanning electron microscopy (SEM) and thermal analyses (TGA and DTA). The results showed that ChG and CChG had a more amorphous structure than that of chitosan, and their thermal stability were slightly lower than that of chitosan. Colloidal silver nanoparticles (AgNPs) were prepared using borohydride reduction method and then investigated as fillers in partially cross-linked chitosan biguanidine. The obtained nanoparticles were uniform and spherical with average size of 9.6 ± 0.5 nm. The prepared CChG/AgNPs composites were characterized for their morphology, thermal properties, cytotoxicity and antimicrobial activity. The SEM images showed that the AgNPs are well imbedded in the CChG matrix. The thermal stability of CChG was improved with incorporation of AgNPs. The CChG and CChG/AgNPs showed less cytotoxicity to breast cancer cells (MCF-7). Compared with chitosan and CChG, the ChG and CChG/AgNPs showed better antimicrobial activity against Streptococcus pneumoniae and Bacillus subtilis as Gram-positive bacteria, Escherichia coli as Gram-negative bacteria and Aspergillus fumigatus, Geotricum candidum and Syncephalastrum recemosum as fungi.     

Ki67 expression in breast cancer: Correlation with prognostic markers and clinicopathological parameters in Saudi patients

Objectives:

To evaluate Ki67 immunoexpression pattern in Saudi breast cancer (BC) patients and investigate any possible predictive or prognostic value for Ki67.

Methods:

This is a retrospective study designed to quantitatively assess the Ki67 proliferative index (PI) in retrieved paraffin blocks of 115 Saudi BC patients diagnosed between January 2005 and March 2015 at the Department of Pathology, King Fahd Hospital, Al Madinah Al Munawarah, Kingdom of Saudi Arabia. The Ki67 PI was correlated with individual and combined immunoprofile data of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) with their clinicopathological parameters.

Results:

Ki67 immunoreactivity was highly expressed (>25% of the tumor cells were positive) in 85 (73.9%) patients. The Ki67 PI was significantly associated with poor prognostic clinicopathological parameters including old age (p<0.02), high tumor grade (p<0.01), lymph node metastasis (p<0.001), and Her-2/neu positivity (p<0.009). However, the association with ER positivity, PR positivity, tumor size, and lymphovascular invasion were not statistically significant. The Ki67 PI was significantly associated with BC molecular subtypes that were Her2/neu positive (luminal B and HER-2) subtypes compared with the Her2/neu negative (luminal A) subtype (p<0.04).

Conclusion:

The Ki67 PI is significantly higher in Saudi BC patients comparing with the reported literature. Ki67 PI was highest in the HER-2 and luminal-B molecular subtypes. Along with other prognostic indicators, Ki67 PI may be useful in predicting prognosis and management of Saudi BC patients.Breast cancer (BC) is one of the most common malignancy in the world.1 Although in the Kingdom of Saudi Arabia (KSA), the incidence of BC is much lower than in the Western world; it is still the most common malignancy in the Saudi women. According to the Saudi Cancer registry,2 BC accounted for approximately 23% of all the newly diagnosed female cancers. An additional significant fact on BC in KSA is its special presentation; as it predominantly affects the younger population, frequently presents as higher histological grades and in advanced clinical stages.2-4 Apart from the problem of its being highly prevalent globally and locally; BC has also shown its divergent nature with regards to its clinical course, response to treatment, and prognostic outcomes. Thus, the new molecular classification of BC has emerged on the basis of biomarkers. In the initial stages, the hormones namely, the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) played their roles. It was only 15 years ago, that the molecular classification of BC was proposed by Californian scientists, initially there were 4 major classes: luminal-like, basal-like, normal-like, and Her2 positive.5 Consequently, a fifth class was added, dividing one of the major luminal class to luminal A and luminal B classes.6-8 Ki67 had been known to be an important proliferation biomarker since 1980s. It has recently become an essential component of routine biomarker profile for BC, along with ER, PR, and Her2, to assist the oncologists in delivering optimum treatment to BC patients. Its role as a poor prognostic biomarker is well established, and a number of studies have found a significant correlation between Ki67 positivity with that of histological parameters such as nuclear grades and mitotic figures.9 Recent studies have also proved its predictive role in both the antihormonal therapy and chemotherapy for the efficacy of the treatment. The aim of this study is to examine the Ki67 biomarker in the BC patients and the immunohistochemically on the paraffin embedded blocks. Subsequently, to correlate the Ki67 findings with individual and combined immunoprofile data of ER, PR, and Her2/neu, as well as with their clinicopathological parameters to identify any specific differences in our BC cases as compared with western cases. This is may be important in investigating any predictive or prognostic role of Ki67 in managing BC patients in KSA population.     

Design,synthesis, biological evaluations,molecular docking,and in vivo studies of novel phthalimide analogs

A series of novel phthalimide analogs containing an indole or brominated indole moiety were synthesized and their antimicrobial activity was evaluated. Compound 8 showed a broad spectrum activity, revealing 53–67% of erythromycin activity on the tested bacteria and 60–70% of miconazole activity on the tested fungi. Anticancer activity was evaluated on the cell lines HepG2, MCF‐7, A549, H1299, and Caco2. The results revealed that the new phthalimide analog 8 has broad‐spectrum anticancer activity toward all the tested cancer cell lines, followed by compound 11 , which showed good activity toward all the tested cell lines except for MCF‐7. The ability of the promising analogs 5 , 8 , and 11 to bind to topoisomerase II DNA gyrase was investigated. Caspase‐3 activation and Bcl‐2 assay of the best active derivatives 8 , 11 in addition to compound 5 were evaluated. The antifibrotic activity was studied in an in vivo model and the histopathological studies revealed that treatment with the new compound 8 improved the fibrotic liver tissues to normality.

     

Recurrent subcutaneous emphysema of the face: a challenging clinical problem

In the neck or face, there are different causes for subcutaneous emphysema such as injury to the sinuses, the hypopharynx, the laryngotracheal complex, the pulmonary parenchyma, the esophagus or the presence of gas-forming organisms. However, factitious subcutaneous emphysema, a rare cause, must be considered in the differential diagnosis. In this clinical report, we discuss a 20-year-old girl who was under follow-up because of recurrent subcutaneous emphysema of the face and periorbital area.After 2 years of work-ups, including a period of close observation in the intensive care unit, self air injection by syringe was found as the cause of recurrent subcutaneous emphysema of the face, and the patient was labeled as having factitious recurrent subcutaneous emphysema. Therefore, when a patient presents with unexplained recurrent subcutaneous emphysema, one should suspect self-infliction and examine for puncture marks.     

The effect of systemic erythropoietin and oral prednisolone on recent-onset non-arteritic anterior ischemic optic neuropathy: a randomized clinical trial

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the effect of systemic erythropoietin, as well as oral steroids, in the management of recent-onset non-arteritic...     

Responsiveness of selected outcome measures of participation restriction and quality of life in patients with multiple sclerosis

Purpose: To evaluate the responsiveness of two outcome measures of participation restriction [as measured by the Community Integration Questionnaire (CIQ)] and quality of life [as measured by the Multiple Sclerosis Quality of Life (MSQOL)] following a physiotherapy intervention in patients with multiple sclerosis (MS). Method: A sample of 265 patients completed both instruments first at the time of initial visit and then after 4–6 weeks physiotherapy. In addition, patients were asked to complete the 7-point global rating scale as an external criterion of change at the post-intervention time. The responsiveness was evaluated using the receiver operating characteristics (ROC) method and the correlation analysis. Two useful statistics were area under the ROC curve (AUC) and the minimally clinically important difference (MCID). The AUC and correlation coefficient greater than 0.70 were considered as acceptable responsiveness. Results: The CIQ achieved the acceptable responsiveness with an AUC of 0.81. However, the AUCs of 0.61 and 0.66 were obtained for the MSQOL physical and mental, respectively. Moreover, good correlation coefficient was obtained for the CIQ (Gamma?=?0.76) while fair correlations of 0.28 and 0.33 were obtained for the MSQOL physical and mental, respectively. The MCIDs were approximately 0.50, 1.5 and 2.5 points for the CIQ, MSQOL physical and mental, respectively. Conclusions: In contrast to the MSQOL, the CIQ was responsive outcome measure in detecting changes in participation restriction of patients with MS. Moreover, the MCID values obtained in this study will help the clinicians and researchers to determine if a patient with MS has experienced a true change following physiotherapy intervention.

• Implications for Rehabilitation

• The results provide valuable information regarding to the ability of two outcome measures (i.e. the CIQ and MSQOL) to detect treatment effects in patients with MS.

• In contrast to the MSQOL, the CIQ is a responsive measure to changes in participation restriction due to physiotherapy.

• A patient with MS had to change at least 0.50 point on the CIQ, 1.5 points on the MSQOL physical and 2.5 points on the MSQOL mental to be judged as having clinically changed.