Stem cell implantation in the treatment of peripheral vascular disease

Treatment options of ischemic vascular disease of the lower limbs are a challenged field that necessitates new therapeutic modalities. Stem cell transplantation offers a promising achievement of therapeutic angiogenesis in patients with ischemic limbs. Our study investigated the efficacy and safety of the implantation of autologous peripheral blood mononuclear cells (PBMNCs) mobilized by granulocyte colony-stimulating factor (G-CSF) in patients with chronic limb ischemia. Twenty-four patients with chronic lower limb ischemia were enrolled and divided randomly into two groups: the implanted group (n?=?12) and the control group (n?=?12). In the implanted group, the patients received subcutaneous injections of recombinant human G-CSF (300 μg/day) for 5 days to mobilize stem/progenitor cells, and their PBMNCs were harvested using a blood cell separator and were implanted by multiple intramuscular injections into the ischemic limbs, while the control group was injected with sterile saline and received conventional medical treatment. All patients were followed up after 12 weeks. At the end of the follow-up period, the main manifestations significantly improved in patients of the implanted group compared with the control group. The mean of rest pain decreased from the baseline level of 6.42?±?2.15 to 1.67?±?0.389 (P?<?0.001). The mean of pain-free walking distance increased from 25.00?±?8.90 to 409.00?±?104.00 (P?<?0.001). The mean ankle–brachial pressure index increased from 0.45?±?0.12 to 0.79?±?0.38 (P?=?0.005). Seven out of nine limb ulcers and wounds (77.8 %) of implanted patients healed after cell implantation. Two lower limb amputations (16.67 %) occurred in the implanted patients. In contrast, eight control patients (66.67 %) had to receive lower limb amputation. Implantation of stem/progenitor cells is a feasible and readily available effective strategy for therapeutic angiogenesis in patients with chronic limb ischemia.     

Effect of CYP2C9 gene polymorphisms on response to treatment with sulfonylureas in a cohort of Egyptian type 2 diabetes mellitus patients

Oral hypoglycemics are a widely prescribed group of drugs for the management of type 2 diabetes mellitus. Sulfonylureas (SUs) are the cornerstone of type 2 diabetes pharmacotherapy. The enzyme cytochrome P450 2C9 (CYP2C9) is the main enzyme that catalyzes the biotransformation of SUs. It is encoded by the polymorphic gene CYP2C9 with two allelic variants namely CYP2C9*2 and CYP2C9*3 coding for variant allozymes with reportedly decreased metabolic capacity resulting in decreased SUs clearance and consequently prolonged and exacerbated action. The aim of this study was to investigate the influence of genetic polymorphisms of CYP2C9 on the response to glibenclamide, a second-generation sulfonylurea. Hundred type 2 diabetic patients were enrolled in the study. Genotyping was done on the LightCycler 2 by real-time polymerase chain reaction (PCR) hybridization probe assay. The results are the following: 53 patients were carriers of the wild genotype (CYP2C9*1/*1), 20 were heterozygous for the variant CYP2C9*2 allele (CYP2C9*1/*2), 18 were heterozygous for the variant CYP2C9*3 allele (CYP2C9*1/*3), and 9 were double heterozygous for both mutant alleles (CYP2C9*2/*3); of those double mutant genotype patients, two were also homozygous for the mutant CYP2C9*2 allele (CYP2C9*2/*2) and one patient was homozygous for the mutant CYP2C9*3 allele (CYP2C9*3/*3). Although there was no significant difference in drug dosage between the four groups, there was however a significant association of the CYP2C9*2/*3 genotype with better glycemic control. As conclusion, the better glycemic control observed can probably be attributed to slower metabolism of SUs by the carriers of the CYP2C9*2/*3 genotype and consequently longer half-life or exacerbated effect of the SUs administered.     

The efficacy and safety of extended adjuvant temozolomide following concurrent radio-chemotherapy among Egyptian patients with newly diagnosed glioblastoma multiforme

Although concurrent radio-chemotherapy and adjuvant temozolomide (TMZ) treatment for 6 cycles has been established as a standard of care for newly diagnosed glioblastoma multiforme (GBM) patients, the recommended duration of adjuvant TMZ remains a matter of debate. Hereby, we aimed to report for the first time our experience from Upper Egypt through comparing survival and toxicity profile between two treatment modalities of adjuvant TMZ (> six cycles versus six cycles) and delineating factors of prognostic significance in Egyptian patients with newly diagnosed GBM treated by radiation therapy with concomitant and adjuvant TMZ. Between June 2016 and February 2018, the medical records of 121 patients were eligible to be retrospectively reviewed to extract the study relevant data. All patients received concurrent radio-chemotherapy, followed by TMZ for 6 cycles in 29 patients (Group 1) and for >6 cycles in 26 patients (Group 2). Patients in Group 1 had a median PFS of 15 months (95% CI: 10.215-19.785), while those in Group 2 had a median PFS of 18 months (95% CI: 16.611-19.389). After a median follow up duration of 20 months (range: 12-41), the median OS was 18 months (95% CI: 13.420-22.580) in Group 1 and 22 months (95% CI: 18.777-25.223) in Group 2. There was no statistically significant correlation between the number of chemotherapy cycles and PFS (P=0.513) or OS (P=0.867). The extent of surgical resection was the only independent prognostic factor for both PFS (P=0.015) and OS (P=0.028) by multivariate analysis. Three grade ≥3 hematologic toxicity were encountered in 3 patients. One in the six-cycle group (neutropenia), and two in the extended cycles group (one had neutropenia and the other one developed thrombocytopenia). No statistically significant difference in the toxicity profile between both groups. The results of our study suggest that extended TMZ therapy is safe and tolerable, however it did not significantly improve PFS or OS as compared to the standard six-cycle course. Larger randomized studies are required to shed more light on this issue.     

Interferon‐gamma serum level and immunohistochemical expression of CD8 cells in tissue biopsies in patients with alopecia areata in correlation with trichoscopic findings

Alopecia areata (AA) is an autoimmune form of nonscarring hair loss. The aim of the study was to assess the serum concentration of interferon gamma (IFN‐γ) and CD8 cell expression in lesional skin biopsies in correlation with the disease severity, activity, duration, and trichoscopic findings in patients with AA. The study included 30 patients with AA and 15 age‐ and sex‐matched healthy controls. Trichoscopy was performed and photographs were captured for the alopecic areas, and the enzyme‐linked immunosorbent assay technique was used for serum level of IFN‐γ assessment and immunohistochemistry for CD8 cells. The results obtained indicate that IFN‐γ serum level in patients was significantly higher than that of control subjects, and significantly correlated with the activity status and the duration of the disease. CD8+ T cells infiltrate intensity significantly correlated with severity. Yellow dots (YDs), vellus hair, black dot, and exclamation marks were the most common trichoscopic findings. The presence of black dots significantly correlated to the disease activity, duration, serum IFN‐γ, and CD8+ infiltrate intensity. The presence of YDs significantly correlated with the mean serum IFN‐γ level. Exclamation marks significantly correlated with the disease activity and the degree of CD8+ infiltrate. In conclusion, trichoscopy could be a reliable indicator of the IFN‐γ serum level and CD8+ T cell infiltrate intensity in AA patient.     

Diagnostic significance of miR‐21, miR‐141, miR‐18a and miR‐221 as novel biomarkers in prostate cancer among Egyptian patients

Prostate cancer (PC) is considered as the fifth cause of cancer deaths worldwide. The exact etiopathogenesis is unclear; however, genetic predisposition, hormonal influencers, lifestyle and environmental factors act as major contributors. It has been found that several miRNAs may play a crucial role in cancer initiation and progression. Here, in this study, we evaluated the peripheral blood levels of miR‐21, miR‐141, miR‐221 and miR‐18a expression among 80 prostate cancer patients (50 localised and 30 metastatic) and 30 benign prostatic hyperplasia patients compared to 50 normal control subjects, using RT‐PCR. Our results of analysis of miR‐21, miR‐141, miR‐18a and miR‐221 in the plasma of PC patients showed that miR‐18a is a powerful discriminator of PC patients from healthy controls as it had the highest AUC (0.966; 95% CI, 0.937–1.000), while miR‐221 provided better differentiation of metastatic from localised PC (sensitivity was 92.9% at 100% specificity), and when we combine miR‐18a and miR‐221 for differentiating patients with MPC, it will increase the sensitivity to 96.4% at a specificity of 100% (AUC, 0.997; 95% CI, 0.988–1.0) (p < .000). This current study recommends that analysis of these miRNAs might have clinical value in enhancing PSA testing.     

Diabetic foot disease:From the evaluation of the “foot at risk” to the novel diabetic ulcer treatment modalities

The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy(DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk foot are essential for the prevention of foot ulceration and amputation. Proper assessment of the diabetic foot ulceration and appropriate management ensure better prognosis. Management is based on revascularization procedures, wound debridement, treatment of infection and ulcer offloading. Management and type of dressing applied are tailored according to the type of wound and the foot condition. The scope of this review paper is to describe the diabetic foot syndrome starting from the evaluation of the foot at risk for ulceration, up to the new treatment modalities.     

Serum cystatin C as an early predictor of acute kidney injury in preterm neonates with respiratory distress syndrome

Abstract

Preterm neonates with respiratory distress syndrome (RDS) are at increased risk of acute kidney injury (AKI). Our study aimed at determining whether serum cystatin C (sCysC) on day 3 of life (D3) can early predict AKI in preterm neonates with RDS. This prospective study was conducted on 75 preterm neonates; 50 with RDS and 25 without RDS. On D3, sCysC, serum creatinine (sCr) and blood urea nitrogen (BUN) were measured and estimated glomerular filtration rate (eGFR) was calculated. sCr and BUN levels were measured again on days 5 and 7. Neonates were evaluated for development of AKI during first week of life according to the modified pediatric RIFLE (pRIFLE) criteria. Thirteen neonates with RDS developed AKI (26%).There was no significant difference between RDS and control groups with respect to sCysC. RDS neonates with AKI had significantly higher sCysC than those without AKI (1.62?±?0.12 versus 1.16?±?0.09?mg/l; p?<?.001). RDS grade III–IV neonates had significantly higher sCysC than RDS grade I–II. There was a significant positive correlation between D3 sCysC and (D5 and D7 sCr and BUN). Receiver operating characteristic (ROC) curve showed that D3 sCysC can predict AKI in preterm neonates with RDS at a cutoff point of >1.3?mg/l with sensitivity of 92.30% and specificity of 96%. We conclude that neonates with RDS are at increased risk of AKI. sCysC on day 3 of life can predict AKI earlier than Cr and eGFR.