A comparative safety review of histone deacetylase inhibitors for the treatment of myeloma

Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.

Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.

Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity.     

Silicone-based simulation models for peripheral nerve microsurgery

Background

There is a need for a peripheral nerve model on which surgeons-in-training can simulate the repair of nerve injuries at their own pace. Although practicing on animal models/cadavers is considered the “gold standard” of microsurgical training, the proposed model aims to provide a platform for improving the technical skills of surgical trainees prior to their practice on cadaver/animal models. In addition, this model has the potential to serve as a standardized test medium for assessing the skill sets of surgeons.

Polyester film strips coated with photographic gelatin containing immobilized glucose oxidase hardened by chromium(III) sulphate.

Glucose oxidase was immobilized into photographic gelatin hardened by chromium(III) sulphate. The enzyme-gelatin mixture was coated on polyester film strips which allowed easy and simple handling during assays. The effect of gelatin and cross-linker concentrations on water content and enzymatic activity was studied. The effect of pH during immobilization and that of incubation temperature on maximum activity were examined. Enzyme leakage tests were carried out during reuse number studies. Consecutive use of strips followed by washing and resting between uses were found to affect the reuse number. A maximum immobilization of 68% was reached under optimal conditions. Mechanical stability and leakage were found to be functions of gelatin and cross-linker concentrations. Photographic gelatin was found to have many capabilities with extraordinary characteristics as a carrier on immobilization.     

Relationship between Pollen Counts and Weather Variables in East-Mediterranean Coast of Turkey

BACKGROUND: Aeroallergen sampling provides information regarding the onset, duration and severity of the pollen season that clinicians use to guide allergen selection for skin testing and treatment. OBJECTIVES: This atmospheric survey reports (1) airborne pollen contributions in Adana in one-year period (2) pollen onset, duration and peak level (3) the relationship between airborne pollen and selected meteorological variables and; (4) effects on symptoms in pollen allergic children. METHODS: Pollen sampling was performed with a volumetric Burkard Spore Trap. Meteorological data were measured daily from April 2001 to April 2002. Asthma symptom scores were investigated in 186 pollen allergic children that were on follow up in pediatric allergy outpatient clinics during same period. RESULTS: Average measurements included 82.5% tree pollen, 7.7% grass pollen and 9.8% herb pollen 54 taxa were identified during one year. The most prominent tree pollens were Cupressaceae, Eucalyptus and Pinus. The most common herb was Chenopodiaceae pollen family. When airborne pollen levels were examined in relation to single meteorological conditions; daily variations in total pollen counts were not significantly correlated with any variable studied (humidity, rainfall, temperature and wind) (p > 0.05). On the other hand, statistically significant relationship between pollen concentration and symptom scores were found (p > 0.05). Positive correlations were seen between both Gramineae and Herb pollen, and humidity and rainfall from March to July. However, positive correlations were detected between tree pollen counts and temperature and humidity in May and June. CONCLUSION: This survey is the first volumetric airborne pollen analysis conducted in the survey area in Adana. This study suggested that the effects of weather on pollen count and symptom scores in this population could not be clearly identified with the evaluation of one-year data. However, pollen counts had effect on allergic symptoms in pollen allergic children. Examination of the complex interaction of multiple whether parameters would perhaps more fully elucidate the relationship between meteorology and aerobiology and provide the clinician with information necessary to forecast pollen prevalence. An awareness of the ever chancing, local aeroallergen patterns requires regular monitoring. Such awareness serves as a useful guide in the effective testing and treatment of atopic patients.     

ASO Visual Abstract: Robotic Posterior Retroperitoneal Adrenalectomy: Patient Selection and Long-Term Outcomes

Annals of Surgical Oncology -     

Comparison of flexible ureterorenoscopy and mini-percutaneous nephrolithotomy in treatment of lower calyceal stones smaller than 2 cm

To compare the outcomes of flexible ureterorenoscopy (F-URS) and mini-percutaneous nephrolithotomy (mini-PNL) in the treatment of lower calyceal stones smaller than 2?cm. Patients who underwent F-URS and mini-PNL for the treatment of lower calyceal stones smaller than 2?cm between March 2009 and December 2014 were retrospectively evaluated. Ninety-four patients were divided into two groups by treatment modality: F-URS (Group 1: 63 patients) and mini-PNL (Group 2: 31 patients). All patients were preoperatively diagnosed with intravenous pyelography or computed tomography. Success rates for F-URS and mini-PNL at postoperative first month were 85.7% and 90.3%, respectively. Operation time, fluoroscopy time, and hospitalization time for F-URS and mini-PNL patients were 44.40?min, 2.9?min, 22.4?h, and 91.9?min, 6.4?min, and 63.8?h, respectively. All three parameters were significantly shorter among the F-URS group (p?0.001). Postoperative hemoglobin drop was significantly lower in F-URS group compared to?mini-PNL group (0.39?mg/dL vs. 1.15?mg/dL, p?=?0.001). A comparison of complications according to the Clavien classification demonstrated significant differences between the groups (p?=?0.001). More patients in the F-URS groups require antibiotics due to urinary tract infection, and more patients in the?mini-PNL group required ureteral double J catheter insertion under general anesthesia. Although both F-URS and?mini-PNL have similar success rates for the treatment of lower calyceal stones, F-URS appears to be more favorable due to shorter fluoroscopy and hospitalization times; and lower hemoglobin drops. Multicenter and studies using higher patient volumes are needed to confirm these findings.     

The Effects of the Enriched Environment on Sympathetic Skin Response in Pentylenetetrazol-Kindled Rats

Epilepsy is a neurodegenerative disease that interrupts the normal electrical activity of the brain and promotes abnormal wiring in this organ.Epileptic seizures are often associated with significant changes in the functioning of the autonomic nervous system(ANS).     

Cytokines,adipocytokines and inflammatory markers in patients on continuous ambulatory peritoneal dialysis and hemodialysis

Background: Cytokines are essential mediators of immune response. Chronic renal failure patients suffer from chronic inflammation that results from factors such as impaired renal function, accumulation of uremic toxins and bio incompatibility of dialyzer membranes. These patients are also at increased risk of cardiovascular diseases. We have evaluated cytokines, adipocytokines and inflammatory markers in patients with chronic renal failure undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD).

Material and methods: We have determined serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), leptin and ghrelin levels of chronic renal failure patients treated with either HD (n?=?20) or CAPD (n?=?20). TNF-α, IL-6, ghrelin and leptin measurements were performed by commercially available kits based on enzyme-linked immunosorbent assay (ELISA) method. hsCRP levels were determined by turbidimetric methods.

Results: Serum TNF-α and IL-6 levels of patients on HD were significantly higher than those of the ones on CAPD (p?<?0.05). Ghrelin, leptin and hsCRP concentrations were similar in both groups.

Conclusions: We can conclude that cytokine production is more obvious in HD process.     

Blastic Plasmacytoid Dendritic Cell Neoplasm: Single Center Experience on a Rare Hematological Malignancy

PurposeBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and poor prognostic hematological malignancy. There is still no standard treatment established for BPDCN patients. We aim to summarize the main clinical, biological features and treatment of 9 BPDCN patients.MethodsNine patients with BPDCN who had been diagnosed between July 2008 and December 2018 in Ankara University School of Medicine, were retrospectively evaluated.ResultsAll patients (n = 9) were male, median age was 64 (21–80). Five patients (55.6%) had bone marrow infiltration, 5 patients (55.6%) cutaneous lesions, 6 patients (66.7%) lymph node involvement, 2 patients (22.2%) central nervous system involvement and 2 patients (22.2%) spleen involvement at time of diagnosis. Complex karyotype was observed in 2 patients. CHOP was given to 5 patients (55.6%), hyper-CVAD to 2 patients (22.2%), fludarabine, cyclophosphamide and mitoxantrone to 1 patient (11.1%) and cyclophosphamide, etoposide, methylprednisolone to 1 patient (11.1%) as first line chemotherapy. Four patients (44.4%) underwent allogeneic hematopoietic stem cell transplantation (AHSCT) in complete remission (CR) 1. Venetoclax was given to a transplant ineligible patient who had skin and lymph node involvement, with the off-label use. The median follow-up time was 15.9 months (3–48.6 months). Estimated median overall survival was 15.9 + 1.6 (95% CI 12.7–19.1) months.ConclusionIntensive induction therapies followed by AHSCT in CR seems to be best approaches for patients with BPDCN. Thus, more effective treatment strategies particularly targeted therapies should be warranted to improve the survival of patients with this rare disease.