Toxicity and cosmesis following partial breast irradiation consisting of 40 Gy in 10 daily fractions

PurposeTo assess the toxicity and cosmetic results in breast cancer patients undergoing adjuvant partial breast irradiation (PBI) to a total dose of 40 Gy in 10 daily fractions (4 Gy/fraction).Methods and materialsPatients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old and treated with breast conservative surgery for early stage (pT1–T2 pN0–N1a) invasive ductal carcinoma.Results77 patients were enrolled. Median follow-up was 18 months. The proposed schedule was well tolerated. One patient reported Grade 3 pain at the site of irradiation. Four (5%) patients experience Grade 2 erythema. Late Grade 2 and 1 fibrosis was observed in 3 (4%) and 14 (18%) patients, respectively. Cosmesis was judged “good/excellent” and “poor” in 75 (97%) and in 2 (3%) patients, respectively.Conclusions40 Gy in 10 daily fractions, 4 Gy/fraction, is a well tolerated regimen to deliver PBI.     

Modern drug delivery strategies applied to natural active compounds

Introduction: Colloidal drug delivery systems (CDDSs) are innovative carriers that have been studied in pharmaceutical field from many years to overcome unfavorable physical and chemical features of synthetic drugs. Recently the use of CDDS as carriers for phytochemicals has seen an exponential increase which, in some cases, has led to the rediscovery of ancient and forgotten natural molecules.

Area covered: This article focuses on the main features of CDDS, particularly micro- and nanoemulsions, vesicular carriers and micro- and nanoparticles, loaded with natural active compounds. A detailed review of the literature is presented, introducing the importance of these systems in terms of their capability to optimize the stability of phytochemicals, their absorption through biological membranes and their bioavailability.

Expert opinion: The delivery of phytochemicals is problematic due to poor solubility, poor permeability, low bioavailability, instability in biological milieu and extensive first-pass metabolism. Global research efforts investigating nanotechnology have attempted to overcome these limitations rediscovering and, in some cases, ‘discovering ex novo’ unexpected virtues and benefits associated to these compounds. The ‘nanotechnological approach’ can definitely enhance the pharmacokinetics and therapeutic index of natural active compounds and improve their performance in therapy.     

Long-term efficacy of the trans-obturator and retropubic mid-urethral slings for stress urinary incontinence: update from a randomized clinical trial

Purpose

To report the extended long-term results of the use of tension-free vaginal tape(TVT) and trans-obturator tape (TOT) for the treatment of female stress urinary incontinence (SUI).

Methods

A prospective, multicentre randomized clinical trial comparing the use of TVT and TOT was used to evaluate 87 patients. The inclusion criteria were stress or mixed UI associated with urethral hyper mobility (the stress component was clinically predominant), while the exclusion criteria were previous anti-incontinence surgery and/or pelvic organ prolapse. The objective cure criteria were a negative provocative stress test and a negative 1-h pad test, with no further treatment for SUI. The subjective cure criteria were a 3-day voiding diary, quality-of-life questionnaires (UDI6–IIQ7), and patient satisfaction on a scale from 0 to 10.

Results

Eighty-seven patients were evaluated (47 TOT and 40 TVT) at a median follow-up of 100 months. Subjective and objective cure rates were 59.6 and 70.2 % in the TOT group and 75 and 87.5 % in the TVT group. The mid-to-long-term trend was a decreasing continence rate in patients who underwent TOT, compared with a stable rate for TVT. The Kaplan–Meier survival curve showed that continence rate decreased for up to 25 months after surgery, with stabilization thereafter for the TVT group while continuing to drop in the TOT group, with no inter-group difference.

Conclusion

The patients in both groups were highly satisfied at long-term follow-up. The overall continence rate worsened for both groups within 25 months. While the results tend to stabilize in the TVT group, a further decline in the TOT was observed.

     

Risk factors for osteoporotic fractures in persons with spinal cord injuries and disorders

Summary

Clinical risk factors for fracture were explored among Veterans with a spinal cord injury. At the end of 11 years of follow-up, the absolute risk of fracture was approximately 20 %. Among the clinical and SCI-related factors explored, a prior history of fracture was strongly associated with incident fracture.

Introduction

Few studies to date have comprehensively addressed clinical risk factors for fracture in persons with spinal cord injury (SCI). The purpose of this study was to identify risk factors for incident osteoporotic fractures in persons with a SCI that can be easily determined at the point of care.

Methods

The Veteran’s Affairs Spinal Cord Dysfunction Registry, a national database of persons with a SCI, was used to examine clinical and SCI-related risk factors for fracture. Incident fractures were identified in a cohort of persons with chronic SCI, defined as SCI present for at least 2 years. Cox regression models were used to estimate the risk of incident fractures.

Results

There were 22,516 persons with chronic SCI included in the cohort with 3365 incident fractures. The mean observational follow-up time for the overall sample was 6.2 years (median 6.0, IQR 2.9–11.0). The mean observational follow-up time for the fracture group was 3.9 years (median 3.3, IQR 1.4–6.1) and 6.7 years (median 6.7, IQR 3.1–11.0) for the nonfracture group. By the end of the study, which included predominantly older Veterans with a SCI observed for a relatively short period of time, the absolute (i.e., cumulative hazard) for incident fractures was 0.17 (95%CI 0.14–0.21). In multivariable analysis, factors associated with an increased risk of fracture included White race, traumatic etiology of SCI, paraplegia, complete extent of SCI, longer duration of SCI, use of anticonvulsants and opioids, prevalent fractures, and higher Charlson Comorbidity Indices. Women aged 50 and older were also at higher risk of sustaining an incident fracture at any time during the 11-year follow-up period.

Conclusions

There are multiple clinical and SCI-related risk factors which can be used to predict fracture in persons with a SCI. Clinicians should be particularly concerned about incident fracture risk in persons with a SCI who have had a previous fracture.

     

Effects of repetitive transcranial magnetic stimulation on spike-and-wave discharges

Aim of this study was to evaluate the effect of 5Hz-suprathreshold repetitive transcranial magnetic stimulation (rTMS) on the duration of the spike-and-wave discharges (SWDs) in a patient presenting idiopathic absence seizures. At the moment of the study the patient presented a mild blunting of consciousness due to the high frequency of absences and EEG recordings showed sub-continuous, generalized, symmetrical and synchronous 3c/s SWDs, petit mal status. Trains of 10 stimuli (120% resting motor threshold) were delivered at 5Hz frequency at the beginning of the SWDs. 5Hz-rTMS trains significantly changed the EEG activity by reducing the duration of SWDs without changing the intervals between two consecutive discharges. rTMS had not significant after-effects on the epileptic activity and patient's clinical status. Despite the limitations of a single case report, our neurophysiological findings suggest that 5Hz-suprathreshold rTMS delivered in short trains induces a transitory interference of the ongoing epileptic activity.     

Preparation and in vitro evaluation of melatonin-loaded HA/PVA gel formulations

Melatonin-loaded hyaluronic acid (HA) and poly(vinyl alcohol) (PVA) gels were prepared by using freeze–thaw technique and an emulsion method followed by freeze–thaw technique to produce a new synergistic system for topical application. Freeze–thaw hydrogels and emulgels were characterized by means of Fourier transform infrared spectroscopy, rheology and swelling tests. The porous structure of the hydrogels was shown by scanning electron microscopy observations and thermal properties were tested by differential scanning calorimetry measurements. Bioadhesion and in vitro release characterization of formulations were performed by texture profile analysis and dialysis bag method, respectively. The pore size of both formulations was ranging from 900?nm to 30?μm. Melatonin showed a good compatibility with the polymeric matrices as the pores were smaller for the drug-loaded systems. In vitro release studies showed that the release was improved by emulgel formulations. After 24?h, the release percentage was found to be 13.240%?±?1.094 and 15.192%?±?2.270 for hydrogel and emulgel, respectively. Emulgels had better bioadhesion properties than simple freeze–thaw samples. As a conclusion, regarding the in vitro characterization studies HA and PVA hydrogel and emulgel formulations and their lyophilized forms could be promising systems for topical application of melatonin.     

Allogeneic hematopoietic stem cell transplantation for neuromyelitis optica

Neuromyelitis optica is a rare neurological autoimmune disorder characterized by a poor prognosis. Immunosuppression can halt disease progression, but some patients are refractory to multiple treatments, experiencing frequent relapses with accumulating disability. Here we report on durable clinical remissions after allogeneic hematopoietic stem cell transplantation in 2 patients suffering from severe forms of the disease. Immunological data evidenced disappearance of the pathogenic antibodies and regeneration of a naive immune system of donor origin. These findings correlated with evident clinical and radiological improvement in both patients, warranting extended clinical trials to investigate this promising therapeutic option. ANN NEUROL 2014;75:447–453     

Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma

The pathogenesis of AIDS-related non-Hodgkin lymphomas (AIDS-NHLs) is associated with chromosomal translocations that deregulate the expression of various oncogenes. Recently, a novel mechanism of genetic lesion, termed aberrant hypermutation, has been identified in diffuse large B-cell lymphoma (DLBCL) of immunocompetent hosts. In these tumors, the somatic hypermutation (SHM) process that normally targets immunoglobulin V (IgV) genes in B cells appears to misfire and causes mutations in the 5' sequences of multiple proto-oncogenes, including PIM-1, PAX-5, RhoH/TTF, and c-MYC. To investigate whether aberrant hypermutation occurs also in AIDS-NHL, we studied the mutation profile of these 4 genes in various histologic subtypes. Mutations in 1 gene or more were detected in 19 of 39 (48.7%) AIDS-NHL cases (10 of 18 AIDS-diffuse large B-cell lymphoma; 4 of 11 AIDS-Burkitt lymphoma; 4 of 6 AIDS-primary effusion lymphoma; 1 of 4 AIDS-primary central nervous system lymphoma), with 9 of 39 (23.1%) cases carrying mutations in 2 or more genes. Overall, PIM-1 was mutated in 5 of 39 (12.8%), PAX-5 in 8 of 39 (20.5%), RhoH/TTF in 9 of 39 (23.1%), and c-MYC in 7 of 27 (25.9%) AIDS-NHL cases. Mutations were represented mainly by single base pair substitutions (n = 63) with rare deletions/insertions (n = 5) and displayed features typical of the IgV-associated SHM process. In addition, a number of mutations in PIM-1 and c-MYC were found to affect coding exons, leading to amino acid substitutions with likely functional consequences. Analysis of intraclonal heterogeneity documented that the aberrant hypermutation activity may be ongoing in at least some cases. These data indicate that aberrant hypermutation is associated with various subtypes of AIDS-NHL and may represent a major contributor to their pathogenesis.