Influence of Glass Forming Ability on the Physical Stability of Supersaturated Amorphous Solid Dispersions

In this study, the influence of the glass-forming ability (GFA) of a drug on its physical stability in a supersaturated solid dispersion was investigated. Nine drugs were classified according to their GFA using their respective critical cooling rate. Their respective solubility in poly(vinylpyrrolidone-co-vinyl acetate) 6:4 (PVPVA64) was predicted using the melting point depression method based on the Flory-Huggins lattice theory. Supersaturated amorphous solid dispersions at a level of 25% w/w drug above saturation solubility in the polymer were prepared by film-casting, and their respective physical stability at temperatures of 10°C or 20°C above or below their respective T_g (dry conditions) was monitored by the use of polarized light microscopy. This study showed that drugs with good GFA (class 3) on average have higher physical stability in supersaturated amorphous solid dispersion compared to drug with modest GFA (class 2), which in turn have higher physical stability in supersaturated amorphous solid dispersion than drugs with poor GFA (class 1). These results indicate that the GFA of a drug and its physical stability in a supersaturated amorphous solid dispersion stored at a temperature above or below its T_g are correlated.     

Targeted vessel reconstruction in non‐contrast‐enhanced steady‐state free precession angiography

Image quality in non‐contrast‐enhanced (NCE) angiograms is often limited by scan time constraints. An effective solution is to undersample angiographic acquisitions and to recover vessel images with penalized reconstructions. However, conventional methods leverage penalty terms with uniform spatial weighting, which typically yield insufficient suppression of aliasing interference and suboptimal blood/background contrast. Here we propose a two‐stage strategy where a tractographic segmentation is employed to auto‐extract vasculature maps from undersampled data. These maps are then used to incur spatially adaptive sparsity penalties on vascular and background regions. In vivo steady‐state free precession angiograms were acquired in the hand, lower leg and foot. Compared with regular non‐adaptive compressed sensing (CS) reconstructions (CS_low), the proposed strategy improves blood/background contrast by 71.3 ± 28.9% in the hand (mean ± s.d. across acceleration factors 1–8), 30.6 ± 11.3% in the lower leg and 28.1 ± 7.0% in the foot (signed‐rank test, P < 0.05 at each acceleration). The proposed targeted reconstruction can relax trade‐offs between image contrast, resolution and scan efficiency without compromising vessel depiction. Copyright © 2016 John Wiley & Sons, Ltd.     

Immunohistochemical detection of pS2 protein and heat shock protein-70 in pancreatic adenocarcinomas. Relationship with disease extent and patient survival

We investigated pS2 and HSP-70 protein expression in 36 pancreatic adenocarcinomas for their effect on disease extent and patient outcome. The cases were reviewed, histologically diagnosed, typed, graded, and staged. Lymphatic vessel, blood vessel and perineural invasion as well as lymph node, resection margin and adjacent organ involvements were re-evaluated. The standard streptavidin biotin immunperoxidase method was used for immunostaining with pS2 and HSP-70 antibodies. Cytoplasmic staining with both antibodies was scored semiquantitatively. The scores were compared with histopathological prognostic parameters using statistical methods. Standard prognostic parameters and staining scores were tested by survival analysis in terms of their effect on survival. All the tumors showed a positive cytoplasmic reaction with HSP-70 antibody. Seventy-seven percent of the tumors showed positive cytoplasmic staining with pS2 antibody (22.2% +, 13.9% ++ and 41.7% +++). There was a statistically significant difference between HSP-70 staining scores with N status and final stages of the tumors (Chi-square, p = 0.03 and p = 0.026, respectively), while neither direct nor inverse correlation was detected for both parameters. PS2 staining scores showed no statistically significant relationship with tumor grade T, M status, perineural invasion, lymph and blood vessel invasion. In tumors with extensive staining with pS2, tumor stage tended to be low (Chi square, p = 0.024, Kendall Tau-b, r: -0.336, p = 0.036). There was a statistically significant difference and inverse correlation between tumors with extensive pS2 staining and tumors with less intense staining in terms of lymph node metastasis (Chi-square, p = 0.041, Kendall Tau: p = 0.024, r = -0,373). In the R0 resection group, in univariate analysis, we found that with higher scores of HSP-70 staining, the prognosis of the patient tended to improve. (Cox regression, p = 0.013). In multivariate analysis, HSP-70 expression was found to be an independent prognostic factor. We found no relationship between pS2 staining and patient survival.     

Role of cytological characteristics of benign thyroid nodules on effectiveness of their treatment with levothyroxine

Introduction

Levothyroxine (LT4) therapy has been used for the treatment of euthyroid nodular goiter, but there are controversial results about its usefulness. We aimed to evaluate the possible role of benign nodules’ cytological characteristics in response to LT4 therapy.

Material and methods

In total, 93 patients with 128 nodules were included in the study; 74 of the nodules were treated with LT4 (group 1), and 54 of them had no medication (group 2). The subgroups consisted of adenomatous nodules, colloid nodules and cystic nodules.

Results

In group 1, mean thyroid volume and mean nodule volume were reduced significantly (p = 0.002 and p = 0.022, respectively) with low-normal level thyrotropin (TSH) suppression (between 0.3 mIU/ml and 1.0 mIU/ml), while there were no significant changes in group 2. When we evaluated changes of the initial and last nodule volumes in cytological subgroups, only colloid nodules in group 1 had significant reduction (p = 0.040) and the others had no significant changes. By omitting the colloid nodules, when the other nodules were revaluated, there were no significant changes in either group.

Conclusions

On the basis of these results, obtained from a large sample of Anatolian patients, it is possible that LT4 therapy leads to significant reductions of both thyroid volume and nodule size in colloid nodules, but not in other kinds of benign nodules.     

Sarcopenia is associated with increased severe postoperative complications after colon cancer surgery

IntroductionStudies have shown that sarcopenia is associated with poor outcomes in patients with gastrointestinal cancer undergoing surgery. We aimed to investigate the relationship between postoperative complications of sarcopenic patients who had been operated on for colon cancer and the effects on short-term mortality.Material and methodsIn this study, patients who had undergone colon cancer surgery between January 2013 and December 2018 were collected retrospectively. Sarcopenia was diagnosed by the skeletal muscle index (SMI) derived from a preoperative computed tomography scan. Multiple logistic regression analysis was performed to determine whether sarcopenia is associated with postoperative major complications (POMC).ResultsThe study included 160 patients with a mean age of 62.4 ±12.6 years. Clavien-Dindo grade 1–2 (minor) complications were not significantly different between the groups (p = 0.896). However, grade ≥ 3 (major) complications were detected in 13 (17.8%) patients in the sarcopenic group (SG) and in 5 patients in the non-sarcopenic group (NSG) (5.7%) (p = 0.016). Length of intensive care unit (ICU) stay was longer in SG (p = 0.002) and there was no difference between 1-month and 6-month mortality rates (p = 0.273 and p = 0.402, respectively). According to univariate analyses, sarcopenia and age over 65 years were related to POMC. In multivariate analyses, sarcopenia (odds ratio = 3.039; 95% confidence interval 1.008–9.174; p = 0.048) and advanced age (odds ratio = 3.246; 95% confidence interval 1.078–9.803; p = 0.036) were found to be independent risk factors for POMC.ConclusionsThis study showed that while sarcopenia is a risk factor for POMC, sarcopenia also prolongs the duration of ICU stay. Also sarcopenia has no effect on short-term mortality.     

Comparison of pain threshold,health and functional status of females with fibromyalgia and multiple sclerosis: a pilot study

Objectives. Fibromyalgia (FM) and multiple sclerosis (MS) are known to cause disability and have an impact on physical functioning, social functioning, and emotional well-being of affected individuals. The aim of this study was to compare pressure pain threshold, health and functional status in females with FM and MS who were ambulatory. Methods. Control point scores (CPS), total myalgic scores (TMS; using an algometer), tender point (TP) counts, and chronic widespread pain were assessed in females with FM and MS and in healthy age-matched female controls. The Fibromyalgia Impact Questionnaire (FIQ), and the Nottingham Health Profile were performed. The Kurtzke Expanded Disability Status Scale (EDSS) was used to estimate the disability status of persons with MS. Results. Fibromyalgia patients have significantly lower CPS and TMS than MS patients and controls. Multiple sclerosis patients had similar CPS but significantly lower TMS compared to controls. Tender point counts were significantly higher in FM than MS patients and controls. Patients with MS had a higher numbers of TPs with respect to controls. Chronic widespread pain was reported by only three patients with MS and these patients did not meet FM criteria for tender point counts. Fibromyalgia patients had significantly lower FIQ-first item scores than MS patients. FM patients had higher NHP section scores in pain, social isolation, emotional reaction, sleep and energy, but similar physical mobility compared to MS patients. In MS patients energy and physical mobility dimension of NHP and FIQ-first item scores correlated with EDSS (r=0.42, P=0.047, r=0.83, P=0.001, and r=0.62, P=0.001, respectively). Conclusion. This cross-sectional study warrants further research comparing FM and MS, which share a lot of clinical and psychosocial features or may coexist. Chronic pain and related fatigue, social and emotional reactions and disability seem to be important components in FM, so taking care of these components, in other words a biopsychosocial model, may improve disease outcome and quality of life not only in FM but also in MS.     

Impaired semen parameters in patients with confirmed SARS-CoV-2 infection: A prospective cohort study

In this prospective study, we investigated the impact of SARS-CoV-2 infection on semen parameters in a cohort of men who had recently recovered from COVID-19. A total of 24 men who had recently recovered from mild COVID-19 were included in the study. Their semen parameters were normal before COVID-19 according to the World Health Organization 2010 reference values. Semen samples were collected from these participants in the recovery phases of COVID-19. To determine the effect of SARS-CoV-2 infection on semen parameters, the patients' pre-COVID-19 and post-COVID-19 semen analyses were compared. The mean age of the participants was 34.7 ± 6.4 years. The median interval between the positive nasopharyngeal swab test and obtaining semen samples was 111.5 (158) days. There was no significant difference in semen parameters before and after COVID-19 in terms of semen volume (p = .56), sperm concentration (p = .06), and progressive motility (p = .14). Total motility (p = .01) and total motile sperm count (p = .02) decreased significantly after SARS-CoV-2 infection compared to the pre-infection values. This study demonstrated that sperm motility and total motile sperm count were the semen parameters which showed a significant reduction in cases with a history of mild COVID-19.     

Lymphovascular space involvement is the sole independent predictor of lymph node metastasis in clinical early stage endometrial cancer

Purpose

To determine clinicopathological risk factors associated with lymph node metastasis in endometrial cancer (EC).

Methods

Clinicopathological data of patients who underwent comprehensive surgical staging for clinical early stage EC between 2001 and 2010 at Hacettepe University Hospital was retrospectively reviewed.

Results

Two hundred and sixty-one patients were included. There were 26 patients (10.0 %) with lymph node metastasis. Of these, 14 (5.4 %) had pelvic lymph node metastasis, 8 (3.1 %) had both pelvic and paraaortic lymph node metastasis, and 4 (1.5 %) had isolated paraaortic metastasis. Univariate analysis revealed tumor size >2 cm, type II cancer, grade III histology, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, and presence of lymphovascular space involvement (LVSI) as significant clinicopathological factors associated with retroperitoneal lymph node metastasis. For paraaortic metastasis either isolated or with pelvic lymph node metastasis, significant factors were grade III disease, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, pelvic lymph node metastasis, and presence of LVSI. The only factor associated with isolated paraaortic lymph node metastasis was LVSI. Multivariate analysis revealed LVSI as the only independent factor for both retroperitoneal and paraaortic lymph node metastasis (odds ratio 14.9; 95 % confidence interval 3.8–59.0; p < 0.001, and odds ratio 20.9; 95 % confidence interval 1.9–69.9; p = 0.013, respectively).

Conclusion

Lymphovascular space involvement is the sole predictor of lymph node metastasis in EC. Therefore, LVSI status should be requested from the pathologist during frozen examination whenever possible to consider when a decision to perform or omit lymphadenectomy is made.     

Cutaneous anthrax of the hand and its reconstruction with a reverse-flow radial forearm flap

Bacillus anthracis infection can lead to necrosis in tissues and may manifest as a fatal disease in human beings. The authors present a patient with a large area of skin necrosis on the dorsum of the hand that was reconstructed with a reverse flow-through radial forearm flap, and they discuss the relevant literature. To the authors' knowledge, this is the first published report of such extensive necrosis resulting from anthrax limited to the extensor retinaculum of the hand.