J. Clin. Med., Volume 7, Issue 4 (April 2018) – 28 articles

Colovaginal and/or rectovaginal fistulas cause significant and distressing symptoms, including vaginitis, passage of flatus/feces through the vagina, and painful skin excoriation. These fistulas can be a challenging condition to treat. Although most fistulas can be treated with surgical repair, for those patients who are not operative candidates, limited options remain. As minimally-invasive interventional techniques have evolved, the possibility of fistula occlusion has enriched the therapeutic armamentarium for the treatment of these complex patients. In order to offer optimal treatment options to these patients, it is important to understand the imaging and anatomical features which may appropriately guide the surgeon and/or interventional radiologist during pre-procedural planning. Full article

Quadrilateral space syndrome (QSS) is a rare disorder characterized by axillary nerve and posterior humeral circumflex artery (PHCA) compression within the quadrilateral space. Impingement is most frequently due to trauma, fibrous bands, or hypertrophy of one of the muscular borders. Diagnosis can be complicated by the presence of concurrent traumatic injuries, particularly in athletes. Since many other conditions can mimic QSS, it is often a diagnosis of exclusion. Conservative treatment is often first trialed, including physical exercise modification, physical therapy, and therapeutic massage. In patients unrelieved by conservative measures, surgical decompression of the quadrilateral space may be indicated. Full article

We created, posted, and updated radiology department anticoagulation guidelines and identified various steps in the process, including triggering events, consensus building, legal analysis, education, and distribution of the guidelines to nurses and clinicians. Supporting data collected retrospectively, before and after implementation, included nursing satisfaction survey results and the number of procedure cancellations. After the guidelines were developed and posted, significantly fewer procedures were cancelled, nursing satisfaction was higher, and radiologists performed procedures with less variability. Anecdotally, radiologists had fewer queries about anticoagulation. The development and dissemination of radiologic procedure anticoagulation guidelines should be considered as a departmental quality improvement project. Full article

Object. Utilization of pedicle screws (PS) for spine stabilization is common in spinal surgery. With reliance on visual inspection of anatomical landmarks prior to screw placement, the free-hand technique requires a high level of surgeon skill and precision. Three-dimensional (3D), computer-assisted virtual neuronavigation improves the precision of PS placement and minimization steps. Methods. Twenty-three patients with degenerative, traumatic, or neoplastic pathologies received treatment via a novel three-step PS technique that utilizes a navigated power driver in combination with virtual screw technology. (1) Following visualization of neuroanatomy using intraoperative CT, a navigated 3-mm match stick drill bit was inserted at an anatomical entry point with a screen projection showing a virtual screw. (2) A Navigated Stryker Cordless Driver with an appropriate tap was used to access the vertebral body through a pedicle with a screen projection again showing a virtual screw. (3) A Navigated Stryker Cordless Driver with an actual screw was used with a screen projection showing the same virtual screw. One hundred and forty-four consecutive screws were inserted using this three-step, navigated driver, virtual screw technique. Results. Only 1 screw needed intraoperative revision after insertion using the three-step, navigated driver, virtual PS technique. This amounts to a 0.69% revision rate. One hundred percent of patients had intraoperative CT reconstructed images taken to confirm hardware placement. Conclusions. Pedicle screw placement utilizing the Stryker-Ziehm neuronavigation virtual screw technology with a three step, navigated power drill technique is safe and effective. Full article

Predicting outcomes in patients with hepatocellular carcinoma (HCC) who undergo locoregional therapies remains a substantial clinical challenge. The purpose of this study was to investigate pre-procedure diffusion weighted magnetic resonance imaging (DW-MRI) as an imaging biomarker for tumoral response to therapy for patients with HCC undergoing drug eluting embolic (DEE) chemoembolization and radioembolization. A retrospective review of HCC patients who underwent DEE chemoembolization or radioembolization was performed. Of the 58 patients who comprised the study population, 32 underwent DEE chemoembolization and 26 underwent radioembolization. There was no significant difference in median apparent diffusion coefficient (ADC) values across the two treatment groups (1.01 × 10⁻³ mm²/s, P = 0.25). The immediate objective response (OR) rate was 71% (40/56). Tumors with high ADC values were found to have a higher probability of OR within 90 days (odds ratio 4.4, P = 0.03). Moreover, index lesion specific progression free survival (PFS) was greater for high ADC tumors, independent of conventional predictors of treatment response (hazard ratio 0.44, P = 0.01). Low ADC was associated with poorer PFS (P = 0.02). Pre-procedure ADC < 1.01 × 10⁻³ mm²/s is an independent predictor of poorer immediate OR and index lesion specific PFS in patients with HCC undergoing DEE chemoembolization or radioembolization. Full article

Critical limb ischemia (CLI) is a terminal stage of peripheral arterial disease that, in the absence of intervention, may lead to lower extremity amputation or death. Endovascular interventions have become a first-line approach to the management of CLI and have advanced considerably within the past decade. This review summarizes the types of percutaneous devices and the techniques that are available for the management of CLI and the data supporting their use. These include devices that establish and maintain vessel patency, including percutaneous transluminal angioplasty, drug-coated balloons, bare metal stents, drug-eluting stents, bioresorbable vascular scaffolds, and atherectomy; devices that provide protection from embolization; and, cell-based therapies. Additionally, ongoing trials with important implications for the field are discussed. Full article

Because conventional body mass index (cBMI) does not reflect fluid accumulation, modified BMI (mBMI, serum albumin multiplied by cBMI) is a more accurate measure of malnutrition status. This study aimed to determine whether mortality after intensive care unit (ICU) admission was associated with cBMI, mBMI, and/or serum albumin levels. The medical records of patients who were admitted to a tertiary hospital ICU between 1 January 2012 and 31 July 2016 were retrospectively reviewed. In total, 6169 ICU-admitted patients were included in the analyses. Multivariate Cox regression analyses revealed that low cBMI, mBMI and albumin level were significantly associated with 30-day and 1-year mortality after ICU admission (hazard ratio < 1.0, p < 0.05). The adjusted area under the curve (AUC) of mBMI for 1-year mortality was significantly higher than that of cBMI (p < 0.001), but not significantly different from that of albumin level (p = 0.098). Low values of mBMI, cBMI and albumin were independently associated with 30-day and 1-year mortality after ICU admission. Combining cBMI and albumin (mBMI) did not increase the validity of the AUC of albumin for 1-year mortality after ICU admission. Our study showed that serum albumin alone, rather than mBMI (combining cBMI), is recommended in predicting mortality among ICU patients. Full article

Background: This study analyzes data related to Hospital (HOS), Public Treatment Service Dedicated to Drug Addicts (SERD), or Community Mental Health Center (CMHC) clients with a first diagnosis of Pathological Gambling (PG) in the period 2000/2016 in Northern Italy. The aims were to describe trends and characteristics of pathological gamblers (PGs) and to estimate the prevalence of other diagnoses before or after the diagnosis of PG. Methods: Participants aged over 17 years with an ICD-9 or ICD-10 PG diagnosis were selected. Results: 680 PGs were identified, mean age 47.4 years, 20% female, 13% non-natives, 30% had other mental disorders diagnoses, 9% had alcohol dependence syndrome, and 11% had drug dependence. Most participants with comorbid disorders were diagnosed before PG, with a more elevated prevalence regarding mental disorders. Almost seven years had elapsed on average between the first admission and the diagnosis of PG. Conclusions: The results of this study highlight a growing demand for PG treatment addressed not only to SERD, but also to psychiatric and hospital services, based on the increase in SERD attendance from 2013. Many of them had already been treated for mental health problems before, but their percentage remained costant over time. Full article

Background: Children with autism spectrum disorder (ASD) require neurological evaluation to detect sensory-motor impairment. This will improve understanding of brain function in children with ASD, in terms of minor neurological dysfunctions (MNDs). Methods: We compared 32 ASD children without intellectual disability (IQ ≥ 70) with 32 healthy controls. A standardized and age-specific neurological examination according to Touwen was used to detect the presence of MNDs. Particular attention was paid to severity and type of MNDs. Results: Children with ASD had significantly higher rates of MNDs compared to controls (96.9% versus 15.6%): 81.3% had simple MNDs (p < 0.0001) and 15.6% had complex MNDs (p = 0.053). The prevalence of MNDs in the ASD group was significantly higher (p < 0.0001) than controls. With respect to specific types of MNDs, children with ASD showed a wide range of fine manipulative disability, sensory deficits and choreiform dyskinesia. We also found an excess of associated movements and anomalies in coordination and balance. Conclusions: Results replicate previous findings which found delays in sensory-motor behavior in ASD pointing towards a role for prenatal, natal and neonatal risk factors in the neurodevelopmental theory of autism. Full article

Pertrochanteric femur fractures are considered amongst the most commonly encountered fractures in the geriatric age group. We evaluated radiographic and functional outcomes of patients with unstable pertrochanteric fractures treated with the proximal femur nail antirotation (PFNA). Between March 2013 and December 2015, fifty patients (28 male and 22 females with a mean age of 72.8 years (range, 20–94)) with unstable pertrochanteric fractures (AO 31.A2 and 31.A3) were fixed with the PFNA at our institution, and they were retrospectively evaluated. Forty one patients were treated with short PFNA and nine with long PFNA. Operative time ranged between 30 and 150 (average 73.60) min, blood loss ranged between 50 and 250 (average 80) milliliter and hospital stay ranged between 3 and 18 (6.86) days. The mean follow-up period was 18 months (range, 11–31). At final follow-up, solid union of all fractures had been achieved without any implant-related complications, the mean Harris Hip Score (HHS) was 79.34 ± 9.10 points and the mean neck-shaft angle was 127.2° ± 5.07°. No significant differences were encountered between the functional and radiographic outcomes of the PFNA with regards to the AO fracture classification and the implant version. PFNA is a recommended option for the treatment of unstable pertrochanteric fractures owing to its easy insertion, reduced blood loss, stable fixation and satisfactory functional and radiological outcomes. Full article

Venous disease is more common than peripheral arterial disease. Pathophysiologically, venous disease can be associated with obstruction, reflux, or both. A common feature in chronic venous disease is ambulatory venous hypertension. Inflammatory and pro-thrombotic mechanisms can be activated. The current therapies, including compression, ablation, and recanalization are discussed. Full article

Objectives: The adverse effects of smoking in various pathologies are mediated by its effects on the inflammatory system. The monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) has recently emerged as an indicator of inflammation. We aimed to investigate the relationship between MHR and cigarette smoking. Patients and Methods: Three hundred and ninety seven consecutive participants who smoke and 515 healthy subjects with no history of smoking enrolled in the study. Complete blood count parameters and lipid profile were analyzed in all study participants. Smoking habits were calculated as pack.years and number of cigarettes smoked per day. Results: MHR levels were significantly higher in smokers compared to non-smokers (respectively, 15.71 (12.02–20.00) and 11.17 (8.50–14.16), p < 0.0001)). Pearson’s correlation analysis revealed a weak but positive correlation between pack.year and MHR in the smokers group, and there was a moderate positive correlation between the number of cigarettes smoked daily and MHR in the group. In receiver operating characteristics (ROC) analyses, it was determined that a MHR value >13.00 measured in smoker participants at application had a predictive specificity of 66.6% and sensitivity of 70.0% for smoking (area under the curve [AUC] 0.729, 95% CI 0.696, 0.762; p < 0.0001). Conclusions: Elevated MHR is associated with cigarette smoking and may be a useful indicator of a systemic inflammatory response in smokers. Smoker participants who have high MHR levels can easily be identified during routine complete blood count (CBC) analysis and could possibly benefit from preventive treatment. Full article

Current therapy of Clostridium difficile diarrhea (CDD) is problematic. Optimal treatment for CDD remains oral vancomycin, but there is little data on oral vancomycin dosing regimens. The objective of this C. difficile diarrhea study was to compare the efficacy of “high dose” vancomycin, 500 mg (PO) q6h, as sole treatment and in those who after 72 h failed to respond to conventional doses of oral vancomycin, 125–250 mg (PO) q6h. Hospitalized adults with CDD were evaluated by various oral vancomycin regimens, i.e., a conventional dose group (125–250 mg (PO) q6h), a “high dose escalation” dose group (250 mg → 500 mg (PO) q6h), and a “high dose” group (500 mg (PO) q6h). Oral vancomycin treatment groups were compared by time to improvement, i.e., decrease in >50% of watery stools/day and duration of therapy. The high dose escalation and high dose oral vancomycin groups showed the most rapid resolution of diarrhea. There was marked decrease in stools/day after “high dose” vancomycin escalation from conventional dosing, i.e., 250 mg (PO) q6h → 500 mg (PO) q6h. This study demonstrated that “high dose” escalation or initial high dose oral vancomycin, i.e., 500 mg (PO) q6h was the most efficacious regimen for CDD. Full article

Percutaneous coronary intervention (PCI) with stenting for the treatment of acute coronary syndrome (ACS) is the contemporary standard of care. Such treatment is followed by dual antiplatelet therapy (DAPT) comprising of aspirin and a P2Y12 inhibitor. The efficacy of this therapy has been well established but the optimal duration of DAPT remains elusive, and has thus far attracted a prodigious deal of scientific attention. The decision regarding DAPT duration can be clinically challenging in the modern era with the evolution of newer stents, more potent antiplatelet agents, and novel anticoagulant drugs in addition to an older patient population with multiple comorbidities. Major societal guidelines have emphasized comprehensive assessment of ischemic and bleeding risk, in turn recommending individualization of DAPT duration, thus encouraging “shared decision making”. The following review is aimed at critically evaluating the available evidence to help make these crucial clinical decisions regarding duration of DAPT and triple therapy. Full article

The aim of this study was to investigate the effect of topically applied ocular anesthetic proparacaine on conjunctival and nasal bacterial mucosal flora in patients with dry eye disease. A Schirmer test was done with (group 1) and without (group 2) topical anesthetic proparacaine to 40 patients in each group. Conjunctival and nasal cultures were obtained before and 10 min after performing the Schirmer test. The bacterial culture results and the isolated bacteria were recorded in two groups. Patients’ mean age was 62 years (70 female, 10 male). Before the application of topical anesthetic, 50 (62.5%) and 62 (77.5%) had positive conjunctival and nasal culture, respectively, with the most commonly isolated organism being coagulase-negative Staphylococcus in each group. In group 1 the conjunctival bacterial culture positivity rate decreased from 26 (65%) to six (15%) eyes (p < 0.001); however, this rate decreased slightly from 24 (60%) to 20 (50%) eyes in group 2 (p > 0.05). For the nasal cultures, the bacterial culture positivity rate decreased from 80% to 20% and from 75% to 65% in groups 1 (p < 0.001) and 2 (p > 0.05), respectively. Topical ocular anesthetic proparacaine has antibacterial activity in both conjunctival and nasal flora in patients with dry eye disease. Full article

Data evaluating the effect of asymptomatic effects of radiation on thyroid hormone panels and ultrasonographic abnormalities among radiology technologists are scarce. This study aimed to determine the asymptomatic effect of radiation in a total of 39 male and 11 female exposed radiology technologists working in radiology departments, and a total of 34 male and 16 female age-matched controls working in other departments in the same hospital. The level of triiodothyronine (T₃), thyroxine (T₄) and thyroid-stimulating hormone (TSH) were evaluated using Enzyme Linked Immunosorbent Assay (ELISA). Thyroid ultrasonographic evaluation outcomes were given as normal or abnormal. There was significant interaction between exposure and gender in the mean TSH and T₄ but not T₃. The mean TSH for exposed men was significantly higher than that among non-exposed men (2.28 mIU/L vs. 1.59 mIU/L; p-value = 0.003). The mean TSH was not significantly different between exposed and non-exposed women. The mean T₄ for exposed men was significantly higher when compared with non-exposed men (11.1 pmol/L vs. 10.05 pmol/L; p-value = 0.005). In the non-exposed group, 93.8% of women and 94.1% of men had T₄ values lower than established normal reference range, while in the exposed group, 90.9% of women and 74.4% of men had low values of T₄. There was no significant difference in mean T₃ between exposed and non-exposed groups for men and women. Furthermore, there were no significant differences in the thyroid gland ultrasonographic findings between exposed and non-exposed groups. Occupational radiation exposure is associated with increased means of TSH and T₃, especially among men. Full article

Autism spectrum disorder (ASD) is estimated to affect one in 68 children. Given the increase in both prevalence and awareness of ASD, it is critical to provide accurate and timely diagnosis. However, ASD often co-occurs with other disorders, making diagnosis difficult. The objective of the current case study was to provide two examples of differential diagnosis in ASD and post-traumatic stress disorder (PTSD) observed in an autism clinic. In both cases, the goal was to decide whether each child should be given a diagnosis of ASD, PTSD, or both. Full article

By the sixth decade of life, nearly one quarter of the population has substantial muscle atrophy, or sarcopenia. Despite the creation of a standardized definition of sarcopenia by the European Working Group on Sarcopenia in Older People, variability may exist in the diagnostic criteria utilized for clinical sarcopenia research. The primary objectives of this review were to characterize diagnostic criteria used for measurement of sarcopenia in original studies, and to describe associations between sarcopenia and important clinical outcomes. We performed a literature review of the term “sarcopenia” in PubMed. Inclusion criteria were English language, original data, a clear and specific definition for diagnosing sarcopenia, and the analysis of sarcopenia’s effect on a clinical outcome. A total of 283 studies met inclusion criteria. More than half of the included sarcopenia investigations were level IV studies (54.1%), while 43.1% provided level II evidence. Under one third (27.6%) of studies examined sarcopenia with regard to surgical outcomes. In terms of diagnostic criteria for sarcopenia, 264 (93.3%) studies used measures of skeletal muscle mass, with dual energy X-ray absorptiometry (DEXA) being the most common modality (43.6%). Sarcopenia was found to be a consistent predictor of chronic disease progression, all-cause mortality, poorer functional outcomes, and postoperative complications. In conclusion, there is substantial evidence that sarcopenia impacts both medical and surgical outcomes. However, current research has utilized heterogeneous diagnostic criteria for sarcopenia. Further efforts to standardize the modalities used to diagnose sarcopenia in clinical research and practice will help strengthen our ability to study this important phenomenon. Full article

The association between the Pro12Ala polymorphism of the PPARγ2 gene, type 2 diabetes (T2D), and obesity in certain ethnic populations has been reported. However, this relationship has not yet been described among diabetes patients in Nigeria. This study investigated the relationship between the Pro12Ala polymorphism in the PPARγ2 gene, obesity, and lipid abnormalities characterizing T2D among patients in Nigeria. This case-control study recruited 73 T2D and 75 non-diabetic (ND) patients. Demographic and clinical data were collected and blood glucose levels together with serum lipid profile for patients were measured. Pro12Ala polymorphism in the PPARγ2 gene was genotyped by restriction fragment length-Polymerase Chain Reaction (RFLP-PCR). The PPAR-γ2 gene (amplicon size = 270 base pair) was successfully amplified for all samples. Following restriction enzyme digestion and analysis by agarose gel electrophoresis, amplicons from samples showed a band of size 270 bp and were of the wild homozygous Pro/Pro genotype. Ala12 variant was totally absent from the study population. Obesity, estimated using Body Mass Index (BMI) and waist circumference (WC), was significantly higher (p < 0.05) in T2D patients compared to the non-diabetic patients. More so, the prevalence of lipid abnormalities; hypercholesterolaemia (TC > 200 mg/dL), hypertriglyceridaemia (TG > 150 mg/dL), high HDL (>100 mg/dL), and low HDL (<50 mg/dL) was significantly greater (p < 0.001) in T2D patients compared to non-diabetic patients. Results obtained further indicated lack of significant association between PPAR-γ2 gene polymorphism, T2D, and obesity. However, obesity and dyslipidaemia were strongly associated in T2D patients. Full article

Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers. Full article

The therapeutic effects of voluntary exercise on the recovery of long-gap nerve injury following the bridging of an acellular conduit filled with human skeletal muscle-derived stem cells (Sk-SCs) have been described. Human Sk-SCs were sorted as CD34⁺/45⁻ (Sk-34) cells, then cultured/expanded under optimal conditions for 2 weeks. Surgery to generate a long-gap sciatic nerve injury was performed in athymic nude mice, after which the mice were divided into exercise (E) and non-exercise (NE) groups. The mice were housed in standard individual cages, and voluntary exercise wheels were introduced to the cages of the E group one week after surgery. After 8 weeks, the human Sk-34 cells were actively engrafted, and showed differentiation into Schwann cells and perineurial cells, in both groups. The recovery in the number of axons and myelin in the conduit and downstream tibial nerve branches, and the lower hindlimb muscle mass and their tension output, was consistently higher by 15–25% in the E group. Moreover, a significantly higher innervation ratio of muscle spindles, reduced pathological muscle fiber area, and acceleration of blood vessel formation in the conduit were each observed in the E group. These results showed that the combined therapy of tube-bridging, Sk-34 cell transplantation, and voluntary exercise is a potentially practical approach for recovery following long-gap nerve injury. Full article

The aim of this article is to investigate pathological subjects from a population through different physical factors. To achieve this, particle swarm optimization (PSO) and K-means (KM) clustering algorithms have been combined (PSO-KM). Datasets provided by the literature were divided into three clusters based on age and weight parameters and each one of right tibial external rotation (RTER), right tibial internal rotation (RTIR), left tibial external rotation (LTER), and left tibial internal rotation (LTIR) values were divided into three types as Type 1, Type 2 and Type 3 (Type 2 is non-pathological (normal) and the other two types are pathological (abnormal)), respectively. The rotation values of every subject in any cluster were noted. Then the algorithm was run and the produced values were also considered. The values of the produced algorithm, the PSO-KM, have been compared with the real values. The hybrid PSO-KM algorithm has been very successful on the optimal clustering of the tibial rotation types through the physical criteria. In this investigation, Type 2 (pathological subjects) is of especially high predictability and the PSO-KM algorithm has been very successful as an operation system for clustering and optimizing the tibial motion data assessments. These research findings are expected to be very useful for health providers, such as physiotherapists, orthopedists, and so on, in which this consequence may help clinicians to appropriately designing proper treatment schedules for patients. Full article

Human hepatocellular carcinoma (HCC) is the fifth most common cancer and is associated with poor prognosis worldwide. The molecular mechanisms underlying the pathogenesis of HCC have been an area of continuing interest, and recent studies using next generation sequencing (NGS) have revealed much regarding previously unsettled issues. Molecular studies using HCC samples have been mainly targeted with the aim to identify the fundamental mechanisms contributing to HCC and identify more effective treatments. In response to cellular stresses (e.g., DNA damage or oncogenes), activated p53 elicits appropriate responses that aim at DNA repair, genetic stability, cell cycle arrest, and the deletion of DNA-damaged cells. On the other hand, the murine double minute 2 (MDM2) oncogene protein is an important cellular antagonist of p53. MDM2 negatively regulates p53 activity through the induction of p53 protein degradation. However, current research has shown that the mechanisms underlying MDM2-p53 interactions are more complex than previously thought. Microarray data have added new insight into the transcription changes in HCC. Recently, Nutlin-3 has shown potency against p53-MDM2 binding and the enhancement of p53 stabilization as well as an increment of p53 cellular accumulation with potential therapeutic effects. This review outlines the molecular mechanisms involved in the p53-MDM2 pathways, the biological factors influencing these pathways, and their roles in the pathogenesis of HCC. It also discusses the action of Nutlin-3 treatment in inducing growth arrest in HCC and elaborates on future directions in research in this area. More research on the biology of p53-MDM2 interactions may offer a better understanding of these mechanisms and discover new biomarkers, sensitive prognostic indicators as well as new therapeutic interventions in HCC. Full article

Adult-onset Still’s disease (AOSD) is an autoimmune inflammatory disorder. Glucocorticoids are often used for AOSD, which may induce complicating glucocorticoid-induced osteoporosis (GIO). An anti-resorption drug, denosumab, has recently been approved for osteoporosis treatment in Japan. However, the drug’s efficacy for GIO in AOSD is largely unknown. This retrospective, consecutive case series investigated two patients with GIO in AOSD to examine the effects of denosumab on bone metabolism. Bone turnover markers, and bone mineral density (BMD) of the lumbar 1–4 spine (L-BMD) and bilateral total hips (H-BMD) were followed for six months in a male patient and for twelve months in a female patient. No fractures or severe side effects, such as hypocalcemia, were observed during the observational period. Bone turnover markers were basically suppressed, and L-BMD and H-BMD were increased by denosumab in both patients. Our findings suggest that denosumab is a suitable candidate drug for GIO in AOSD. Full article

Bruton’s tyrosine kinase (BTK) is a critical terminal enzyme in the B-cell antigen receptor (BCR) pathway. BTK activation has been implicated in the pathogenesis of certain B-cell malignancies. Targeting this pathway has emerged as a novel target in B-cell malignancies, of which ibrutinib is the first-in-class agent. A few other BTK inhibitors (BTKi) are also under development (e.g., acalabrutinib). While the predominant action of BTKi is the blockade of B-cell receptor pathway within malignant B-cells, increasing the knowledge of off-target effects as well as a potential role for B-cells in proliferation of solid malignancies is expanding the indication of BTKi into non-hematological malignancies. In addition to the expansion of the role of BTKi monotherapy, combination therapy strategies utilizing ibrutinib with established regimens and combination with modern immunotherapy compounds are being explored. Full article

Epigenetic modifications have been identified as being responsible for the de-differentiation of thyroid tissue and its malignant transformation. Cell proliferation inhibitory effects of the pan-deacetylase inhibitors panobinostat, SAHA and Trichostatin A (TSA), the modulation of the sodium iodide symporter (NIS; SLC5A5), thyroid transcription factor 1 (TTF1), high mobility group A2 (HMGA2), and H19 and their putative targeting miRNAs have been evaluated in vitro. The cell viability was measured in five thyroid cancer cell lines (FTC133, TPC1, BCPAP, 8505C, C643) by real time cell analyzer xCELLigence. Expression of the above mentioned markers was performed by RT-qPCR and Western Blot. Radioiodine up-take was detected by Gamma Counter with I¹³¹. Cell viability decreased after treatment in all five cell lines. 10 nM panobinostat; 1 µM TSA or 10 µM SAHA caused a significant over-expression of NIS transcript in all five cell lines, whereas NIS protein was up-regulated in FTC133, BCPAP, and C643 cell lines only. Radioiodine up-take increased in FTC133 and C643 cells after 48 h of treatment with 10 nM panobinostat and 1 µM TSA. A significant down-regulation of the oncogene HMGA2 was detected in all five cell lines; except for TPC1 cells that were treated with 1 µM TSA. In accordance, hsa-let-7b-5p and hsa-let-7f-5p were stable or significantly over-expressed in all of the cell lines, except for TPC1 cells that were treated with 10 µM SAHA. TTF1 was significantly down-regulated in FTC133, BCPAP, and 8505C cells; whereas, TPC1 and C643 showed an up-regulated or stable expression. TTF1 was over-expressed in samples of human anaplastic thyroid cancer; whereas, it was down-regulated in follicular and undetectable in papillary thyroid cancer. H19 was over-expressed after 48 h treatment, except for BCPAP cells that were treated with panobinostat and SAHA. H19 was differently expressed in human anaplastic, follicular and papillary thyroid tumor samples. Deacetylase inhibitors reduced cell viability, restored NIS and H19, and suppressed the oncogenes HMGA2 and TTF1 in thyroid cancer cells. Full article

Nutrition care should be an integral part of general practitioners’ (GPs’) daily work with patients. The aim of this study was to assess the attitudes of Croatian GPs toward nutrition and nutrition care, and to evaluate the interconnection between their attitudes and implementation of nutrition care in GPs offices. A cross-sectional study was conducted among 17.0% of randomly selected GPs, from May to July of 2013, via a specially designed anonymous questionnaire. The study showed that 36.0% of the Croatian GPs had satisfactory number of positive attitudes (5 or more) toward nutrition and nutrition care. There was statistically significant difference in the median number of positive attitudes based on the additional education of GPs in nutrition and their ailment from chronic diseases (p < 0.001 and p = 0.022, respectively). The Spearman rank correlation between GPs’ attitudes toward nutrition and nutrition care and their practice, i.e., the implementation of nutrition care in GPs’ everyday work with patients was r_s = −0.235 (p < 0.001). In order to provide nutrition care in GPs’ offices in Croatia, strategies for changing GPs’ attitudes toward nutrition and nutrition care are needed. Full article