Med. Sci., Volume 7, Issue 3 (March 2019) – 17 articles

Background: Variations in blood glucose levels over a given time interval is termed as glycemic variability (GV). Higher GV is associated with higher diabetes-related complications. The current study was done with the aim of detecting the sensitivity of various GV indices among individuals with type 2 diabetes mellitus of different glycemic control status. Methods: We performed a longitudinal study among individuals with type 2 diabetes mellitus (T2DM) who were participating in a two-week diabetes self-management education (DSME) program. Participants were categorized by their HbA1c as poor (≥8%), acceptable (7%–8%), and optimal control (<7%). Continuous glucose monitoring (CGM) sensors recorded interstitial glucose every 15 min from day 1. The evaluated GV measures include standard deviation (SD), coefficient of variation (CV), mean amplitude of glycemic excursion (MAGE), continuous overlapping net glycemic action (CONGA), mean of daily difference for inter-day variation (MODD), high blood glucose index (HBGI), and low blood glucose index (LBGI). Results: A total of 41 study participants with 46347 CGM values were available for analysis. Of 41 participants, 20 (48.7%) were in the poor, 10 (24.3%) in the acceptable, and 11 (26.8%) in the optimal control group. The GV indices (SD; CV; MODD; MAGE; CONGA; HBGI) of poorly controlled (77.43; 38.02; 45.82; 216.63; 14.10; 16.62) were higher than acceptable (50.02; 39.32; 30.79; 138.01; 8.87; 5.56) and optimal (34.15; 29.46; 24.56; 126.15; 8.67; 3.13) control group. Glycemic variability was reduced in the poorly and acceptably controlled groups by the end of the 2-week period. There was a rise in LBGI in the optimally controlled group, indicating pitfalls of tight glycemic control. Conclusion: Indices of glycemic variability are useful complements, and changes in it can be demonstrated within short periods. Full article

Resistance to anticancer drugs limits the effectiveness of chemotherapy in cancers. Melanoma cell lines B16F10C and A375C (parental) and B16F10R and A375R (drug-resistant sublines) were used to test radiation sensitization potential of valproic acid (VPA), an inhibitor of Histone deacetylase2 (HDAC2) and LDN193189 (BMP inhibitor). Inhibitors of other signaling pathways were tested for cross-resistance with the resistant cell lines. Cells were pretreated with low concentrations of VPA/ LDN193189 and exposed to 2 Gy radiation for radiation sensitization experiments. Assays-3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), live/dead, clonogenic, and melanin estimation were performed to test the effects of radiation sensitization. Interactions of VPA and HDAC2 were studied in silico. Dose-dependent growth inhibition was observed with all tested drugs. Radiation sensitization of melanoma cells with low dose of VPA induced synergistic cell death, decreased clonogenicity, and decreased melanin content. In silico docking showed two stable interactions between Arg39 of HDAC2 and VPA. In conclusion, pretreatment with low doses of VPA has a potential for sensitizing melanoma cells to low doses of radiation. The binding of VPA to HDAC2 reverses the drug resistance in melanoma and induces the cell death. Sensitization effects of VPA can be used for targeting drug-resistant cancers. Full article

Fetal sex has been identified as an important factor influencing pregnancy outcomes, but its impact on fetal heart rate (FHR) variability in uncomplicated pregnancies is still unclear. The objective of the study was to assess short-term variability (STV) and other computerized cardiotocography (cCTG) parameters in relation to fetal sex during fetal antepartum surveillance. We retrospective compared cCTG parameters of male and female fetuses in uncomplicated singleton pregnancies at term. In addition to univariate analysis, a multivariate analysis was performed taking into account maternal characteristics. A total of 689 cCTG recordings were analyzed: 335 from male fetuses and 354 from female fetuses. Analysis of cCTG results by fetal sex showed no significant difference in percentage of signal loss, number of contractions, movements, accelerations and decelerations, long-term variability (LTV), and STV at both uni-and multivariate analysis. There was a statistically significant difference for baseline FHR at the univariate analysis, which was not confirmed by a multivariate analysis. Our results suggest that fetal sex did not affect cCTG parameters in uncomplicated term singleton pregnancies, and therefore it does not need to be taken into account when interpreting cCTG in physiological conditions. Full article

Polycystic ovary syndrome (PCOS) is a metabolic disorder with reproductive consequences. Hence, the synergy of the dual maternal challenges of difficulties with conception, set on a background of metabolic disorder and inflammation, understandably leads to increased obstetric risk for the woman. Furthermore, she is more likely than her peers to require assistance with conception, either through induction of ovulation with the attendant risk of a multiple gestation, or in vitro fertilization (IVF) with its recognized increased obstetric risk for woman and her child. The increased obstetric risk for a woman with PCOS is manifested with an increased rate of miscarriage, gestational diabetes, hypertensive disorder and premature delivery. These obstetric complications are due to impairment of placental function, systemic inflammation and metabolic disorder and are markers for the woman herself of her predisposition to cardiometabolic disorder in later life. Consequently, it is inevitable that this environment may induce changes in the fetus during pregnancy, leading to an intergenerational risk from maternal PCOS. Full article

Background: Pazopanib was approved for advanced soft tissue sarcoma as a second- or third-line therapy based on the clinical trial “Pazopanib for metastatic soft-tissue sarcoma” (PALETTE). We hypothesized that the real-world experiences may be significantly different from the clinical trial results. Methods: We analyzed the response pattern of patients with advanced soft tissue and bone sarcoma who received pazopanib treatment between 1 January 2011 and 31 October 2018 in Kaiser Permanente Northern California. Results: A total of 123 patients with 23 different histologic subtypes were assessable. One patient with low-grade fibromyxoid sarcoma obtained complete response (CR) after 2 months of treatment with pazopanib, 12 patients (9.7%) obtained partial response (PR), 34 patients (27.6%) had stable disease (SD), while 76 patients (61.8%) developed progressive disease (PD). The disease control rate (DCR) was 46.3% (CR + PR + SD). Among the 12 patients with PR, 3 had undifferentiated pleomorphic sarcoma (UPS), 4 had leiomyosarcoma (LMS), 2 had pleomorphic rhabdomyosarcoma, 1 had pleomorphic liposarcoma, 1 had dedifferentiated liposarcoma, and 1 had angiosarcoma. The median duration of response was 9 months. Two patients with Ewing’s sarcoma had SD for 6 and 13 months, and two patients with osteosarcoma had SD for 6 and 9 months. Among 65 patients assessed at 8 weeks, 9 had a response, and 10 had SD. Among 104 patients assessed at 12 weeks, 12 had a response, and 26 had SD. The median progression-free survival (PFS) was approximately 3 months for all 123 cases and for patients with UPS and LMS. Conclusions: Our cohort of patients with advanced soft tissue and bone sarcoma in Northern California treated with pazopanib had diverse histologic subtypes. The response rate (CR + PR) was higher than that of the PALETTE trial, while the DCR and the median PFS were significantly lower. The observation of PR in two patients with liposarcoma and durable SD in several patients with bone sarcoma indicates that pazopanib has activity in liposarcoma and bone sarcoma. Full article

Traumatic brain injury (TBI) and its potential long-term consequences are of major concern for public health. Neurorehabilitation of affected individuals has some specific characteristics in contrast to neurorehabilitation of patients with acquired brain lesions of other aetiology. This review will deal with the clinical consequences of the distinct lesions of TBI. In severe TBI, clinical course often follows a typical initial sequence of coma; followed by disturbed consciousness; later, post-traumatic agitation and amnesia; and finally, recovery of function occurs. In the different phases of neurorehabilitation, physicians should be aware of typical medical complications such as paroxysmal sympathetic hyperactivity, posttraumatic hydrocephalus, and posttraumatic neuroendocrine dysfunctions. Furthermore, we address questions on timing and on existing evidence for different rehabilitation programmes and for holistic neuropsychological rehabilitation approaches. Full article

The latest data from the United States and Europe reveal that rare small intestine cancer is on the rise, with the number of cases having more than doubled over the past 40 years in the developed world. Mortality has grown at a slower pace, thanks to improvements in early diagnosis and treatment, as well as a shift in the etiology of neoplasms affecting the small intestine. Nevertheless, 5-year survival for small intestine adenocarcinomas has lingered at only 35%. Lifestyle in developed nations, including the rise in obesity and physical inactivity, consumption of alcohol, tobacco, and red and processed meats, and occupational exposures may be to blame for the proliferation of this rare cancer. Identification of hereditary and predisposing conditions, likely to blame for some 20% of cases, may help prevent and treat cancers of the small intestine. Studies of the neoplasm have been limited by small sample sizes due to the rarity of the disease, leaving many questions about prevention and treatment yet to be answered. Full article

The correlation between aspirin sensitivity, asthma, and nasal polyposis was recognized in the early 20th century. Today, this classic triad of symptoms, eponymously named Samter’s Triad, is known as aspirin exacerbated respiratory disease (AERD). Aspirin exacerbated respiratory disease affects approximately 0.3–0.9% of the general population in the USA and approximately 7% of asthmatic patients. The management of AERD is challenging as no single modality has proven to have high rates of symptom control. Consequently, disease management typically involves a multimodality approach across both medical and surgical disciplines. This review describes the epidemiology of AERD and the current state-of-the-art as it relates to the underlying pathophysiologic mechanisms of this disease process. A significant proportion of the review is focused on the appropriate diagnostic workup for AERD patients including the utility of aspirin provocation testing. The spectrum of medical treatments, including aspirin desensitization and recently introduced immunotherapies, are discussed in detail. Furthermore, surgical approaches to disease control, including advanced endoscopic techniques, are reviewed and treatment outcomes presented. Full article

Sport-related concussion (SRC) is a highly prevalent injury predominantly affecting millions of youth through high school athletes every year. In recent years, SRC has received a significant amount of attention due to potential for long-term neurologic sequelae. However, the acute symptoms and possibility of prolonged recovery account for the vast majority of morbidity from SRC. Modifying factors have been identified and may allow for improved prediction of a protracted course. Potential novel modifying factors may include genetic determinants of recovery, as well as radiographic biomarkers, which represent burgeoning subfields in SRC research. Helmet design and understanding the biomechanical stressors on the brain that lead to concussion also represent active areas of research. This narrative review provides a general synopsis of SRC, including relevant definitions, current treatment paradigms, and modifying factors for recovery, in addition to novel areas of research and future directions for SRC research. Full article

Palliative and hospice care aims to improve quality of life of patients’ relatives, but still little is known about their specific problems and needs. We present a comprehensive literature update. Narrative review to present an expert overview of peer-reviewed, English-written original research publications and reviews on psychosocial and existential problems, supportive needs as well as interventions for relatives during the patients’ disease trajectory published between January 2017 and November 2018. A total of 64 publications were included. Relatives report high rates of psychological and existential distress, burden and psychological morbidity during the total disease trajectory of the patient. In addition, relatives report an alarmingly high number of unmet needs with information being the central issue. Relatives’ problems and needs are part of complex systems influenced by various socio-demographic factors and patient–relatives-interactions and dependency between different psychological phenomena. First support interventions for relatives during disease trajectory have proven feasible and secondary data from randomized studies suggest beneficial effects of providing early palliative care also for relatives. Relatives should be addressed to a still larger extent in the daily practice of palliative and hospice care, thus further research to reveal more detailed systematic information is needed to improve relatives’ psychological burden and quality of life. Full article

Lead exposure among pregnant U.S. women was examined via the National Health and Nutrition Examination Survey (NHANES) 2009–2016 data to examine its role in bad cholesterol and oxidative stress. Mean values of the clinical markers non-high density lipoprotein cholesterol (non-HDL-c) and gamma-glutamyl transferase (GGT), a marker of oxidative stress, were explored. In four quartiles of lead exposure, clinical makers were compared. Binary logistic regression predicted the likelihood of elevated clinical markers in pregnant compared to non-pregnant women, while linear regression was used to examine associations between blood lead levels (BLL) and the clinical markers of interest. Mean non-HDL-c was statistically significantly more elevated in pregnant women than non-pregnant women. Mean GGT levels were more statistically significantly elevated in the highest quartile of BLL exposure among pregnant women than in the lower quartiles. In binary logistic regression models, pregnant women were statistically significantly more likely to have elevated non-HDL-c, while in linear regression BLL was statistically significantly associated with GGT levels in pregnant women. Lead exposure in pregnant women is an issue of public health concern that must continue to be studied. Full article

Although there is a contemporary consensus of managing a severe disease with multi-targeted approach-based therapeutic combinations, it should not be ignored that certain patho-biological pathways are shared by distinct medical conditions and can be exploited to develop an exceptional type of medication conferring a dual efficacy. This article thus presents a spectrum of emerging molecular targets that substantially contribute to the pathogenesis of both fibrotic and neoplastic disorders, including kinase activities, cytokine cascades, and protein dynamics among others. Moreover, recently approved therapeutic agents in this regard have been sorted out to corroborate the drug’s ability upon targeting each one of these molecular pathways to treat fibrosis and cancer simultaneously. It not only streamlines an overlapping mechanistic profile in the pathogenesis across these two medical conditions, but also inspires clinicians and pharmaceutical innovation to tackle concomitant diseases, such as fibrosis and cancer, with an optimally efficacious medication. Full article

We have carried out a retrospective study of chromosome anomalies associated with increased nuchal translucency (NT) in order to compare yield rates of karyotype, chromosome microarray analysis (CMA), and non-invasive prenatal testing (NIPT) in this condition. Presenting with increased NT or cystic hygroma ≥3.5 mm as an isolated sign, 249 fetuses underwent karyotype and/or CMA from 11 to 18 gestational weeks. Karyotype and fluorescence in situ hybridization (FISH) analyses detected 103 chromosomal anomalies including 95 aneuploidies and eight chromosomal rearrangements or derivatives. Further, seven pathogenic copy number variants (CNV), five likely pathogenic CNVs, and 15 variants of unknown significance (VOUS) were detected by CMA in fetuses with normal karyotype. Genetic testing is now facing new challenges due to results with uncertain clinical impacts. Additional investigations will be necessary to interpret these findings. More than 15% of the anomalies that we have diagnosed with invasive techniques could not be detected by NIPT. It is therefore definitely not recommended in the case of ultrasound anomalies. These results, while corroborating the use of CMA in fetuses with increased NT as a second tier after rapid aneuploidy testing, do not suggest a dismissal of karyotype analysis. Full article

Anorexigenics are compounds capable of reducing or suppressing appetite. Their three main types act on different neurotransmitters, either norepinephrine, serotonin or a combination of both. Among the drugs that act on norepinephrine are fenproporex, amfepramone and clobenzorex. Derivatives of the thyroid hormone triiodothyronine have also been associated with weight loss and used as a controversial treatment for obesity, despite their known cardiovascular side effects. Recent data suggest a possible vasodilating effect for these four substances that might be beneficial in a subset of patients. Herein we performed a systematic review of the literature (with emphasis on recent reports) to determine the implications and mechanisms of the vasodilating effects of some anorectics, specifically fenproporex, clobenzorex, amfepramone and triiodothyronine. Data analysis showed these four drugs to be vasodilating agents for rat aortic rings. The different mechanisms of action include endothelium-dependent vasodilation via activation of the NO-cGMP-PKG pathway and the opening of calcium-activated potassium channels. The finding of vasodilating activity indicates a potential role for some anorexigenic drugs in the treatment of obesity in hypertensive patients. Further in vivo studies are needed to test the clinical benefits of these four drugs. Full article

Chronic rhinitis is defined as an inflammation of the nasal epithelium, and is characterized by the presence of two or more specific nasal symptoms including obstruction, rhinorrhea, sneezing, and/or itching for at least 12 weeks. In childhood, this clinical entity is very common and carries a significant socioeconomic burden. The impact on the physical, social, and psychological well-being of family cannot be underestimated. Rhinitis is an umbrella term which includes different phenotypes of rhinitis with distinct underlying pathophysiologic mechanisms. In most cases the diagnosis of rhinitis is rather straightforward; however, sometimes when based on clinical symptomatology, characterization may be challenging. Herein, we provide guidance for getting all the data needed for the differential diagnosis of rhinitis based on medical history and clinical examination. Full article

Moderate to severe traumatic brain injuries (TBI) require treatment in an intensive care unit (ICU) in close collaboration of a multidisciplinary team consisting of different medical specialists such as intensivists, neurosurgeons, neurologists, as well as ICU nurses, physiotherapists, and ergo-/logotherapists. Major goals include all measurements to prevent secondary brain injury due to secondary brain insults and to optimize frame conditions for recovery and early rehabilitation. The distinction between moderate and severe is frequently done based on the Glascow Coma Scale and therefore often is just a snapshot at the early time of assessment. Due to its pathophysiological pathways, an initially as moderate classified TBI may need the same sophisticated surveillance, monitoring, and treatment as a severe form or might even progress to a severe and difficult to treat affection. As traumatic brain injury is rather a syndrome comprising a range of different affections to the brain and as, e.g., age-related comorbidities and treatments additionally may have a great impact, individual and tailored treatment approaches based on monitoring and findings in imaging and respecting pre-injury comorbidities and their therapies are warranted. Full article

Differential diagnosis of lymphocytic pleural effusions between tuberculous (TBE) and malignant (ME) effusion is usually difficult in daily practice. Our aim was to develop a score to differentiate TBE from ME effusions. A cohort of 138 consecutive patients with pleural effusion was prospectively studied from May 2014 through June 2017. Glucose, lactate dehydrogenase (LDH), proteins, white cell count, lactic acid, and pH in the pleural fluid were measured. Pleural effusions other than lymphocytic, patients with a final diagnosis other than tuberculosis or malignancy, and patients who met Light’s criteria for transudate were excluded. Eighty-two samples (47 TBE and 35 ME) were included in the analysis. Using logistic regression analysis and Wald test, we developed a score including age, glucose, proteins, and lactic acid. The receiver operating characteristic curve (ROC) for the score was determined, and the area under the curve (AUC) was calculated. A cutoff of eight points was required to achieve 93.5% sensitivity, 78% specificity, and a likelihood ratio of 4.26 to distinguish tuberculosis from malignant pleural effusion. The AUC of the score was 0.915 (95% CI = 0.82–0.96). Full article