Utmost Importance In Clinical Practice Research Articles

Challenges in periodic revision of genetic testing results: Comparison of the main classification guidelines and report of a retrospective analysis involving BRCA1/BRCA2 variants of uncertain significance

In the context of cancer predisposition syndromes, it is widely known that the correct interpretation of germline variants identified in multigene panel testing is essential for adequate genetic counseling and clinical decision making, in which variants of uncertain significance (VUS) are not considered actionable findings. Thus, their periodic re-evaluation using appropriate guidelines is notably important. In the present study, we compared the performance of the main variant classification guidelines (ACMG, Sherloc and ENIGMA) in variant reassessment, using as input a BRCA1/2 VUS case series (retrospective analysis) from Brazil, an ethnically diverse and admixed country with substantial challenges in VUS reclassification. As main findings, two of the 15 VUS analyzed were reclassified as likely pathogenic by the 3 guidelines, BRCA1 c.4987-3C > G (rs397509213) and BRCA2 c.7868A > G (rs80359012). Moreover, challenges in variant classification and reassessment are described and additional in silico data about structural impact of the variant BRCA2 c.7868A > G are provided. We hypothesize that the establishment of a framework to reassess VUS could improve this process in health centers that have not yet implemented this practice. Results of this study underscore that periodic monitoring of the functional, clinical, and bioinformatics data of a VUS by a multidisciplinary team are of utmost importance in clinical practice. When there is a specific guideline for a given gene, such as ENIGMA for BRCA1/2, it should be considered the first option for variant assessment. Finally, recruitment of VUS carriers and their relatives to participate in variant segregation studies and publication of VUS reclassification results in the international scientific literature should be encouraged.

Predictive Power of Hemorrhagic Transformation Scores in Real Life Stroke Patients Undergone to Urgent Reperfusion: A Brief Report

Introduction and aim: Hemorrhagic transformation (HT) is the most feared complication in acute phase of ischemic stroke. Predicting HT is of utmost importance in clinical practice. In the latest years a lot of HT prediction scores have been proposed, but their comparison in real life lack. Therefore, the aim of our study was to provide information about this topic. Materials and Methods: We retrospectively calculated THRIVE, SPAN-100, MSS score, SITS-ICH and GRASPS scores in patients consecutively admitted in our Stroke Unit along two years. To evaluate their predictive power, the area under the curve (AUC) of the Receiver Operating Characteristic (ROC) curve was calculated. Results: Study population was composed by ninety-one patients (51.6% females) with mean age 80.1 ± 11.3 years. Seventy-four (81.3%) patients undergone to systemic intravenous alteplase, seven (7.7%) to mechanical thrombectomy, ten (11%) to systemic intravenous alteplase plus mechanical thrombectomy. Eighteen patients (19.7%) presented HT. MSS score was the best prognosticator of HT, however the predictive power of the five analyzed score was low, ranging from and none of the score resulted significantly superior to the others. Conclusion: Our real-life study showed a low predictive power of a lot of HT prediction scores. Further prospective studies are warranted.

Association Between Fear of Falling and Frailty in Community-Dwelling Older Adults: A Systematic Review.

Background/ObjectiveFear of falling (FoF) and frailty are common problems in older adults. FoF can lead to self-imposed restriction of activities and then further decline in physical capacities that predispose older adults to frailty. Evaluating the association of these two geriatric syndromes may be the first step for understanding their complex relationship and might ultimately lead to establishing therapeutic goals and guiding treatments for older adults with frailty. This systematic review was conducted to provide evidence regarding the association between FoF and frailty.MethodsAll the articles that provided information on the association between FoF and frailty were selected from PubMed, Scopus, CINAHL, and EMBASE in search of relevant papers. Articles reporting information on the association between FoF (exposure) and frailty (outcome), with older adults (age ≥60 years) living in the community (ie, living either at home or in places of residence that do not provide nursing care or rehabilitation) were included. Only original articles with observational design (cross-sectional or longitudinal/cohort) were included. The methodological quality of included articles was evaluated independently by the two assessors through the Newcastle-Ottawa Scale (NOS) and the Joanna Briggs Institute (JBI) critical appraisal checklist for longitudinal and cross-sectional studies, respectively.ResultsThe initial searches found 4,342 articles, of which 10 articles were included in this review: 7 cross-sectional and 2 longitudinal studies, and 1 study with cross-sectional and longitudinal analyses. The total sample was composed of 6,294 community-dwelling older adults (61.8% women). Among the longitudinal studies, adjusted odds ratios ranged from 1.18 (95% CI = 1.02; 1.36) to 9.87 (95% CI = 5.22; 18.68), while the adjusted odds ratios of the cross-sectional studies ranged from 1.04 (95% CI = 1.02; 1.07) to 7.16 (95% CI = 2.34; 21.89).ConclusionFoF increases the risk of frailty in community-dwelling older adults. The knowledge of this association is of utmost importance in clinical practice, since it can help health professionals in the development of rehabilitation, prevention, and health promotion protocols. In addition, these findings can contribute to the development of public health policies and actions aimed at reducing the FoF and consequently the frailty.ProsperoCRD42021276775.

Management of Osteoporosis in Men: A Narrative Review.

Male osteoporosis is a still largely underdiagnosed pathological condition. As a consequence, bone fragility in men remains undertreated mainly due to the low screening frequency and to controversies in the bone mineral density (BMD) testing standards. Up to the 40% of overall osteoporotic fractures affect men, in spite of the fact that women have a significant higher prevalence of osteoporosis. In addition, in males, hip fractures are associated with increased morbidity and mortality as compared to women. Importantly, male fractures occur about 10 years later in life than women, and, therefore, due to the advanced age, men may have more comorbidities and, consequently, their mortality is about twice the rate in women. Gender differences, which begin during puberty, lead to wider bones in males as compared with females. In men, follicle-stimulating hormones, testosterone, estrogens, and sex hormone-binding levels, together with genetic factors, interact in determining the peak of bone mass, BMD maintenance, and lifetime decrease. As compared with women, men are more frequently affected by secondary osteoporosis. Therefore, in all osteoporotic men, a complete clinical history should be collected and a careful physical examination should be done, in order to find clues of a possible underlying diseases and, ultimately, to guide laboratory testing. Currently, the pharmacological therapy of male osteoporosis includes aminobisphosphonates, denosumab, and teriparatide. Hypogonadal patients may be treated with testosterone replacement therapy. Given that the fractures related to mortality are higher in men than in women, treating male subjects with osteoporosis is of the utmost importance in clinical practice, as it may impact on mortality even more than in women.

Over-feeding the gut microbiome: A scoping review on health implications and therapeutic perspectives.

The human gut microbiome has gained increasing attention over the past two decades. Several findings have shown that this complex and dynamic microbial ecosystem can contribute to the maintenance of host health or, when subject to imbalances, to the pathogenesis of various enteric and non-enteric diseases. This scoping review summarizes the current knowledge on how the gut microbiota and microbially-derived compounds affect host metabolism, especially in the context of obesity and related disorders. Examples of microbiome-based targeted intervention strategies that aim to restore and maintain an eubiotic layout are then discussed. Adjuvant therapeutic interventions to alleviate obesity and associated comorbidities are traditionally based on diet modulation and the supplementation of prebiotics, probiotics and synbiotics. However, these approaches have shown only moderate ability to induce sustained changes in the gut microbial ecosystem, making the development of innovative and tailored microbiome-based intervention strategies of utmost importance in clinical practice. In this regard, the administration of next-generation probiotics and engineered microbiomes has shown promising results, together with more radical intervention strategies based on the replacement of the dysbiotic ecosystem by means of fecal microbiota transplantation from healthy donors or with the introduction of synthetic communities specifically designed to achieve the desired therapeutic outcome. Finally, we provide a perspective for future translational investigations through the implementation of bioinformatics approaches, including machine and deep learning, to predict health risks and therapeutic outcomes.

Narcissistic Personality Traits and Sexual Dysfunction in Women: The Role of Body Image Self-Consciousness

BackgroundIndividuals with narcissistic traits, specifically vulnerable ones, are more prone to experiencing concerns related to self-worth and physical appearance and to showing heightened sensitivity to appearance evaluation. Negative body image and body image self-consciousness may, in turn, undermine sexual functioning, especially when apprehension is related to body appearance in sexual contexts. MethodsWe aimed to evaluate the associations between self-reported pathological narcissistic traits, both grandiose and vulnerable, and sexual functioning in a large sample of nonclinical women (N = 656). Furthermore, we tested the mediating role of body image self-consciousness in these associations. OutcomesSexual functioning was measured through the Female Sexual Function Index. ResultsThe results highlight that vulnerable narcissistic traits are associated with lower sexual functioning, this association being mediated by higher levels of body image self-consciousness. Conversely, grandiose narcissistic traits are linked to lower body image self-consciousness and, consequently, higher levels of sexual functioning. Clinical ImplicationsConsidering the link between body image self-consciousness and sexuality is of utmost importance in clinical practice with women, as well as in promoting positive body appreciation. Clinicians working with individuals presenting with pathological personality traits should consider including an assessment of their sexual functioning. S Pavanello Decaro, M Di Sarno, A Anzani, et al. Narcissistic Personality Traits and Sexual Dysfunction in Women: The Role of Body Image Self-Consciousness. J Sex Med 2021;18:1891–1898.

Pediatric thiamine deficiency disorders in high-income countries between 2000 and 2020: a clinical reappraisal.

Often thought to be a nutritional issue limited to low‐ and middle‐income countries (LMICs), pediatric thiamine deficiency (PTD) is perceived as being eradicated or anecdotal in high‐income countries (HICs). In HICs, classic beriberi cases in breastfed infants by thiamine‐deficient mothers living in disadvantaged socioeconomic conditions are thought to be rare. This study aims to assess PTD in HICs in the 21st century. Literature searches were conducted to identify case reports of PTD observed in HICs and published between 2000 and 2020. The analyzed variables were age, country, underlying conditions, clinical manifestations of PTD, and response to thiamine supplementation. One hundred and ten articles were identified, totaling 389 PTD cases that were classified into four age groups: neonates, infants, children, and adolescents. Eleven categories of PTD‐predisposing factors were identified, including genetic causes, lifestyle (diabetes, obesity, and excessive consumption of sweetened beverages), eating disorders, cancer, gastrointestinal disorders/surgeries, critical illness, and artificial nutrition. TD‐associated hyperlactatemia and Wernicke encephalopathy were the most frequent clinical manifestations. The circumstances surrounding PTD in HICs differ from classic PTD observed in LMICs and this study delineates its mutiple predisposing factors. Further studies are required to estimate its magnitude. Awareness is of utmost importance in clinical practice.

English

Major sources of the vascular supply of the gastrointestinal tract are the celiac trunk (CT) and superior mesenteric artery (SMA) which are the main proximal branches of the abdominal aorta. The CT gives rise to three branches normally as follows: left gastric artery (LGA), common hepatic artery (CHA) and splenic artery (SA). The branching pattern of the CT is considered as the most literature explained anatomical pattern.1 After the CT, the abdominal aorta gives the second named branch as superior mesenteric artery. Vascular variations of the celiac trunk and superior mesenteric artery are common and had been described earlier.2 These variations are caused due to the aberrant embryological development of splanchnic arteries. The incidence of hepato-spleno-mesenteric trunk has been reported by various authors as 0.68 %,3 0.7 %,4 0.3 %,5 0.4 %,6 or 1 %.7 The importance of knowledge of these variations lies in preplanning of invasive surgical techniques, organ transplantation, diagnosis, prevention, and management of some metastatic tumours and to overcome the catastrophic consequences like bowel ischemia due to common trunk.8 Hence a better understanding of these anatomical variations is considered vital for surgeons or radiologists for appropriate planning and conduction of surgical procedures or interventions.9 Most of the anatomical variations in abdominal aorta branches are asymptomatic and incidental findings while imaging for other aetiologies. But the identification of such vascular variations is of utmost importance in clinical practice. The Hepatospleno-mesenteric trunk [HSMT] is one of those variations and was less frequently reported. The authors describe a case report of the hepato-spleno-mesenteric trunk which was incidentally detected in the multi detector computed tomography study of the abdomen of a 54-year-old male patient who had been diagnosed to have chronic liver disease and hepatic encephalopathy. The origin of the HSMT [with a diameter of 11mm] occurs from the abdominal aorta at the level of the L2 vertebral body and is divided into the hepatosplenic trunk [diameter of 7 mm] and superior mesenteric artery [diameter of 7.5 mm] after coursing for a length of 28 mm. The hepatosplenic trunk ascends superiorly for a length of 20 mm and divided into two terminal branches: common hepatic (6 mm) and splenic artery (6 mm).

An unusual variation in the termination of facial artery in south Indian population: A human cadaveric case report

The facial artery is an important artery of the face, prone to many variations. Identification of these variations is of utmost importance in clinical practice, especially rhinoplastic and orofacial surgeries and also super selective chemotherapy procedures. In this case report, we report a bilateral facial artery variation encountered in a male cadaver during routine dissection. Instead of terminating as the angular artery, the facial artery terminated as the superior labial artery, giving the lateral nasal artery as a smaller branch, much closer to the midline than normal. A prominent pre-masseteric branch was noticed along with smaller branches from the infraorbital artery which offered possible compensation for the short facial artery. The case reported is a type II variation according to Bayram classification, and a type C variation as per Loukas classification. This variation is very rare and should be kept in mind while performing any surgical procedures of the face.

Vertical Tooth Root Fracture Detection through Cone-beam Computed Tomography: An Umbrella Review Protocol Testing Four Hypotheses

Detecting vertical root fractures represents an immense challenge for oral health professionals. One of the main tools used to detect this type of biological complication is the periapical radiograph. However, conventional radiography consists of two-dimensional imaging that is limited by the superimposition of bony structures that complicate the detection of root fractures. The alternative, a Cone-Beam Computed Tomography (CBCT) scan, cannot be prescribed in every case since radiation should be kept to a minimum as stipulated by the “As Low As Reasonably Achievable” (ALARA) principle. Therefore, to justify the use of a CBCT scan to detect a vertical tooth root fracture, the clinician must prove that it has significant benefits over traditional imaging. Since few systematic reviews have compared CBCT technology to traditional radiography for the diagnosis of vertical root fractures, it is of utmost importance in clinical practice, especially in endodontology and clinical dental medicine, where the available reviews are examined to generate a clinical recommendation. The four hypotheses of this protocol are that (1) CBCT is superior to traditional radiography for detecting vertical root fractures of vital teeth; (2) CBCT is superior to traditional radiography for detecting longitudinal root fractures of vital teeth with radiopaque restorations; (3) CBCT is superior to traditional radiography for detecting vertical root fractures of root-filled teeth without a radiopaque post that may cause artifacts; and (4) CBCT is superior to traditional radiography for detecting vertical root fractures of root-filled teeth with a radiopaque post regardless of its longitude. To test these hypotheses, all the current secondary resources related to the aim of this meta-review are evaluated. If there is sufficient evidence to support clinical decisions, then the appropriate recommendations will be formulated. PROSPERO ID: CRD42018067792

Pain and quality of life after endodontic surgery with or without advanced platelet-rich fibrin membrane application: a randomized clinical trial.

Clinical evidence of the autologous platelet concentrates effects on the patient-reported outcome measures (PROMs) after endodontic surgery is still limited. To investigate the effect of the advanced platelet-rich fibrin (A-PRF+) membrane application upon patient postoperative pain, and quality of life in endodontic surgery. A two-parallel-arm randomized clinical trial was made comparing endodontic surgery with or without A-PRF+ as adjunctive treatment. Fifty individuals comprehending 50 apical lesions (second premolar to the second premolar) of upper maxilla were included. Pain perception and quality of life (functional limitations and other symptoms) were assessed 1week after surgery using a visual analog scale and a Likert scale-based questionnaire. Descriptive analysis was done using χ2 and t test. Binary logistic regression, ANOVA-type statistic, and GEE analysis were used for inferential analysis. Pain perception was mild in both groups [A-PRF+ 12.7 ± 8.5] versus [no A-PRF+ 20.7 ± 16.3]; it proved less variable during the first 4days in test group, showing lower extreme pain values (p = 0.096). Analgesic use was similar in both groups. Controls reported significantly worse sleep and speech functions (p < 0.05). Bleeding and bad taste/breath were the most discriminative symptoms. Postoperative pain perception was mild in endodontic surgery of the upper anterior maxilla. Differences in pain perception were not statistically significant. The use of A-PRF+ afforded less variable pain perception than in the controls. Altered quality of life parameters were more prevalent in the control group and prove significant for speech and sleep functions. Patient-related outcomes are of utmost importance in clinical practice. The use of A-PRF+ provides an affordable and safe alternative to improve postoperative quality of life in endodontic surgery.

The Multiple Sclerosis Inventory of Cognition for Adolescents (MUSICADO): A brief screening instrument to assess cognitive dysfunction, fatigue and loss of health-related quality of life in pediatric-onset multiple sclerosis.

Screening for cognitive impairment (CI), fatigue and also Health-related quality of life (HRQoL) in patients with pediatric-onset multiple sclerosis (POMS) is of utmost importance in clinical practice. The aim of this study was to establish a new and validated pediatric screening tool "MUSICADO" that is easy to use and time economical. 106 patients with POMS aged 12-18 years and 210 healthy controls (HCs) stratified for age and education underwent neuropsychological testing including a screening test "Multiple Sclerosis Inventory of Cognition" for adults and 8 standardized cognitive tests and established scales to assess fatigue and HRQoL. The phonemic verbal fluency task (RWT "s-words"), the Trail Making Test A (TMT-A), and the Digit Span Forward discriminated significantly between patients and HCs (p=0.000, respectively) and showed the highest proportion of test failure in patients (24.5%, 17.9%; 15.1%, respectively). Therefore, they were put together to form the cognitive part of the "MUSICADO". After applying a scoring algorithm with balanced weighting of the subtests and age and education correction and a cut-off score for impairment, 35.8% of patients were categorized to be cognitively impaired (specificity: 88.6%). Fatigue was detected in 37.1% of the patients (specificity: 94.0%) and loss of HRQoL in 41.8% (specificity 95.7%) with the screening version, respectively. The MUSICADO is a newly designed brief and easy to use screening test to help to early identify CI, fatigue, and loss of HRQoL in patients with POMS as cut scores are provided for all three items. Further studies will have to show its usability in independent samples of patients with POMS.

Prevalence of Depression Among Iranian Women with Breast Cancer: A Systematic Review and Meta-Analysis

Context: Depression is common among breast cancer (BC) patients. Several studies have evaluated the prevalence of depression among BC patients in Iran. Hence, in order to have more in-depth knowledge regarding its prevalence, all available studies were systematically reviewed and their data were analyzed using a meta-analysis. Evidence Acquisition: A systematic search was conducted to find all published studies on the prevalence of depression in BC patients in the international databases (Medline/PubMed, Scopus, Embase, Google Scholar, and Web of Sciences), and Iranian databases (Scientific Information Database, MagIran, IranMedex, and IranDoc) until February 2016. This systematic review was done according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results: In total, nine eligible papers (out of 240) were entered into the analysis. The overall prevalence of depression in BC patients was 44% (95% CI: 35% - 52%). The results of Cochran’s test showed the heterogeneity of the studies (Q = 1678.2, df = 8, I2 = 89.4%, P < 0.001). Conclusions: BC patients are at risk of depression; hence, its detection is of utmost importance in clinical practice.

Estimation of platelet counts: auto analyzer versus counts from peripheral blood smear based on traditional and platelet: red blood cell ratio method

Introduction: Accurate platelet counts are of utmost importance in clinical practice The methods used for estimating platelet count are: Manual method using counting chamber, Examination of a peripheral blood smear (PBS) and automated hematology analyzers Automated hematology analyzers produce erroneous results in the presence of particles of similar size and/or light scatter like fragmented red blood cells (RBC), microcytic RBCs and in the presence of giant platelets and platelet clumps. Aims and Objectives: Comparison of platelet count by three methods: 1. Automated six part analyzer. Traditional method: Counting average platelets per ten high power fields and multiplying the same by 15,000. 3. From smear by counting the number of platelets per 1000 RBCs and calculating the platelet count on the basis of platelet: RBC ratio. Methods: Ethylene Diamine Tetra-acetic acid (EDTA) samples for platelet counts over a period of two months were analyzed by the above-mentioned methods. Statistical software SPSS 2 and independent T tests were used to compare the variables between the groups. Sensitivity and specificity of the methods was calculated. Results: 250 EDTA samples were analyzed of which normal platelet counts were (56.4%) thrombocytopenic (35.2%) and thrombocytosis (8.4%). There was no significant difference between the platelet counts done by the auto analyzer compared with traditional (P value 0.50) and platelet: RBC ratio method (0.906). Specificity of the methods was 99.1% and the sensitivity was 92.5%. Conclusion: Platelet counts by traditional and platelet: RBC ratio can be used as alternate reliable methods as compared to the auto analyzers.

Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and do not carry a significant risk for liver-related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349-360).

Abstract 4876: Low frequent ALK hotspot mutations in neuroblastoma tumors detected by ultra deep sequencing: Implications for ALK inhibitor treatment

Abstract Background The pediatric cancer neuroblastoma (NB) is heterogeneous in terms of both genotype and clinical behavior. NB patients show complex patterns of genetic abnormalities, which may include amplification, translocation or oncogenic mutations of ALK kinase in sporadic and familial cases. Three hot spot residues (F1174, F1245, and R1275) localized within the kinase domain of ALK, accounts for 85% of mutant ALK in NB. In this study we used ultra deep sequencing for sensitive detection of ALK mutations. Methods To detect the sub-clonal ALK mutations in 105 neuroblastoma tumors that can remain undetected using Sanger chemistry, we used two different approaches; hybridization-based Haloplex kit (Agilent) and PCR-based amplicon sequencing, both sequenced on the MiSeq Illumina platform. Coverage, uniformity and variant calling ability showed similar performance between both methods. Findings ALK mutations were detected in 14/105 patients (13%) whereof six with allele frequency below 20%. At the I1171 locus an ALK mutation was detected in one case with variant allele frequency as low as 2.6%, the lowest level detected in our cohort. Mutations at the F1174 hotspot were observed in nine cases: six cases with F1174L, while the remaining three showed F1174C, F1174S and F1174I substitutions, with mutated allele fractions ranging from 14% to 60%. Interestingly the patient harboring F1174S mutation with 58% frequency, in parallel contained a small sub-clone of F1174I mutation with 8% frequency of the mutated allele. F1245-codon alterations were detected in three cases: two F1245I mutations and one F1245C mutation, with frequencies of 14%, 51% and 52%, respectively. A single case showed a L1240V variant with a mutated allele fraction at 57%. Sanger sequencing of all ALK mutated samples could confirm ALK status for all samples with variant allele fraction above 15%. Because of the limits of detection, 4 out of 6 samples with a mutated allele fraction below 15% would have gone undetected relying on Sanger sequencing. Our results fail to reveal a distinct mutation spectrum in relation to neuroblastoma genomic subtypes. Moreover, a variety of neuroblastic tumours, from benign ganglioneuroma to very aggressive metastatic neuroblastoma, could be observed in the context of ALK mutation. Interpretation These results indicate that, in neuroblastoma, ALK mutations can be present at sub-clonal level with the possibility of subsequent clonal expansion at the time of progression. Tyrosine kinase inhibitors have become the gold standard therapy in treating ALK positive NBs, making diagnostic high sensitive detection of ALK mutations a necessary step in identifying optimal treatment modalities. This study is of utmost importance in clinical practice, highlighting the potential of NGS and the importance of serial samplings for therapeutic decisions. Citation Format: Susanne M. Fransson, Niloufar Javanmardi, Rose-Marie Sjoberg, Per Kogner, Tommy Martinsson. Low frequent ALK hotspot mutations in neuroblastoma tumors detected by ultra deep sequencing: Implications for ALK inhibitor treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4876. doi:10.1158/1538-7445.AM2017-4876

Computational estimation of the severity of coronary lesions with intravascular ultrasound images: a pilot study.

The fast and accurate hemodynamic functional assessment of the coronary vasculature is of utmost importance in clinical practice due to the fact that Cardiovascular Diseases have become the leading cause of death globally. In this work we propose a novel method that combines two of the most efficient methods of hemodynamic status assessment of coronary arteries, Intravascular UtraSound and virtual Functional Assessment Index, an index that correlates well to the measured Fractional Flow Reserve. One Left Anterior Descending segment was reconstructed both in a straight manner (using only IVUS images) as well as using the actual 3D geometry of the vessel (using IvUS images combined with the respective coronary angiographic images [2]). The generated vFAI values were almost identical (Straight=0.80, 3D=0.79), presenting a relative error of 1.27%, thus proving the efficacy of the proposed method. We also calculated the Endothelial Shear Stress for the two models under rest (i.e. flow rate of 1 ml/s), observing a similar trend throughout the artery, but with a statistically important relative error of 13.49%, as expected.

Fecal calprotectin: its scope and utility in the management of inflammatory bowel disease.

Gastrointestinal symptoms such as abdominal pain, dyspepsia, and diarrhea are relatively nonspecific and a common cause for seeking medical attention. To date, it is challenging for physicians to differentiate between functional and organic gastrointestinal conditions and it involves the use of serological and endoscopic techniques. Therefore, a simple, noninvasive, inexpensive, and effective test would be of utmost importance in clinical practice. Fecal calprotectin (FC) is considered to be a reliable biomarker that fulfills these criteria. FC can detect intestinal inflammation, and its level correlates well with macroscopic and histological inflammation as detected by colonoscopy and biopsies, respectively. FC has a decent diagnostic accuracy for differentiating organic diseases and functional disorders because of its excellent negative predictive value in ruling out inflammatory bowel disease (IBD) in symptomatic undiagnosed patients. There is accumulating evidence that FC has been effectively used to monitor the natural course of IBD, to predict relapse, and to see the response to treatment. This novel biomarker has the ability to assess mucosal healing (MH), which is a therapeutic goal in IBD management. A literature search was carried out using PubMed with the keywords FC, IBD, intestinal inflammation, and MH. In our review, we provide an overview of the utility and scope of FC as a biomarker in patients with IBD as well as undiagnosed patients with lower gastrointestinal symptoms.

Accuracy of commonly used equations for estimating glomerular filtration rate in Nepalese population

Introduction - Estimation of glomerular filtration is of utmost importance in clinical practice. Various equations have been developed in different populations based on serum creatinine. These equations have not yet been validated in the Nepalese population. This study was conducted to compare the accuracy Cockcroft Gault and Modification of Diet in Renal Disease equations for estimating the glomerular filtration rate in Nepalese population. Methods - A total of 100 patients with chronic kidney disease were included in the study. Fifty patients had serum creatinine less than 1.5 mg/dl and 50 patients had serum creatinine more than or equal to 1.5 mg/dl. Glomerular Filtration Rate was measured as creatinine clearance from 24 hour timed urinary collections and estimated using both the Cockcroft-Gault and Modification of Diet in Renal Disease equations for all the patients. The degree of accuracy of each equation was calculated by the coefficient of determination(R2). Results - The mean glomerular filtration rate estimated from the Cockcroft Gault equation was 51.29 ml/min/1.73sqm and mean glomerular filtration rate estimated from the Modification of Diet in Renal Disease equation was 48.41 ml/min/1.73sqm whereas the mean measured GFR was 53.30ml/ min/1.73sqm. The coefficient of determination (R2) was calculated for both the equations. The Cockcroft Gault equation was more accurate in the Nepalese population (R2=0.88) than the Modification of Diet in Renal Disease equation whose coefficient of determination was 0.84. Conclusions - In the Nepalese population the Cockcroft Gault equation was more accurate in estimating the glomerular filtration rate in comparison to the Modification of Diet in Renal Disease equation . DOI: http://dx.doi.org/10.3126/jaim.v1i2.6503 Journal of Advances in Internal Medicine 2012;01(02):52-3

Mechanical prophylaxis of venous thromboembolism in ill hospitalized medical patients: evidence and guidelines

Venous thromboembolism (VTE) represents one of the leading causes of mortality and morbidity in ill medical patients. Avoiding VTE is therefore of utmost importance in clinical practice. VTE prophylaxis can be assured by pharmacological strategies, such as heparinoids, unfractioned heparin, low molecular weight heparins, fondaparinux or oral anticoagulants and, when these are contraindicated, by mechanical measures, such as graduated compression stockings (GCS) and/ or intermittent pneumatic compression (ICP). However, due to the lack of solid literature evidence, VTE mechanical prophylaxis is not standardized in hospitalized ill medical patients. Much recently, findings from randomized clinical trials on VTE prophylaxis in ill medical patients, such as CLOTS I in patients with stroke and LIFENOX in patients with other kind of medical diseases, seem to increase doubts and reduce certainness in this context and recommendations from guidelines don’t help in reducing confusion. Therefore the aim of this review is to focus on mechanical prophylaxis of VTE in hospitalized ill medical patients.http://dx.doi.org/10.7175/rhc.v3i3.202