Neoadjuvant chemotherapy in breast cancer-response evaluation and prediction of response to treatment using dynamic contrast-enhanced and diffusion-weighted MR imaging

Objective To explore the predictive value of MRI parameters and tumour characteristics before neoadjuvant chemotherapy (NAC) and to compare changes in tumour size and tumour apparent diffusion coefficient (ADC) during treatment, between patients who achieved pathological complete response (pCR) and those who did not. Methods Approval by the Regional Ethics Committee and written informed consent were obtained. Thirty-one patients with invasive breast carcinoma scheduled for NAC were enrolled (mean age, 50.7; range, 37–72). Study design included MRI before treatment (Tp0), after four cycles of NAC (Tp1) and before surgery (Tp2). Data in pCR versus non-pCR groups were compared and cut-off values for pCR prediction were evaluated. Results Before NAC, HER2 overexpression was the single significant predictor of pCR (p=0.006). At Tp1 ADC, tumour size and changes in tumour size were all significantly different in the pCR and non-pCR groups. Using 1.42×10−3 mm2/s as the cut-off value for ADC, pCR was predicted with sensitivity and specificity of 88% and 80%, respectively. Using a cut-off value of 83% for tumour volume reduction, sensitivity and specificity for pCR were 91% and 80%. Conclusion ADC, tumour size and tumour size reduction at Tp1 were strong independent predictors of pCR

The pectoralis minor length test: a study of the intra-rater reliability and diagnostic accuracy in subjects with and without shoulder symptoms

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedBackground. Postural abnormality and muscle imbalance are thought to contribute to pain and a loss of normal function in the upper body. A shortened pectoralis minor muscle is commonly identified as part of this imbalance. Clinical tests have been recommended to test for shortening of this muscle. The aim of this study was to evaluate the intra-rater reliability and diagnostic accuracy of the pectoralis minor length test. Methods. Measurements were made in 45 subjects with and 45 subjects without shoulder symptoms. Measurements were made with the subjects lying in supine. In this position the linear distance from the treatment table to the posterior aspect of the acromion was measured on two occasions (separated by a minimum of 30 minutes and additional data collection on other subjects to reduce bias) by one rater. The reliability of the measurements was analyzed using intraclass correlation coefficients (ICC), 95% confidence intervals (CI) and standard error of measurement (SEM). The diagnostic accuracy of the test was investigated by determining the sensitivity, specificity, positive and negative likelihood ratios of the test against a 'gold standard' reference. The assessor remained 'blinded' to data input and the measurements were staggered to reduce examiner bias. Results. The pectoralis minor length test was found to have excellent intra-rater reliability for dominant and non-dominant side of the subjects without symptoms, and for the painfree and painful side of the subjects with symptoms. The values calculated for the sensitivity, specificity, positive and negative likelihood ratios suggest this test performed in the manner investigated in this study and recommended in the literature, lacks diagnostic accuracy. Conclusion. The findings of this study suggest that although the pectoralis minor length test demonstrates acceptable clinical reliability, its lack of specificity suggests that clinicians using this test to inform the clinical reasoning process with regard treatment planning must do so with caution. Trial registration. National Research Register: N0060148286.Peer reviewe

Common Missense Variant in the Glucokinase Regulatory Protein Gene Is Associated With Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations

OBJECTIVE—Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCKR locus in samples of non-European ancestry and to fine- map across the associated genomic interval

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Clinical measurement of the thoracic kyphosis : a study of the intra-rater reliability in subjects with and without shoulder pain

BACKGROUND: Clinical sagittal plane assessment of the thoracic kyphosis angle is considered an essential component of the postural examination of patients presenting with upper body pain syndromes. Cervical headaches and conditions involving the shoulder, such as subacromial pain syndrome, have all been associated with an increase in the thoracic kyphosis. Concomitantly a decrease in the thoracic kyphosis as a result of a stretching and strengthening rehabilitation programme is believed to be associated with a reduction in symptoms and pain and improvement in function. Clinicians generally measure the sagittal plane kyphosis angle visually. There is no certainty that this method is reliable or is capable of measuring angular changes over time or in response to intervention. As such a simple and reliable clinical method of measuring the thoracic kyphosis would enable clinicians to record this information. The aim of this investigation was to determine the intra-tester reliability of measuring the thoracic kyphosis angle using a clinical method METHODS: Measurements were made in 45 subjects with and 45 subjects without upper body symptoms. Measurements were made with the subjects in relaxed standing. Two gravity dependent inclinometers were used to measure the kyphosis. The first was placed over the region of the 1st and 2nd thoracic spinous processes. The other, over the region of the 12th thoracic and 1st lumbar spinous processes. The angle produced by each inclinometer was measured 3 times in succession. Each set of 3 measurements was made on two occasions (separated by a minimum of 30 minutes and additional data collection involving 46 further measurements of posture and movement on the same and an additional subject before the thoracic kyphosis measurements were re-measured) by one rater. The reliability of the measurements was analyzed using 2-way ANOVA intraclass correlation coefficients (ICC), 95% confidence intervals (CI) and standard error of measurement (SEM) for precision, for a single measurement [ICC(single)] and the average of 3 measures [ICC(average)]. The assessor remained 'blinded' to data input and the measurements were staggered to reduce examiner bias. RESULTS: The measurement of the thoracic kyphosis as used in this investigation was found to have excellent intra-rater reliability for both subjects with and without symptoms. The ICC(single) results for the subjects without symptoms were, .95; (95% CI .91-.97). The corresponding ICC(average) results were; .97; (95% CI .95-.99). The results for the subjects with symptoms were; 93; (95% CI .88-.96), for ICC(single) and for ICC(average); .97; (95% CI .94-.98). The SEM results for subjects without and with symptoms were 1.0 degrees and 1.7 degrees , respectively. CONCLUSIONS: The findings of this immediate test-retest reliability study suggest that the clinical measurement of the thoracic kyphosis using gravity dependent inclinometers demonstrates excellent intra-rater reliability. Additional research is required to determine the inter-rater reliability of this method

Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA

Deficiency in monoamine oxidase A (MAOA), an enzyme that degrades serotonin and norepinephrine, has recently been shown to be associated with aggressive behavior in men of a Dutch family. A line of transgenic mice was isolated in which transgene integration caused a deletion in the gene encoding MAOA, providing an animal model of MAOA deficiency. In pup brains, serotonin concentrations were increased up to ninefold, and serotonin-like immunoreactivity was present in catecholaminergic neurons. In pup and adult brains, norepinephrine concentrations were increased up to twofold, and cytoarchitectural changes were observed in the somatosensory cortex. Pup behavioral alterations, including trembling, difficulty in righting, and fearfulness were reversed by the serotonin synthesis inhibitor parachlorophenylalanine. Adults manifested a distinct behavioral syndrome, including enhanced aggression in males