A Prospective Analysis on Functional Outcomes Following Extended Latissimus Dorsi Flap Breast Reconstruction.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesTo prospectively assess the functional effect of using the extended latissimus dorsi flap in immediate breast reconstructions.A total of 15 consecutive patients undergoing breast reconstruction with extended latissimus dorsi flap participated. Shoulder range of motion, muscle strength, lateral flexion of the torso, and position of scapula were measured pre-operatively and 1, 6, and 12 months post-operatively, in addition to donor-site post-operative complications.At 12 months post-operatively, patients had achieved full range of shoulder movement, when compared to pre-operative values. Lateral flexion of the torso was, however, significantly reduced bilaterally at 1 and 6 months post-operatively (p = 0.001, p = 0.01) and to the not operated side at 12 months (p = 0.01). Muscle strength in flexion-extension-internal rotation was significantly (p = 0.01) reduced on the operated side 12 months post-operatively. All but one patient had numbness around the donor-site scar 12 months post-operatively, 33% had slight adhesions but all were pain free.Although invariably, patients having extended latissimus dorsi flap may expect to achieve full range of shoulder movement, they should be informed of possible functional consequences and the time and effort it takes to recover. Further research is needed to investigate the potential long-term functional implications that extended latissimus dorsi flap may have as a result of changes in the lateral flexion of the torso and scapula position

Ukierunkowane molekularnie leczenie chorych na raka tarczycy — przegląd badań klinicznych

Purpose of review. Several new targeted therapies with multikinase inhibitors targeting vascular endothelial growth factor (VEGF), rearranged during transfection and v-raf murine sarcoma viral oncogene homolog B1 pathways have been tested in clinical trials for radioiodine-refractory differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) in the past 10 years. Recent findings. Results of the fi rst phase III trial of VEGF-targeted therapy (sorafenib) in DTC were presented in June 2013, and two phase III trials with VEGF and rearranged during transfection-targeted therapies (vandetanib and cabozantinib) in MTC have led to approval by US Food and Drug Administration in the past 2 years. Whereas such therapies increase median progression-free survival compared to placebo, there is no therapy proven to improve overall survival yet. Signifi cant potential adverse event risks associated with such therapies need to be recognized. Dissemination of knowledge about targeted therapies is critical for various medical specialists as patient care for thyroid cancers is best delivered in a multidisciplinary setting. Summary. Successful development of targeted systemic therapies in DTC and MTC in the past 5 years is incredibly exciting in the fi eld and patients with advanced DTC/MTC now have new standard-of-care therapy options.Cel przeglądu. W ciągu ostatnich 10 lat w kilku badaniach klinicznych oceniano rolę wielokinazowych inhibitorów czynnika wzrostu śródbłonka naczyń (VEGF), protoonogenu RET (REarranged during Transfection) i protoonkogennej kinazy serynowo-treoninowej BRAF (v-raf murine sarcoma viral oncogene homolog B1) w leczeniu chorych na zróżnicowanego raka tarczycy (DTC) opornego na jod radioaktywny oraz raka rdzeniastego tarczycy (MTC). Najnowsze odkrycia. W czerwcu 2013 roku przedstawiono wyniki pierwszego badania III fazy dotyczącego leczenia ukierunkowanego przeciwko VEGF (sorafenib) w DTC, a w ciągu ostatnich 2 lat wyniki dwóch innych badań III fazy analizujących leki skierowane przeciwko VEGF i RET (wandetanib i kabozantynib) w MTC, które doprowadziły do rejestracji tych leków przez amerykańską Agencję ds. Żywności i Leków. W porównaniu z placebo, leczenie ukierunkowane wydłużało medianę czasu przeżycia wolnego od progresji, jednak żaden z ocenianych schematów terapeutycznych nie wpływał na przeżycie całkowite. Planując leczenie należy brać pod uwagę ryzyko istotnych działań niepożądanych. Postępowanie terapeutyczne u chorych na raka tarczycy ma charakter wielodyscyplinarny, dlatego istotne znaczenie ma popularyzacja wiedzy na temat leczenia ukierunkowanego molekularnie wśród lekarzy różnych specjalności. Podsumowanie. Znaczący rozwój metod leczenia ukierunkowanego molekularnie sprawił, że w ciągu ostatnich 5 lat pojawiły się nowe opcje terapeutyczne dla chorych na zaawansowane DTC/MTC

Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesLynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.Ohio State University (OSU) Comprehensive Cancer Center OSU Colorectal Cancer Research fund Obrine-Weaver Fund Pelotonia Fellowship Award deCODE genetic

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report

BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection. METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis. RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives. CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.)

Modern temporal network theory: A colloquium

The power of any kind of network approach lies in the ability to simplify a complex system so that one can better understand its function as a whole. Sometimes it is beneficial, however, to include more information than in a simple graph of only nodes and links. Adding information about times of interactions can make predictions and mechanistic understanding more accurate. The drawback, however, is that there are not so many methods available, partly because temporal networks is a relatively young field, partly because it more difficult to develop such methods compared to for static networks. In this colloquium, we review the methods to analyze and model temporal networks and processes taking place on them, focusing mainly on the last three years. This includes the spreading of infectious disease, opinions, rumors, in social networks; information packets in computer networks; various types of signaling in biology, and more. We also discuss future directions.Comment: Final accepted versio