Sentinel Lymph Node Dissection in Locally Recurrent Breast Cancer

Annals of Surgical Oncology - The aim of this study was to investigate the use of sentinel lymph node dissection (SLND) in the treatment of patients with locally recurrent breast cancer. A total of...     

Perception of sexuality and fertility in women living with HIV: a questionnaire study from two Nordic countries

Introduction

As the human immunodeficiency virus (HIV)-positive population ages, issues concerning sexuality and fertility, among others, are becoming relevant. HIV is still surrounded by stigma and taboos, and there have been few studies conducted in industrialized settings concerning these questions. We therefore wanted to investigate the perception of sexuality and fertility in women living with HIV (WLWH) in an industrialized setting, using a questionnaire.

Methods

WLWH were recruited at their regular outpatient clinic visits, at the major Departments of Infectious Diseases in Denmark and Finland, from January 2012 to October 2013. A questionnaire was developed, study participants were informed of the nature of study and, if they agreed to participate and signed a consent form, they filled in the questionnaire. Demographic information on the participants was obtained from patient files (in Finland) or from a national HIV cohort (in Denmark). Statistical analysis was performed using STATA^®, version 11.

Results

In total, 560 women were included in the study. The median age was 44 years. The majority were of white European origin, with fully suppressed HIV viral load, CD4 cell count >350 µL and mild or no symptoms of their HIV infection. A total of 62% were sexually active, stating condom use as their sole form of contraception. Of the sexually inactive women, one-third were in steady relationships. Eighty percent reported prior pregnancies, of which the majority had one or more children. Most children were born prior to the women''s HIV diagnosis and the mode of conception was predominantly natural. One-quarter of the participating women desired pregnancy, while more than half did not. The remaining quarter either stated that they already had the desired number of children or chose not to answer the question. Fourteen percent stated that their HIV diagnosis ended their wish for children; of these women, the median time of diagnosis was between 1995 and 1996. Pregnancy had been attempted unsuccessfully in one-quarter of study participants. The final question inquired what the risk of mother-to-child transmission was, with all precautions taken. Fifteen percent estimated the risk to be above two percent.

Conclusions

In conclusion, the majority of WLWH in industrialized settings in Denmark and Finland have few HIV-related symptoms, are sexually active and have a strong desire for children.     

Functional characterization of BRCA1 gene variants by mini-gene splicing assay

Mutational screening of the breast cancer susceptibility gene BRCA1 leads to the identification of numerous pathogenic variants such as frameshift and nonsense variants, as well as large genomic rearrangements. The screening moreover identifies a large number of variants, for example, missense, silent, and intron variants, which are classified as variants of unknown clinical significance owing to the lack of causal evidence. Variants of unknown clinical significance can potentially have an impact on splicing and therefore functional examinations are warranted to classify whether these variants are pathogenic or benign. Here we validate a mini-gene splicing assay by comparing the results of 24 variants with previously published data from RT-PCR analysis on RNA from blood samples/lymphoblastoid cell lines. The analysis showed an overall concordance of 100%. In addition, we investigated 13 BRCA1 variants of unknown clinical significance or putative variants affecting splicing by in silico analysis and mini-gene splicing assay. Both the in silico analysis and mini-gene splicing assay classified six BRCA1 variants as pathogenic (c.80+1G>A, c.132C>T (p.=), c.213−1G>A, c.670+1delG, c.4185+1G>A, and c.5075−1G>C), whereas six BRCA1 variants were classified as neutral (c.-19-22_-19-21dupAT, c.302−15C>G, c.547+14delG, c.4676−20A>G, c.4987−21G>T, and c.5278−14C>G) and one BRCA1 variant remained unclassified (c.670+16G>A). In conclusion, our study emphasizes that in silico analysis and mini-gene splicing assays are important for the classification of variants, especially if no RNA is available from the patient. This knowledge is crucial for proper genetic counseling of patients and their family members.     

Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study

Preimplantation genetic diagnosis (PGD) for monogenic disorders currently involves polymerase chain reaction (PCR)-based methods, which must be robust, sensitive and highly accurate, precluding misdiagnosis. Twelve adverse misdiagnoses reported to the ESHRE PGD-Consortium are likely an underestimate. This retrospective study, involving six PGD centres, assessed the validity of PCR-based PGD through reanalysis of untransferred embryos from monogenic-PGD cycles. Data were collected on the genotype concordance at PGD and follow-up from 940 untransferred embryos, including details on the parameters of PGD cycles: category of monogenic disease, embryo morphology, embryo biopsy and genotype assay strategy. To determine the validity of PCR-based PGD, the sensitivity (Se), specificity (Sp) and diagnostic accuracy were calculated. Stratified analyses were also conducted to assess the influence of the parameters above on the validity of PCR-based PGD. The analysis of overall data showed that 93.7% of embryos had been correctly classified at the time of PGD, with Se of 99.2% and Sp of 80.9%. The stratified analyses found that diagnostic accuracy is statistically significantly higher when PGD is performed on two cells versus one cell (P=0.001). Se was significantly higher when multiplex protocols versus singleplex protocols were applied (P=0.005), as well as for PGD applied on cells from good compared with poor morphology embryos (P=0.032). Morphology, however, did not affect diagnostic accuracy. Multiplex PCR-based methods on one cell, are as robust as those on two cells regarding false negative rate, which is the most important criteria for clinical PGD applications. Overall, this study demonstrates the validity, robustness and high diagnostic value of PCR-based PGD.     

Interaction between warfarin and cannabis

Delta‐9‐tetrahydrocannabinol (THC), the main psychoactive cannabinoid in cannabis, may inhibit the cytochrome P450 enzyme CYP2C9. Consequently, cannabis use might infer a risk of drug‐drug interaction with substrates for this enzyme, which includes drugs known to have a narrow therapeutic window. In this study, we describe a case report of a 27‐year‐old man treated with warfarin due to mechanical heart valve replacement who presented with elevated international normalized ratio (INR) value (INR = 4.6) following recreational cannabis use. We conducted a review of the available literature, using the PubMed and EMBASE databases while following PRISMA guidelines. Following screening of 85 articles, three eligible articles were identified, including one in vitro study and two case reports. The in vitro study indicated that THC inhibits the CYP2C9‐mediated metabolism of warfarin. One case study reported of a man who on two occasions of increased marijuana use experienced INR values above 10 as well as bleeding. The other case study reported of a patient who initiated treatment with a liquid formulation of cannabidiol for the management of epilepsy, ultimately necessitating a 30% reduction in warfarin dose to maintain therapeutic INR values. The available, although sparse, data suggest that use of cannabinoids increases INR values in patients receiving warfarin. Until further data are available, we suggest patients receiving warfarin be warned against cannabis use.     

Longing for existential recognition: A qualitative study of everyday concerns for people with somatoform disorders

Objective

Patients with somatoform disorders could be vulnerable to stressors and have difficulties coping with stress. The aim was to explore what the patients experience as stressful and how they resolve stress in everyday life.

Methods

A cross-sectional retrospective design using 24 semi-structured individual life history interviews. Data-analysis was based on grounded theory.

Results

A major concern in patients was a longing for existential recognition. This influenced the patients' self-confidence, stress appraisals, symptom perceptions, and coping attitudes. Generally, patients had difficulties with self-confidence and self-recognition of bodily sensations, feelings, vulnerability, and needs, which negatively framed their attempts to obtain recognition in social interactions. Experiences of recognition appeared in three different modalities: 1) “existential misrecognition” covered the experience of being met with distrust and disrespect, 2) “uncertain existential recognition” covered experiences of unclear communication and a perception of not being totally recognized, and 3) “successful existential recognition” covered experiences of total respect and understanding. “Misrecognition” and “uncertain recognition” related to decreased self-confidence, avoidant coping behaviours, increased stress, and symptom appraisal; whereas “successful recognition” related to higher self-confidence, active coping behaviours, decreased stress, and symptom appraisal.

Conclusion

Different modalities of existential recognition influenced self-identity and social identity affecting patients' daily stress and symptom appraisals, self-confidence, self-recognition, and coping attitudes. Clinically it seems crucial to improve the patients' ability to communicate concerns, feelings, and needs in social interactions. Better communicative skills and more active coping could reduce the harm the patients experienced by not being recognized and increase the healing potential of successful recognition.