Prophylactic nipple-sparing mastectomy with immediate breast reconstruction: results of a French prospective trial.

BACKGROUND: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is used increasingly when performing a prophylactic mastectomy. Few prospective studies have reported on complication rates. This complementary trial to the French prospective multicentre MAPAM trial aimed to evaluate the nipple-areola complex (NAC) necrosis rate in prophylactic NSM with IBR. METHODS: Patient characteristics and surgical data were recorded. Morbidity after prophylactic NSM with a focus on NAC necrosis was analysed. RESULTS: Among 59 women undergoing prophylactic NSM, 19 (32 per cent) of the incisions were partly on the NAC. Reconstructions were performed with 46 definitive implants and 13 expanders. The crude rate of postoperative complications was 25 per cent (15 patients). Complete NAC necrosis was reported in two women (3 per cent) and partial or total necrosis in nine (15 per cent). No NAC resection was necessary. Median BMI was lower in women with total or partial NAC necrosis compared with the others (20.0 versus 21.3 kg/m2 respectively; P = 0.034). CONCLUSION: Results of this prospective study confirm that prophylactic NSM with IBR is associated with a low risk of total NAC necrosis.

The patient advisor, an organizational resource as a lever for an enhanced oncology patient experience (PAROLE-onco): a longitudinal multiple case study protocol.

BACKGROUND: Quebec is one of the Canadian provinces with the highest rates of cancer incidence and prevalence. A study by the Rossy Cancer Network (RCN) of McGill university assessed six aspects of the patient experience among cancer patients and found that emotional support is the aspect most lacking. To improve this support, trained patient advisors (PAs) can be included as full-fledged members of the healthcare team, given that PA can rely on their knowledge with experiencing the disease and from using health and social care services to accompany cancer patients, they could help to round out the health and social care services offer in oncology. However, the feasibility of integrating PAs in clinical oncology teams has not been studied. In this multisite study, we will explore how to integrate PAs in clinical oncology teams and, under what conditions this can be successfully done. We aim to better understand effects of this PA intervention on patients, on the PAs themselves, the health and social care team, the administrators, and on the organization of services and to identify associated ethical and legal issues. METHODS/DESIGN: We will conduct six mixed methods longitudinal case studies. Qualitative data will be used to study the integration of the PAs into clinical oncology teams and to identify the factors that are facilitators and inhibitors of the process, the associated ethical and legal issues, and the challenges that the PAs experience. Quantitative data will be used to assess effects on patients, PAs and team members, if any, of the PA intervention. The results will be used to support oncology programs in the integration of PAs into their healthcare teams and to design a future randomized pragmatic trial to evaluate the impact of PAs as full-fledged members of clinical oncology teams on cancer patients' experience of emotional support throughout their care trajectory. DISCUSSION: This study will be the first to integrate PAs as full-fledged members of the clinical oncology team and to assess possible clinical and organizational level effects. Given the unique role of PAs, this study will complement the body of research on peer support and patient navigation. An additional innovative aspect of this study will be consideration of the ethical and legal issues at stake and how to address them in the health care organizations.

High-fat meal increases peripheral blood mononuclear cell pro-inflammatory cytokine expression in African-American women.

African-American (AA) women have elevated predominance of inflammatory diseases concurrent with local inflammation resulting in compromised metabolic function. The purpose of the study was 2-fold: 1) to examine the gene and protein expression of pro- and anti-inflammatory cytokine secretion by peripheral blood mononuclear cells (PBMC) obtained from AA and Caucasian-American (CA) women in response to an acute high-fat meal; and 2) to explore the influence of race (AA vs. CA) on PBMC reactivity. Ten AA and 11 CA women consumed a high-fat meal with baseline and 4 h postprandial venous blood draws. PBMCs were incubated for 3 h then messenger RNA expression and supernatant protein concentration was used to examine inflammatory profiles. All women had a postprandial increase in interleukin (IL)-8 gene expression, IL-8 protein concentration, and tumor necrosis factor alpha (TNF-α) protein concentration (P < 0.05). AA women had a postprandial increase in IL-6, IL-8, and TNF-α protein concentration (P < 0.05). AA women had higher postprandial IL-1ß protein concentration and IL-8 gene expression compared with CA women (P < 0.05). Our data uncovers the specific impact of race and time on pro-inflammatory PBMC (IL-1ß, IL-6, IL-8, and TNF-α) expression profiles in response to an acute high-fat meal challenge. Novelty: African Americans have higher predominance of inflammatory disease. We explored the potential race impact on peripheral blood mononuclear cell reactivity in response to a meal. A pro-inflammatory response to an acute high-fat meal with race impact was observed possibly contributing to health disparities impacting African-American women.

Pharmacological and non-pharmacological treatments for neuropathic pain: Systematic review and French recommendations.

Neuropathic pain remains a significant unmet medical need. Several recommendations have recently been proposed concerning pharmacotherapy, neurostimulation techniques and interventional management, but no comprehensive guideline encompassing all these treatments has yet been issued. We performed a systematic review of pharmacotherapy, neurostimulation, surgery, psychotherapies and other types of therapy for peripheral or central neuropathic pain, based on studies published in peer-reviewed journals before January 2018. The main inclusion criteria were chronic neuropathic pain for at least three months, a randomized controlled methodology, at least three weeks of follow-up, at least 10 patients per group, and a double-blind design for drug therapy. Based on the GRADE system, we provide weak-to-strong recommendations for use and proposal as a first-line treatment for SNRIs (duloxetine and venlafaxine), gabapentin and tricyclic antidepressants and, for topical lidocaine and transcutaneous electrical nerve stimulation specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a second-line treatment for pregabalin, tramadol, combination therapy (antidepressant combined with gabapentinoids), and for high-concentration capsaicin patches and botulinum toxin A specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a third-line treatment for high-frequency rTMS of the motor cortex, spinal cord stimulation (failed back surgery syndrome and painful diabetic polyneuropathy) and strong opioids (in the absence of an alternative). Psychotherapy (cognitive behavioral therapy and mindfulness) is recommended as a second-line therapy, as an add-on to other therapies. An algorithm encompassing all the recommended treatments is proposed.

Antiproliferative potential of solidagenone isolated of Solidago chilensis

ABSTRACT Plants are considered among the main sources of biologically active chemicals. The species Solidago chilensis Meyen, Asteraceae, is native to the southern parts of South America, where the aerial parts of the plant are commonly used for the treatment of inflammatory conditions. However, the effects of S. chilensis on human cancer cells remain to be elucidated. In this study, we evaluated the antiproliferative effects of the hydroalcoholic and dichloromethane extracts of S. chilensis, as well as their chemical constituents quercitrin and solidagenone against the five human tumor cell lines in vitro. The dichloromethane extract showed a promisor antiproliferative effects in vitro, especially against glioma cell line. Besides, the hydroalcoholic extract and quercitrin were inactive. The diterpene solidagenone showed highly potent antiproliferative effects against breast (MCF-7), kidney (786-0), and prostate cancer (PC-3) cells (total growth inhibition: TGI < 6.25 µg/ml). Solidagenone meets the theoretical physico-chemical criteria for bioavailability of drugs, according to the "Rule of Five" and, by theorical studies, the observed biological effects were probably related to the interaction of the molecule with nuclear receptors and as an enzymatic inhibitor. This study contributes to chemical study and to the identification of antiproliferative molecules in S. chilensis.

Nipple sparing mastectomy for breast cancer is associated with high patient satisfaction and safe oncological outcomes.

BACKGROUND: The preservation of the nipple areolar complex (NAC) for cancer treatment is still a matter of debate because of suspected increase of local recurrence and surgery-specific complications. The aim of the study was to investigate both the relapse risk associated with nipple sparing mastectomy (NSM) for breast cancer and women's satisfaction with preservation of the NAC. METHODS: We included retrospectively all patients who had skin-sparing mastectomy (SSM) or NSM from 2007 to 2012 for breast cancer or ductal carcinoma in situ (DCIS). We compared NSM and SSM group for oncological and surgical outcomes. Patients' satisfaction and quality of life has been evaluated by a specifically designed questionnaire. RESULTS: We included 63NSM (41.5%) and 89SM (58.5%). Eighty-nine (58.6%) patients had DCIS, and the other had small invasive disease. Median follow-up was 42 (IQR: 18-58) months. Local recurrence rate was 1.7% (n=1) in the NSM group and 0% in the SSM group without recurrence in the preserved nipple. After NSM, one patient had complete NAC necrosis, and three patients suffered partial necrosis. Satisfaction with the NAC was higher in the NSM group compared to the SSM group with delayed reconstruction of the nipple (75% vs. 59%, P=0.14). Patients with NSM required less psychological support before (P=0.028) and immediately after surgery (P=0.14) than patients in the SSM group. CONCLUSION: NSM can successfully and safely be performed for pre-invasive and small invasive breast cancer. Besides esthetic aspects, preserving the nipple may ease the acceptance of these radical form of surgery.

Complication-related removal of totally implantable venous access port systems: Does the interval between placement and first use and the neutropenia-inducing potential of chemotherapy regimens influence their incidence? A four-year prospective study of 4045 patients.

BACKGROUND: Totally implantable venous access port systems are widely used in oncology, with frequent complications that sometimes necessitate device removal. The aim of this study is to investigate the impact of the time interval between port placement and initiation of chemotherapy and the neutropenia-inducing potential of the chemotherapy administered upon complication-related port removal. PATIENTS AND METHODS: Between January 2010 and December 2013, 4045 consecutive patients were included in this observational, single-center prospective study. The chemotherapy regimens were classified as having a low (<10%), intermediate (10-20%), or high (>20%) risk for inducing neutropenia. RESULTS: The overall removal rate due to complications was 7.2%. Among them, port-related infection (2.5%) and port expulsion (1%) were the most frequent. The interval between port insertion and its first use was shown to be a predictive factor for complication-related removal rates. A cut-off of 6 days was statistically significant (p = 0.008), as the removal rate for complications was 9.4% when this interval was 0-5 days and 5.7% when it was ≥6 days. Another factor associated with port complication rate was the neutropenia-inducing potential of the chemotherapy regimens used, with removal for complications involved in 5.5% of low-risk regimens versus 9.4% for the intermediate- and high-risk regimens (p = 0.003). CONCLUSION: An interval of 6 days between placement and first use of the port reduces the removal rate from complications. The intermediate- and high-risk for neutropenia chemotherapy regimens are related to higher port removal rates from complications than low-risk regimens.

Inhibition of Cav3.2 T-type Calcium Channels by Its Intracellular I-II Loop.

Voltage-dependent calcium channels (Cav) of the T-type family (Cav3.1, Cav3.2, and Cav3.3) are activated by low threshold membrane depolarization and contribute greatly to neuronal network excitability. Enhanced T-type channel activity, especially Cav3.2, contributes to disease states, including absence epilepsy. Interestingly, the intracellular loop connecting domains I and II (I-II loop) of Cav3.2 channels is implicated in the control of both surface expression and channel gating, indicating that this I-II loop plays an important regulatory role in T-type current. Here we describe that co-expression of this I-II loop or its proximal region (Δ1-Cav3.2; Ser(423)-Pro(542)) together with recombinant full-length Cav3.2 channel inhibited T-type current without affecting channel expression and membrane incorporation. Similar T-type current inhibition was obtained in NG 108-15 neuroblastoma cells that constitutively express Cav3.2 channels. Of interest, Δ1-Cav3.2 inhibited both Cav3.2 and Cav3.1 but not Cav3.3 currents. Efficacy of Δ1-Cav3.2 to inhibit native T-type channels was assessed in thalamic neurons using viral transduction. We describe that T-type current was significantly inhibited in the ventrobasal neurons that express Cav3.1, whereas in nucleus reticularis thalami neurons that express Cav3.2 and Cav3.3 channels, only the fast inactivating T-type current (Cav3.2 component) was significantly inhibited. Altogether, these data describe a new strategy to differentially inhibit Cav3 isoforms of the T-type calcium channels.

Dual-energy contrast-enhanced digital mammography in routine clinical practice in 2013.

To date, analysis of the vascularisation of breast lesions mainly relies on MR imaging. However, the accessibility of MRI is sometimes limited and has led to the development of new means of imaging, such as dual-energy contrast-enhanced mammography, which provides data on the vascularisation of the breast along with the usual morphological information. The purpose of this paper is to present this new imaging technique as well as the recent references, illustrated by clinical reports derived from our everyday practice to focus on the advantages and disadvantages of this new breast exploration. Dual-energy contrast-enhanced mammography is a recent, seemingly promising technique, in the management of breast cancer. The main advantages consist of its easy installation, the good tolerance and the comfort in the interpretation of difficult to read mammograms. However, the indications and the role of dual-energy contrast-enhanced mammography still have to be determined within the diagnostic strategy of breast tumours. New studies are expected, especially to compare dual-energy contrast-enhanced mammography with breast MRI.

Founder niche constrains evolutionary adaptive radiation.

Adaptive radiation of a lineage into a range of organisms with different niches underpins the evolution of life's diversity. Although the role of the environment in shaping adaptive radiation is well established, theory predicts that the evolvability and niche of the founding ancestor are also of importance. Direct demonstration of a causal link requires resolving the independent effects of these additional factors. Here, we accomplish this using experimental bacterial populations and demonstrate how the dynamics of adaptive radiation are constrained by the niche of the founder. We manipulated the propensity of the founder to undergo adaptive radiation and resolved the underlying causal changes in both its evolvability and niche. Evolvability did not change, but the propensity for adaptive radiation was altered by changes in the position and breadth of the niche of the founder. These observations provide direct empirical evidence for a link between the niche of organisms and their propensity for adaptive radiation. This general mechanism may have rendered the evolutionary dynamics of extant adaptive radiations dependent on chance events that determined their founding ancestors.

Health burden of co-morbid asthma and allergic rhinitis in West Indian children.

BACKGROUND: Co-morbid allergic rhinitis (AR) and asthma has not been studied in Caribbean countries where there is a high prevalence of childhood asthma. METHODS: Using the International Primary Care Airways Group (IPAG) guidelines to determine AR, care-givers of 393 (response rate=100%) children attending asthma clinics in selected public sector health facilities in Trinidad, West Indies, were interviewed. RESULTS: Children (393) were between 2-17 years and included 239 (60.8%) boys and 154 (39.2%) girls. As many as 53.9% of children sampled (95% CI 45.9-55.8) suffered from AR. Children exposed to household smoking were nearly twice as likely to have AR (p<0.0041, OR=1.9, CI 1.22-2.88). Significantly (p<0.01) more asthmatics with AR (154, 58.6%) visited Accident and Emergency (A&E) in the past 12 months. The odds of visiting A&E at least once in the past 12 months for asthmatics with AR were 1.75 (95% CI 1.15-2.68). The average frequency of A&E visits was higher in children who also suffered from AR (1.75 vs 1.36, p<0.04). Age was negatively correlated (-0.21, p<0.005) with exacerbation frequency for asthmatics without AR suggesting A&E visits are independent of age in co-morbid disease. More children with AR (>60%) suffer day and night symptoms (p<0.001), and miss school (59.8%) (p<0.03) at least once a week (p<0.002) than asthmatics without AR (OR=1.5, 95% CI=1.03-2.30). CONCLUSIONS: AR is prevalent in 53.9% of Trinidadian children with asthma. The burden of co-morbid disease in asthmatic children is associated with increased likelihood of asthma-related A&E visits, day and night symptoms and absence from school.

[Uncommon clinical presentation of a gestational choriocarcinoma]. / Présentation inhabituelle d'un choriocarcinome gestationnel.

Gestational choriocarcinoma is a rare malignant tumour with a strong metastatic potential. We report a case of a 31-year-old patient with a gestational trophoblastic tumor revealed by renal and pulmonary metastases, one year after a normal pregnancy. The diagnosis was established by the pathologist on the radical nephrectomy specimen. The evolution was quickly favorable after adequate treatment using multiagent chemotherapy. This case highlights the polymorphic aspects of the gestational choriocarcinoma and stresses the importance of a betaHCG assessment anytime abnormal symptoms occur in the outcome of a pregnancy.

[Management of endometriosis of the urinary tract]. / Prise en charge de l'endométriose urinaire.

Endometriosis of the urinary tract (bladder and/or ureter) is rare and concerns 1-2% of cases of endometriosis. Surgical management is usually mandatory. Rate of peri operative morbidity is low. There is a risk of functional (dysuria, chronic hypogastric pains, imperiosity) and anatomical recurrences (0-15 and 0-10% respectively). Surgical treatment of bladder and/or ureteral endometriosis requires informed consent of patients and multidisciplinary management.

Paradoxical potentiation of neuronal T-type Ca2+ current by ATP at resting membrane potential.

Despite the marked influence on neuronal physiology of the low-voltage activated T-type Ca(2+) currents, little is known about the intracellular pathways and neurotransmitters involved in their regulations. Here, we report that in thalamocortical neurons a phosphorylation mechanism induces an increase both in the current amplitude (1.5 +/- 0.27-fold in the ventrobasal nucleus) and its inactivation kinetics. Dialysis of the neuron with an ATP-free solution suppresses the T-current potentiation, whereas it becomes irreversible in the presence of ATPgammaS. Phosphorylation occurs when the channels are inactivated and is slowly removed when they recover from inactivation and remain in closed states (time constants of the induction and removal of the potentiation: 579 +/- 143 msec and 4.9 +/- 1.1 sec, respectively, at 25 degrees C). The resulting apparent voltage sensitivity of this regulation follows the voltage dependence of the current steady-state inactivation. Thus, the current is paradoxically inhibited when the preceding hyperpolarization is lengthened, and maximal currents are generated after transient hyperpolarizations with a duration (0.7-1.5 sec) that is defined by the balance between the kinetics of the dephosphorylation and deinactivation. In addition, the phosphorylation will facilitate the generation of T current at resting membrane potential. This potentiation, which is specific to sensory thalamocortical neurons, would markedly influence the electroresponsiveness of these neurons and represent the first evidence of a regulation of native Cav3.1 channels.

The risk of hospital-acquired GB virus C infection: a pilot case-control study.

The risk of hospital-acquired infection with GB virus C (GBV-C) was explored among 42 patients. The factors independently associated with detection of GBV-C RNA in serum were bronchoscopic examination [adjusted odds ratio (OR)=18.1 (95% confidence interval 1.3-255.3), P=0.03] and a history of illicit drug use [OR=14.5 (1.0-218.7), P=0.05]. In this cohort of patients, invasive procedures appear to be associated with GBV-C infection but not with hepatitis C virus (HCV) infection.