Laparoscopic repair of iatrogenic celiac artery injury during median arcuate ligament release: A retrospection and tips at troubleshooting.

ABSTRACT: Median arcuate ligament (MAL) syndrome or celiac artery (CA) compression syndrome previously treated mainly by vascular surgeons using the open approach is now being increasingly performed by general surgeons with training in advanced laparoscopy. Although this approach has all the advantages of minimal access surgery, the procedure is fraught with serious complications like injury to major vascular structures during dissection. Vascular injury by far is the major cause of conversion to open procedure. Herein, we report a laparoscopic repair of iatrogenic CA injury by intra-corporeal suturing during MAL release. We also elaborate the causes, the preventive measures that can be applied to avoid such catastrophic occurrences in future. To the best of our knowledge, this is the first report of a laparoscopic repair of CA bleed during MAL release.

Love in the Time of Corona: Predicting Willingness to Engage in Sexting During the First COVID-19-Related Lockdown.

When the COVID-19 pandemic began, in early 2020, lockdowns limited the options for physical intimacy and many resorted to technology-mediated forms of intimacy such as sexting. However, it is unclear what predicted willingness to engage in sexting during the lockdown. The present study filled this gap by investigating COVID-19-related social isolation, privacy concerns, age, and gender as predictors of willingness to engage in sexting. We further examined an interaction of COVID-19-related social isolation and privacy concerns on willingness to engage in sexting. We conducted online surveys with 494 young adults (Study 1) and with a quota-based sample of 437 adults (Study 2) in Austria. In both studies, negative binomial regressions revealed a positive effect of COVID-19-related social isolation on willingness to engage in sexting. Privacy concerns hindered young adults in Study 1 from engaging in sexting but not relatively older adults in Study 2. However, in neither study did privacy concerns moderate the effect of COVID-19-related social isolation on willingness to engage in sexting: Even individuals with high privacy concerns were more willing to sext under conditions of social isolation, suggesting that the need for intimacy outweighed the need for privacy protection. Gender had no effect in either study, indicating that men and women used sexting to cope with the unprecedented COVID-19-related situation.

eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies.

In BRAF(V600)-mutant tumours, most mechanisms of resistance to drugs that target the BRAF and/or MEK kinases rely on reactivation of the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signal transduction pathway, on activation of the alternative, PI(3)K-AKT-mTOR, pathway (which is ERK independent) or on modulation of the caspase-dependent apoptotic cascade. All three pathways converge to regulate the formation of the eIF4F eukaryotic translation initiation complex, which binds to the 7-methylguanylate cap (m(7)G) at the 5' end of messenger RNA, thereby modulating the translation of specific mRNAs. Here we show that the persistent formation of the eIF4F complex, comprising the eIF4E cap-binding protein, the eIF4G scaffolding protein and the eIF4A RNA helicase, is associated with resistance to anti-BRAF, anti-MEK and anti-BRAF plus anti-MEK drug combinations in BRAF(V600)-mutant melanoma, colon and thyroid cancer cell lines. Resistance to treatment and maintenance of eIF4F complex formation is associated with one of three mechanisms: reactivation of MAPK signalling, persistent ERK-independent phosphorylation of the inhibitory eIF4E-binding protein 4EBP1 or increased pro-apoptotic BCL-2-modifying factor (BMF)-dependent degradation of eIF4G. The development of an in situ method to detect the eIF4E-eIF4G interactions shows that eIF4F complex formation is decreased in tumours that respond to anti-BRAF therapy and increased in resistant metastases compared to tumours before treatment. Strikingly, inhibiting the eIF4F complex, either by blocking the eIF4E-eIF4G interaction or by targeting eIF4A, synergizes with inhibiting BRAF(V600) to kill the cancer cells. eIF4F not only appears to be an indicator of both innate and acquired resistance but also is a promising therapeutic target. Combinations of drugs targeting BRAF (and/or MEK) and eIF4F may overcome most of the resistance mechanisms arising in BRAF(V600)-mutant cancers.

Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma with KIR3DL2 and NKp46 expression in a human immunodeficiency virus carrier.

Primary cutaneous aggressive epidermotropic T-cell lymphoma (PCAETCL) is a very rare lymphoma characterized by rapidly growing necrotic cutaneous lesions with an epidermotropic CD8+ T-cell neoplastic infiltrate observed histopathologically. It is associated with a very poor outcome, despite aggressive multi-agent chemotherapy. We report a 49-year-old human immunodeficiency virus (HIV)-infected patient who developed PCAETCL with associated marked vascular injury leading to diffuse purpuric and necrotic lesions complicated by recalcitrant hemophagocytic activation syndrome. The lymphoma strongly and diffusely expressed CD158k/KIR3DL2 at the protein and transcript level and NKp46 transcripts, in addition to CD8 and cytotoxic proteins. We observed a diffuse CD158k/KIR3DL2 protein expression in another case of PAETCL, not associated with immunodeficiency, which was used as a positive control. PCAETCL can develop in HIV-infected patients and may present in vasculitis-like fashion. The possible role of immunosuppression and/or HIV in oncogenesis can be postulated, as patients infected with HIV may develop anti-HIV cytotoxic CD8+ lymphoproliferations. The frequency of CD158k/KIR3DL2 and NKp46 expression in PCAECL remains to be studied in a series of cases, and may represent interesting targets for future treatments.

Kidney injuries related to ipilimumab.

Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse events" (irAEs). IrAEs mainly include colitis, dermatitis, hepatitis, endocrinopathies; uveitis, iridocyclitis, neuropathies, and inflammatory myopathy have occasionally been reported. Kidney involvement is rare. We report 2 cases of acute granulomatous interstitial nephritis and present, based on literature review, renal disorders related to Ipilimumab therapy. Autoimmune symptoms have to be carefully checked for patients treated with CTLA-4 inhibitors. In order to reduce the risk of sequelae, early recognition of irAEs and treatment initiation are crucial.

Fear of Missing Out, Reflective Smartphone Disengagement, and Loneliness in Late Adolescents.

Reflective smartphone disengagement (i.e., deliberate actions to self-regulate when and how one should use one's smartphone) has become a necessary skill in our ever-connected lives, contributing to a healthy balance of related benefits and harms. However, disengaging from one's smartphone might compete with impulsive psychosocial motivators such as fear of missing out (FoMO) on others' rewarding experiences or feelings of loneliness. To shed light into these competitive processes, the present paper disentangles the reciprocal, over-time relationships between reflective smartphone disengagement, FoMO, and loneliness using data from a two-wave panel study among emerging adults (16-21 years of age). Measurement-invariant structural equation modeling suggests that FoMO and reflective smartphone disengagement negatively predict each other over time, indicating a possible spiraling process. In addition, reflective smartphone disengagement was also negatively related to feelings of loneliness. Together, these findings underline (a) how young people's impulsive and reflective system compete with each other over control of their smartphone usage, where (b) psychosocial benefits of reflective smartphone disengagement were validated among emerging adults, potentially helping them to strengthen the benefits and limit the harms of permanent interactions with and through technology.

Association of Vitiligo With Tumor Response in Patients With Metastatic Melanoma Treated With Pembrolizumab.

IMPORTANCE: Vitiligo is an autoimmune skin disorder that reacts against melanocytes. The association of vitiligo with tumor response in patients with melanoma who undergo immunotherapy has been reported but is still controversial. OBJECTIVE: To prospectively evaluate the appearance of vitiligo in patients receiving pembrolizumab, a monoclonal antibody directed against the programmed death cell receptor. DESIGN, SETTING, AND PARTICIPANTS: This prospective observational study was conducted from January 1, 2012, through September 24, 2013, in a single tertiary care hospital with a unit dedicated to patients with melanoma. Sixty-seven patients with metastatic melanoma who received pembrolizumab treatment in the context of a phase 1 study were included and screened for the emergence of vitiligo. Data were collected from January 1, 2012, to February 28, 2014, and analyzed from February through December 2014. MAIN OUTCOMES AND MEASURES: Objective tumor response with regard to the occurrence of vitiligo in patients receiving pembrolizumab therapy. Correlation between vitiligo occurrence and overall survival was also estimated using the Kaplan-Meier product-limit method and compared with a log-rank test. To prevent guarantee- or lead-time bias, a landmark analysis approach after 12, 16, and 20 weeks of treatment was retained. RESULTS: Of the 67 patients included in the study, 17 (25%) developed vitiligo during pembrolizumab treatment and 50 (75%) did not. An objective (complete or partial) response to treatment was associated with a higher occurrence of vitiligo (12 of 17 [71%] vs 14 of 50 [28%]; P = .002). The time to onset of vitiligo ranged from 52 to 453 (median, 126) days from the start of treatment. Of the 17 patients with vitiligo, 3 (18%) had a complete response, 9 (53%) had a partial response, 3 (18%) had stable disease, and 2 (12%) had progressive disease at the final follow-up. All the patients treated with pembrolizumab who developed vitiligo were alive at the time of analysis, with a median follow-up of 441 days. CONCLUSIONS AND RELEVANCE: Vitiligo, a clinically visible immune-related adverse event could be associated with clinical benefit in the context of pembrolizumab treatment.

Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF-CRAF Heterodimerization.

BRAF inhibitors (BRAFi) elicit therapeutic responses in metastatic melanoma, but alarmingly, also induce the formation of secondary benign and malignant skin tumors. Here, we report the emergence and molecular characterization of 73 skin and extracutaneous tumors in 31 patients who underwent BRAFi therapy. The majority of patients presented with classic epidermal tumors such as verrucous papillomas, keratoacanthomas, and squamous cell carcinomas (SCC). However, 15 patients exhibited new or rapidly progressing tumors distinct from these classic subtypes, such as lymph node metastasis, new melanomas, and genital and oral mucosal SCCs. Genotyping of the tumors revealed that oncogenic RAS mutations were found in 58% of the evaluable tumor samples (38/66) and 49% of the control tumors from patients not treated with BRAFi (30/62). Notably, proximity ligation assays demonstrated that BRAF-CRAF heterodimerization was increased in fixed tumor samples from BRAFi-treated patients compared with untreated patients. Our findings reveal that BRAF-CRAF complex formation is significantly associated with BRAFi treatment, and may therefore serve as a useful biomarker of BRAFi-induced cutaneous and extracutaneous tumor formation.

[Detection of residual microscopic disease in melanoma: interest of the sentinel lymph node procedure?]. / Détection de la maladie micrométastatique résiduelle du mélanome: le rôle du ganglion sentinelle.

The prognosis of metastatic melanoma, despite many important and recent progresses, remains poor. The detection of microscopic disease must be a key point in fundamental and clinical research. Current recommendations, with clinical and radiological monitoring, only permit to detect macroscopic relapses. No seric tumor marker is presently sufficiently reproducible and determinant to be used in clinical practice to precociously diagnose a relapse. The sentinel lymph node procedure is currently the only technique largely used to determine microscopic metastasis. This technique allows defining a group of patients with poor prognosis but its therapeutic impact remains discussed. Completion lymph node dissection of the area after positive sentinel lymph node is currently performed but its real benefit to improve overall survival must be proved. Interferon is now the only treatment approved in adjuvant setting, but its interest remains discussed. Therapeutic trials are ongoing to really identify patients who could benefit from adjuvant treatment with interferon. Other trials probably more attractive (anti-CTLA4, BRAF and MEK inhibitors), with molecules recently approved in metastatic phase are also ongoing.

Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with node-positive breast cancer.

PURPOSE: The Docetaxel Epirubicin Adjuvant (DEVA) trial evaluated the efficacy and toxicity of incorporating docetaxel after epirubicin to create a sequential anthracycline-taxane regimen in early breast cancer. PATIENTS AND METHODS: After complete tumor excision, postmenopausal women with node-positive early breast cancer were randomly assigned to either epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks for six cycles (EPI × 6) or three cycles of epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks followed by three cycles of docetaxel 100 mg/m(2) on day 1 every 3 weeks (EPI-DOC). A subset of patients also participated in a quality of life (QOL) study. The primary end point was disease-free survival (DFS). RESULTS: From 1997 to 2005, 803 patients entered DEVA (EPI × 6, n = 397; EPI-DOC, n = 406). At a median follow-up of 64.7 months (interquartile range, 45.2 to 84.4 months), 198 DFS events had been reported (EPI × 6, n = 114; EPI-DOC, n = 84). The 5-year DFS rates were 72.7% (95% CI, 68.0% to 77.3%) for epirubicin alone and 79.5% (95% CI, 75.2% to 83.8%) for epirubicin followed by docetaxel; evidence of improvement in DFS was observed with EPI-DOC (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.91; P = .008). One hundred twenty-seven patients have died (EPI × 6, n = 75; EPI-DOC, n = 52); a reduction in deaths was observed with EPI-DOC (HR, 0.66; 95% CI, 0.46 to 0.94; P = .02). The 5-year overall survival rates were 81.8% (95% CI, 77.7% to 85.9%) for epirubicin and 88.9% (95% CI, 85.5% to 92.2%) for epirubicin followed by docetaxel. Assessment of toxicity and QOL showed that EPI-DOC was associated with greater toxicity but with no difference in QOL between arms during follow-up. CONCLUSION: These results suggest, within a relatively small trial, that substitution of docetaxel for epirubicin for the last three cycles of chemotherapy results in improved outcome in postmenopausal women with node-positive, early breast cancer compared with six cycles of epirubicin monotherapy.

Evaluation and comparison of tests to detect methicillin resistant S. aureus.

BACKGROUND AND OBJECTIVES: Phenotypic methods for detection of methicillin resistant Staphylococcus aureus (MRSA) have been compared with the gold standard which, as of now, is by the detection of mecA gene and femA gene by polymerase chain reaction (PCR). Discrepancies in detection have an adverse effect on patient management, thereby highlighting the importance of accuracy in detection. Our study aims to evaluate the efficacy of cefoxitin disk diffusion test to detect MRSA and compare it with other phenotypic and molecular methods. METHODOLOGY: The study was conducted from June 2006 to December 2007 and included 610 Staphylococcus aureus (S. aureus) isolates obtained from clinical samples. All isolates were tested for MRSA using oxacillin screen agar plates with 6 microg/ml of oxacillin, cefoxitin disk diffusion using 30 microg disk and MIC of oxacillin. Selected isolates (55) were tested for presence of mecA gene and Fem A gene by PCR. RESULTS: Out of 610 isolates, MRSA was identified in 34.09% by cefoxitin disk diffusion, 34.9% by oxacillin screen agar, 34.4% by MIC and 37.3% by oxacillin disk diffusion. When selected isolates were tested with molecular methods, the cefoxitin disk diffusion and PCR tests were comparable. DISCUSSION: Prevalence of MRSA (34.09%) is quite high as in other studies. The oxacillin disk diffusion test which was used routinely earlier is showing low specificity (56%). Among all phenotypic methods, cefoxitin disk diffusion and PCR alone have similar sensitivity and specificity. CONCLUSION: Results of cefoxitin disk diffusion test are in concordance with the PCR for mecA gene. Thus, the test can be an alternative to PCR for detection of MRSA in resource constraint settings.