Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer.

The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.

Simplified risk-prediction for benchmarking and quality improvement in emergency general surgery. Prospective, multicenter, observational cohort study.

BACKGROUND AND AIMS: Emergency General Surgery (EGS) conditions account for millions of deaths worldwide, yet it is practiced without benchmarking-based quality improvement programs. The aim of this observational, prospective, multicenter, nationwide study was to determine the best benchmark cutoff points in EGS, as a reference to guide improvement measures. METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending EGS patients on a 24-h, 7-days a week basis, enrolled consecutive patients requiring an emergent/urgent surgical procedure. Patients were stratified into cohorts of low (i.e., expected morbidity risk <33%), middle and high risk using the novel m-LUCENTUM calculator. RESULTS: A total of 7258 patients were included; age (mean ± SD) was 51.1 ± 21.5 years, 43.2% were female. Benchmark cutoffs in the low-risk cohort (5639 patients, 77.7% of total) were: use of laparoscopy ≥40.9%, length of hospital stays ≤3 days, any complication within 30 days ≤ 17.7%, and 30-day mortality ≤1.1%. The variables with the greatest impact were septicemia on length of hospital stay (21 days; adjusted beta coefficient 16.8; 95% CI: 15.3 to 18.3; P < .001), and respiratory failure on mortality (risk-adjusted population attributable fraction 44.6%, 95% CI 29.6 to 59.6, P < .001). Use of laparoscopy (odds ratio 0.764, 95% CI 0.678 to 0.861; P < .001), and intraoperative blood loss (101-500 mL: odds ratio 2.699, 95% CI 2.152 to 3.380; P < .001; and 500-1000 mL: odds ratio 2.875, 95% CI 1.403 to 5.858; P = .013) were associated with increased morbidity. CONCLUSIONS: This study offers, for the first time, clinically-based benchmark values in EGS and identifies measures for improvement.

Cardiovascular Adverse Events Reported in Placebo Arm of Randomized Controlled Trials in Parkinson's Disease.

BACKGROUND: Parkinson's disease and cardiovascular disease are highly prevalent conditions in the elderly. Evidence shows inconsistent findings regarding the association between Parkinson's disease and cardiovascular events. OBJECTIVE: We sought to evaluate the proportion of cardiovascular adverse events among Parkinson's disease patients included in the placebo arm of randomized controlled trials. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2017. Randomized, placebo-controlled trials in Parkinson's disease were included. The primary outcome was the proportion of major cardiovascular adverse events, defined as myocardial infarction, stroke, peripheral artery disease, and sudden death. A random-effects meta-analysis was performed to derive pooled estimates of the proportion of adverse events and corresponding 95% confidence intervals (CIs). RESULTS: 236 randomized controlled trials were included, 80% (n = 189; 14704 patients) of which reported data on cardiovascular adverse events. The pooled proportion of major cardiovascular events ranged from 0.00% to 0.06% and the proportion of all cardiovascular adverse events was 3.33% (95% CI: 2.14, 4.70%), and ranged from 1.71% in de novo Parkinson's disease patients to 4.56% in patients receiving levodopa as their only antiparkinsonian medication. The most common adverse events were hypertension and orthostatic hypotension. CONCLUSIONS: These results suggest that the proportion of major cardiovascular adverse events is low and that blood pressure abnormalities are the most frequent cardiovascular adverse event.

Mucoepidermoid carcinoma of the retromolar region: case report / Carcinoma mucoepidermoide em região retromolar: relato de caso

ABSTRACT The present study aimed to report a case of mucoepidermoid carcinoma (MEC), focusing on its clinical-pathological characteristics. At intraoral clinical examination, a nodular lesion was observed in the right pterygomandibular raphe region, with three years of evolution. An incisional biopsy was performed, and the diagnostic hypotheses of salivary gland injury and sialadenitis were considered. Histopathologically, a malignant neoplastic process characterized by the proliferation of epidermoid, intermediate and mucosal cells was observed. The histopathological diagnosis of MEC was emitted. The present case praises the importance of early diagnosis and correct management of this disease, providing a better prognosis for these patients.

RESUMEN Reportamos un caso de carcinoma mucoepidermoide (CME) con enfoque en sus rasgos clinicopatológicos. En la exploración clínica intraoral, se observó una lesión de aspecto nodular en región del rafe pterigomandibular derecho, con tiempo de evolución de tres años. Se realizó una biopsia por incisión, considerándose las hipótesis diagnósticas de lesión de glándula salival y sialadenitis. Histopatológicamente, se observó un proceso neoplásico maligno caracterizado por la proliferación de células epidermoides, intermedias y mucosas. El diagnóstico histopatológico fue de CME. El presente caso destaca la importancia del diagnóstico temprano y del manejo correcto de esa enfermedad, ofreciendo un mejor pronóstico para los pacientes portadores de CME.

RESUMO Relatamos um caso de carcinoma mucoepidermoide (CME) com enfoque em suas características clinicopatológicas. No exame clínico intraoral, observou-se lesão de aspecto nodular em região de rafe pterigomandibular direita, com tempo de evolução de três anos. Biópsia incisional foi realizada, e as hipóteses diagnósticas de lesão de glândula salivar e sialadenite foram consideradas. Histopatologicamente, observou-se um processo neoplásico maligno caracterizado pela proliferação de células epidermoides, intermediárias e mucosas. O diagnóstico histopatológico de CME foi emitido. O presente caso enaltece a importância do diagnóstico precoce e do correto manejo dessa patologia, proporcionado um melhor prognóstico para os pacientes portadores de CME.

Pretransplant Biopsy of Marginal Kidneys: Is It Necessary?

INTRODUCTION: Pretransplant kidney biopsy from marginal donors is used to guide the decision of whether to accept or discard organs for transplantation; however, there is controversy about this procedure, and the need for a pretransplant biopsy is still a debate. We sought to determine if histologic evaluation before implantation of marginal kidneys would influence the outcome. METHODS: A retrospective observational cohort study of marginal donor transplants at Centro Hospitalar e Universitário de Coimbra was done. From 2009 to 2016, 650 marginal kidney transplants were analyzed. We evaluated long-term graft survival in a cohort of patients who received marginal kidneys. The recipients were divided into 2 groups based on whether a pretransplant donor biopsy was performed. Continuous variables were summarized by mean and standard deviation or median and range, as applicable. Categorical variables were summarized by relative and absolute frequencies. The survival analysis was obtained and plotted using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The median age of recipients and donors were statistically different between both groups (P < .001), with the donors and the recipients being younger in the group without a pretransplant biopsy. The median cold ischemia time was higher in the biopsy group (P = .01). The survival analysis showed that graft survival didn't differ between the groups (P = .2). CONCLUSIONS: Selection of kidneys based on histological findings may not influence the graft survival and implies a higher cold ischemia time. More data are necessary to provide insight into which clinical, histologic, and biochemical parameters are necessary for decision making on kidney acceptance.

Nocebo response in Parkinson's disease: A systematic review and meta-analysis.

OBJECTIVE: To estimate the magnitude of the nocebo response in Parkinson's disease and explore possible associations with study characteristics. METHODS: Databases were searched up to February 2017. Placebo-controlled, parallel-group randomized controlled trials investigating pharmacological interventions in people with Parkinson's disease were included. Data were derived from the last measured within-group response in the placebo and intervention arms of randomized controlled trials, after independent extraction. A random-effects model was used to pool study data. The main outcome was the nocebo response, measured as the proportion of placebo-treated participants experiencing any adverse events (AEs). We also measured the proportion of patients with serious AEs (SAEs), and the rates of study dropouts (including due to AEs) and death. PROSPERO registration number is CRD42017070471. RESULTS: We included 236 randomized controlled trials, with a combined population of 17,381 participants allocated to placebo. The nocebo response was 56.0% (95% CI, 51.7%-60.4%; 148 trials; I2 = 98%). SAEs were reported in 4.0% (95% CI, 3.4%-4.6%, 157 trials; I2 = 73%) of placebo-treated patients, dropouts in 14.0% (95% CI, 12.5%-15.5%, 225 trials; I2 = 91%), dropouts due to AEs in 5.7% (95% CI, 5.1%-6.4%, 219 trials; I2 = 73%). Deaths occurred in 0.6% (95% CI, 0.5%-0.7%, 227 trials; I2 = 0%). Similar proportions were identified in patients in intervention arms. CONCLUSIONS: The magnitude of the nocebo response in parallel-designed randomized controlled trials in Parkinson's disease is substantial and should be considered in the interpretation of safety results and in the design and interpretation of future clinical trials.

Spironolactone effect on potassium supplementation in paediatric cardiac intensive care patients.

WHAT IS KNOWN: Spironolactone is used in paediatric patients with heart disease, yet few data are available regarding the impact on potassium supplementation. OBJECTIVE: We sought to determine the effect of spironolactone on potassium supplementation in paediatric cardiac intensive care patients. METHODS: A retrospective, propensity matched cohort study was designed. Patients were included in the study if they received furosemide therapy in the cardiac intensive care unit at our institution. Patients who received spironolactone were matched to patients who did not receive spironolactone. Data collection included patient demographics, diuretic data, potassium monitoring, and total milliequivalents of potassium administered during the cardiac intensive care unit stay. RESULTS AND DISCUSSION: A total of 448 patients met study criteria median age 0.43 (IQR 0.06-3.52) years, 58.9% male. Intensive care unit length of stay was 7 (IQR 3-17) days, cardiovascular surgery occurred in 90.4%. Patients had a mean 4.6±2.6 potassium concentrations assessed per day (29.5%±19.4%<3.5 mmol/L, and 2.9%±6.5%>5.5 mmol/L). Patients received a median of 5.1 mEq/kg (0-323.4 mEq/kg) of potassium. Spironolactone (n=224) was administered for 2 days (IQR 1-4) at mean dose of 0.64±0.54 mg kg-1  d-1 . Median total mEq/kg of potassium administered did not differ between groups (4.6 mEq/kg (IQR 0.66-16.8) vs 6.5 mEq/kg (IQR 1.3-18.3 mEq/kg), P=.13). Potassium laboratory values did not differ in hypokalemia (27.8%±19.1% vs 31.2%±19.5%, P=.06) or hyperkalemia (2.8%±5.4% vs 3.2%±7.5%, P=.49) between groups. WHAT IS NEW: Spironolactone supplementation did not reduce the need for potassium supplementation in paediatric cardiac intensive care patients. CONCLUSION: The routine use of spironolactone in the paediatric cardiac intensive care population may not be more efficacious than potassium supplementation for maintenance of serum potassium concentrations.

CYP2D6*4 polymorphism: A new marker of response to hormonotherapy in male breast cancer?

BACKGROUND: Tamoxifen remains the standard hormonotherapy for Male breast cancer patients (MBC). Previous studies, in women, tried to evaluate the impact of CYP2D6 polymorphisms in tamoxifen efficacy with conflicting results. Herein we analyze the relation between CYP2D6*4 polymorphism and survival in MBC patients. PATIENTS AND METHODS: Fifty-three patients, proposed to tamoxifen in adjuvant setting, were enrolled. Clinical information was collected from records and histological revision with additional immunochemistry analysis was done to better characterize the tumors. Comprehensive CYP2D6*4 genotyping from blood or tumor tissue was performed and translated into two predicted metabolic activity groups. RESULTS: Patients included in the two CYP2D6*4 groups did not differ concerning to age, histological characteristics, and primary treatments performed. Median age at diagnosis was 63 years-old and patients were submitted at least to mastectomy and adjuvant hormonotherapy. Recurrence was observed in 7 patients (13.2%) and 13 patients (25.5%) died with a 5-year disease-free survival of 86.2%. The poorer metabolizer group had a high risk for recurrence (p = 0.034) and this outcome effect remains in different subgroups: in tumors larger than 2 cm (p < 0.001), nodal status, N0 vs N+ (p = 0.04) and in advanced stage, stage III (p < 0.001). Poorer metabolizer patients had also a worse overall survival when tumors were larger than 2 cm (p = 0.03). CONCLUSIONS: In our series, there was an association between CYP2D6*4 polymorphism and a probability of recurrence, with a consistent effect in risk groups defined by classic prognostic factors. Multicentric studies with larger samples are needed to validate these results.

Recurrent urinary tract infections in kidney transplant recipients.

Urinary tract infection (UTI) constitutes the most frequent infection among kidney transplantation (KT) patients. The epidemiology and specific risk factors for recurrent UTI after KT have not been well studied. The aim of this work was to assess the incidence, pathogenic spectrum, and risk factors for recurrent post-KT UTI. This observational, cross-sectional study included all patients admitted to our transplantation department with a diagnosis of post-KT UTI from January 2010 to December 2011. Recurring post-KT UTI was defined as ≥ 2 UTIs in 6 months or ≥ 3 UTIs in 12 months. Factors associated with recurrent post-KT UTI were assessed using logistic regression analysis. The 154 patients were diagnosed with 315 episodes of post-KT UTI (28.6%), with recurrent post-KT UTI among 72% of cases. Most recurrent UTIs (73.6%) occurred during the first year after KT. Klebsiella species was the most common isolated pathogen (53.2%), being a serious problem for multidrug-resistance (odds ratio [OR], 13; 95% confidence interval [CI] 5.9-28.6; P < .001). The presence of nosocomial infection (OR, 2.8; 95% CI, 1.4-5.4; P < .003) and multidrug-resistant bacteria (OR, 3.8; 95% CI, 2-7.2; P < .001) emerged as independent predictors of recurrent post-KT UTI. KT recipient demographics and characteristics, factors related to KT and urologic complications, did not differ significantly between patients with versus without recurrent post-KT UTI. In conclusion, in a unit where recurrent post-KT UTI incidence was 72% and Klebsiella species was the prevailing uropathogen, nosocomial infection and multidrug-resistant bacteria appeared to be independent predictive factors for recurrent post-KT UTI.

[Neurosurgical embryology. Part 7: Development of the spinal cord, the spine and the posterior fossa]. / Développement de la moelle épinière, du rachis et de la fosse posterieure.

The spinal cord arises from the most caudal domain of the neural tube whereas the vertebrae develop from the para-axial mesoderm (namely the somites). The development of the spinal cord and the vertebrae is so intimately linked that it is more convenient to present it in the same chapter. The neural tube is formed from the neural plate during neurulation. This tube is submitted to a double gradient of diffusible molecules that lead to the ventro-dorsal polarization of the tube. This polarization is figured as the emergence of sub-domains that contain progenitors engaged in a specific lineage. Axial organs induce the dissociation of the somites, giving rise to the dermatome, myotome and sclerotome. Vertebrae derive from the sclerotome after the so-called resegmentation of the somites. During this process, a caudal hemi-somite is associated with the rostral hemi-somite of the next caudal somite to differentiate into the vertebra. The occipital bone forms the major part of the walls of the posterior fossa. This bone develops from the para-axial mesoderm for its sub-tentorial part whereas its sus-tentorial derives from neural crest cells.

[Molecular control of ventro-dorsal polarization of the spinal neural tube in vertebrates]. / Le contrôle moléculaire de la polarisation ventro-dorsale du tube neural spinal chez les vertébrés.

The embryonic neural tube gives rise to the whole central nervous system (CNS) in vertebrates. The establishment of a dorsoventral axis in the neural tube is one of the first step to achieve the polarisation observed in the adult CNS: the dorsal aspect of it receives sensory inputs from the periphery and in response, the ventral aspect sends signals by motor cells: the motor neurones. This polarization is induced early in embryonic development by the signals secreted by polarizing centres such as the roof plate and the floor plate (e.g. BMP and Sonic Hedgehog). Since the neuroepithelium is sensitive to these signals, these cells respond by expressing sets of transcription factors in specific domains. Different combinations of transcription factors create progenitor domains that eventually give rise to post-mitotic neurones of different subtype in the dorso-ventral axis of the neural tube.

The ethics of information disclosure in HIV disease and cancer: a study of medical residents attitudes.

The study analyzes medical residents (MRs) attitudes on the ethics of information disclosure in two case scenarios--HIV disease and cancer. A purposeful sample of 120 MRs took part in a self-completion questionnaire administered. Responses were factor analyzed and three factors (17 statements) protecting rights of (1) spouse/family, (2) patient and (3) society, were retained for study. Analysis revealed that: (1) MRs perceived greater justification (P < 0.0001) in protecting family rights in HIV disease and patient rights (P < 0.0001) in cancer; (2) male MRs were significantly more inclined to protect spouse/family rights (P < 0.01) in HIV disease, when compared to female MRs; and (3) international MRs were significantly more inclined to protect spouse/family (P < 0.05) and societal rights (P < 0.01) in HIV disease, compared with United States MRs. Perception differences by MRs on ethics of information disclosure in HIV disease and cancer are based on MRs gender and their cultural background. It is important to document and address these attitudes during residency training.

An assessment of residents' competence in the delivery of bad news to patients.

PURPOSE: To assess the level of residents' competence in delivering bad news to patients. METHOD: In June 1995, 25 residents (of 116) in the Wayne State University general internal medicine residency program volunteered to participate in the study, which consisted of videotaped interviews of a simulated patient whose profile had been developed to highlight the delivery of a diagnosis of lung cancer. The residents were evaluated using an instrument based on a review of the current literature regarding the skills considered necessary for giving bad news in a caring and informative manner. The instrument contained 16 items, seven in the informative category and nine in the affective category. Each item was rated on a five-point Likert scale (from 1 = "doesn't do this" to 5 = "does this very well"). A rating of > or = 4 on any item indicated competence in the skill area measured by that item. All interviews included in the study were rated by all six of the authors. Interrater reliability was calculated to be .91. RESULTS: In all, 22 interviews (three by women, 19 by men) were included in the study. The residents' ages ranged from 26 to 35 years; the numbers of years since graduation from medical school ranged from two to six. Twenty were third- or fourth-year residents ready to graduate; the other two were completing their first year. Mean ratings in the informative category ranged from 1.51 to 4.51; for three items, mean ratings were > or = 4. The total mean rating for all the items in this category was 3.42. Mean ratings in the affective category ranged from 1.15 to 4.75; for three items, mean ratings were > or = 4. The total mean rating for all the items in this category was 3.45. CONCLUSION: The residents showed a general lack of competence in delivering bad news. The skill items with the lowest ratings were primarily related to eliciting the patient's perspective, which may represent a weakness on the part of the residency program in teaching the residents to use a "patient-centered" interviewing style. The results of this study will form the basis of a curriculum to improve residents' comfort with and skills for delivering bad news to patients.