Tissue-conserving surgery for prognosis,treatment, and function preservation

Objectives: To describe an approach based on initial tissue-conserving surgery used to obtain histologically determined prognostic information that has therapeutic implications and the potential to enhance preservation of function. Study Design: Analysis of a group of patients with head and neck cancer treated initially with tissue-conserving surgery based on Mohs' histographic sectioning and selected neck dissection to derive histologically determined prognostic information with therapeutic implications and preservation in function. Methods: This study is primarily based on an analysis of patients from January 1, 1989, through June 4, 1996 assigned to a protocol evaluating resection of oral cavity squamous cell cancer with margin control using Mohs' histographic technique and/or a group of patients with neck assessment of N0 on clinical examination who are undergoing supraomohyoid neck dissections. Results: Thirty-three primary tumor resections were performed using the Mohs' technique, and 54% required two or more Mohs' sections before clear histologic margins were obtained following resection based on clinically determined negative margins. There were 44 patients who underwent unilateral or bilateral supraomohyoid neck dissections, and 33% had occult, histologically positive nodes. When compared with the disease of the neck specimens, a preoperative computed tomography scan had a sensitivity of 25%, a specificity of 77%, and an accuracy of 63%. Conclusions: This report describes the effectiveness of Mohs' histographic sectioning and selective neck dissection as a means of determining prognostic information that can be used to develop a focused and cost-effective treatment program that, along with contemporary reconstructive techniques, provides a potential enhancement of function preservation. Laryngoscope, 108:1599–1604, 1998     

Expression of cytochrome p450 and other biotransformation genes in fetal and adult human nasal mucosa.

Despite recent progress in the identification and characterization of numerous nasal biotransformation enzymes in laboratory animals, the expression of biotransformation genes in human nasal mucosa remains difficult to study. Given the potential role of nasal biotransformation enzymes in the metabolism of airborne chemicals, including fragrance compounds and therapeutic agents, as well as the potential interspecies differences between laboratory animals and humans, it would be highly desirable to identify those biotransformation genes that are expressed in human nasal mucosa. In this study, a global gene expression analysis was performed to compare biotransformation enzymes expressed in human fetal and adult nasal mucosa to those expressed in liver. The identities of a list of biotransformation genes with apparently nasal mucosa-selective expression were subsequently confirmed by RNA-polymerase chain reaction (PCR) and DNA sequencing of the PCR products. Further quantitative RNA-PCR experiments indicated that, in the fetus, aldehyde dehydrogenase 6 (ALDH6), CYP1B1, CYP2F1, CYP4B1, and UDP glucuronosyltransferase 2A1 are expressed preferentially in the nasal mucosa and that ALDH7, flavin-containing monooxygenase 1, and glutathione S-transferase P1 are at least as abundant in the nasal mucosa as in the liver. The nasal mucosal expression of CYP2E1 was also detected. These findings provide a basis for further explorations of the metabolic capacity of the human nasal mucosa for xenobiotic compounds.     

Cognitive improvement in schizophrenic patients does not require a serotonergic mechanism: randomized controlled trial of olanzapine vs amisulpride.

Combined serotonin-2A (5-HT(2A)) and dopamine-2 (D2) receptor blockade has been proposed as a candidate mechanism by which second-generation antipsychotics (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in contrast to antipsychotics of the first generation. The SGA amisulpride, however, only binds to D2/D3 receptors, which makes it an interesting tool to test this assumption. In a randomized controlled trial, 52 schizophrenic patients were allocated to treatment with either olanzapine (10-20 mg/day) or amisulpride (400-800 mg/day). A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive improvements of moderate size were observed, with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs. Importantly, amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5-HT(2A)/D2 receptor blockade is probably not necessary for cognitive improvement by SGAs.     

Neural processing associated with cognitive empathy in pedophilia and child sexual offending

Behavioral studies found evidence for superior cognitive empathy (CE) in pedophilic men without a history of child sexual offending (P − CSO) compared to pedophilic men with a history of child sexual offending (P + CSO). Functional magnetic resonance imaging (fMRI) studies also point to differences between P − CSO and P + CSO. Neural processing associated with CE has not yet been investigated. Therefore, the present study aimed to explore the neural correlates of CE in subjects with pedophilia with (P + CSO) and without (P − CSO) child sexual offending. 15 P + CSO, 15 P − CSO and 24 teleiophilic male controls (TC) performed a CE task during fMRI. We observed reduced activation in the left precuneus (Pcu) and increased activation in the left anterior cingulate cortex (ACC) in P − CSO compared to P + CSO. P − CSO also showed stronger connectivity between these regions, which might reflect a top-down modulation of the Pcu by the ACC toward an increased self-focused emotional reaction in social situations. There was also evidence for increased right superior temporal gyrus activation in P − CSO that might constitute a potentially compensatory recruitment due to the dampened Pcu activation. These findings provide first evidence for altered neural processing of CE in P − CSO and underline the importance of addressing CE in pedophilia and CSO in order to uncover processes relevant to effective prevention of child sexual abuse.     

Evaluation of continuous aspiration of subglottic secretions in prevention of microaspiration during general anesthesia: a randomized controlled pilot study

AimTo assess the difference between endotracheal tubes (ETT) with continuous suction of subglottic secretions (CASS) and standard ETT in preventing secretions movement from the pharynx into the trachea, past the inflated cuff during general anesthesia.MethodsThis randomized, controlled trial enrolled 50 patients who underwent general anesthesia for elective abdominal surgery lasting longer than two hours. They received either ETT with CASS: Teleflex ISIS HVT (GISIS, n = 17) or Mallinckrodt TaperGuard Evac (GEvac, n = 17), or ETT without suction: Mallinckrodt Intermediate Hi-Lo (GStand, n = 16). Methylene blue dye solution (10 mL) was delivered into the hypopharynx every 60 minutes. Subglottic secretions were continuously suctioned. Fiberoptic bronchoscopy was performed every 20 minutes and during tracheal extubation to evaluate the dye location.ResultsThe groups did not differ in age, sex, body mass index, race, American Society of Anesthesiologists status, and surgery type. Dye migrated past the inflated cuff into the distal trachea in no patient with ETT with CASS and in 13% of patients with standard ETT. On tracheal extubation, dye migrated into the distal trachea more often in the GStand group (56%), compared with the GEvac (13%) and GISIS group (29%) (P = 0.045). The GISIS group had 26 ± 19 mL of secretions suctioned from above the inflated cuff, while the GEvac group had 13 ± 10 mL (P = 0.05).ConclusionCompared with standard ETT, ETT with CASS efficiently removed secretions during general anesthesia, prevented secretions from migrating past the inflated cuff, and significantly reduced the amount of secretions that reached the distal airways on tracheal extubation.ClinicalTrial.gov identification number{"type":"clinical-trial","attrs":{"text":"NCT01386879","term_id":"NCT01386879"}}NCT01386879

Postoperative pulmonary complications (PPC) commonly lead to morbidity and mortality in patients managed with general anesthesia for major surgery. In a systematic review of PPC after non-cardiothoracic surgery, the average incidence was 3.4% with a range from 1% to over 40% (1). Elderly and diabetic patients had the highest incidence. The incidence in abdominal surgery was 14.2% (1). A prospective multicenter study with a heterogeneous surgical population of almost 2500 patients revealed a 5.0% incidence of PPC; with a high mortality in patients who developed PPC (2). Patients with evidence of microaspiration have about three times higher incidence of postoperative pneumonia compared with patients without microaspiration (40% vs 12%), with mortality rate of 19.2% if they develop pneumonia (3).Endotracheal tubes (ETT) with continuous aspiration of subglottic secretions (CASS) are recommended in intensive care unit (ICU) patients requiring prolonged mechanical ventilation to prevent ventilator-associated pneumonia (4). A meta-analysis showed almost a 50% reduction of ventilator-associated pneumonia in patients receiving ETT with CASS in the ICU compared with standard ETT (5). It is unknown if using an ETT with CASS intraoperatively reduces the incidence of PPC in patients undergoing prolonged general anesthesia, and are extubated at the end of surgery.We hypothesized that a subglottic suction ETT with CASS would effectively remove secretions that accumulate above the inflated cuff and decrease the volume of secretions aspirated into the distal trachea during general anesthesia with mechanical ventilation and during tracheal extubation. The primary aim of the study was to evaluate whether there is a difference between three types of ETT in preventing the movement of methylene blue dye from the pharynx into the trachea, past the inflated cuff. The secondary objectives were to evaluate whether there is a difference in the volume, pH, and bacterial load of the secretions aspirated from above the subglottic suction ETT cuff.     

Theoretical and Experimental Models to Evaluate the Possibility of Corrosion Resistant Concrete for Coastal Offshore Structures

This study built theoretical and practical models to evaluate the corrosion resistance of concrete for coastal offshore structures in Vietnam. A mathematical model was developed in the form of a system of nonlinear partial differential equations characterizing the diffusion “free calcium hydroxide” in a solid of a concrete structure. The model describes the process of non-stationary mass conductivity observed in the “concrete structure—marine environment” system under non-uniform arbitrary initial conditions, as well as combined boundary conditions of the second and third kind, taking into account the nonlinear nature of the coefficients of mass conductivity k and mass transfer β. It was shown that the solution of the boundary value problem of non-stationary mass conductivity allows us to conclude about the duration of the service life of a concrete structure, which will be determined by the processes occurring at the interface: in concrete—mass conductivity, depending on the structural and mechanical characteristics of hydraulic structures, and in the liquid phase—mass transfer, determined by the conditions of interaction at the interface of the indicated phases.     

Gaps and opportunities in the treatment of relapsed-refractory multiple myeloma: Consensus recommendations of the NCI Multiple Myeloma Steering Committee

A wide variety of new therapeutic options for Multiple Myeloma (MM) have recently become available, extending progression-free and overall survival for patients in meaningful ways. However, these treatments are not curative, and patients eventually relapse, necessitating decisions on the appropriate choice of treatment(s) for the next phase of the disease. Additionally, an important subset of MM patients will prove to be refractory to the majority of the available treatments, requiring selection of effective therapies from the remaining options. Immunomodulatory agents (IMiDs), proteasome inhibitors, monoclonal antibodies, and alkylating agents are the major classes of MM therapies, with several options in each class. Patients who are refractory to one agent in a class may be responsive to a related compound or to a drug from a different class. However, rules for selection of alternative treatments in these situations are somewhat empirical and later phase clinical trials to inform those choices are ongoing. To address these issues the NCI Multiple Myeloma Steering Committee formed a relapsed/refractory working group to review optimal treatment choices, timing, and sequencing and provide recommendations. Additional issues considered include the role of salvage autologous stem cell transplantation, risk stratification, targeted approaches for genetic subsets of MM, appropriate clinical trial endpoints, and promising investigational agents. This report summarizes the deliberations of the working group and suggests potential avenues of research to improve the precision, timing, and durability of treatments for Myeloma.Subject terms: Combination drug therapy, Cancer therapeutic resistance, Targeted therapies     

Formation and Thermal Stability of the ω-Phase in Ti–Nb and Ti–Mo Alloys Subjected to HPT

This paper discusses the features of ω-phase formation and its thermal stability depending on the phase composition, alloying element and the grain size of the initial microstructure of Ti–Nb and Ti–Mo alloys subjected to high-pressure torsion (HPT) deformation. In the case of two-phase Ti–3wt.% Nb and Ti–20wt.% Nb alloys with different volume fractions of α- and β-phases, a complete β→ω phase transformation and partial α→ω transformation were found. The dependence of the α→ω transformation on the concentration of the alloying element was determined: the greater content of Nb in the α-phase, the lower the amount of ω-phase that was formed from it. In the case of single-phase Ti–Mo alloys, it was found that the amount of ω-phase formed from the coarse-grained β-phase of the Ti–18wt.% Mo alloy was less than the amount of the ω-phase formed from the fine α′-martensite of the Ti–2wt.% Mo alloy. This was despite the fact that the ω-phase is easier to form from the β-phase than from the α- or α′-phase. It is possible that the grain size of the microstructure also affected the phase transformation, namely, the fine martensitic plates more easily gain deformation and overcome the critical shear stresses necessary for the phase transformation. It was also found that the thermal stability of the ω-phase in the Ti–Nb and Ti–Mo alloys increased with the increasing concentration of Nb or Mo.