Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026: 05/29/17

Δευτέρα 29 Μαΐου 2017

Incidence and predictors of massive bleeding in children undergoing liver transplantation: A single-center retrospective analysis

Summary

Background

Liver transplantation represents a major surgery involving a highly vascular organ. Reports defining the scope of bleeding in pediatric liver transplants are few.

Aims

We conducted a retrospective analysis of liver transplants performed at our pediatric tertiary care center to quantify blood loss, blood product utilization, and to determine predictors for massive intraoperative bleeding.

Methods

Pediatric patients who underwent isolated liver transplantation at Boston Children's Hospital between 2011 and 2016 were included. The amount of blood product transfused in the perioperative period and the incidence of postoperative complications were reported. Univariable and multivariable logistic regressions were used to determine predictors for massive bleeding, defined as estimated blood loss exceeding one circulating blood volume within 24 hours.

Results

Sixty-eight children underwent liver transplantation during the study period and were included in the analysis. Multivariable logistic regression analysis identified the following independent predictors of massive bleeding: preoperative hemoglobin level <8.5 g/dL (OR 11.09, 95% CI 1.87-65.76), INR >1.5 (OR 11.62, 95% CI 2.36-57.26), platelet count <100 10⁹/L (OR 7.92, 95% CI 1.46-43.05), and surgery duration >600 minutes (OR 6.97, 95% CI 0.99-48.92).

Conclusions

Pediatric liver transplantation is associated with substantial blood loss and a significant blood product transfusion burden. A 43% incidence of massive bleeding is reported. Further efforts are needed to improve bleeding management in this high-risk population.

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Giant cell tumor in the sphenoid sinus and ethmoid sinus during childhood, and it is thought that optic atrophy was caused by compressive optic neuropathy.

http://orlhealth.blogspot.com/2017/05/giant-cell-tumor-in-sphenoid-sinus-and.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Laparoscopic sigmoidectomy combined with uterus excision for colouterine fistula caused by sigmoid colon diverticulitis: A case report

Abstract

A case of colouterine fistula caused by colonic diverticulitis that was successfully treated laparoscopically is presented. A 74-year-old woman visited us with lower abdominal discomfort and vaginal excretion with minor fecal contamination. Mild tenderness was observed in her lower abdomen. Blood examinations revealed elevated white blood cell count and C-reactive protein. Sigmoid colon diverticulitis was revealed on CT, and her condition was diagnosed as colouterine fistula. Hinchey classification was stage I. After 2 weeks of conservative therapy, her symptoms were reduced, and the white blood cell count and C-reactive protein level decreased. However, fecal contaminated vaginal excretion continued. The patient underwent laparoscopic sigmoidectomy combined with uterus excision, and she has been in good health for the 3 years since the operation. Although colouterine fistula is usually treated with open surgery, patients with controlled and well-localized inflammation may be good candidates for a laparoscopic approach.

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“Influence of possible predictor variables on the outcome of primary oral squamous cell carcinoma: a retrospective study of 392 consecutive cases at a single centre”— methodological issues

We read the paper by Loeffelbein and colleagues, published online in the International Journal of Oral and Maxillofacial Surgery in December 2016, with enthusiasm1. The authors aimed to examine tumour-specific and patient-related risk factors in a large single-centre cohort, i.e., factors that have a considerable effect on postoperative survival following ablative tumour surgery with elective neck dissection and immediate microvascular reconstruction in oral squamous cell carcinoma. It was concluded that postoperative survival does not depend only on tumour-related characteristics.

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The Cisplatin Total Dose and Concomitant Radiation in Locoregionally Advanced Head and Neck Cancer: Any Recent Evidence for Dose Efficacy?

Opinion statement

Concurrent chemoradiotherapy (CRT) with high-dose (100 mg/m²), single-agent cisplatin is considered the standard of care for locoregionally advanced head and neck cancer (LAHNC). Poor compliance often due to significant treatment-related toxicities observed during CRT regimen has stimulated research efforts to examine for evidence of the optimal cumulative cisplatin dose and schedule. The findings from this systematic literature review demonstrate that there are insufficient prospective, randomized controlled data to determine the optimal total dose (and schedule) of cisplatin to administer concomitantly with radiotherapy in the treatment of LAHNC. Given the clinical challenges associated with administering concurrent CRT with single-agent high-dose cisplatin, as well as the long-term toxicities accompanying this treatment, an examination of the available literature for evidence of dose efficacy is of continued clinical interest. Moving forward, it is critical that researchers include complete descriptions of key disease and treatment variables (i.e. treatment compliance and HPV status) to inform and strengthen clinical decisions. The substantial heterogeneity of LAHNC has led to the focus of recent research efforts to risk-stratify using a combination of clinical and molecular markers (e.g. HPV status). Thus, the optimal total dose (and schedule) of cisplatin may need to be modified to reflect the specific characteristics of the individual patient subpopulations being treated. At present, CRT remains the standard of care for LAHNC, but this field is rapidly evolving. National and international clinical trials are ongoing to evaluate treatment de-intensification in favourable risk patient subsets and treatment intensification in poor-risk patient subsets, these will provide evidence-based guidance to individualize therapy with the ultimate goal of improving patient outcomes.

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Overview of the 8th Edition TNM Classification for Head and Neck Cancer

Opinion Statement

The main purpose of the TNM system is to provide an anatomic-based classification to adequately depict cancer prognosis. Accurate cancer staging is important for treatment selection and outcome prediction, research design, and cancer control activities. To maintain clinical relevance, periodical updates to TNM are necessary. The recently published 8th edition TNM classification institutes the following changes to the staging of head and neck (excluding thyroid cancer): new stage classifications [HPV-related oropharyngeal cancer (HPV+ OPC) and soft tissue sarcoma of the head and neck (HN-STS)] and modification of T and N categories [T and N categories for nasopharyngeal cancer (NPC), T categories for oral cavity squamous cell carcinomas (OSCC), N categories for non-viral related head and neck cancer and unknown primary (CUP), and T categories for head and neck cutaneous carcinoma]. These changes reflect better understanding tumor biology and clinical behavior (e.g., HPV+ OPC and HN-STS), improved outcomes associated with technical advances in diagnosis and treatment (e.g., NPC), evolving knowledge about additional prognostic factors and risk stratification from research and observation (e.g., inclusion of depth of invasion variable for OSCC, inclusion of extranodal extension variable for all non-viral head and neck cancer, and reintroduction of size criteria for non-Merkel cell cutaneous carcinoma of the head and neck). This review summarizes the changes and potential advantages and limitations/caveats associated with them. Further evidence is needed to evaluate whether these changes would result in improvement in TNM stage performance to better serve the needs for clinical care, research, and cancer control.

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Prognostic Value of Perineural Invasion in Resected Gastric Cancer Patients According to Lauren Histotype

Abstract

The purpose of this study is to investigate perineural invasion (PNI) as a prognostic factor in gastric cancer patients. 455 patients submitted to extended (D2 or more) lymphadenectomy (median number of 39 retrieved lymph nodes, range: 15–140) between 1995 and 2012 were retrospectively studied. Patients were categorized in two groups according to the PNI status, and PNI positivity was assessed in presence of cancer cells in the perinerium or the neural fascicles using hematoxylin and eosin staining. Median follow-up for surviving patients was 80.3 months. Survival analysis was performed by univariate and multivariate analysis, using a Cox proportional hazards model. 162 patients (33.9%) had positive PNI; this was strongly associated with advanced stages of disease, residual tumor, lymphovascular invasion, Lauren diffuse-mixed histotype and tumor size. Five-year cancer-related survival was 65,7% and 20,6% in PNI negative vs. positive groups, respectively (p < 0.001). The prognostic impact of PNI at univariate analysis was particularly evident in patients submitted to R0 surgery, early as well as advanced stage, advanced nodal stage and T status. At multivariate analysis, PNI did not result statistically significant in the overall series, but emerged as an independent prognostic factor in the group of patients with Lauren intestinal histotype (p = 0.005, hazard ratio: 1.99, 95% confidence interval 1.24–3.19). PNI is related to advanced stage and poor long-term survival in gastric cancer, and may serve as an adjunctive prognostic factor in the intestinal histotype.

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Prognostic Value of Perineural Invasion in Resected Gastric Cancer Patients According to Lauren Histotype

Abstract

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Airborne gamma-ray spectrometry data processing using 1.5D inversion

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): Eugene Druker
Standard processing of Airborne Gamma-Ray Spectrometry data generally gives good results when the measurement conditions are almost constant within several footprint area sizes, with the possible exception of flight height variations in a small range. In practice, deviations, such as large or abrupt changes of flight height and/or rugged terrain are not so rare and lead to certain problems. This article proposes a different approach where the solutions of inverse problems are used for data processing. The approach is quite natural in the processing of field data measured along the flight lines: it explicitly takes into account 1.5D survey models and flight parameters – from topography to sources distribution on the surface. Also, it clearly demonstrates that the inverse problem of the Airborne Gamma-Ray Spectrometry does not have a unique solution. This feature can be used in accordance with the underlying geological problem since various formulations of inverse problems can lead to various geological solutions. The use of the approach is illustrated by several examples given for flight lines and survey areas. This approach can be particularly useful in situations where geological, geophysical and/or geographic survey conditions are far from the standard assumptions.

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Longitudinal study of quality of life in advanced cancer patients on home parenteral nutrition

Abstract

Since there is little knowledge regarding the quality of life (QoL) of cancer patients on home parenteral nutrition (HPN), we planned a prospective, longitudinal, double-center study to investigate the changes of QoL in these patients. One hundred and eleven adult cancer patients who were candidates for HPN following the indications of the European guidelines were consecutively enrolled. For QoL analysis, EORTC QLQ-C30 questionnaires were filled at the HPN start and after 1, 2, 3, and 4 months, and scores changes over time were analyzed according to the univariate mixed-effects linear model for repeated measures. Most patients had gastrointestinal cancers, were severely malnourished, and were in stage IV; two-thirds were still receiving oncologic treatments. Median weight loss over 3 months and body mass index were 11.7% and 20.7, respectively. Median survival was 4.7 (1–42) months; 67 and 34% of patients survived 3 and 6 months, respectively. Global QoL, physical functioning, role functioning, emotional functioning, appetite loss, and fatigue scores had a statistically significant trend over time (P < 0.001, P < 0.001, P = 0.007, P < 0.001, P = 0.004, P = 0.022, respectively). At the univariate analyses, the determinants significantly associated with changes in trend over time for physical, role, and emotional functioning were oncologic treatments (P < 0.001, P = 0.014, P = 0.040, respectively) and for appetite loss they were weight loss and Karnofsky performance status (P = 0.003, P = 0.023, respectively). Global QoL, physical, role, and emotional functioning improved during HPN even in advanced cancer patients on oncologic treatments.

In this prospective, longitudinal study that included 111 adults advanced cancer patients, global quality of life, physical functioning, role functioning, and emotional functioning had a statistically significant trend over time. At the univariate analyses, the determinants significantly associated with changes in trend over time for physical, role, and emotional functioning were oncologic treatments. Global quality of life improved during home parenteral nutrition even in advanced cancer patients on oncologic treatments.

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Low-level laser therapy (780 nm) combined with collagen sponge scaffold promotes repair of rat cranial critical-size defects and increases TGF-β, FGF-2, OPG/RANK and osteocalcin expression

Summary

The aim of this study was to evaluate the effect of collagen sponge scaffold (CSS) implantation associated with low-level laser therapy (LLLT) on repairing bone defects. A single 5-mm cranial defect was surgically created in forty Wistar rats, which then received one of the following four interventions (n = 10 per group): no treatment (G0); bone defect implanted with collagen sponge scaffold (CSS) alone (G1); defect treated with low-level laser therapy (LLLT) (wavelength 780 nm; total energy density 120 J/cm²; power 50 mW) alone (G2); and CSS associated with LLLT treatment (G3). After surgery, animals in each group were euthanized at 21 days and 30 days (n = 5 per euthanasia time group). Bone formation was monitored by X-ray imaging analysis. Biopsies were collected and processed for histological analysis and immunohistochemical evaluation of transforming growth factor-beta (TGF-β), fibroblast growth factor-2 (FGF-2), osteoprotegerin (OPG) and receptor activator of nuclear factor ƙ (RANK). Osteocalcin (OCN) was detected by immunofluorescence analysis. Compared to the G0 group, defects in the 30-day G3 group exhibited increased bone formation, both by increase in radiopaque areas (P < 0.01) and by histomorphometric analysis (P < 0.001). The histopathological analysis showed a decreased number of inflammatory cells (P < 0.001). The combined CCS + LLLT (G3) treatment also resulted in the most intense immunostaining for OPG, RANK, FGF-2 and TGF-β, and the most intense and diffuse OCN immunofluorescent labelling at 30 days postsurgery (G3 vs. G0 group, P < 0.05). Therefore, the use of CCS associated with LLLT could offer a synergistic advantage in improving the healing of bone fractures.

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Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer

Background and Objectives

Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy.

Methods

A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin.

Results

The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P < 0.0001), compared to controls.

Conclusions

Our study indicates that prolonged ischemic preconditioning is safe and does not interfere with subsequent esophagectomy. Complete ischemic preconditioning increased neovascularization in the distal gastric conduit.

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Comparison of the prognostic values of selected inflammation based scores in patients with medullary thyroid carcinoma: A pilot study

Background

The significance of inflammation based scores including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and plasma fibrinogen remains unclear in medullary thyroid carcinoma (MTC). We aimed to compare the prognostic value of these scores.

Methods

Seventy-eight patients newly diagnosed as MTC with operation in our institution from May 2009 to September 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were calculated to compare the prognostic value of these scores.

Results

Increased PLR was predictive of lymph node metastasis (AUC = 0.644, P = 0.022), capsule invasion (AUC = 0.666, P = 0.007), advanced tumor stages (AUC = 0.657, P = 0.011), and recurrence (AUC = 0.655, P = 0.049). Increased fibrinogen was predictive of lymph node metastasis (AUC = 0.669, P = 0.006) and capsule invasion (AUC = 0.631, P = 0.038). Reduced PNI was predictive of recurrence (AUC = 0.655, P = 0.049). Kaplan-Meier analyses and Cox regression analysis revealed that PLR was a significant predictor for recurrence.

Conclusions

PLR, fibrinogen, and PNI are all predictive. Specially, PLR is superior to other inflammation based scores in terms of prognostic ability.

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Recurrence patterns of retroperitoneal leiomyosarcoma and impact of salvage surgery

Background

Optimal treatment strategies for retroperitoneal leiomyosarcoma (RPLMS), particularly recurrent disease, are unknown.

Methods

We searched the tumor registry at The University of Texas MD Anderson Cancer Center (MDACC) to identify patients with RPLMS treated between 1994 and 2013.

Results

We identified 172 patients with a diagnosis of a RPLMS. Among the 85 patients who underwent complete resection included in the survival analysis, the median overall survival (OS) was 8.3 years (95% confidence interval [CI], 5.7-12.3), 5-year local recurrence rate was 21%, and 5-year distant metastasis rate was 47%. Among 114 patients who experienced recurrence, patients who underwent salvage surgery for recurrent disease had longer OS after recurrence than patients who did not undergo salvage surgery (median survival after recurrence 5.6 vs 3.3 years, 3-year OS rates after recurrence 72.6% vs 58.1%, HR 0.402 [95%CI, 0.243-0.666]; P = 0.0004). Whether salvage surgery was performed for local or distant recurrence was not associated with OS. Patients who had a longer disease-free interval (≥12 months) had better progression-free survival after salvage surgery than those who had a shorter interval (HR, 0.437 [95%CI, 0.244-0.783]; P = 0.0055).

Conclusions

We recommend that salvage surgery be considered for selected patients with local or distant recurrence of RP LMS.

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TGFβ pathway deregulation and abnormal phospho-SMAD2/3 staining in hereditary cerebral hemorrhage with amyloidosis-Dutch type

Abstract

Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is an early onset hereditary form of cerebral amyloid angiopathy (CAA) pathology, caused by the E22Q mutation in the amyloid β (Aβ) peptide. Transforming Growth Factor β1 (TGFβ1) is a key player in vascular fibrosis and in the formation of angiopathic vessels in transgenic mice. Therefore we investigated whether the TGFβ pathway is involved in HCHWA-D pathogenesis in human postmortem brain tissue from frontal and occipital lobes. Components of the TGFβ pathway were analyzed with quantitative RT-PCR. TGFβ1 and TGFβ Receptor 2 (TGFBR2) gene expression levels were significantly increased in HCHWA-D in comparison to the controls, in both frontal and occipital lobes. TGFβ-induced pro-fibrotic target genes were also upregulated. We further assessed pathway activation by detecting phospho-SMAD2/3 (pSMAD2/3), a direct TGFβ down-stream signaling mediator, using immunohistochemistry. We found abnormal pSMAD2/3 granular deposits specifically on HCHWA-D angiopathic frontal and occipital vessels. We graded pSMAD2/3 accumulation in angiopathic vessels and found a positive correlation with the CAA load independent of the brain area. We also observed pSMAD2/3 granules in a halo surrounding occipital vessels, which was specific for HCHWA-D. The result of this study indicates an upregulation of TGFβ1 in HCHWA-D, as was found previously in AD with CAA pathology. We discuss the possible origins and implications of the TGFβ pathway deregulation in the microvasculature in HCHWA-D. These findings identify the TGFβ pathway as a potential biomarker of disease progression and a possible target of therapeutic intervention in HCHWA-D. This article is protected by copyright. All rights reserved.

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Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury

ABSTRACT

Objective: Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analysed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI.

Methods: Highly selective ELISAs were used to analyse N-terminally intact and truncated Aβ40 and Aβ42, as well as Aβ oligomers/protofibrils, in human brain tissue, surgically resected from severe TBI patients (n=12; mean age 49.5 ± 19 years) due to life-threatening brain swelling/haemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n=5), to post-mortem tissue of neurologically intact subjects (n=4) and to cortical biopsies obtained at surgery for idiopathic normal pressure hydrocephalus patients (iNPH; n=4).

Results: The levels of Aβ40 and Aβ42 were not elevated by TBI. The levels of Aβ oligomers/protofibrils in TBI were similar to those in the significantly older AD patients and increased compared to neurologically intact and iNPH controls (P<0.05). Moreover, TBI patients carrying the AD risk genotype Apolipoprotein E epsilon3/4 (APOE ε3/4; n=4) had increased levels of Aβ oligomers/protofibrils (P<0.05) and of both N-terminally intact and truncated Aβ42 (P<0.05) compared to APOE ε3/4-negative TBI patients (n=8). Neuropathological analysis showed insoluble Aβ aggregates (commonly referred to as Aβ plaques) in three TBI patients, all of whom were APOE ε3/4 carriers.

Interpretation: Soluble intermediary Aβ aggregates form rapidly after TBI, especially among APOE ε3/4 carriers. Further research is needed to determine whether these aggregates aggravate the clinical short- and long-term outcome in TBI. This article is protected by copyright. All rights reserved.

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Sleep quality subtypes predict health-related quality of life in children

Publication date: July 2017
Source:Sleep Medicine, Volume 35
Author(s): Christopher A. Magee, Laura Robinson, Carol Keane
ObjectiveThis paper aimed to investigate whether distinct sleep quality subtypes predicted health-related quality of life in a nonclinical sample of children.MethodsThis paper utilized data from two waves of the Longitudinal Study of Australian Children, a cohort study that follows a representative population of children in Australia. This paper examined data from Waves 4 and 5 of the LSAC (covering the period 2010–2012) and included 3974 children aged 10–11 years at Wave 4 (51.4% male). Multiple dimensions of sleep quality were assessed using a combination of child- and parent-reported measures. Health-related quality of life (HRQOL) was assessed through the Pediatric Quality of Life Inventory.ResultsLatent class analysis indicated six distinct sleep quality classes in children, namely good sleep, moderate sleep quality, mild sleep disturbances, short sleep, long sleep, and disordered sleep. In general, the disordered sleep and minor sleep disturbance classes had poorer HRQOL, which worsened over time. The long sleep and moderate sleep quality classes also showed some decreases in HRQOL over time.ConclusionsThis study demonstrates that there are distinct sleep quality subtypes in children that could have implications for HRQOL. These findings may inform future strategies to promote improved sleep and HRQOL in children.

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Validation of the Lithuanian Version of the Speech Handicap Index

The objective is to study the cultural adaptation and validation of the Speech Handicap Index (SHI) questionnaire to the Lithuanian language.

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Recovery From Heavy Vocal Loading in Women With Different Degrees of Functional Voice Problems

This is a longitudinal, case-control clinical trial.

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The Exploration of an Objective Model for Roughness With Several Acoustic Markers

In voice assessment, the evaluation of voice quality is a major component in which roughness has received wide acceptance as a major subtype of abnormal voice quality. The aim of the present study was to develop a new multivariate acoustic model for the evaluation of roughness.

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Upper-airway flow limitation and transcutaneous carbon dioxide during sleep in normal pregnancy

Sleep during pregnancy involves a physiological challenge to provide sufficient gas exchange to the fetus. Enhanced ventilatory responses to hypercapnia and hypoxia may protect from deficient gas exchange, but sleep-disordered breathing (SDB) may predispose to adverse events. The aim of this study was to analyze sleep and breathing in healthy pregnant women compared to non-pregnant controls, with a focus on CO2 changes and upper-airway flow limitation.

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Efficacy and safety of almorexant in adult chronic insomnia: a randomized placebo-controlled trial with an active reference

The orally active dual OX1R and OX2R antagonist, almorexant, targets the orexin system for the treatment of primary insomnia. This clinical trial assessed the effect of almorexant on sleep maintenance and other sleep endpoints, and its safety and tolerability in adults.

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Gray matter abnormalities of the dorsal posterior cingulate in sleep walking

This study aimed to determine whether voxel-based analysis of T1 weighted magnetic resonance imaging (MRI) and diffusion tensor imaging is able to detect alterations of gray and white matter morphometry as well as measures of mean diffusivity and fractional anisotropy in patients with non-rapid eye movement parasomnia.

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Postnatal treatment of women with narcolepsy who choose to breastfeed-time for a reappraisal?

Primum non-nocere, (first, do no harm) a loose translation of a line from the Hippocratic oath that most physicians take upon graduating from medical school, should be a guiding principle of medical practice. [1] In obstetrics and pediatrics, this philosophy was fashionable in terms of advising postpartum women concerning nursing who were on long-term medications. Generally, this was not to mix pharmaceutical agents with breastfeeding. This was a no win dilemma (ie, a Sophie’s Choice) for many women who were being treated for chronic illnesses; choosing between taking their medications and forgoing nursing, and therefore, depriving their baby of the benefits of breast milk (or to nurse and stop their medications, and run the risk of exacerbating their underlying condition).

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Sex and age differences in the associations between sleep behaviors and all-cause mortality in older adults: results from the National Health and Nutrition Examination Surveys

Our aim was to examine sex- and age-specific relationships of sleep behaviors with all-cause mortality rates.

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The relationship between weight change and daytime sleepiness: the Sleep Heart Health Study

Through a causal framework, we aim to assess the association between weight change and daytime sleepiness, and the role of obstructive sleep apnoea (OSA) in this relationship.

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Cytokine storm and sepsis disease pathogenesis

Abstract

Infectious diseases are a leading cause of death worldwide. Sepsis is a severe clinical syndrome related to the host response to infection. The severity of infections is due to an activation cascade that will lead to an autoamplifying cytokine production: the cytokine storm. Cytokines are a broad category of relatively small proteins (<40 kDa) that are produced and released with the aim of cell signaling. Our understanding of the processes that trigger this tremendous amount of cytokine production has made dramatic progress over the last decades, but unfortunately, these findings could not translate yet into effective treatments; so far, all clinical trials targeting cytokine production or effects failed. This review aims to summarize the pathophysiology of the cytokine storm; to describe the type, effects, and kinetics of cytokine production; and to discuss the therapeutic challenges of targeting cytokines. New promising therapeutic strategies focusing on the endothelium, as a source and a target of cytokines, are described.

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Molecular pathogenesis of viral hemorrhagic fever

Abstract

The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation. Among these cell populations, monocytes and macrophages are proposed to produce damaging inflammatory cytokines, while infected dendritic cells fail to undergo proper maturation, potentially impairing adaptive immunity. Uncontrolled virus replication and accompanying inflammatory responses are thought to promote vascular leakage and coagulopathy. However, the specific molecular pathways that underlie these features of VHF remain poorly understood. The arenavirus Lassa virus and the flavivirus yellow fever virus exhibit similar molecular pathogenesis suggesting common underlying mechanisms. Because non-human primate models that closely mimic VHF are available for Ebola, Lassa, and yellow fever viruses, we propose that comparative molecular studies using these models will yield new insights into the molecular underpinnings of VHF and suggest new therapeutic approaches.

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Genetics of rheumatoid arthritis susceptibility, severity, and treatment response

Abstract

A decade after the first genome-wide association study in rheumatoid arthritis (RA), a plethora of genetic association studies have been published on RA and its clinical or serological subtypes. We review the major milestones in the study of the genetic architecture of RA susceptibility, severity, and response to treatment. We set the scientific context necessary for non-geneticists to understand the potential clinical applications of human genetics and its significance for a stratified approach to the management of RA in the future.

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New fronts emerge in the influenza cytokine storm

Abstract

Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described as a “cytokine storm,” associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33—amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here, we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.

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Gillies temporal incision: an alternate approach to superficial temporal artery biopsy

The main complications of a biopsy of the superficial temporal artery using a standard preauricular approach include scars on the face, weakness of the temporal branch of the facial nerve, and the possible harvest of a disease-free segment of artery. We describe a modification of the Gillies temporal approach, which when placed at the junction of the frontal and parietal branch can be easily modified to harvest either branch. It avoids scarring to the face as it is hidden within the hairline. The incision placed with specific measurements and palpation is easily reproducible.

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Re: Wrong tooth extraction: an examination of ‘Never Event’ data

I read with interest the recent study by Pemberton et al concerning wrong tooth extractions.1 In many ways it is surprising that extraction of a wrong tooth is the most common wrong site event, given that many of these procedures are done under local anaesthesia and the patient often knows which tooth or teeth are to be removed. Although the authors were not able to comment on the causes, as with many cases of human error, they are likely to be multifactorial. Ineffective communication is widely regarded as one of the highest causes of error.

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The Exploration of an Objective Model for Roughness With Several Acoustic Markers

Publication date: Available online 29 May 2017
Source:Journal of Voice
Author(s): Ben Barsties v. Latoszek, Marc De Bodt, Ellen Gerrits, Youri Maryn
ObjectiveIn voice assessment, the evaluation of voice quality is a major component in which roughness has received wide acceptance as a major subtype of abnormal voice quality. The aim of the present study was to develop a new multivariate acoustic model for the evaluation of roughness.MethodIn total, 970 participants with dysphonia and 88 participants with normal voice were included. Concatenated voice samples of continuous speech and sustained vowel [a:] were perceptually judged on roughness severity. Acoustic analyses were conducted on the voiced segments of the continuous speech sample plus sustained vowel as well. A stepwise multiple linear regression analysis was applied to construct an acoustic model of the best acoustic predictors. Concurrent validity, diagnostic accuracy, and cross-validation were verified on the basis of Spearman correlation coefficient (rs), several estimates of the receiver operating characteristics plus the likelihood ratio, and iterated internal cross-correlations.ResultsSix experts were included for perceptual analysis based on acceptable rater reliability. Stepwise multiple regression analysis yielded a 12-variable acoustic model. A marked correlation was identified between the model and the perceptual judgment (rs = 0.731, P = 0.000). The cross-correlations confirmed a high comparable degree of association. However, the receiver operating characteristics and likelihood ratio results showed the best diagnostic outcome at a threshold of 2.92, with a sensitivity of 51.9% and a specificity of 94.9%.ConclusionsCurrently, the newly developed roughness model is not recommended for clinical practice. Further research is needed to detect the acoustic complexity of roughness (eg, multiplophonia, irregularity, chaotic structure, glottal fry, etc).

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Recovery From Heavy Vocal Loading in Women With Different Degrees of Functional Voice Problems

Publication date: Available online 29 May 2017
Source:Journal of Voice
Author(s): Susanna Whitling, Viveka Lyberg-Åhlander, Roland Rydell
Type of StudyThis is a longitudinal, case-control clinical trial.ObjectivesThis study aims to track recovery time following a vocal loading task (VLT) imposing vocal fatigue and to explore if patients with functional dysphonia (FD) are worse affected by vocal loading, and if these patients take longer than others to recover.MethodsFifty (n = 50) female participants in four vocal subgroups on a spectrum of everyday vocal loading and functional voice complaints, including n = 20 patients with FD, took part in a clinical VLT, inflicting vocal fatigue through loud speech in ambient noise. Short-term recovery was explored through self-assessment of unspecified voice problems every 15 minutes for 2 hours following loading. Long-term recovery was tracked through self-assessments of specific voice symptoms during 3 days following vocal loading. Effects of heavy vocal loading were evaluated through voice recordings, long-time-average spectrum, perceptual assessments, and assessments of digital imaging performed pre- and post vocal loading.ResultsPatients with FD did not return to baseline for unspecified voice problems within 2 hours of vocal loading and were worse affected by vocal loading than other groups. Women with high everyday vocal loading with no voice complaints identified vocal loading more evidently than other groups. Long-term recovery took 7–20 hours for all groups.ConclusionsShort-term recovery is slower for patients with FD and these patients are worse affected by a VLT than others.

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Validation of the Lithuanian Version of the Speech Handicap Index

Publication date: Available online 29 May 2017
Source:Journal of Voice
Author(s): Ruta Pribuisiene, Vykintas Liutkevicius, Kipras Pribuisis, Virgilijus Uloza
ObjectiveThe objective is to study the cultural adaptation and validation of the Speech Handicap Index (SHI) questionnaire to the Lithuanian language.MethodsCultural adaptation and validation of the translated Lithuanian version of the SHI (SHI-LT) was performed as described by the Scientific Advisory Committee of the Medical Outcomes Trust. The SHI-LT was completed by 46 patients after total laryngectomy and by 60 healthy subjects of the control group. Validity and reliability of the SHI-LT were evaluated.ResultsThe SHI-LT showed a statistically significant high internal consistency and test-retest reliability (Cronbach's α = 0.96–0.98). Good validity of SHI-LT was reflected by statistically significant (P < 0.001) difference between the mean scores of the patients and control groups (74.7 ± 26.9 and 5.5 ± 6.5, respectively). No age or gender dependence of SHI-LT was found (P > 0.05). Receiver operating characteristic test indicated that SHI-LT scores exceeding 17.0 points (cutoff value) distinguish patients from healthy controls, with a sensitivity of 97.8% and specificity of 95.0%.ConclusionSHI-LT is considered to be a valid and reliable speech assessment tool for Lithuanian-speaking patients after laryngectomy.

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Local effects of epidermal growth factor on the wound healing in esophageal anastomosis: An experimental study

Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Ayşe Bülbül Adam, Mustafa Yaşar Özdamar, Hacı Hasan Esen, Engin Günel
ObjectiveIn this study with the experimental model of primary repair of esophageal atresia(EA), we investigated the effects of the epidermal growth factor(EGF) on wound healing in the anastomosis of EA.Materials and methodsForty rabbits that were performed a resection of a 1-cm segment of the cervical esophagus followed by the end-to-end anastomosis were divided into four groups. Group I (7-day group) and III (21-day group), the control groups, had no EGF applied to the anastomosis. In group II (7-day group) and group III (21-day group), all around the anastomoses were locally covered with 100 μg/kg EGF. Group 1, 2 and 3, 4 were sacrificed on the 7th and 21st day, respectively. We investigated and compared with bursting pressure, vascularization around the anastomotic line by histopathology, inflammation, and fibroblast granulation as well as hydroxyproline level by biochemical.ResultsNo significant difference was found at vascularization and inflammation between all of the groups (p > 0.05). Considering the critical parameters of the groups, at bursting pressure difference was found between group 1 and 2 as well as 3 and (p < 0.05). At fibroblast granulation and hydroxyproline level, no difference was found between group 1 and 2 (p > 0.05) but the difference between group 3 and 4 (p < 0.05).ConclusionEGF might be useful in preventing anastomotic leakage of esophageal atresia in primary anastomosis of esophageal atresia by accelerating wound healing process and increasing the stability of the anastomotic line.

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An evaluation of oxidative and nitrosative stress in children-who-stutter and its relationship to severity

Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Nagihan Bilal, Selman Sarica, Ergül Belge Kurutas, Ebru Findikli, İsrafil Orhan, Erkan Oner, Adem Doganer, Saime Sagiroglu, Mehmet Akif Kilic
ObjectivesAlthough there has been much research into the cause of stuttering, it has not yet been fully clarified. There is known to be a close relationship between stress severity and stuttering. The aim of this study was to evaluate the levels of oxidative and nitrosative stress by comparing a stuttering group and a control group. It was also aimed to evaluate the relationship between the oxidative and nitrosative stress levels and the severity of the stutter.MethodsThe study included a total of 80 individuals, comprising a study group of 40 and a control group of 40. The severity of the stutter in the patient group was evaluated with the Stuttering Severity Instrument 3 (SSI). Blood samples were taken from both the patient and control groups and malondialdehyde (MDA), 3 nitrotyrosine (3-NT), nitric oxide (NO), catalase (CAT), and superoxide dismutase (SOD) concentrations were examined.ResultsIn the stuttering patients, MDA, 3-NT, NO, CAT, and SOD activity were determined to be statistically significantly higher than those of the control group (all p:0.001). In the ROC analysis, there was good diagnostic value for NO, with the area under the curve as 1.0. A direct, positive, statistically significant correlation was determined between SSI points and MDA values (r = 0.317, p = 0.046).ConclusionThe results of the study showed that the oxidative and nitrosative stress levels of the stuttering patients were higher than those of the control group. With 100% sensitivity and specificity, it is thought that NO in particular could be important for the diagnosis and treatment of these patients. As the severity of the stutter increased, so there was an increase in MDA, suggesting that MDA is important in stuttering.

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Airway stenting in a child with spondyloepiphyseal dysplasia congenita: 13-Year survival

Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Raffaella Nenna, Fabio Midulla, Laura Masi, Giacomo Maria Bacci, Antonella Frassanito, Roberto Baggi, Maria Luisa Brandi, Stefano Avenali, Lorenzo Mirabile, Paola Serio
We describe the case of a boy with spondyloepiphyseal dysplasia congenita. At birth, he experienced severe respiratory distress necessitating tracheotomy. Endoscopy done because mechanical ventilation failed to resolve desaturations disclosed severe tracheo-bronchomalacia. A Polyflex silicone stent was placed in the trachea (replaced by Y-Dumon stent) and 2 Palmaz metallic stents in the mainstem bronchi (overlapped with 2 Jomed stents 5 years later). Airway stenting guaranteed a suitable respiratory status and allowed a child who was expected to die at birth, to reach 13.5 years old in good conditions.

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The Exploration of an Objective Model for Roughness With Several Acoustic Markers

Recovery From Heavy Vocal Loading in Women With Different Degrees of Functional Voice Problems

Validation of the Lithuanian Version of the Speech Handicap Index

Rho-associated protein kinase 2 (ROCK2): a new target of autoimmunity in paraneoplastic encephalitis

Onconeural antibodies are associated with cancer and paraneoplastic encephalitis. While their pathogenic role is still largely unknown, their high diagnostic value is undisputed. In this study we describe the ...

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Evolving Concepts in Atopic Dermatitis

Abstract

Purpose of Review

Tremendous advances have been made in the field of atopic dermatitis in the past 5 years. We will explore developments in burden of disease, co-morbidities, pathogenesis, prevention, and management.

Recent Findings

The tremendous burden moderate to severe atopic dermatitis (AD) places on families from a medical, psychosocial, and financial perspective has been characterized. Epidemiologic studies have identified intriguing new associations beyond the well-characterized “atopic march” of food allergies, asthma, and hay fever. Studies of primary prevention have gained traction including the remarkable impacts of early emollient therapy. Basic advances have simultaneously elucidated the nature of atopic inflammation, setting the stage for an explosion of new potential therapeutic targets. After a fallow period of nearly 15 years without a substantial therapeutic advance, this year has already seen two new FDA-approved treatments for AD.

Summary

AD has a tremendous impact on quality of life with an underappreciated burden of disease; there are important newly described co-morbidities including ADHD and anemia; new insights into etio-pathogenesis have paved the way for novel topical therapies like crisaborole, and new systemic interventions like dupilumab.

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T Cells in Allergic Asthma: Key Players Beyond the Th2 Pathway

Abstract

Asthma is a common chronic lung disease that affects 300 million people worldwide. It causes the airways of the lungs to swell and narrow due to inflammation (swelling and excess mucus build-up in the airways) and airway constriction (tightening of the muscles surrounding the airways). Atopic asthma is the most common form of asthma, and is triggered by inhaled allergens that ultimately promote the activation of the Th2-like T cells and the development of Th2-mediated chronic inflammation. Different subsets of T cells, including T follicular helper cells, tissue-resident T, cells and Th2 effector cells, play different functions during allergic immune response. Dendritic cells (DCs) are known to play a central role in initiating allergic Th2-type immune responses and in the development of the T cell phenotype. However, this function depends on the complex interaction with other cells of the immune system and determines whether the response to environmental allergens will be one of tolerance or allergic inflammation. This review discusses cell interactions leading to the initiation and maintenance of allergic Th2-type immune responses, particularly those associated with allergic asthma.

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In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells

Abstract

Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34⁺ progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 10⁸ pDC can be produced from a typical cord blood unit. Blocking the aryl hydrocarbon receptor (AHR) pathway significantly increased the yield of pDC. When compared to pDC isolated from peripheral blood, in vitro differentiated pDC (ivD-pDC) exhibited an increased capacity to induce NK cell-mediated killing of ALL. Although ivD-pDC produced lower amounts of IFN-α than peripheral blood pDC upon TLR activation, they produced more IFN-λ2, known to play a critical role in the induction of anti-tumoral NK cell functions. Both TLR-9 and TLR-7 ligands triggered pDC-induced NK cell activation, offering the possibility to use any clinical-grade TLR-7 or TLR-9 ligands in future clinical trials. Finally, adoptive transfer of ivD-pDC cultured in the presence of an AHR antagonist cured humanized mice with minimal ALL disease. Collectively, our results pave the way to clinical-grade production of sufficient numbers of human pDC for innate immunotherapy against ALL and other refractory malignancies.

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The Cisplatin Total Dose and Concomitant Radiation in Locoregionally Advanced Head and Neck Cancer: Any Recent Evidence for Dose Efficacy?

Opinion statement

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Overview of the 8th Edition TNM Classification for Head and Neck Cancer

Opinion Statement

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Effect of different levels of intermittent hypoxia on autophagy of hippocampal neurons

Abstract

Purpose

The current study was carried out to assess the effects of different levels of intermittent hypoxia (IH) on autophagy in hippocampal neurons, and explore the extent, frequency and duration of IH for researching on autophagy in hippocampal neurons.

Methods

Hippocampal neurons were exposed to different levels of IH. To analyze the oxygen level of neuronal exposure environment, we detected the oxygen concentration in the chamber by O₂ analyzer, and monitored the oxygen partial pressure (PO₂), carbon dioxide partial pressure (PCO₂), and pH in the culture media by blood gas analyzer. After 4-, 8-, and 12-h IH, the morphology and quantity of neurons, as well as the expression of light chain 3 (LC3)-II positive dots were observed by immunofluorescence. The expression of apoptosis marker protein cleaved caspase-3 and autophagy marker protein LC3 were examined by western blotting.

Results

The oxygen level in the chamber and the neuronal culture media both reached to the values set previously in three models. The level of cleaved caspase-3 and LC3 had no significant changes in IH-1 group. The morphology and quantity had no significant changes, while the levels of cleaved caspase-3 and LC3 were both increased in IH-2 group. The quantity of neurons was reduced significantly, and the chromatin condensed and nuclei fragmented in IH-3 group.

Conclusions

The effects of varying degrees of IH on autophagy in hippocampal neurons are different. The IH model, hypoxia phase (1.5% O₂, 5% CO₂, and balance N₂) for 5 min and reoxygenation phase (21% O₂, 5% CO₂, and balance N₂) for 10 min, may be the best condition for researching on autophagy in hippocampal neurons.

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Glycated hemoglobin and sleep apnea syndrome in children: beyond the apnea–hypopnea index

Abstract

Purpose

Snoring and obstructive sleep apnea syndrome (OSA) are frequent conditions in pediatrics. Glycated hemoglobin (Hb_A1C) is a useful homeostatic biomarker of glycemia and may reflect alterations deriving from sleep breathing disorders. The aim of this study was to relate the severity of OSA with blood Hb_A1C levels in children.

Methods

A descriptive observational study in snoring patients was performed. All patients underwent a sleep study and classified either as simple snorers (apnea–hypopnea index; AHI ≤ 1 episodies/h) or as OSA patients (AHI > 1 episodes/h). In the following morning, a blood glycemic profile (fasting glucose, insulin, Hb_A1C, and the HOMA index) was performed to every individual.

Results

A total of 48 patients were included. Hb_A1C levels were shown to be increased in the moderate OSA (AHI > 5 episodes/h) group (5.05 ± 0.25 vs. 5.24 ± 0.29%; p = 0.019). Significant correlations were found between Hb_A1C values and AHI (r = 0.345; p = 0.016) and also with oxygen desaturation index (r = 0.40; p = 0.005). Correlations remained significant after adjusting by age and body mass index. The AHI-associated change in Hb_A1C was 13.4% (p = 0.011).

Conclusions

In the pediatric population, Hb_A1C is a biomarker associated with OSA severity, and this relationship is age- and obesity-independent. The fact that this association was observed in snoring patients could help the physician in the distinction between those patients affected with OSA and those with simple snoring. Therefore, Hb_A1C measurement could play a major role in the diagnosis and the management of the syndrome.

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Cognitive tasks promote automatization of postural control in young and older adults

Publication date: September 2017
Source:Gait & Posture, Volume 57
Author(s): Alexandra Potvin-Desrochers, Natalie Richer, Yves Lajoie
Researchers looking at the effects of performing a concurrent cognitive task on postural control in young and older adults using traditional center-of-pressure measures and complexity measures found discordant results. Results of experiments showing improvements of stability have suggested the use of strategies such as automatization of postural control or stiffening strategy. This experiment aimed to confirm in healthy young and older adults that performing a cognitive task while standing leads to improvements that are due to automaticity of sway by using sample entropy. Twenty-one young adults and twenty-five older adults were asked to stand on a force platform while performing a cognitive task. There were four cognitive tasks: simple reaction time, go/no-go reaction time, equation and occurrence of a digit in a number sequence. Results demonstrated decreased sway area and variability as well as increased sample entropy for both groups when performing a cognitive task. Results suggest that performing a concurrent cognitive task promotes the adoption of an automatic postural control in young and older adults as evidenced by an increased postural stability and postural sway complexity.

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Paradigm shift of therapeutic management of brain metastases in EGFR-mutant non-small cell lung cancer in the era of targeted therapy

Abstract

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations commonly present brain metastases (BM) at the time of NSCLC diagnosis or during the clinical course. Conventionally, the prognosis of BM has been extremely poor, but the advent of EGFR-tyrosine kinase inhibitors (TKIs) has drastically improved the prognosis in these patients. Despite the presence of the blood–brain barrier, EGFR-TKIs have dramatic therapeutic effects on both BM and extracranial disease. In addition, recent systemic chemotherapies reportedly play a role in controlling BM. These treatment modalities can potentially replace whole brain radiotherapy (WBRT) to prevent or delay neurocognitive decline. Therefore, how to utilize these treatments is one issue. The other issue is what kind of treatment is best for recurrence after TKI therapy. Recent reports have shown a positive effect of a combination therapy of EGFR-TKI and radiotherapy on BM. Although neurocognitive decline is underscored when WBRT is considered, a survival benefit from WBRT has been proven especially in the potential long survivors with good prognostic index, especially disease-specific graded prognostic index (DS-GPA). In this review, treatment strategy including chemotherapeutic agents and radiotherapy is discussed in terms of risk–benefit balance in conjunction with DS-GPA.

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In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells

Abstract

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Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy

Abstract

The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described “vaccinal effect” exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets (“conventional” CD4⁺ and CD8⁺, FOXP3⁺CD25^bright Treg, and “innate-like” CD56⁺) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4⁺ T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4⁺ T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4⁺ and CD8⁺ T cell subsets associated with higher frequencies of IFNγ⁺ and GrzB⁺ cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.

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Ethical considerations of neuro-oncology trial design in the era of precision medicine

Abstract

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

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Laparoscopic cholecystectomy for cholelithiasis in children with sickle cell disease

Abstract

Patients with sickle cell disease (SCD) suffer from an increased incidence of gallstone formation due to hemolysis of sickled red blood cells; this leads to an increased level of bilirubin in secreted bile that becomes a nidus for pigment stone formation. Laparoscopic cholecystectomy (LC) is considered a standard operative procedure for gallstone disease mainly due to lower postoperative wound complaints, faster recovery, better postoperative cosmetic results, shorter hospital stay, and earlier return to work. Although numerous studies have been published addressing both the advantages and complications of LC in acute calcular cholecystitis, there is still limited evidence concerning the safety and efficacy of LC for the management of cholelithiasis in pediatric patients with SCD, and controversies remain unresolved. In this review, we aim to comprehensively study the available literature and propose evidence-based practice recommendations for the optimal management of gallstones in pediatric SCD patients. The current practice differs greatly depending on the prevalence of SCD in a particular geographic area. We acknowledge the limited number of patients reported, the lack of randomized control trials addressing the practice of specific recommendations, and the need for further evidence-based studies.

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Anatomy of the cutaneous lymphatic system of the trunk: a clinico-anatomical study of 90 cutaneous melanomas

Abstract

Purpose

The cutaneous lymphatic system of the trunk is a complex network, the anatomical knowledge of which remains unclear. The lymphatic system plays a major role in the dissemination of lymphophilic cancers like melanomas. The aim of this study was to improve our knowledge, optimize the care of patients with cutaneous tumors of the trunk, and to use our clinical experience of the topography of pathologic lymph nodes related to cutaneous melanomas and depicted by lymphoscintigraphy.

Materials and methods

This prospective study included 90 consecutive patients who had primary resection of cutaneous melanoma of the trunk between June 2011 and January 2015. All patients had lymphatic mapping by lymphoscintigraphy, followed by sentinel lymph node procedure. We compared data of lymphatic imaging (lymphoscintigraphy and SPECT-CT) and surgery. We divided the trunk into 36 regions based on cutaneous anatomical landmarks to determine the topography of the lymphatic system for each tumor.

Results

Our study showed cutaneous lymphatic drainage of melanomas of the trunk in 16 different areas. This drainage could be single or multiple. We observed that drainage could be controlateral in medial regions of the trunk, and lymphatic pathway could be retrograde. This drainage could be bilateral for medial regions and mainly into axillary areas for regions above L1 level. Posterior regions of the trunk had more diversity of drainage areas than anterior regions.

Conclusions

Cutaneous lymphatic drainage of the trunk was not limited to axillary and inguinal areas, showed interindividual variability, and was single or multiple, unilateral or bilateral, and unpredictable.

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Ultrasound biomechanical anatomy of the soft structures in relation to the ulnar nerve in the cubital tunnel of the elbow

Abstract

Background

Chronic ulnar nerve entrapment worsened by elbow flexion is the most common injury, but rare painful conditions may also be related to ulnar nerve instability. The posterior bundle of the medial collateral ligament (pMCL) and the retinaculum, respectively form a soft floor and a ceiling for the cubital tunnel. The aim of our study was to dynamically assess these soft structures of the cubital tunnel focusing on those involved in the biomechanics of the ulnar nerve.

Methods

Forty healthy volunteers had a bilateral ultrasonography of the cubital tunnel. Elbows were scanned in full extension, 45° and 90°, and maximal passive flexion. Morphological changes of the nerve and related structures were dynamically assessed on transverse views.

Results

Both the pMCL and the retinaculum tightened with flexion. During elbow flexion, the tightening of the pMCL superficially moved the ulnar nerve remote from the osseous floor of the retroepicondylar groove. A retinaculum was visible in all 69 tunnels with stable nerves (86.3%), tightened in flexion, but absent in 11 tunnels with unstable nerves (13.7%). The retinaculum was fibrous in 60 elbows and muscular in nine, the nine muscular variants did not significantly influence the biomechanics of stable nerves. Stable nerves flattened in late flexion between the tightened pMCL and retinaculum, whereas unstable nerves transiently flattened when translating against the anterior osseous edge of the groove.

Conclusion

The retinaculum and the pMCL are key structures in the biomechanics of the ulnar nerve in the cubital tunnel of the elbow.

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Effect of different levels of intermittent hypoxia on autophagy of hippocampal neurons

Abstract

Purpose

Methods

Results

Conclusions

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Glycated hemoglobin and sleep apnea syndrome in children: beyond the apnea–hypopnea index

Abstract

Purpose

Methods

Results

Conclusions

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Nu Vert-Bleu II

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Trichosporon asahii and Candida tropicalis together growing green-bluish in a chromogenic medium as a cut-out that resembles the famous Matisse's artwork Nu Bleu II. They can be found colonizing healthy skin as in the cut-out and, although both are yeast and opportunistic pathogens causing both...

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Assessment of airway compression on chest radiographs in children with pulmonary tuberculosis

Abstract

Background

Because small, pliable paediatric airways are easily compressed by enlarged lymph nodes, detection of radiographic airway compression might be an objective criterion for diagnosing pulmonary tuberculosis.

Objective

To investigate the frequency and inter-observer agreement of airway compression on chest radiographs in children with pulmonary tuberculosis compared to those with a different lower respiratory tract infection.

Materials and methods

Chest radiographs of children with suspected pulmonary tuberculosis were read by two readers according to a standardised format and a third reader when there was disagreement. Radiographs of children with proven pulmonary tuberculosis were compared to those with a different lower respiratory tract infection. We evaluated frequency and location of radiographic airway compression. Findings were correlated with human immunodeficiency virus (HIV) status and age. We assessed inter-observer agreement using kappa statistics.

Results

We reviewed radiographs of 505 children (median age 25.9 months, interquartile range [IQR] 14.3–62.2). Radiographic airway compression occurred in 54/188 (28.7%) children with proven pulmonary tuberculosis and in 24/317 (7.6%) children with other types of lower respiratory tract infection (odds ratio [OR] 4.9; 95% confidence interval [CI] 2.9–8.3). A higher frequency of radiographic airway compression occurred in infants (22/101, or 21.8%) compared to older children (56/404, or 13.9%; OR 1.7; 95% CI 1.0–3.0). We found no association between airway compression and HIV infection. Inter-observer agreement ranged from none to fair (kappa of 0.0–0.4).

Conclusion

There is a strong association between airway compression on chest radiographs and confirmed pulmonary tuberculosis. However this finding’s clinical use as an objective criterion for diagnosis of pulmonary tuberculosis in children is limited by poor inter-observer agreement.

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Bioavailability of Metals at a Southeastern Brazilian Coastal Area of High Environmental Concern Under Anthropic Influence: Evaluation Using Transplanted Bivalves ( Nodipecten nodosus ) and the DGT Technique

Abstract

Metals are commonly determined in aquatic organisms, primarily using bivalves to provide important data on their bioavailability. The technique of diffusive gradients in thin films (DGTs) has also been employed to assess the concentration of metals in freshwater and marine environments, determining their lability. The present work evaluated and compared the labile and bioavailable concentrations of Cd, Co, Cu, Mn, Ni and Pb in seawater from Ilha Grande Bay, RJ, using DGT and transplanted bivalves (Nodipecten nodosus), respectively. The scallops and DGTs were immersed in water at three sampling locations within the bay from July to September 2012 (winter campaign) and from December 2012 to February 2013 (summer campaign). The metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). DGT technique was successfully used to determine the concentrations of metals in waters, except for Pb when short deployment times were used. All metals were determined using transplanted bivalves (N. nodosus), but pre-exposure to Cd was evident, which made the interpretation of the data for this analyte difficult. The data on metal lability in Ilha Grande Bay waters obtained from the DGT technique were correlated with the metal bioavailability determined in the soft tissues of the transplanted N. nodosus for Co, Cu, Mn, Ni and Pb. This is the first evaluation of this type for this area of high environmental concern. Both techniques revealed that Náutico was the location with the highest concentration of metals in the study area.

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Radiologically occult medulloblastoma with hydrocephalus: case report

Abstract

Introduction

There have been no reports of occult medulloblastoma nor noncommunicating hydrocephalus due to radiologically occult brain tumors. Herein, we report radiologically occult medulloblastoma with noncommunicating hydrocephalus.

Case report

A 3-year-old boy presented with macrocephaly, visual field constriction, and papilledema. Neuroimagings showed enlargement of the ventricles without any mass lesions. The CT cisternography did not show influx of the contrast into the ventricles, which suggested local cerebrospinal fluid (CSF) circulatory disturbance at the outlet of the fourth ventricle. Due to possible obstructive nature of hydrocephalus, endoscopic third ventriculostomy (ETV) was performed. Three months after the ETV, he presented with repeated vomiting. Neuroimagings showed a 3-cm fourth ventricular mass with progressive hydrocephalus. Surgical resection was performed, which revealed the pathology was medulloblastoma.

Conclusion

We report the case of radiologically occult medulloblastoma which was demonstrated radiologically in the follow-up period of ETV for noncommunicating hydrocephalus of uncertain etiology. This is the first description of a radiologically occult medulloblastoma and also the first description of an occult brain tumor with noncommunicating hydrocephalus. The occult brain tumor may be included in the etiology of hydrocephalus.

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The influence of ancient Greek thought on fifteenth century anatomy: Galenic influence and Leonardo da Vinci

Abstract

Leonardo da Vinci (1452–1519) can be called one of the earliest contributors to the history of anatomy and, by extension, the study of medicine. He may have even overshadowed Andreas Vesalius (1514–1564), the so-called founder of human anatomy, if his works had been published within his lifetime. While some of the best illustrations of their time, with our modern knowledge of anatomy, it is clear that many of da Vinci’s depictions of human anatomy are inaccurate. However, he also made significant discoveries in anatomy and remarkable predictions of facts he could not yet discover with the technology available to him. Additionally, da Vinci was largely influenced by Greek anatomists, as indicated from his ideas about anatomical structure. In this historical review, we describe da Vinci’s history, influences, and discoveries in anatomical research and his depictions and errors with regards to the musculoskeletal system, cardiovascular system, nervous system, and other organs.

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Antenatal management of fetal neurosurgical diseases

Abstract

The advance in the imaging tools during the pregnancy (ultrasound and magnetic resonance) allowed the early diagnose of many fetal diseases, including the neurological conditions. This progress brought the neurosurgeons the possibility to propose treatments even before birth. Myelomeningocele is the most recognized disease that can be treated during pregnancy with a high rate of success. Additionally, this field can be extended to other conditions such as hydrocephalus and encephaloceles. However, each one of these diseases has nuances in the diagnostic evaluation that should fit the requirements to perform the fetal procedure and overbalance the benefits to the patients. In this article, the authors aim to review the neurosurgical aspects of the antenatal management of neurosurgical conditions based on the experience of a pediatric neurosurgery center.

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Comprehensive analysis of Iranian reports of pediatric central nervous system tumors

Abstract

Purpose

Iran lacks a national registry reporting the data of central nervous system (CNS) tumors in children. Consequently, treatment success and failure rates are unknown, and a centralized system for disease-management recommendations does not exist.

Methods

To critically evaluate the current state of pediatric CNS tumor studies and reporting in Iran, we performed an extensive retrospective analysis of all known reports identified with multiple search engines.

Results

Of 409 initially retrieved articles, we evaluated 123 matching our inclusion criteria. We further narrowed these reports to 74 by excluding studies pertaining to adult patients only, non-CNS tumors, or brain metastases. We also excluded studies that were performed outside of Iran or that did not contain relevant data from our analysis. We divided the remaining studies into those describing exclusively pediatric patients (3484 patients) and those describing mixed populations of adults and children (18,641 patients). In total, our analysis included 22,125 patients.

Conclusions

We identified many limitations in the reporting of studies describing the treatment or prevalence of CNS tumors in children in Iran. Our results may guide future efforts in Iran to improve the care for children with CNS tumors and may provide a valuable template for other comprehensive country- and disease-specific retrospective analyses.

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Improving efficacy and efficiency through the implementation of a new organisational model in a Radiation Oncology Department

Abstract

Background

To evaluate a new organisational model, “process management” (PM), implemented in the Hospital Universitario Virgen de la Victoria (HUVV) compared with traditional models used in other Radiation Oncology Departments (RODs), in terms of efficacy and efficiency.

Methods

The study period ranged from September 2011 to August 2012. Efficacy was assessed, comparing the number of patients attended in first consultation and treated per month, average waiting time from referral to first visit and average waiting time from first visit to treatment. Data were collected from two public hospitals in Andalusia: the HUVV and another Public Hospital in Andalusia (PHA1). Efficiency was assessed comparing the costs per patient attended in first visit and treated at HUVV in 2012 compared with those of a second Public Hospital in Andalusia (PHA2) for 2008. The number of sessions saved using hypofractionation versus classical schemes during the year 2012 in HUVV was estimated, and the money saved was calculated.

Results

In the efficacy analysis, we found significant differences in the average waiting time for first visit, start of treatment, and the number of patients seen and treated annually. After calculating the total cost generated in the ROD, the efficiency analysis showed a lower cost per patient attended in first visit (EUR 599.17) and per patient treated (EUR 783.50), with a saving of 6035 sessions using hypofractionated schemes.

Conclusions

Process management in an ROD reduces time, both to first medical visit and to treatment initiation, allowing an optimisation of linear accelerator (LINAC) capacity.

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Improving efficacy and efficiency through the implementation of a new organisational model in a Radiation Oncology Department

Abstract

Background

Methods

Results

Conclusions

Process management in an ROD reduces time, both to first medical visit and to treatment initiation, allowing an optimisation of linear accelerator (LINAC) capacity.

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Πληροφορίες

Δευτέρα 29 Μαΐου 2017

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