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Κυριακή 8 Ιουλίου 2018

Head and Neck Cancer Survivorship Care: A Review of the Current Guidelines and Remaining Unmet Needs

Opinion statement

A larger proportion of patients with head and neck cancers (HNC) are now surviving, constituting up to 3% of all cancer survivors. This is likely due in part to the increase in HPV-related oropharyngeal cancers affecting younger individuals and with a better prognosis and to the improved outcomes of other HNCs as well over the last two decades. Most studies have previously been focusing on improving risk stratification, treatment and disease-related outcomes. Over the last decade, there has been an evolving interest in the field of survivorship care. Despite the collaborative efforts from a multidisciplinary team in managing cancer and treatment-related side-effects and in improving survivors' overall quality of life (QOL), it has been reported that up to 60–65% of patients have at least one unmet need. The purpose of this article is to review current guidelines for HNC survivorship care and identify areas of unmet need. Over the last 5 years, multiple groups have published guidelines describing survivorship care issues and their possible management. Although a very comprehensive and informative first initiative, multiple issues need to be further evaluated. These include how to best support patients and their partners' fear of cancer recurrence, to provide coordinated care among all physicians, to identify and meet patients' needs in local multidisciplinary teams and to institute measures to ensure every individual's access to high-quality patient-centred care. Furthermore, experts may consider engaging in further dialog with primary care physicians (PCP) to improve sharing of survivorship care. More should be learned about PCPs' comfort levels in providing such care and whether further steps are required to facilitate a seamless. Transition of care and accessibility to specialized care as needed.



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Access to new drugs for rare disorders in Canada [Letters]



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Validation and refinement of a clinical decision rule for the use of computed tomography in children with minor head injury in the emergency department [Research]

BACKGROUND:

There is uncertainty about which children with minor head injury need to undergo computed tomography (CT). We sought to prospectively validate the accuracy and potential for refinement of a previously derived decision rule, Canadian Assessment of Tomography for Childhood Head injury (CATCH), to guide CT use in children with minor head injury.

METHODS:

This multicentre cohort study in 9 Canadian pediatric emergency departments prospectively enrolled children with blunt head trauma presenting with a Glasgow Coma Scale score of 13–15 and loss of consciousness, amnesia, disorientation, persistent vomiting or irritability. Phys icians completed standardized assessment forms before CT, including clinical predictors of the rule. The primary outcome was neurosurgical intervention and the secondary outcome was brain injury on CT. We calculated test characteristics of the rule and used recursive partitioning to further refine the rule.

RESULTS:

Of 4060 enrolled patients, 23 (0.6%) underwent neurosurgical intervention, and 197 (4.9%) had brain injury on CT. The original 7-item rule (CATCH) had sensitivities of 91.3% (95% confidence interval [CI] 72.0%–98.9%) for neurosurgical intervention and 97.5% (95% CI 94.2%–99.2%) for predicting brain injury. Adding "≥ 4 episodes of vomiting" resulted in a refined 8-item rule (CATCH2) with 100% (95% CI 85.2%–100%) sensitivity for neurosurgical intervention and 99.5% (95% CI 97.2%–100%) sensitivity for brain injury.

INTERPRETATION:

Among children presenting to the emergency department with minor head injury, the CATCH2 rule was highly sensitive for identifying those children requiring neurosurgical intervention and those with any brain injury on CT. The CATCH2 rule should be further validated in an implementation study designed to assess its clinical impact.



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Maternal peanut consumption and risk of peanut allergy in childhood [Commentary]



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Recommendations on screening for asymptomatic bacteriuria in pregnancy [Guideline]



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Sexual harassment rampant in science and worst in medicine, says report [News]



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A 63-year-old returned traveller with fever, rash, hepatitis and eosinophilia [Practice]



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The collaborative chronic care model for mental health should be implemented in Canada [Letters]



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Facing grief [Humanities]



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Trump administration shutters clinical guidelines database [News]



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Healthy-vaccinated effect [Letters]



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Medical students risk disappointment when applying to both Canada and US for residency [News]



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The hygiene hypothesis: immunological mechanisms of airway tolerance

Eline Haspeslagh | Ines Heyndrickx | Hamida Hammad | Bart N Lambrecht

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BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells

Abstract
The transcription factor BCL11B is essential for development of the nervous and the immune system, and Bcl11b deficiency results in structural brain defects, reduced learning capacity, and impaired immune cell development in mice. However, the precise role of BCL11B in humans is largely unexplored, except for a single patient with a BCL11B missense mutation, affected by multisystem anomalies and profound immune deficiency. Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B. Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency. Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo. A further frameshift mutation was transmitted from a similarly affected mother. Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient. Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice. Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice. Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. In addition, we suggest that missense mutations affecting specific sites within zinc-finger domains might result in distinct and more severe clinical outcomes.

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Use of an Intravascular Temperature Control Catheter for Rewarming of Hypothermic Trauma Patients with Ongoing Hemorrhagic Shock After Combined Damage Control Thoracotomy and Laparotomy: A Case Series

Publication date: Available online 8 July 2018

Source: Injury

Author(s): Byron C. Drumheller, Deborah M. Stein, Thomas M. Scalea

Abstract
Background

Correction of hypothermia is a key component of the resuscitation of critically injured patients with hemorrhagic shock who require damage control surgery. External rewarming methods may not be sufficient in this population, while extracorporeal techniques lack widespread feasibility. Intravascular catheter-based temperature modulation is increasingly being employed in different critically ill patient populations but has not been described as part of a damage control resuscitation strategy in trauma patients.

Methods

We retrospectively reviewed the medical records of all patients admitted to our multi-trauma intensive care unit from July 1, 2015 – December 31, 2017 in whom an intravascular temperature control catheter (IVTCC) was employed for rewarming from hypothermia during the immediate postoperative resuscitation of continued hemorrhage after undergoing combined damage control thoracotomy and laparotomy for trauma. All patients received baseline treatment with active external rewarming modalities and inline fluid/blood warmers. Core temperature values over the first 24 hours of hospital admission were analyzed. Efficacy (rewarming rate) and safety (associated adverse events) of the IVTCC system were determined.

Results

Three patients (age 22 ± 4.6, 100% male, 100% torso gunshot wounds with prehospital cardiac arrest) meeting the inclusion criteria were treated with the IVTCC system during the study period. Temperature at the start of rewarming using the IVTCC ranged from 30.1–35.5°C. Despite ongoing severe hemorrhagic shock (24-hour ICU blood product requirement: 104 ± 44 units), a mean rewarming rate of 1.04 ± 0.63°C/hour was achieved. One patient suffered an uncomplicated catheter-associated deep vein thrombosis. Two of the 3 patients survived to hospital discharge with intact cognitive function.

Conclusions

Use of an IVTCC may be a minimally-invasive, practical, and effective method for rewarming critically ill trauma patients with ongoing hemorrhagic shock after multi-cavitary damage control surgery. Further studies are needed to compare this technology with currently available rewarming methods.



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Integrating Extended Focused Assessment with Sonography for Trauma (eFAST) in the Initial Assessment of Severe Trauma: Impact on the Management of 756 Patients

Publication date: Available online 8 July 2018

Source: Injury

Author(s): Laurent Zieleskiewicz, Raphaelle Fresco, Gary Duclos, François Antonini, Calypso Mathieu, Sophie Medam, Coralie Vigne, Marion Poirier, Pierre-Hugues Roche, Pierre Bouzat, François Kerbaul, Ugo Scemama, Thierry Bège, Pascal Alexandre Thomas, Xavier Flecher, Emmanuelle Hammad, Marc Leone

Abstract
Background

Before total body computed tomography scan, an initial rapid imaging assessment should be conducted in the trauma bay. It generally includes a chest x-ray, pelvic x-ray, and an extended focused ultrasonography assessment for trauma. This initial imaging assessment has been poorly described since the increase in the use of ultrasound. Therefore, our study aimed to evaluate the diagnostic accuracy and therapeutic impact of this initial imaging work-up in severe trauma patients. A secondary aim was to assess the therapeutic impact of a chest x-ray according to the lung ultrasonography findings.

Methods

Patients with severe trauma who were admitted directly to our level 1 trauma center were consecutively included in this retrospective single center study. The diagnostic accuracy, therapeutic impact, and appropriate decision rate were calculated according to the initial assessment results of the whole body computed tomography scan and surgery reports.

Results

Among the 1,315 trauma patients admitted, 756 were included in this research. Lung ultrasound showed a higher diagnostic accuracy for haemothorax and pneumothorax cases than the chest x-ray. Sensitivity and specificity of the abdominal ultrasound to detect intraperitoneal effusion were 70% and 96%, respectively. The initial assessment had a therapeutic impact in 76 (10%) of the patients, including 16 (2%) immediate laparotomies and 58 (7%) chest tube insertions. The pelvic x-ray had no therapeutic impact, and when the lung ultrasound was normal, the chest x-ray had a therapeutic impact of only 0.13%. Combining the chest x-ray and lung ultrasound allowed adequate management of all the pneumothorax and haemothorax cases. Only one of the 756 patients had initial management that was judged as inappropriate. This patient had a missed pelvic disjunction with active retroperitoneal bleeding, and underwent an inappropriate immediate laparotomy.

Conclusions

In our cohort, the initial imaging assessment allowed appropriate decisions in 755 of 756 patients, with a global therapeutic impact of 10%. The pelvic x-ray had a minimal therapeutic impact, and in the patients with normal lung ultrasounds, the chest x-ray marginally affected the management of our patients. The potential consequences of abandoning systematic chest and pelvic x-rays should be investigated in future randomized prospective studies.



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Involvement of Flavonoids from the Leaves of Carya cathayensis Sarg. in Sirtuin 1 Expression in HUVEC Senescence

Atherosclerosis is the commonest cause of death in the world and one of the most important processes that occurs with increasing age because it is accompanied by progressive endothelial dysfunction. Recent studies demonstrated that Sirtuin 1 (SIRT1) might potentially affect cell senescence. However, the effect of SIRT1 on the regulation of human umbilical vein endothelial cell (HUVEC) senescence with total flavonoids (TFs) has not been addressed previously. This study investigated how SIRT1 functions in the process of HUVEC senescence when TFs are present and identified the potential molecular mechanisms involved. Using a model of HUVEC senescence induced by angiotensin II, TFs pretreatment reduced the percentage of senescence-associated β-galactosidase (SA-β-gal) cells and p53 mRNA expression. The level of SIRT1 protein and E2F1 decreased during HUVEC senescence and could be partially recovered when cells were coincubated with TFs, while the levels of proteins p53 and p21 increased during cell senescence and diminished in response to the TFs treatment. When coincubated with 20 mM nicotinamide, the results with SA-β-gal-positive cells and the expression of SIRT1, E2F1, p53, and p21 were contrary to that obtained with only TFs pretreatment. The data indicate that the TFs exert their effect on HUVEC senescence through SIRT1.

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Short-Term and Long-Term Effects of Riding for Children with Cerebral Palsy Gross Motor Functions

Aim. To evaluate the effects of riding for beginners (short-term) and advanced (long-term) riders with cerebral palsy on their whole mobility. The study involved 15 subjects (two girls and eleven boys). The subjects were aged from 3 to 19 years (8.73 years ± 5.85). All of the subjects had been diagnosed with a spastic form of cerebral palsy. The duration of the participation differed as follows: the advanced subjects had been riding for 1-4 years (2.66 years ± 1.16), while the beginners have been riding for two weeks (10 sessions). Group I (advanced riders) consisted of eight subjects (7 boys and 1 girl) who had therapy sessions regularly once a week and differed only in terms of the duration of their participation in the experiment. Group II (beginners) consisted of seven children (1 girl and 6 boys) who participated in only 10 riding sessions. All of the subjects were assessed according to the Gross Motor Function Measure (GMFM) and Gross Motor Function Classification System for CP (GMFCS) both before the investigation and after it. Conclusions. Ten riding lessons did not have an influence on the beginner riders with cerebral palsy gross motor functions and their gross motor function level did not change. However, in half of the advanced riders with cerebral palsy, the gross motor functions significantly improved. Meanwhile, the level of the performance of the gross motor skills in the four advanced riders increased, but this difference was not statistically significant.

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Incidental Finding of Left Ventricular False Chamber: Diagnostic and Therapeutic Implications

We present the case of a 75-year-old man with incidental finding of a left ventricular false chamber at echocardiography. A multimodality imaging approach including also transesophageal echocardiography and cardiac magnetic resonance imaging allowed to better characterize the lesion and identify it as a pseudoaneurysm. Surgery showed an infective aetiology, which is rare, due to the finding of a large abscess in the cavity.

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Corrigendum to “Proteomic-Based Approaches for the Study of Cytokines in Lung Cancer”



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Antimycobacterial Activity and Safety Profile Assessment of Alpinia galanga and Tinospora cordifolia

Tuberculosis (TB) remains a common deadly infectious disease and worldwide a major health problem. The current study was therefore designed to investigate the in vitro antimycobacterial activity of different extracts of Alpinia galanga and Tinospora cordifolia. Moreover, a safety assessment for both plants was carried out. Dichloromethane and ethanolic extracts of each plant were examined against H37Rv INH-sensitive and resistant INH strains of Mycobacterium tuberculosis. The safety assessment of both plants has been performed through in vivo acute and chronic toxicity studies in animal model. Body weight, food consumption, water intake, organ's weight, and haematological and biochemical parameters of blood and serum were evaluated. The extracts of A. galanga and T. cordifolia produced significant and dose-dependent inhibitory activity with maximum effect of 18-32% at 50 μg/ml against both strains of M. tuberculosis. No effect on the body weight or food and water consumption was observed but A. galanga caused significantly an increase in the relative weight of the heart, liver, spleen, and kidney. Haematological studies of both plants revealed a slight but significant fall in the RBC and WBC level as well as haemoglobin and platelets. In addition, A. galanga extracts increased significantly liver enzymes and bilirubin and glucose.

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Critical Contextual Elements in Facilitating and Achieving Success with a Person-Centred Care Intervention to Support Antipsychotic Deprescribing for Older People in Long-Term Care

Antipsychotic and other tranquilising medicines are prescribed to help care staff manages behaviour in one-quarter of older people living in Australian long-term care homes. While these medicines pose significant health risks, particularly for people with dementia, reliance on their use occurs when staff are not educated to respond to resident behaviour using nonpharmacological approaches. The Halting Antipsychotic use in Long-Term care (HALT) single-arm study was undertaken to address this issue with 139 people 60 years and over with behaviours of concern for staff living in 24 care homes. A train-the-trainer approach delivered person-centred care education and support for 22 HALT (nurse) champions and 135 direct care staff, dementia management education for visiting general practitioners (GP) and pharmacists, use of an individualised deprescribing protocol for residents, and awareness-raising for the resident's family. The HALT champions completed open-ended questionnaires and semistructured interviews to identify the contextual elements they considered most critical to facilitating, educating care staff, and achieving success with the study intervention. They reported that person-centred approaches helped care staff to respond proactively to resident behaviours in the absence of antipsychotic medicines; the champions considered that this required strong managerial support, champion empowerment to lead change, reeducation of care staff, and the cooperation of families and GPs.

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A Rare and Potentially Catastrophic Infection: Primary Intestinal Aspergillosis—Case Report in an HIV Patient

Aspergillus species are ubiquitous in nature; however, infection is uncommon, except in immunocompromised or immunosuppressed hosts. We present the case of a 71-year-old woman with a history of human immunodeficiency virus infection who presented with fever, weight loss, and diarrhea, posteriorly diagnosed with intestinal aspergillosis after examination of a segmental enterectomy piece. The diagnosis was made postmortem once the patient died after fast and progressive deterioration in the postoperative period.

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The Appearance of The Infraorbital Canal and Infraorbital Ethmoid (Haller’s) Cells on Panoramic Radiography of Edentulous Patients

Objectives. The aim of the study is to detect the prevalence and the characteristics of infraorbital canal and Haller's cells on panoramic radiography of edentulous patients. Methods. The study group comprised 291 panoramic radiographs of edentulous patients. Radiographs were interpreted for the visibility and characteristics of infraorbital canal and Haller's cells. For classification of infraorbital canal, a method based on the image characteristics of the border of the canal (Types I, II, and III) was used. Haller's cells were grouped according to the number and the shape of loculations. Results. Infraorbital canal was observed in 246 (84.6%) radiographs. The most prevalent of the observed canals were Type III for both sides (39.9 % for right and 32.3% for left side). The visibility of Haller's cells was 23.7%. The frequencies of Haller's cells' visibility were approximately equal for both genders. There is no significant difference between genders for the visibility of infraorbital canal and Haller's cells. Conclusions. The surgeons, implantologists, and radiologists should take into consideration infraorbital canal and Haller's cell for planning implant surgery of maxillary anterior region and undefined orofacial pain for edentulous patients.

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Retracted: The Copper Radioisotopes: A Systematic Review with Special Interest to 64Cu



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