Routine removal of the carotid sheath as part of neck dissection is unnecessary if grossly uninvolved as seen intra-operatively

The aim of this research was to determine the pathologic invasion of the carotid sheath (CS) when found grossly uninvolved during surgery, in patients undergoing neck dissection for head and neck squamous cell carcinoma (HNSCC). A prospective study was undertaken in 70 consecutive patients with biopsy proven HNSCC, without prior history of any treatment, undergoing neck dissection, in whom the CS was found grossly uninvolved intra-operatively, were included. A total of 80 neck dissections were performed. Supra-omohyoid neck dissections for clinically N0 neck and appropriate modified radical neck dissections for clinically N+ neck were carried out. 129 CS were dissected separately and thoroughly examined by well trained head and neck pathologists for tumour infiltration and the presence of lymphatic tissue. On microscopic examination, 27 patients were N0 status and the remaining 43 (61.4%) had at least one metastatic lymph node (N+). None of 129 CS specimens show the presence of normal lymphatic tissue or metastatic tumour deposits. The authors think that avoiding resection of the CS in the absence of gross invasion by nodal disease is possible without jeopardising oncologic safety. A preserved CS might offer protection to the important neurovascular structures and reduce significant morbidity.     

A comparison of vitamin D activity in paired non-malignant and malignant human breast tissues

Links between a low vitamin D status and an increased risk of breast cancer have been observed in epidemiological studies. These links have been investigated in human tissue homogenates and cultured cell lines. We have used non-malignant, malignant and normal reduction mammoplasty breast tissues to investigate the biological and metabolic consequences of the application of vitamin D to intact ex vivo human breast tissue. Tissues were exposed to 1α,25(OH)(2)D(3) (1,25D; active metabolite) and 25(OH)D (25D; pre-metabolite). Changes in mRNA expression and protein expression after vitamin D exposure were analysed. Results indicate that while responses in normal and non-malignant breast tissues are similar between individuals, different tumour tissues are highly variable with regards to their gene expression and biological response. Collectively, malignant breast tissue responds well to active 1,25D, but not to the inactive pre-metabolite 25D. This may have consequences for the recommendation of vitamin D supplementation in breast cancer patients.     

A case of an atypically large proximal 15q deletion as cause for Prader–Willi syndrome arising from a de novo unbalanced translocation

We describe an 11 month old female with Prader–Willi syndrome (PWS) resulting from an atypically large deletion of proximal 15q due to a de novo 3;15 unbalanced translocation. The 10.6 Mb deletion extends from the chromosome 15 short arm and is not situated in a region previously reported as a common distal breakpoint for unbalanced translocations. There was no deletion of the reciprocal chromosome 3q subtelomeric region detected by either chromosomal microarray or FISH. The patient has hypotonia, failure to thrive, and typical dysmorphic facial features for PWS. The patient also has profound global developmental delay consistent with an expanded, more severe, phenotype.     

Increased risk of pneumonia among ventilated patients with traumatic brain injury: every day counts!

Background

Patients with traumatic brain injury (TBI) frequently require mechanical ventilation (MV). The objective of this study was to examine the association between time spent on MV and the development of pneumonia among patients with TBI.

Materials and methods

Patients older than 18 y with head abbreviated injury scale (AIS) scores coded 1–6 requiring MV in the National Trauma Data Bank 2007–2010 data set were included. The study was limited to hospitals reporting pneumonia cases. AIS scores were calculated using ICDMAP-90 software. Patients with injuries in any other region with AIS score >3, significant burns, or a hospital length of stay >30 d were excluded. A generalized linear model was used to determine the approximate relative risk of developing all-cause pneumonia (aspiration pneumonia, ventilator-associated pneumonia [VAP], and infectious pneumonia identified by the International Classification of Disease, Ninth Revision, diagnosis code) for each day of MV, controlling for age, gender, Glasgow coma scale motor score, comorbidity (Charlson comorbidity index) score, insurance status, and injury type and severity.

Results

Among the 24,525 patients with TBI who required MV included in this study, 1593 (6.5%) developed all-cause pneumonia. After controlling for demographic and injury factors, each additional day on the ventilator was associated with a 7% increase in the risk of pneumonia (risk ratio 1.07, 95% confidence interval 1.07–1.08).

Conclusions

Patients who have sustained TBIs and require MV are at higher risk for VAP than individuals extubated earlier; therefore, shortening MV exposure will likely reduce the risk of VAP. As patients with TBI frequently require MV because of neurologic impairment, it is key to develop aggressive strategies to expedite ventilator independence.     

Synthesis and in vitro anti-proliferative evaluation of naphthalimide–chalcone/pyrazoline conjugates as potential SERMs with computational validation

A series of naphthalimide-chalcone/pyrazoline conjugates was prepared and evaluated for their anti-breast cancer potential against estrogen responsive, i.e. MCF-7 (ER+), and triple-negative, i.e. MDA-MB-231 (ER−), cell lines. The structure-activity-relationship (SAR) was deduced based on the influence of linker length, substituents on the phenyl ring and the generated functionalities, on anti-proliferative activities. Docking simulations further delineate the type of interactions of the designed molecules with the selected targets. This report discloses the scope of triazole tethered naphthalimide-chalcone/pyrazoline conjugates as anti breast cancer agents.

Design, synthesis and anti-proliferative evaluation of naphthalimide–chalcone/pyrazoline conjugates.     

Early use of MRI improves diagnostic accuracy in young adults with stroke

ObjectivesThe misdiagnosis of acute ischemic stroke in young adults is a significant problem since patients may have many decades of potential disability. Also, proven therapies for acute stroke may not be administered if there is an initial misdiagnosis. We assessed the hypothesis that early use of MRI, arrival by ambulance, and presentation to a Primary Stroke Center (PSC) would be associated with a reduced rate of misdiagnosis.MethodsA prospective database of young adults (ages 16–49 years) with ischemic stroke (final diagnosis provided by vascular neurologists) was reviewed. We collected information on several variables, including age, race, arrival by ambulance, whether brain MRI was performed within 48 h, and initial presentation to a PSC. Variables were tested against emergency department (ED) misdiagnosis using univariate and multivariate methods.Results77 patients with a mean age of 37.9 years were reviewed. 48.3% of patients arrived by ambulance, 53.2% had a brain MRI within 48 h, and 23.4% initially presented to a PSC. The overall rate of ED misdiagnosis was 14.5%. In multivariate testing, performance of MRI within 48 h (p = 0.023) was associated with a lower rate of misdiagnosis and age < 35 years was linked with greater likelihood of misdiagnosis (p = 0.047).ConclusionsEarly performance of MRI leads to greater accuracy of stroke diagnosis in young adults presenting to the ED. Patients less than age 35 years have a greater risk of misdiagnosis. ED physicians and neurologists should consider early use of MRI in young adults with stroke-like deficits and diagnostic uncertainty.