Objective To describe the epidemiological characteristics and survival of desmoplastic melanoma of the head and neck (DMHN) and discuss the factors influencing survival variation among DMHN, DM of other sites (DMnHN), and conventional melanoma of the head and neck (CMHN). Study Design Retrospective cohort study. Setting Surveillance, Epidemiology, and End Results (SEER) database (years 1992-2013). Subjects and Methods Incidence and survival data for 1095 patients with DMHN, 1139 patients with DMnHN, and 40,257 patients with CMHN were obtained. Kaplan-Meier and Cox proportional hazards regression models were used to calculate survival outcomes. Results Patients with DMHN were diagnosed at greater Breslow thickness ( P < .001), stage ( P < .001), and Clark's level ( P < .001) compared to DMnHN and CMHN. Kaplan-Meier survival analysis demonstrated disease-specific survival (DSS) at 5 and 10 years for DMHN to be 80.5% and 74.7%, respectively, compared with 89.1% and 86%, respectively, for DMnHN and 88.1% and 83%, respectively, for CMHN (log-rank test; P < .001). On multivariate Cox regression analysis, age at diagnosis ( P < .001), Breslow depth >4.00 mm ( P = .006), lymph node status ( P < .001), and presence of ulceration ( P < .001) were found to be independent predictors of DSS for DMHN. Conclusion The increasing incidence and poor survivability of DMHN compared to DMnHN and CMHN are parsimoniously explained by the later stage of disease and depth of invasion at diagnosis, highlighting the importance of improved diagnosis and awareness of DMHN.

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Pulmonary dysfunction is a prevalent and potentially debilitating late effect of pediatric cancer treatment. We postulated that age, as a surrogate for respiratory developmental status, might be associated with vulnerability to pulmonary injury. Materials and Methods: Sixty-one children treated with lung radiation at our institution who had undergone a pulmonary function test (PFT) between 1995 and 2016 were analyzed. Data collection included age at diagnosis and treatment, radiation dose and location, spirometry, and plethysmography results. PFTs were normalized according to age, sex, height, and ethnicity, and transformed into standardized z-scores. Obstructive disease was defined as forced expiratory volume in 1 second z score/forced vital capacity z score < À1.645, restrictive as total lung capacity z score < e1.645, and abnormal diffusion as diffusing capacity of the lung for carbon monoxide z score < À1.645. We determined the incidence of PFT abnormalities in our population and estimated the relative risk of developing pulmonary abnormalities using models adjusted for age. Results: At a mean age of 24 years (range, 12-31) and time from radiation of 9 years (range, 1-20), the cumulative incidence of any pulmonary abnormality was 34.4%. Among patients with an abnormal PFT, diffusing and restrictive abnormalities were most common (57.1% and 52.4%). When stratified by age at radiation treatment, 66.7% of patients <5 years had a PFT abnormality, compared with 47.6% for aged 5 to 13 and 20.6% for patients >13. Compared with patients >13 years, those <5 years and 5 to 13 years at radiation treatment had a significantly increased risk of an abnormal PFT with an odds ratio of 7.71 (95% confidence interval, 1.17, 51.06) and 3.51 (95% confidence interval, 1.06, 11.57), respectively (P <. 035). Furthermore, this association remained when examining each type of abnormality (P > .05). Conclusions: PFT abnormalities were common among our cohort of childhood cancer survivors treated with lung radiation. Younger age at treatment is associated with an increased risk of developing pulmonary dysfunction, presumably owing to developmental immaturity.

Leg pain and discomfort are common complaints in any primary physician's clinic. Two common causes of pain or discomfort in legs are nocturnal leg cramps (NLC) and restless leg syndrome (RLS). NLC present as painful and sudden contractions mostly in part of the calf. Diagnosis of NLC is mainly clinical and sometimes involves investigations to rule out other mimics. RLS is a condition characterized by the discomfort or urge to move the lower limbs, which occurs at rest or in the evening/night. The similarity of RLS and leg cramps poses the issue of errors in diagnosing and differentiating the two. In this paper we review the pathopysiology of each entity and their diagnosis as well as treatment. The two conditions are then compared to appreciate the differences and similarities. Finally, suggestions are recommended for complete assessment.

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Alexander disease (AxD) is a rare and fatal neurodegenerative disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). In this report, a mouse model of AxD ( GFAP Tg ; Gfap +/ R236H ) was analyzed that contains a heterozygous R236H point mutation in murine Gfap as well as a transgene with a GFAP promoter to overexpress human GFAP. Using label-free quantitative proteomic comparisons of brain tissue from GFAP Tg ; Gfap +/ R236H versus wild-type mice confirmed upregulation of the glutathione metabolism pathway and indicated proteins were elevated in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which had not been reported previously in AxD. Relative protein-level differences were confirmed by a targeted proteomics assay, including proteins related to astrocytes and oligodendrocytes. Of particular interest was the decreased level of the oligodendrocyte protein, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Ugt8), since Ugt8 -deficient mice exhibit a phenotype similar to GFAP Tg ; Gfap +/ R236H mice ( e.g. , tremors, ataxia, hind-limb paralysis). In addition, decreased levels of myelin-associated proteins were found in the GFAP Tg ; Gfap +/ R236H mice, consistent with the role of Ugt8 in myelin synthesis. Fabp7 upregulation in GFAP Tg ; Gfap +/ R236H mice was also selected for further investigation due to its uncharacterized association to AxD, critical function in astrocyte proliferation, and functional ability to inhibit the anti-inflammatory PPAR signaling pathway in models of amyotrophic lateral sclerosis (ALS). Within Gfap + astrocytes, Fabp7 was markedly increased in the hippocampus, a brain region subjected to extensive pathology and chronic reactive gliosis in GFAP Tg ; Gfap +/ R236H mice. Last, to determine whether the findings in GFAP Tg ; Gfap +/ R236H mice are present in the human condition, AxD patient and control samples were analyzed by Western blot, which indicated that Type I AxD patients have a significant fourfold upregulation of FABP7. However, immunohistochemistry analysis showed that UGT8 accumulates in AxD patient subpial brain regions where abundant amounts of Rosenthal fibers are located, which was not observed in the GFAP Tg ...

Many women physicians have blazed trails and played instrumental roles in advancing the field of Advanced Heart Failure (AHF), Mechanical Circulatory Support (MCS), and cardiac transplantation to its current recognition and glory. In contrast to other areas of cardiology, women have played an integral role in the evolution and emergence of this sub-specialty. Although the ceiling had been broken much later for women cardiothoracic (CT) surgeons in the field of AHF, the ingress of women into surgical fields particularly CT surgery was stonewalled due to pervasive stereotyping. The constancy, commitment, and contributions of women to the field of AHF and MCS cannot be minimized in bringing this field to the forefront of innovation both from technological aspect as well as in redesigning of healthcare delivery models. Integrated team-based approach is a necessity for the optimal care of MCS patients and forced institutions to develop this approach when patients with durable left ventricular assist devices (LVAD) began discharging from the hospitals to local communities. Women in various roles in this field played a pivotal role in developing and designing patient centered care and coordination of care in a multidisciplinary manner. While embracing the challenges and turning them to opportunities, establishing partnerships and finding solutions with expectations to egalitarianism, women in this field continue to push boundaries and subscribe to the continued evolution of the field of AHF and advanced cardiac therapies.

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