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Epidemiology provides a powerful framework for characterizing exposure–disease relationships, but its utility for making causal inferences is limited because epidemiologic data are observational in nature and subject to biases stemming from undetected confounding variables and reverse causation. Mendelian randomization (MR) is an increasingly popular method used to circumvent these limitations. MR uses genetic variants, or instruments, as a natural experiment to proxy an exposure, thus allowing estimation of causal effects upon an outcome that are minimally affected by the usual biases present in epidemiologic studies. Notably, MR relies on three core assumptions related to the selection of the genetic instruments, and adherence to these assumptions must be carefully evaluated to assess the validity of the causal estimates. The goal of this review is to provide readers with a basic understanding of MR studies and how to read and evaluate them. Specifically, we outline the basics of how MR analysis is conducted, the assumptions underlying instrument selection, and how to assess the quality of MR studies. [ABSTRACT FROM AUTHOR]

Objective: Mendelian randomization (MR) has increasingly been utilized as a tool for establishing causal relations between modifiable exposures and osteoarthritis (OA). The goal of this review was to summarize available MR studies of OA that evaluate the causal role of modifiable risk factors on OA. Methods: This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) Extension for Scoping Reviews model. We performed a literature search for relevant studies published before December 2021 across multiple databases using the search terms "osteoarthritis" and ("Mendelian randomization" or "polygenic risk score"). We reported the MR estimates of causal associations between exposures and OA and then assessed methodologic quality of abstracted studies according to their efforts to validate the three key MR assumptions. Results: Our search identified 45 studies reporting on 141 exposure‐association analyses. All studies performed a formal instrumental variable analysis to estimate the causal effect of exposure on OA. Causal associations (P < 0.05) were reported in 60 of these analyses representing 36 unique publications, and MR‐Egger sensitivity analyses were performed in 45 of these analyses. MR studies provided support for causal associations of OA with increased levels of adiposity, coffee consumption, bone mineral density, and sleep disturbance, and decreased levels of serum calcium and low‐density lipoprotein cholesterol. Conclusion: These results highlight the potential benefits of weight reduction and improvement of sleep quality to reduce the risk of OA and call for a better understanding of the relations of coffee consumption and serum calcium to OA risk. [ABSTRACT FROM AUTHOR]

Objective: To describe the national rate of social risk factor screening adoption among federally qualified health centers (FQHCs), examine organizational factors associated with social risk screening adoption, and identify barriers to utilizing a standardized screening tool in 2020. Data Source: 2020 Uniform Data System, a 100% sample of all US FQHCs (N = 1375). Study Design: We used multivariable linear probability models to assess the association between social risk screening adoption and key FQHC characteristics. We used descriptive statistics to describe variations in screening tool types and barriers to utilizing standardized tools. We thematically categorized open‐ended responses about tools and barriers. Data Collection: None. Principal Findings: In 2020, 68.9% of FQHCs screened patients for any social risk factors. Characteristics associated with a greater likelihood of screening adoption included having high proportions of patients best served in a language other than English (18.8 percentage point [PP] increase, 95% CI: 6.0, 31.6) and being larger in size (10.3 PP increase, 95% CI: 0.7, 20.0). Having higher proportions of uninsured patients (14.2 PP decrease, 95% CI: −25.5, −0.3) and participating in Medicaid‐managed care contracts (7.3 PP decrease, 95% CI: −14.2, −0.3) were associated with lower screening likelihood. Among screening FQHCs, the Protocol for Responding to and Assessing Patients' Assets, Risks, and Experiences (PRAPARE) was the most common tool (47.1%). Among non‐screening FQHCs, common barriers to using a standardized tool included lack of staff training to discuss social issues (25.2%), inability to include screening in patient intake (21.7%), and lack of funding for addressing social needs (19.2%). Conclusions: Though most FQHCs screened for social risk factors in 2020, various barriers have prevented nearly 1 in 3 FQHCs from adopting a screening tool. Policies that provide FQHCs with resources to support training and workflow changes may increase screening uptake and facilitate engagement with other sectors. [ABSTRACT FROM AUTHOR]

Arrestins were discovered for their role in homologous desensitization of G‐protein‐coupled receptors (GPCRs). Later non‐visual arrestins were shown to regulate several signaling pathways. Some of these pathways require arrestin binding to GPCRs, the regulation of others is receptor independent. Here, we demonstrate that arrestin‐3 binds the E3 ubiquitin ligase parkin via multiple sites, preferentially interacting with its RING0 domain. Identification of the parkin domains involved suggests that arrestin‐3 likely relieves parkin autoinhibition and/or stabilizes the enzymatically active “open” conformation of parkin. Arrestin‐3 binding enhances ubiquitination by parkin of the mitochondrial protein mitofusin‐1 and facilitates parkin‐mediated mitophagy in HeLa cells. Furthermore, arrestin‐3 and its mutant with enhanced parkin binding rescue mitofusin‐1 ubiquitination and mitophagy in the presence of the Parkinson's disease‐associated R275W parkin mutant, which is defective in both functions. Thus, modulation of parkin activity via arrestin‐3 might be a novel strategy of anti‐parkinsonian therapy. [ABSTRACT FROM AUTHOR]

Background: Dermatologists and other providers play essential roles in managing the dermatologic care of pediatric patients. This study aims to identify patterns and elucidate factors associated with receiving dermatologic care in the United States. Methods: The National Ambulatory Medical Care Survey (NAMCS) was used to identify pediatric patients with dermatologic diagnoses from 2009 to 2015. Clinical and demographic information were evaluated, and visit diagnoses were stratified based on provider type (dermatologists vs. non‐dermatologists). Multivariate logistic regression analysis was used to identify key predictors of outpatient dermatology care for pediatric patients. National estimates of diagnoses were procured using weights provided within the NAMCS database to project disease incidence. Results: A total of 85,217,557 pediatric patients (survey‐weighted) were observed during the study period. Of the sampled patients, 29.3% were evaluated by dermatologists, while 70.7% were seen by non‐dermatology providers. Atopic dermatitis was the most common diagnosis encountered by dermatologists in ages 0–3 years, while unspecified contact dermatitis was the most common diagnosis reported by non‐dermatologists in all age groups. On multivariable logistic regression, ≥1 year of age, Caucasian race, private insurance versus Medicaid, residence in a metropolitan area, referral from another provider, and longer appointment wait time were associated with an increased likelihood of being evaluated by a dermatologist compared to a non‐dermatologist. Conclusions: Non‐dermatologists are responsible for the majority of pediatric dermatologic care. For pediatric patients, health disparities by race, insurance status, and rurality present significant challenges to being evaluated by a dermatologist. [ABSTRACT FROM AUTHOR]

Backgrounds: Telemedicine has been effective in the management of various medical conditions, however, there is limited knowledge of its use in head and neck oncosurveillance. This is of importance currently while trying to mitigate the risk of transmission during the COVID‐19 pandemic. This study aims to evaluate acceptability, satisfaction and perceptions of telemedicine technology among outpatients for head and neck oncologic surveillance. Methods: A cross‐sectional study was conducted for head and neck surgical oncology patients who attended telemedicine consultations between March and October 2020 at the Peter MacCallum Cancer Centre. Data on demographic, socioeconomic and acceptability variables was collected, utilizing Likert scale questions. The primary outcome measures were patient satisfaction and perceptions, while the secondary outcome was access to technology. Results: One hundred and fifteen patients were invited to participate, and 100 were included in the final analysis; 95% of patient's had a positive experience with telemedicine appointments and were willing to have future telemedicine appointments. Regional and rural patients were more accepting of telemedicine consultations, citing savings in travel time and the minimal disruption to normal day‐to‐day activities. All participants had access to telecommunication devices, with 63% having three or more devices. Issues identified include a lack of physical examination by clinician for 65% of participants and the inability to self‐examine for 88% of participants. Conclusion: The study demonstrates patients' acceptance of telemedicine appointments as a component of outpatient surveillance for head and neck surgical oncology. This has benefits during the COVID‐19 pandemic in addition to increasing accessibility for rural patients. [ABSTRACT FROM AUTHOR]

Background: Clinical voice assessment prior to thyroid and parathyroid surgery is essential, but the paradigm of indirect laryngoscopy (IDL), when indicated, has been challenged by the risk of aerosolised SARS‐Cov‐2 during endoscopy of the aerodigestive tract. Translaryngeal ultrasound (TLUS) to assess the vocal cords has been proposed as a safe, non‐invasive and sensitive alternative. The aim of this review was to verify TLUS as a viable tool for perioperative laryngeal assessment. Method: A literature review was performed using Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials and Scopus with the following search strategy: (vocal cord OR vocal fold OR glottic OR glottis OR vocal ligaments OR rima glottidis) AND (ultras* OR sonograph* OR echography OR echotomography). Results: Fifteen studies were included in this review. All studies compared TLUS to IDL in visualizing the vocal cords in adults. Ten studies compared pre‐operative TLUS to IDL where 50.6–100% of vocal cords were successfully visualized. Nine studies compared post‐operative TLUS to IDL and reported visualization between 39.6% and 100%. Pre‐ and post‐operative negative predictive values ranged from 60% to 100%. Conclusion: Whilst promising, successful visualization of the cords is limited by inter‐user variability, older age and male gender. Thus, we see the role of TLUS as an alternative to IDL in the post‐operative setting in the young patient following uncomplicated surgery with a normal voice on clinical examination, to confirm recurrent laryngeal nerve integrity while minimizing the risk of aerosolization. [ABSTRACT FROM AUTHOR]

Background: Post‐operative radiotherapy (PORT) volumes and dose to target structures likely influence swallowing function and quality of life following transoral robotic surgery (TORS). The aim of this study is to analyse disease control and swallowing outcomes in patients undergoing TORS for oropharyngeal squamous cell carcinoma (OPSCC) to determine the impact of omitting the primary site from the PORT treatment volume. Methods: Prospectively collected data from patients that underwent TORS between March 2013 and April 2021 were reviewed. Patients were categorized into three groups: (1) no PORT, (2) PORT to the neck alone or (3) PORT to the primary site and neck. Survival curves were generated according to the Kaplan–Meier method and swallowing was assessed using the Functional Oral Intake Scale, Public Status Scale Head and Neck, MD Anderson Dysphagia Inventory and feeding tube/gastrostomy dependence. Results: A total of 121 patients underwent TORS, of which 103 met inclusion criteria with a median follow up of 2.6 years. No patients developed local recurrence. The 3‐year regional control rates were 90%, 100% and 100% for groups 1, 2 and 3, respectively. Disease‐specific survival was 97% over the study period. Patients that received PORT to both the primary site and the neck (group 3) had worse swallowing outcomes at 12 months. Conclusion: Following TORS for OPSCC, avoiding PORT to the primary site, in appropriately selected patients, appears to be oncologically safe and is associated with superior swallowing outcomes. [ABSTRACT FROM AUTHOR]

Intra‐operative identification and preservation of parathyroid glands is an important but challenging aspect of thyroid surgery. Failure to do so may lead to transient or permanent hypocalcaemia, where the latter represents a serious complication causing life‐long morbidity. It would be beneficial, therefore, if a simple and reliable modality can be developed to assist in the identification of parathyroid glands intra‐operatively. The aim of this literature review is to provide an overview of intra‐operative modalities used to identify parathyroid glands with a particular focus on near‐infrared autofluorescence (NIRAF). Twenty‐seven studies were considered relevant in this literature review. Several modalities have been used to aid parathyroid gland identification, including Raman spectroscopy, indocyanine green angiography, and NIRAF. NIRAF technology allows parathyroid glands to spontaneously give off light (autofluorescence) when exposed to near‐infrared light at a wavelength of 785 nm, creating a contrast between tissues to allow intra‐operative differentiation. Studies utilising NIRAF technology were able to identify 76.3%–100% of parathyroid glands intra‐operatively. Furthermore, two randomised controlled trials comparing NIRAF and white light showed that the use of NIRAF was able to significantly increase the mean number of parathyroid glands detected and reduce the incidence of post‐operative hypocalcaemia. NIRAF is an emerging tool that has been shown to increase the number of intra‐operative parathyroid gland identification and reduce the rate of post‐operative hypocalcaemia in a safe and reproducible manner. Future trials are needed to evaluate the real‐life impact of NIRAF technology in outcomes of patients following thyroid surgery. [ABSTRACT FROM AUTHOR]

The relationship between morphological characteristics of the hip capsule and patient symptoms in the setting of femoroacetabular impingement (FAI) is undefined. In this study, patients with symptomatic FAI prospectively underwent 3T magnetic resonance (MR) imaging of the affected hip and completed the hip disability and osteoarthritis outcome score (HOOS) to determine the correlation between hip capsule anatomy and patient symptoms. Anterior hip capsule volume, posterior capsule volume, anterior‐posterior capsule volume ratio, and proximal‐distal volume ratio in the anterior capsule were quantified and measured using axial‐oblique intermediate‐weighted 3D fast spin echo MR images. A total of 35 patients (35 hips) were included for analysis (mean age: 30.6 years; mean body mass index [BMI]: 24.9 kg/m2; 57% male). The mean alpha angle was 62.2° ± 4.7°, the mean anterior hip capsule volume was 1705.1 ± 450.3 mm3, the mean posterior hip capsule volume was 1284.8 ± 268.5 mm3, the mean anterior to posterior capsule volume ratio was 1.1 ± 0.39, and the mean proximal to distal volume ratio of the anterior capsule was 0.65 ± 0.28. There was no correlation between age, gender, or BMI, and any hip capsule characteristics. Worse scores on the HOOS pain scale were correlated with increased anterior to posterior volume ratio (r = −.38; 95% confidence interval: −0.06 to −0.63). In conclusion, hip capsule morphology correlates with patient symptoms in the setting of FAI as increased anterior capsular volume, relative to posterior capsular volume, is associated with greater patient pain. [ABSTRACT FROM AUTHOR]

Objective: To describe social needs among low‐income adults and estimate the relationship between level of unmet social needs and key indicators of health care access and quality. Data Source: National survey data from 12 states from the 2017 Behavioral Risk Factor Surveillance System, which added a "Social Determinants of Health" Module in 2017. Study Design: We examined differences in eight measures of health care access and quality (eg, check‐up in last 12 months, inability to see doctor due to cost, receipt of eye examination for diabetics) for low‐income adults with 0, 1, 2‐3, and 4+ unmet social needs based on 7 social needs measures. We used adjusted logistic regression models to estimate the association between level of unmet need and each outcome. Principal Findings: Most common unmet social needs included not having enough money for balanced meals (33 percent) or food (32 percent). After adjusting for observable characteristics, higher levels of unmet social need were associated with poorer access and quality. Compared to those with no reported unmet needs, having 4+ unmet needs was significantly associated with reduced probability of having a yearly check‐up (65 percent vs 78 percent, adjusted difference = −7.1 percentage points (PP)), receiving a flu vaccine (33 percent vs 42 percent, adjusted difference = −5.4 PP), having a personal doctor (74 percent vs 80 percent, adjusted difference = −3.1 PP), and having a foot (63 percent vs 80 percent, adjusted difference = −12.8 PP) or eye examination (61 percent vs 73 percent, adjusted difference = −12.6 PP) for diabetic patients, and increased probability of being unable to see a doctor due to cost (44 percent vs 9 percent, adjusted difference = 27.9 PP) and having diabetes affect the eyes (22 percent vs 19 percent, adjusted difference = 8.0 PP) at α = 0.05. Conclusions: Higher levels of unmet social needs were associated with poorer access to and quality of care among low‐income adults. Addressing social needs both inside and outside of health care settings may help mitigate these negative effects. Additional research on if and how to effectively do so is critical. [ABSTRACT FROM AUTHOR]

Background: In sudden and asymmetrical progressive sensorineural hearing loss (SNHL), magnetic resonance imaging (MRI) is required to evaluate retrocochlear pathology and, with recent advances in MRI techniques, inner ear pathology. Given the limited literature regarding inner ear pathology associated with SNHL, we aimed to assess the incidence of retrocochlear and inner ear pathology, and congenital malformation on MRI in sudden SNHL (SSNHL) and progressive SNHL. Methods: A total of 987 acoustic neuroma (AN) protocol MRI internal acoustic meatus studies performed at our institution to investigate SNHL between January 2013 and December 2015 inclusive were identified. Following categorization for indication of SSNHL versus progressive asymmetrical SNHL, MRIs with retrocochlear or inner ear abnormality, congenital malformation or other otology‐related abnormality were identified, and further data were collected for these patients including patient demographics, associated symptomatology, management and outcomes. Results: In SSNHL, aetiological abnormality on MRI was identified for 6.9% patients with AN present on 4% overall. 3.2% of MRIs for progressive asymmetrical SNHL identified a causative lesion with 2.3% of scans overall diagnosing AN. The incidence of congenital inner ear malformation on MRI in the setting of SSNHL and progressive asymmetrical SNHL are 1.7% and 0.6%, respectively. Conclusion: This is the first retrospective study of inner ear MRI abnormalities in both SSNHL and progressive asymmetrical SNHL in Australia and one of the largest cohorts published in the literature to date. MRI must be performed in the setting of SNHL to ensure aforementioned and rarer causative lesions are identified. [ABSTRACT FROM AUTHOR]

By about 2.0 billion years ago (Ga), there is evidence for a period best known for its extended, apparent geochemical stability expressed famously in the carbonate–carbon isotope data. Despite the first appearance and early innovation among eukaryotic organisms, this period is also known for a rarity of eukaryotic fossils and an absence of organic biomarker fingerprints for those organisms, suggesting low diversity and relatively small populations compared to the Neoproterozoic era. Nevertheless, the search for diagnostic biomarkers has not been performed with guidance from paleoenvironmental redox constrains from inorganic geochemistry that should reveal the facies that were most likely hospitable to these organisms. Siltstones and shales obtained from drill core of the ca. 1.3–1.4 Ga Roper Group from the McArthur Basin of northern Australia provide one of our best windows into the mid‐Proterozoic redox landscape. The group is well dated and minimally metamorphosed (of oil window maturity), and previous geochemical data suggest a relatively strong connection to the open ocean compared to other mid‐Proterozoic records. Here, we present one of the first integrated investigations of Mesoproterozoic biomarker records performed in parallel with established inorganic redox proxy indicators. Results reveal a temporally variable paleoredox structure through the Velkerri Formation as gauged from iron mineral speciation and trace‐metal geochemistry, vacillating between oxic and anoxic. Our combined lipid biomarker and inorganic geochemical records indicate at least episodic euxinic conditions sustained predominantly below the photic zone during the deposition of organic‐rich shales found in the middle Velkerri Formation. The most striking result is an absence of eukaryotic steranes (4‐desmethylsteranes) and only traces of gammacerane in some samples—despite our search across oxic, as well as anoxic, facies that should favor eukaryotic habitability and in low maturity rocks that allow the preservation of biomarker alkanes. The dearth of Mesoproterozoic eukaryotic sterane biomarkers, even within the more oxic facies, is somewhat surprising but suggests that controls such as the long‐term nutrient balance and other environmental factors may have throttled the abundances and diversity of early eukaryotic life relative to bacteria within marine microbial communities. Given that molecular clocks predict that sterol synthesis evolved early in eukaryotic history, and (bacterial) fossil steroids have been found previously in 1.64 Ga rocks, then a very low environmental abundance of eukaryotes relative to bacteria is our preferred explanation for the lack of regular steranes and only traces of gammacerane in a few samples. It is also possible that early eukaryotes adapted to Mesoproterozoic marine environments did not make abundant steroid lipids or tetrahymanol in their cell membranes. [ABSTRACT FROM AUTHOR]

Background: Patients treated for renal cell carcinoma (RCC) may be diagnosed with a metachronous, contralateral tumor. We evaluated the risks of contralateral tumor development using the Surveillance, Epidemiology, and End Results database.Methods: Among RCC patients, we identified those with a metachronous, contralateral RCC diagnosed ≥1 year after primary diagnosis. We performed a competing risks analysis to evaluate associations between clinicopathologic factors and metachronous, bilateral RCC. Cumulative incidence and standardized incidence ratios (SIRs) were calculated.Results: There were 80,403 cases of RCC identified, with a median follow-up of 8.3 years; of these, 1063 (1.3%) developed metachronous, contralateral RCC (median of 6 years after diagnosis). The cumulative incidence at 10, 20, and 30 years of follow-up was 1.5%, 3.1%, and 4.7%, respectively. An increased risk was observed among men (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.20-1.55), blacks (HR, 2.00; 95% CI, 1.71-2.33), and those with papillary histology (HR, 1.72; 95% CI, 1.41-2.10). Risk of metachronous disease decreased with increasing age at primary diagnosis (HR per 1-year increase, 0.97; 95% CI, 0.96-0.97). The SIRs were highest among those diagnosed at a younger age and remained elevated even after extended follow-up (>10 years).Conclusions: Our findings suggest that the cumulative incidence of metachronous, contralateral RCC may be higher than previously reported. Younger age, black race, papillary histology, and male sex increase the risk of metachronous, contralateral RCC development. The high SIRs seen in all demographic groups may support a rationale for lifelong surveillance, especially in high-risk subgroups with early disease onset. [ABSTRACT FROM AUTHOR]

Endovascular treatment of intracranial aneurysms with endoluminal flow diverters (single or multiple) has proven to be clinically safe and effective, but is associated with a risk of thromboembolic complications. Recently, a novel biomimetic surface modification with covalently bound phosphorylcholine (Shield Technology™) has shown to reduce the material thrombogenicity of the Pipeline flow diverter. Thrombogenicity of Pipeline Flex, Pipeline Shield, and Flow Redirection Endoluminal Device (FRED) in the presence of human blood under physiological flow conditions—in addition to relative increase in thrombogenicity with multiple devices—remains unknown and was investigated here. Thrombin generation (mean ± SD; μg/mL; thrombin–antithrombin complex or TAT) was measured as FRED (30.3 ± 2.9), Pipeline (13.9 ± 4.4), Pipeline Shield (0.4 ± 0.3), and negative control (no device; 0.1 ± 0.0). Platelet activation (mean ± SD; IU/μL; beta‐thromboglobulin or βTG) was measured as FRED (148 ± 45), Pipeline (92.8 ± 41), Pipeline Shield (16.2 ± 3.5), and negative control (2.70 ± 0.16). FRED was significantly more thrombogenic than Pipeline and Pipeline Shield (p < 0.05) for TAT. Additionally, Pipeline Shield had significantly lower TAT and βTG than the other devices tested (p < 0.05) and these were comparable to the negative control (p > 0.05). TAT and βTG scaled proportionately with multiple Pipeline devices (N = 6) but was unaffected by multiple Pipeline Shield (N = 6) devices—the latter being statistically similar to negative control (p > 0.05). © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3195–3202, 2018. [ABSTRACT FROM AUTHOR]

Dear Editor, Mucoepidermoid carcinoma is typically a low-grade malignancy of the salivary glands. In addition, it is possible that cases of secondary metastasis of mucoepidermoid carcinomas could mistakenly be coded as primary tumors, and the workup and histopathologic examination to exclude another primary site or differentiate this tumor from adenosquamous carcinoma may have varied between patients. Mucoepidermoid carcinoma of the skin: a distinct entity from adenosquamous carcinoma: a case study with a review of the literature. [Extracted from the article]

A significant proportion of prostate cancer diagnoses may be associated with a strong hereditary component. Men who have multiple single-gene polymorphisms and a family history of prostate cancer have a significantly greater risk of developing prostate cancer. Numerous single-gene alterations have been confirmed to increase the risk of prostate cancer. These include breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively), mutL homolog 1 (MLH1), mutS homologs 2 and 6 (MSH2 and MSH6, respectively), postmeiotic segregation increased 2 (PMS2), homeobox B13 (HOXB13), checkpoint kinase 2 (CHEK2), nibrin (NBN), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), and ataxia telangiectasia mutated (ATM). Currently, there are no uniform guidelines on the definition of hereditary prostate cancer and genetic testing. With the advent of next-generation sequencing, which is capable of testing multiple genes simultaneously, and the approval of olaparib for BRCA1/BRCA2 or ATM-mutated, metastatic, castrate-resistant prostate cancer, it is being recognized that the results of genetic testing have an impact on therapeutic strategies. In this review, the authors examine the role of genetic counseling and testing, the challenges of insurance coverage for testing, the available germline and somatic testing panels, and the complexity of each testing method and its implications. Cancer 2018. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Summary: Primary cutaneous CD30+ T cell lymphoproliferative disorders (PCLPD), the second most common type of primary cutaneous T cell lymphomas, accounts for approximately 25–30% of cutaneous T‐cell lymphoma cases. However, only small retrospective studies have been reported. We aimed to identify prognostic factors and evaluate the overall survival (OS) of patients with PCLPD stratified by ethnicity. We identified 1496 patients diagnosed with PCLPD between 2004 and 2014 in the US National Cancer Database. Chi‐square test and anova were used to evaluate differences in demographic and disease characteristics, socioeconomic factors and treatments received. OS was evaluated with the log‐rank test, Cox proportional hazard regression analysis, and propensity score matching. The study included 1267 Caucasians, 153 African Americans (AA), 43 Asians, and 33 of other/unknown ethnicity. Older age, higher Charlson‐Deyo score, higher clinical stage and receipt of chemotherapy were predictors of shorter OS. Primary disease site on a lower extremity was associated with shorter OS, while a head and neck location was associated with longer OS. AA patients had shorter OS when compared to Caucasian patients on multivariate analysis. This ethnic disparity persisted on propensity‐score matched analysis and after matching Caucasian and AA patients on demographic and disease characteristics, socioeconomic factors and treatments received, and age and gender‐matched relative survival analyses. [ABSTRACT FROM AUTHOR]

Summary: Systemic anaplastic lymphoma kinase positive (ALK+) anaplastic large cell lymphoma with extranodal involvement (ALCL‐E) is a rare form of non‐Hodgkin lymphoma. No large study in the literature has compared the survival outcomes among different primary extranodal sites of involvement in ALK+ ALCL‐E. We identified 1306 patients with ALK+ ALCL‐E diagnosed between 2004 and 2014 in the US National Cancer Database, among whom 387 had primary extranodal site in the chest/abdomen/pelvis, 103 in the bone, 62 in the central nervous system, 134 in the head and neck and 620 in the cutaneous/soft tissue. Younger age, lower Charlson‐Deyo score, lower clinical stage, receipt of chemotherapy and receipt of radiotherapy were predictors of longer overall survival. Patients with extranodal involvement of central nervous system and chest/abdomen/pelvis had shorter overall survival than those with involvement of head and neck, bone, and cutaneous/subcutaneous tissue after adjusting for confounding variables. We recommend treating these patients upfront with more aggressive therapy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the outcomes of patients with upper tract urothelial carcinoma (UTUC) with non‐definitive therapy, which currently remains unknown. Patients and Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify individuals with a localised, histologically confirmed kidney/renal pelvis and ureteric UC. Survival analysis using the Kaplan–Meier method was performed. A competing risk model evaluated the cumulative incidence and predictors of cancer‐specific mortality (CSM). Results: We identified 633 (7.6%) individuals who did not receive surgery. These individuals were significantly older (median age 81 vs 71 years, P < 0.001) than surgically managed patients. The median overall survival (OS) was significantly shorter compared to the surgical cohort (1.9 vs 7.8 years, P < 0.001). The 3‐year disease‐specific survival (DSS) for patients without surgery was significantly lower compared to those with surgery, at 73.7% vs 92.4%, respectively (P < 0.001). The 3‐year DSS for patients with high‐grade tumours was worse when compared to patients with low‐grade tumours, at 65.1% vs 82.9%, respectively (P < 0.001). The 3‐year cumulative CSM was 26.3%. On multivariable analysis, older age (hazard ratio [HR] 1.05, P < 0.001) and high tumour grade (HR 1.88, P < 0.001) were predictors of worse outcomes. Conclusions: In this population‐based cohort, 7.6% of patients with UTUC were managed with a non‐definitive approach. The median OS for the untreated cohort was significantly shorter compared to the surgical cohort (1.9 vs 7.8 years, respectively). These data may be helpful in counselling patients who are poor surgical candidates, as non‐definitive therapy may provide reasonable oncological outcomes. [ABSTRACT FROM AUTHOR]

Background: Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer.Methods: The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test.Results: Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P < .0001). Overall, 6.1%, 75.5%, and 18.4% of individuals had positive, negative, and inconclusive results, respectively. The most commonly altered genes included folliculin (FLCN) and fumarate hydratase (FH), which were altered in 1.8% and 1.3% of patients, respectively. Tuberous Sclerosis Complex 2 (TSC2), mesenchymal epithelial transition factor proto-oncogene (MET), and PMS1 homolog 2 (PMS2) had the highest rates of variants of unknown significance, which were identified in 2.7%, 2.2%, and 1.7% of patients, respectively. Early age of onset was the only factor that was identified as predictive of a positive test on multivariate analysis (odds ratio, 0.975; P = .0052) and may be the only identifying characteristic of low-penetrant syndromes, such as those associated with MITF (melanogenesis-associated transcription factor) mutations, which do not have singular histology or a family history of kidney cancer.Conclusions: Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Fine-Gray competing risk analysis was used to evaluate the cumulative incidence of angiosarcoma-specific mortality and mortality from all other causes. Dear Editor, Angiosarcomas are mesenchymal neoplasms with a propensity for early progression and distant metastasis.1 Most studies on cutaneous angiosarcomas have encompassed case reports and series and given its rarity, no evidence-based recommendations currently exist to guide surveillance strategies after treatment.2 Using a cancer registry, we compared the oncologic outcomes of patients with cutaneous angiosarcoma with other competing risks of death. [Extracted from the article]

A 46-year-old male presented with a mobile right parotid mass and normal facial nerve function. It was expected that reoperation would be difficult as the facial nerve would be embedded in the scar tissue4 and would be associated with increased risk of partial or total facial palsy.5,6 However, the graft had integrated with the surrounding parotid tissue and there were minimal signs of inflammation. [Extracted from the article]

Several paediatric weight estimation methods have been described for use when direct weight measurement is not possible. A new age-based weight estimation method has recently been proposed. The Luscombe formula, applicable to children aged 1-10 years, is calculated as (3 × age in years) + 7. Our objective was to externally validate this formula using an existing database. Secondary analysis of a prospective observational cohort study. Data collected included height, age, ethnicity and measured weight. The outcome of interest was agreement between estimated weight using the Luscombe formula and measured weight. Secondary outcome was comparison with performance of Argall, APLS and Best Guess formulae. Accuracy of weight estimation methods was compared using mean difference (bias), 95% limits of agreement, root mean square error and proportion with agreement within 10%. Four hundred and ten children were studied. Median age was 4 years; 54.4% were boys. Mean body mass index was 17 kg/m and mean measured weight was 21.2 kg. The Luscombe formula had a mean difference of 0.66 kg (95% limits of agreement −9.9 to +11.3 kg; root mean square error of 5.44 kg). 45.4% of estimates were within 10% of measured weight. The Best Guess and Luscombe formulae performed better than Argall or APLS formulae. The Luscombe formula is among the more accurate age-based weight estimation formulae. When more accurate methods (e.g. parental estimation or the Broselow tape) are not available, it is an acceptable option for estimating children's weight. [ABSTRACT FROM AUTHOR]

Objective: A new method for estimation of weight in children based on their age has been proposed. The present study aims to validate the Best Guess formulae in a new population of children. Methods: This was a secondary analysis of a database collected for a prospective, observational, cohort study conducted in the Paediatric ED of Sunshine Hospital. Children aged 1–11 years who presented to the ED between 18 August 2005 and 25 February 2006 were included. Actual weight, height, age and ethnicity were obtained. Agreement between estimated weight using the Best Guess formulae and measured weight is reported using mean bias, 95% limits of agreement and proportion within 20% of actual weight. Results: A total of 410 cases were included in the present study. Forty-six per cent were female and median age was 4 years. The mean bias in the 1–5 year group was 0.9 kg, with 95% limits of agreement −3.5 to +5.3 kg. Seventy-six per cent of estimations were within 20% of measured weight. The mean bias in the 5–11 year group was 0.4 kg, with 95% limits of agreement −14.4 to +15.2 kg. In this group, 64% of estimations were within 20% of measured weight. Conclusion: The Best Guess formulae performed moderately well in estimating children's weight, but had a tendency to overestimate weight, particularly in children with lower body mass index. [ABSTRACT FROM AUTHOR]

Primary spindle cell sarcoma is a rare neoplasm with great heterogeneity in clinicopathologic presentation and morphological features. This previous study showed that a superficial, cutaneous, primary site of spindle cell sarcoma was associated with both better overall survival (OS) and disease-specific survival (DSS) than an internal site.[2] Due to the paucity of epidemiological data on this disease, we specifically interrogated outcomes of patients with primary spindle cell sarcoma of the skin. Given that spindle cell sarcoma is a morphologic description of an undifferentiated neoplasm, modern immunohistochemical and molecular tests applied to cases diagnosed in earlier years may have allowed more accurate subclassification. [Extracted from the article]

Audiogram demonstrated right mild-to-moderate sensorineural hearing loss (SNHL) with conductive overlay at 500z and 1000 Hz, and a word recognition score of 60% at 70 dB. There was mild left high-frequency SNHL with a word recognition score of 100% at 60 dB. Tympanograms were type A bilaterally (Fig. a). Computed tomography (CT) revealed an ill-defined lucent mass in the superior right petrous temporal bone that extended into the mastoid antrum with thinning of the tegmen mastoideum and bone erosion involving superior and posterior semicircular canals (SCCs) (Fig. a,b). [Extracted from the article]

Background: The immune system of advanced stage head and neck cancer patients is frequently suppressed. Poor immune function has been correlated with poor clinical outcome. Immunotherapeutic strategies have been previously attempted in an effort to enhance immune function and improve survival. Previous studies have shown surgical suture can be transformed into an immune stimulant capable of activating the T lymphocytes of cancer patients. The development of a process for covalently linking proteins and cytokines to suture could have enormous potential for the in vivo manipulation of the immune system.Hypothesis: We hypothesize proteins and cytokines can be covalently linked to surgical suture while preserving their functional properties.Study Design: Prospective study testing normal donor and head and neck squamous cell carcinoma (HNSCC) patient lymphocytes.Method: Polyester suture was acid hydrolyzed followed by reacting with 1-ethyl-3(-3-dimethylamino propyl carbodiimide) (EDAC) to create a suture-EDAC intermediate. Next, selected proteins (horseradish peroxidase [HRP] or bovine serum albumin [BSA]) or cytokines (interleukin [IL]-2 or interferon [IFN]-gamma) were reacted with the suture-EDAC intermediate to test the covalent linkage of the selected protein or cytokine to suture. Functional activity of the linked proteins was measured spectrophotometrically. The linking of cytokines to suture was tested by stimulating normal donor peripheral blood lymphocytes (PBL) or HNSCC patients' lymphocytes. The functional activity was confirmed by proliferation, enzyme linked immunoadsorbent assay (ELISA), and phenotype expression of T cells. RESULTS The conditions for optimally linking a protein to polyester suture were defined using HRP as a model protein. HRP retained its enzymatic activity. The optimal conditions for linking IL-2 or IFN-gamma were defined. The covalently linked cytokines retained their immune enhancing properties for stimulating PBL and lymph node lymphocytes (LNL) from HNSCC patients to proliferate, generate a TH1 immunologic profile of cytokines (IL-2, IL-12, IFN-gamma), and stimulate T lymphocytes.Conclusion: This is the first report to demonstrate that cytokines can be covalently linked to surgical sutures and retain their immune-stimulating properties. Proteins linked to suture also retained their enzymatic activity. The clinical implications of functionally active cytokines or proteins linked to surgical suture may be very significant in the future for manipulating the immune system in vivo or enhancing wound healing. [ABSTRACT FROM AUTHOR]

Research Objective: Medicaid managed care (MMC) has become the dominant method of delivering health services for low‐income Americans enrolled in Medicaid. Following state decisions to extend Medicaid eligibility through the Affordable Care Act, MMC plans enrolled nearly 80% of newly eligible beneficiaries. Many states are adopting performance measurement systems to hold MMC plans accountable for quality of care. Despite the growing importance of measured quality of care in MMC payment and delivery, there is limited understanding of changes in MMC enrollee characteristics or performance measures associated with Medicaid expansion. We examined changes in plan composition among nonelderly MMC enrollees and measured quality of care associated with Medicaid expansion. Study Design: We used 2012–2018 National Committee on Quality Assurance Adult Medicaid Consumer Assessment of Healthcare Providers and Systems (CAHPS) data, which are enrollee‐level surveys submitted by state Medicaid agencies and individual MMC plans. Enrollee characteristics included age, gender, race/ethnicity, educational attainment, and self‐reported health status. Our four outcomes measured patient experience of care: whether a respondent answered that it was "always or usually" easy to get needed care, had a personal doctor, had timely access to a checkup or routine care, and had timely access to specialty care. We estimated multivariable linear probability models comparing pre‐ versus post‐expansion changes in plan composition and measured quality in expansion versus non‐expansion states. The post‐expansion period was modeled as an event‐study regression to account for changes over time, where the coefficient of interest was a Medicaid expansion‐by‐year term. Models adjusted for sociodemographic characteristics, self‐reported health, and included state, year, and plan fixed effects. Standard errors were clustered at the state level. Population Studied: 315,563 adult MMC enrollees age 18–64 in the 39 states with comprehensive MMC plans. Principal Findings: Medicaid expansion was associated with statistically significant decreases in the proportion of female MMC enrollees (−8.4 percentage points [PP], p < 0.01), and increases in the proportion of MMC enrollees who were age 55–64 (6.8 PP, p < 0.01), White non‐Hispanic (4.4 PP, p < 0.01), and with a college degree or higher (2.3 PP, p < 0.01). Relative to MMC enrollees in non‐expansion states, enrollees in expansion states were significantly less likely to report access to a personal doctor (−1.6 PP, 95% CI ‐3.0 to −0.1 PP, p < 0.05) and less likely to report timely access to specialty care (−2.1 PP, 95% CI ‐3.4 to −0.8 PP, p < 0.01) in the first year after expansion. Differences were not statistically significant by the second year post‐expansion. Conclusions: Medicaid expansion was associated with substantial changes in MMC plan composition, and there were modest, but temporary, reductions in measured quality of care in the first year post‐expansion. Implications for Policy or Practice: States use MMC performance data to assign bonus payments based on meeting or exceeding quality targets, withhold capitated payments, and auto‐assign enrollees to plans. State policymakers should recognize that expansions of Medicaid eligibility may change the composition of plan enrollees, with implications for measured quality of care. Particularly for states that compare a plan's performance on measured quality to national benchmarks, accounting for a state's decision to expand Medicaid may mitigate unfair penalization. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 70-yearold female who was presented with a worsening left sided sensorineural hearing loss (SNHL). It notes that she reported no associated tinnitus or vertigo with a background of bilateral hearing loss for over 10 years and previous industrial noise exposure. The patient's audiogram demonstrated a moderate to severe SNHL with corresponding roll over on speech perception, that is, reduced speech recognition with increased amplification of sound.

The article reports on the societies concerned with the surgical career of medical students. It mentions that the societies are trying to encourage medical students to take surgical career after graduating. In addition, the higher education in Australia and New Zealand give students with surgical training and include it on their curriculum to get the students' interest. Maintenance of the societies and its growth is also presented.

The reaction of UO2(NO3)2, H3PO3, K2(EDTA), H2O2, and Et4NOH in aqueous solution (room temperature, pH 6, 7 d) affords crystals of K14.73 [(UO2)22(O2)15 (HPO3)20(H2O)10] ·38H2O (I) and K12 [(UO2)14(O2)10 (HPO3)12(H2O)6] ·22H2O (II) in yields of 10 and 35%, respectively. [ABSTRACT FROM AUTHOR]

Problem: Dendritic cells (DCs) are the key antigen-presenting cells (APC) for inducing an antigen-specific immune response. Generating DCs from head and neck squamous cell cancer (HNSCC) patients may be a very important initial step in manipulating the patient’s immune system to fight their cancer. In this study we test our ability to generate functional DCs from advanced-stage HNSCC patients’ peripheral blood mononuclear cells (PBMC) or lymph node mononuclear cells (LNMC).Methods: Mononuclear cells were stimulated for 10 days in vitro with soluble IL-4 (90hg/mL)/GM-CSF (100U/mL), then soluble TNFa (20 hg/mL) for 48 hours. Flow cytometry was performed to measure the population of cells, which were CD1a+, CD14-, CD15-, CD80+, CD83+, CD86+, HLA-DR++, and CD4+. DCs were then pulsed with Flu-peptide at increasing concentrations (25, 50, and 100 mg/mL) and used to stimulate Flu-specific T cells from HLA-A2+ individuals. Expansion of Flu-specific T cells was measured by re-exposing T cells to Flu-peptide for 24 hours and measuring intra-cellular expression of IFNg. Experiments were also performed in parallel with normal HLA-A2 donors PBMC.Results: Mononuclear cells from HNSCC patients were able to generate a population of cells expressing CD1a+, CD14-, CD15-, CD80+, CD83+, CD86+, HLA-DR++, and CD4+, consistent with DCs. DCs were effective at stimulating Flu-specific T cells from HLA-A2 positive individuals and increased the percentage of T cells (CD4/CD8) expressing intracellular IFNg after re-exposure to Flu-peptide.Conclusion: DCs could be generated from HNSCC patients’ mononuclear cells. Functionality of these DCs to induce a Flu-specific immune response was demonstrated by increased intra-cellular expression of IFNg in CD4 and CD8 cell populations after re-priming.Significance: DCs may be useful in generating an antigen-specific anti-cancer immune response in HNSCC patients.Support: None reported. [Copyright &y& Elsevier]

Problem: Immunosuppression has been well recognized in head and neck squamous cell carcinoma (HNSCC). We have previously identified increased percentages of T regulator cells (T regs or CD4+/CD25+) from peripheral blood lymphocytes (PBLs) of advanced-stage HNSCC patients. T regs have been implicated in playing a very crucial role in immunosuppression. Previously we developed bioactive sutures that can enhance the immune response of cancer patients. In this study we measured the effect that stimulating HNSCC patients PBLs with bioactive sutures has on the percentage of CD4+/CD25+ T cells.Methods: A group of previously untreated advanced-stage HNSCC patients (n = 10) and controls (n = 7) were studied. PBL were drawn from patients prior to surgery and controls. Lymphocytes were purified by Ficoll-hypaque density centrifugation and stimulated in vitro with a variety of bioactive sutures (anti-CD3/28, anti-CD3/28 + IFNg, anti-CD3/28 + IL-2). The percentage of CD3/CD25, CD4/CD25, CD8/CD25, and annexin-V/propidium iodine positive cells was measured prestimulation and 6 days poststimulation.Results: HNSCC patients demonstrated 21- to 26-fold increases in CD8+/CD25+ and 7- to 8-fold increases in CD4+/CD25+ populations after suture stimulations, while controls demonstrated 36- to 40-fold increases in CD8+/CD25+ and 4-fold increases in CD4+/CD25+. Control PBLs expanded significantly higher percentages (P < 0.05) of CD8+/CD25+ and lower percentages (P < 0.05) of CD4+/CD25+ after suture stimulations compared to HNSCC patients.Conclusion: PBL from advanced-stage HNSCC patients demonstrated enhanced responses to bioactive suture stimulations, with greater expansion in the CD8+/CD25+ than CD4+/CD25+. Control PBL stimulated by bioactive sutures demonstrated even greater expansion of CD8+/CD25+ cells and less expansion of CD4+/CD25+ cells.Significance: Bioactive sutures may be useful for expanding the cytotoxic population of T cells in HNSCC patients to fight cancer.Support: California Cancer Research Program Clinician Scientist Development Award (TYS) [Copyright &y& Elsevier]