Randomized Trial of Postoperative Radiation Therapy After Wide Excision of Neurotropic Melanoma of the Head and Neck (RTN2 Trial 01.09).

BACKGROUND: Cutaneous neurotropic melanoma (NM) of the head and neck (H&N) is prone to local relapse, possibly due to difficulties widely excising the tumor. This trial assessed radiation therapy (RT) to the primary site after local excision. METHODS: Participants from 15 international centers were randomized to observation or RT. The participants were required to have microscopically negative excision margins 5 mm wide or wider and no evidence of disease elsewhere. The primary outcome was time to local relapse. The secondary outcomes included time to any recurrence, overall survival (OS), and toxicity. RESULTS: The trial ceased prematurely due to slow recruitment and the COVID-19 pandemic. During 2009-2020, 50 participants were randomized: 23 to observation and 27 to RT. The most common NM subsites were scalp (32%), midface (22%), and lip (20%). The median depth of invasion was 5 mm, and desmoplasia observed in 69%. The median duration from randomization to last contact was 4.8 years. Four participants (8%) experienced local relapse as a first recurrence during the study period: 3 in the observation arm and 1 in the RT arm (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.03-2.76; p = 0.279). No statistically significant difference in time to any relapse or OS was observed. More than 6 months after randomization, grade 3 or greater toxicity was experienced by 10% of the participants in the observation arm and 12.5% of the participants in the RT arm of the study. CONCLUSION: Due to low accrual, the role of adjuvant RT for cutaneous NM of the H&N excised with microscopically negative margins 5 mm wide or wider remains undefined. Its routine use cannot be recommended. Local relapse might be less common than previously anticipated based on retrospective reports.

Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

The mediating and moderating role of recovery experience between occupational stress and turnover intention in nurses caring for patients with COVID-19.

AIM: This study aimed to investigate the relationships among occupational stress, recovery experience and turnover intention among nurses caring for patients with coronavirus disease 2019 (COVID-19). BACKGROUND: The high turnover intention among nurses affect patient safety quality of patient care. DESIGN: The cross-sectional study design was used. This study was guided by STROBE. METHODS: Convenience sampling identified 202 registered nurses working in the COVID-19 wards of three tertiary general hospitals in two cities in South Korea. The collected data were analysed using SPSS version 26.0, and the PROCESS macro in SPSS was employed to estimate path coefficients and assess the adequacy of the model. The moderating effects of recovery experience on the pathway in which occupational stress of the participants affects turnover intention were verified using model 1 of the SPSS PROCESS macro proposed by Hayes. RESULTS: The recovery experience did not significantly mediate the relationship between occupational stress and turnover intention. However, it had significant moderating effect on the relationship between occupational stress and turnover intention (ß = .005, 95% CI [.001, .010]). The effect of occupational stress on turnover intention was dependent on recovery experience. CONCLUSION: The results revealed that occupational stress among nurses caring for patients with COVID-19 affect the turnover intention and the level of recovery experience moderates this relationship. Thus, not only during the COVID-19 pandemic but also during challenging times of various infectious disease outbreaks, hospitals can enhance the health and well-being of nurses and promote the retention of nursing staff. IMPLICATIONS FOR THE PROFESSION: During the COVID-19 pandemic, nurses have been exposed to understaffing and overwhelming workloads. However, policies for nurses' welfare and benefits are still insufficient, even as the pandemic comes to an end. The results of this study indicate that sufficient rest and appropriate nursing personnel are of utmost importance to nurses. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Reactivation of Bone Lining Cells are Attenuated Over Repeated Anti-sclerostin Antibody Administration.

Reactivation of bone lining cells (BLCs) is a crucial mechanism governing the anabolic action of anti-sclerostin antibody (Scl-Ab) via modeling-based bone formation; however, it remains unclear whether this reactivation can be attenuated after persistent administration of Scl-Ab. Here, we aimed to investigate the reproducibility of persistent Scl-Ab administration for the reactivation of BLCs, and to elucidate the relationship between the activity of BLCs and serum levels of N-terminal procollagen type I (P1NP) during chronic Scl-Ab administration. We conducted an osteoblast lineage tracing study. Briefly, Dmp1-CreERt2(+):Rosa26R mice were injected with 1 mg of 4-hydroxy-tamoxifen weekly from postnatal weeks four to eight. Mice were treated twice with either vehicle or Scl-Ab (25 mg/kg) at weeks 12, 16, and 20, and were euthanized at weeks 8, 12, 13, 16, 17, 20, and 21 (4-6 mice in each group). After euthanization, the number and thickness of X-gal (+) cells on the periosteum of the femoral bones and the serum levels of P1NP were quantified at each time point. Scl-Ab induced a significant increase in the thickness of X-gal (+) cells on periosteal bone surfaces at postnatal weeks 13 (after 1st dose), 17 (after 2nd dose), and 21 (after 3rd dose) compared to that in vehicle-treated mice (all P < 0.001). In the Scl-Ab group, significant increases in the thickness of labeled cells were observed between weeks 16 and 17 and weeks 20 and 21 (both P < 0.001). The percentage increase in X-gal (+) cell thickness was 108.9% from week 12 to week 13, 54.6% from week 16 to week 17, and 49.2% from week 20 to week 21 in the Scl-Ab group. Although Scl-Ab treatment increased the serum levels of P1NP at postnatal weeks 13 and 17 compared with those at week 12 (P = 0.017 and P = 0.038, respectively), the same was not observed at week 21 (P = 0.296). A significant increase in P1NP levels was observed between weeks 16 and 17 and weeks 20 and 21 in the Scl-Ab group (P = 0.005 and P = 0.007, respectively). The percentage increase in P1NP levels was 141.7% from weeks 12 to 13, 114.8% from weeks 16 to 17, and 99.4% from weeks 20 to 21. Serum P1NP levels were positively correlated with X-gal (+) cell thickness (R2 = 0.732, P < 0.001). Reactivation of BLCs is modestly attenuated, but reproducible, during persistent Scl-Ab administration. Serum P1NP levels appear to be an indicator of the impact of Scl-Ab on the conversion of BLCs into mature osteoblasts on periosteal bone surfaces, thus contributing to modeling-based bone formation.

Improved Erythrocyte Deformability Induced by Sodium-Glucose Cotransporter 2 Inhibitors in Type 2 Diabetic Patients.

PURPOSE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are antidiabetic drugs that improve cardiovascular outcomes. Hemoglobin and hematocrit values increase after SGLT-2 inhibitor administration. Although these factors increase blood viscosity and the risk of cardiovascular disease, SGLT-2 inhibitors have protective effects on the cardiovascular system. The mechanisms for this paradoxical phenomenon remain unclear, and the effect of SGLT-2 inhibitors on hemorheology has not been studied. METHODS: We evaluated the hemorheological parameters of 63 patients of whom 38 received metformin with a dipeptidyl peptidase 4 (DPP-4) inhibitor, while 25 received metformin with SGLT-2 inhibitor. Blood viscosity was measured using a cone-and-plate viscometer, erythrocyte aggregation was measured using a modified erythrocyte sedimentation rate method, and erythrocyte membrane fluctuation was measured as deformability, using a diffraction optical tomography. RESULTS: Both blood viscosity and erythrocyte aggregation increased in the SGLT-2 inhibitor group, although erythrocyte deformability was significantly improved compared with that of the DPP-4 inhibitor group (DPP-4 inhibitor 43.71 ± 5.13 nm; SGLT-2 inhibitor 53.88 ± 4.88 nm; p < 0.001). When the two groups were compared after propensity score matching, no differences in blood viscosity at high shear rates and erythrocyte aggregation were observed, although erythrocyte deformability was significantly improved in the SGLT-2 inhibitor group (DPP-4 inhibitor 45.01 ± 5.28 nm; SGLT-2 inhibitor 53.14 ± 4.72 nm; p = 0.001). CONCLUSION: This study demonstrates that erythrocyte deformability was improved in the SGLT-2 inhibitor group compared with that in the DPP-4 inhibitor group. This improvement in erythrocyte deformability is expected to have a protective effect on the cardiovascular system.

Kaposiform haemangioendothelioma in an adult: lack of response to topical sirolimus and response to radiotherapy.

Kaposiform haemangioendothelioma (KHE) is a rare, primarily paediatric tumour with only a handful of case reports in the adult population. Given the paucity of evidence, this article is important in raising awareness of radiotherapy as a suitable and effective treatment in the adult population with KHE and highlights the potential limitations of topical sirolimus in these tumours.

Orthogonal R/G/B Upconversion Luminescence-based Full-Color Tunable Upconversion Nanophosphors for Transparent Displays.

Here, excitation orthogonalized red/green/blue upconversion luminescence (UCL)-based full-color tunable rare-earth (RE) ion-doped upconversion nanophosphors (UCNPs) are reported. The LiREF4-based core/sextuple-shell (C/6S) UCNPs are synthesized, and they consist of a blue-emitting core, green-emitting inner shell, and red-emitting outer shell, with inert intermediate and outermost shells. The synthesized C/6S UCNPs emit blue, green, and red light under 980, 800, and 1532 nm, respectively. Importantly, by combining incident near-infrared (NIR) light with various wavelengths (800, 980, and 1532 nm), full-color UCL including blue, cyan, green, yellow, orange, red, purple, and white UCL is achieved from the single C/6S UCNP composition. The color gamut obtained from the C/6S UCNPs shows 101.6% of the sRGB standard color gamut. Furthermore, transparent C/6S UCNP-polydimethylsiloxane (PDMS) composite is prepared. Full-color display realized in the transparent C/6S UCNP-PDMS composite indicates the feasibility of constructing the C/6S UCNP-based three-dimensional volumetric displays with wide color gamut.

Association of Triglyceride-Glucose Index with Bone Mineral Density in Non-diabetic Koreans: KNHANES 2008-2011.

The association of insulin resistance (IR), as indicated by the homeostasis model assessment of insulin resistance, with bone metabolism is yet to be clarified. We aimed to investigate the relationship of IR with bone mass by using the triglyceride-glucose (TyG) index as an alternative marker of IR. Data of 4810 non-diabetes individuals (2552 men aged ≥ 50 years and 2258 postmenopausal women) from the Korean National Health and Nutritional Examination Survey IV and V were analyzed. Bone mineral density (BMD) at the lumbar spine, femoral neck, total hip, and whole body were measured using dual-energy X-ray absorptiometry. After adjusting for confounding factors, there were inverse relationships of TyG index with femoral neck, total hip, and whole body BMD in men (ß = - 0.085, P < 0.001 at femoral neck; ß = - 0.046, P = 0.037 at total hip; ß = - 0.098, P < 0.001 at whole body). However, in women, femoral neck and whole body BMD were negatively associated with the TyG index (ß = - 0.071, P = 0.008 at femoral neck and ß = - 0.065, P = 0.005 at whole body). The highest TyG index tertile exhibited reduced femoral neck BMD in both sexes (P = 0.003 in men and P = 0.013 in women) and reduced whole body BMD in men (P < 0.001) after adjusting for confounders. When the study subjects were divided into BMI (body mass index) < 23 kg/m2 and ≥ 23 kg/m2 groups, the TyG index was significantly associated with femoral neck BMD only in the women with BMI < 23 kg/m2 (P = 0.009). We observed a significant association between the highest TyG index tertile and low bone mass at the femoral neck in women with BMI < 23 kg/m2 (P = 0.003) that was not observed in women with BMI ≥ 23 kg/m2 and men. In conclusion, IR evaluated using the TyG index was inversely associated with femoral neck BMD in non-diabetic men aged ≥ 50 years and postmenopausal women. The negative influence of IR on femoral neck BMD was robust in the women with BMI < 23 kg/m2. This indicates a differential effect of IR on BMD according to skeletal site, sex, and BMI.

Application of Machine Learning to Identify Clinically Meaningful Risk Group for Osteoporosis in Individuals Under the Recommended Age for Dual-Energy X-Ray Absorptiometry.

Dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing osteoporosis; it is generally recommended in men ≥ 70 and women ≥ 65 years old. Therefore, assessment of clinical risk factors for osteoporosis is very important in individuals under the recommended age for DXA. Here, we examine the diagnostic performance of machine learning-based prediction models for osteoporosis in individuals under the recommended age for DXA examination. Data of 2210 men aged 50-69 and 1099 women aged 50-64 obtained from the Korea National Health and Nutrition Examination Survey IV-V were analyzed. Extreme gradient boosting (XGBoost) was used to find relevant clinical features and applied to three machine learning models: XGBoost, logistic regression, and a multilayer perceptron. For the prediction of osteoporosis, the XGBoost model using the top 20 features extracted from XGBoost showed the most reliable performance with area under the receiver operating characteristic curve (AUROC) of 0.73 and 0.79 in men and women, respectively. We compared the diagnostic accuracy of the Shapley additive explanation values based on a risk-score model obtained from XGBoost and conventional osteoporosis risk assessment tools for prediction of osteoporosis using optimal cut-off values for each model. We observed that a cut-off risk score of ≥ 28 in men and ≥ 47 in women was optimal to classify a positive screening for osteoporosis (an AUROC of 0.86 in men and 0.91 in women). The XGBoost-based osteoporosis-prediction model outperformed conventional risk assessment tools. Therefore, machine learning-based prediction models are a more suitable option than conventional risk assessment methods for screening osteoporosis in individuals under the recommended age for DXA examination.

A challenging TSH/GH co-secreting pituitary adenoma with concomitant thyroid cancer; a case report and literature review.

BACKGROUND: Thyroid stimulating hormone (TSH) secreting pituitary adenoma (TSHoma) with coexisting thyroid cancer is extremely rare, and proper treatment of both diseases may pose a unique clinical challenge. When TSHoma has plurihormonality, particularly involving the co-secretion of growth hormone (GH), management can be more complicated. Herein, we present a difficult-to-manage case of papillary thyroid cancer with an incurable TSH/GH-secreting pituitary adenoma. CASE PRESENTATION: A 59-year-old man was referred to our hospital due to memory impairment and inappropriate TSH level. Sella magnetic resonance imaging revealed a huge pituitary mass extending to the suprasellar area. Clinical diagnosis of TSH/GH co-secreting pituitary adenoma was made based on elevated free T4, total T3, serum α-subunit, insulin-like growth factor-1 levels and non-suppressible GH levels after oral glucose loading. Rectal cancer and multifocal papillary thyroid microcarcinoma (PTMC) were diagnosed during initial screening for internal malignancy; lower anterior resection was performed and close observation was planned for PTMC. Long-acting octreotide therapy was commenced, which resulted in a dramatic reduction in TSHoma size and facilitated control of hormonal excess. Total thyroidectomy and radioactive iodine (RAI) therapy were needed during follow up due to the growth of PTMC. After the surgery, the pituitary adenoma represented resistance to somatostatin analogue therapy and the tumor size gradually increased despite the addition of dopamine agonist therapy. Furthermore, TSH suppressive therapy with levothyroxine was impossible and an adequate TSH level for RAI therapy was unmountable. Late debulking pituitary surgery was ineffective, and the patient gradually deteriorated and lost to follow up. CONCLUSION: We report the first aggravated case of TSH/GH co-secreting pituitary tumor after total thyroidectomy for concomitant multifocal PTMC. Deferring of thyroid surgery until the TSHoma is well controlled may be the optimal therapeutic strategy in patients with TSHoma and coexistent thyroid cancer; ablative thyroid surgery may result in catastrophic pituitary tumor growth.

Surgery is a safe, effective first-line treatment modality for noninvasive prolactinomas.

PURPOSE: Dopamine agonists (DAs) have long been the recommended first-line treatment for prolactinoma. Given the remarkable developments in surgical techniques, however, surgery is on the rise. We compared the treatment outcomes of patients with noninvasive prolactinomas receiving two different initial treatments (DAs and transsphenoidal surgery). METHODS: We reviewed 745 patients with hyperprolactinemia or pituitary tumors treated from 2004 to 2020 at Chonnam National University Hwasun Hospital and identified 310 with prolactinomas. After selecting patients who had pituitary tumors with Knosp grade 0 to 1 with follow-up period over 1 year, 70 patients (29 who underwent surgery and 41 who received DAs as the initial treatment) were finally included for a comparative study. RESULTS: The surgery group exhibited better outcomes in terms of DA-free remission and the structural response, although the tumor size was significantly larger than in the DA group. The groups exhibited comparable results in terms of symptom control and the biochemical response. Univariate and multivariate analyses indicated that surgery as the initial treatment modality provided significantly better clinical outcomes in terms of DA-free remission. In the surgery group, a postoperative prolactin level < 10 ng/mL was the only significant predictor of DA-free remission. CONCLUSIONS: Transsphenoidal surgery showed comparable clinical outcomes in patients with prolactinomas, and low complication rates. The decision regarding the first-line treatment modality for non-invasive prolactinomas should be made on an individual basis.

How prevalent are financial conflicts of interest in dermatology randomized controlled trials? A cross-sectional study.

Since the last assessment of conflicts of interest (COIs) in dermatology randomized controlled trials (RCTs) in 2004, several countries have introduced transparency databases. We assessed the prevalence of financial COIs in dermatology RCTs and quantified payments from study sponsors to academic/clinical authors using transparency databases, which are available in the USA, France, Australia, Belgium and the Netherlands, while the UK has a noncompulsory transparency database. We included RCTs from the top 10 dermatology journals and the top 7 general medical journals published in 2019. The study assessed 83 RCTs, and COIs were identified in 69%. The highest prevalence was in exclusively industry-funded trials (46/47, 98%), which consisted of personal payments to an academic/clinical author (96% of trials) and having authors who were employees/stockholders (96%). Payments were identified for 31/56 (55%) academic/clinical first/final authors (median payment US$28 746, maximum US$597 299, interquartile range US$17 061-146 253), and 24/31 payments (77%) payments were each > US$10 000.

Who writes dermatology randomized controlled trials? The need to specify the role of medical writers.

Medical writers may make major contributions to the preparation of a manuscript, but are not listed as authors. We assessed the prevalence, affiliation and role of medical writers in dermatology randomized controlled trials (RCTs) published in 2019 in the top 7 medical and top 10 dermatology journals. Medical writers were identified in 39/83 trials (47%), all of which were exclusively industry-funded trials (39/47, prevalence 83%). Most studies stated their role as 'medical writing support' and/or 'editorial assistance' (35/39, 90%), but when more information was provided, four studies specified first draft preparation (50% of RCTs in general medical and 1.3% of RCTs in dermatology journals). Medical writers are common in dermatology trials but their role is often vaguely stated. In April 2020 the British Journal or Dermatology and Clinical and Experimental Dermatology adopted CRediT (Contributor Roles Taxonomy), which describes contributions of authors and may help clarify who writes trial manuscripts.

Desmoplastic melanoma: a review of its pathology and clinical behaviour, and of management recommendations in published guidelines.

Desmoplastic melanomas are uncommon. Their behaviour differs from that of other melanoma subtypes; therefore, management guidelines for non-desmoplastic melanomas may not be applicable. This review sought to examine all available evidence relating to the behaviour and management of desmoplastic melanomas, based on review of all relevant English-language publications, and to critically assess the recommendations for their management in current published melanoma management guidelines. Compared with other melanoma subtypes, patients with 'pure' desmoplastic melanomas (where ≥90% of the invasive melanoma is of desmoplastic melanoma subtype) have much lower rates of sentinel node positivity and distant metastasis. Local recurrence rates are higher for desmoplastic melanomas, but resection margins wider than those recommended for non-desmoplastic melanomas have not been shown to be of benefit. Adjuvant radiotherapy reduces the risk of local recurrence when a satisfactory histological clearance (≥8 mm) cannot be achieved. Of 29 published melanoma management guidelines identified, only 11 specified management for desmoplastic melanomas, while seven simply stated that the feature should be reported. Desmoplastic melanoma is a unique melanoma subtype with biology that differs from that of other melanoma subtypes. It requires specific management strategies but few current guidelines address these.

[Determination of the block range of ultrasound-guided lumbar erector spinal plane and its application in lumbar spine surgery].

Objective: To determinate the block range of lumbar erector spinal plane (ESPB), and investigate the efficacy of ESPB in lumbar spine surgery. Methods: Forty patients who underwent posterior lumbar fusion in the Second Affiliated Hospital of Wenzhou Medical University from November 2019 to August 2020 were randomly divided into two groups (with n=20 in each group) using the random number table: the experimental group (group E) and control group (group C). All the patients received ultrasound-guided bilateral ESPB with 20 ml of 0.375% ropivacaine (group E) or equal volume of normal saline (group C) on each side before induction of general anesthesia. The range of weakened temperature sense in each patient was measured at 10 min, 20 min and 30 min after ESPB, respectively. Dosage of analgesic drug, visual analog scale (VAS), and incidence of adverse events were recorded and compared between the two groups. Results: In group E, the dermatomal distribution and area of weakened temperature sense at 10 min, 20 min, 30 min after ESPB were T9-S1 (222±16) cm2, T8-S2 (352±22) cm2, T8-S3 (481±24) cm2, respectively. The intraoperative dosage of remifentanil in group E was (0.76±0.02) mg, which was significantly lower than that of group C (0.97±0.06) mg (P<0.05). Oxycodone consumption in group E at 0-12 h and 12-24 h after surgery was (4.9±0.4) mg and (8.4±1.2) mg, respectively, which were lower than those in group C [(14.5±2.4) mg and (19.3±2.4) mg, respectively] (both P<0.05). The VAS during rest and movement within 24 h after operation in group E were significantly lower than those in group C (both P<0.05). The passive exercise in bed in group E started at (3.3±0.3) h postoperatively, which was earlier than that in group C (4.6±0.3) h (P<0.05). Conclusion: The blocking effects of T12-S1 segment after ultrasound-guided lumbar ESPB is definite, which can effectively decrease the amounts of analgesics during and after the lumbar fusion surgery, reduce postoperative rest and exercise VAS score, and contribute to a rapid recovery of the patients.

Low free T3 to free T4 ratio was associated with low muscle mass and impaired physical performance in community-dwelling aged population.

In aged population, the association of thyroid hormones on physical performance, especially within their normal range, has yet to be elucidated. In this study, individuals with low serum free T3/free T4 were likely to have low muscle mass and impaired physical performance. PURPOSE: We aimed to evaluate the associations of muscle mass, strength, and physical performance with thyroid hormone in an aged euthyroid population from a community-based cohort. METHODS: We examined 918 men aged over 60 years and 1215 postmenopausal women from the Ansung cohort study. Appendicular skeletal muscle mass divided by square of height (ASM/ht2) was used as the muscle mass index. Hand grip strength was measured using a hydraulic dynamometer. Physical performance was assessed using the short physical performance battery (SPPB). RESULTS: Participants with higher tertiles of free T3 and free T3/free T4 were younger and had higher ASM/ht2, stronger hand grip strength, and higher SPPB scores than those in the lower tertiles. In adjusted models, men within higher tertiles of free T3 had higher ASM/ht2 compared with those within lower tertiles (p = 0.033), whereas subjects with higher tertiles of free T4 had lower ASM/ht2 compared with those within lower tertiles (p = 0.043). Subjects within higher tertiles of free T3/free T4 had higher ASM/ht2 (p < 0.001) and better physical performance (p = 0.048) than those within lower tertiles after adjustments. However, free T3, free T4, or free T3/free T4 was not related to hand grip strength after adjustment for covariates. CONCLUSION: Our results thus indicate that in an aged euthyroid population, low serum free T3/free T4 was a better index for low muscle mass and impaired physical performance than serum free T3 or free T4 alone.

Using velocity-pressure loops in the operating room: a new approach of arterial mechanics for cardiac afterload monitoring under general anesthesia.

Cardiac afterload is usually assessed in the ascending aorta and can be defined by the association of peripheral vascular resistance (PVR), total arterial compliance (Ctot), and aortic wave reflection (WR). We recently proposed the global afterload angle (GALA) and ß-angle derived from the aortic velocity-pressure (VP) loop as continuous cardiac afterload monitoring in the descending thoracic aorta. The aim of this study was to 1) describe the arterial mechanic properties by studying the velocity-pressure relations according to cardiovascular risk (low-risk and high-risk patients) in the ascending and descending thoracic aorta and 2) analyze the association between the VP loop (GALA and ß-angle) and cardiac afterload parameters (PVR, Ctot, and WR). PVR, Ctot, WR, and VP loop parameters were measured in the ascending and descending thoracic aorta in 50 anesthetized patients. At each aortic level, the mean arterial pressure (MAP), cardiac output (CO), and PVR were similar between low-risk and high-risk patients. In contrast, Ctot, WR, GALA, and ß-angle were strongly influenced by cardiovascular risk factors regardless of the site of measurement along the aorta. The GALA angle was inversely related to aortic compliance, and the ß-angle reflected the magnitude of wave reflection in both the ascending and descending aortas (P < 0.001). Under general anesthesia, the VP loop can provide new visual insights into arterial mechanical properties compared with the traditional MAP and CO for the assessment of cardiac afterload. Further studies are necessary to demonstrate the clinical utility of the VP loop in the operating room.NEW & NOTEWORTHY Our team recently proposed the global afterload angle (GALA) and ß-angle derived from the aortic velocity-pressure (VP) loop as continuous cardiac afterload monitoring in the descending thoracic aorta under general anesthesia. However, the evaluation of cardiac afterload at this location is unusual. The present study shows that VP loop parameters can describe the components of cardiac afterload both in the ascending and descending thoracic aorta in the operating room. Aging and cardiovascular risk factors strongly influence VP loop parameters. The VP loop could provide continuous visual additional information on the arterial system than the traditional mean arterial pressure and cardiac output during the general anesthesia.

Chd7 Is Critical for Early T-Cell Development and Thymus Organogenesis in Zebrafish.

Coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness (CHARGE) syndrome is a congenital disorder affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding a chromatin-remodeling protein. Immunodeficiency and reduced T cells have been noted in CHARGE syndrome. However, the mechanisms underlying T lymphopenia are largely unexplored. Herein, we observed dramatic decrease of T cells in both chd7knockdown and knockout zebrafish embryos. Unexpectedly, hematopoietic stem and progenitor cells and, particularly, lymphoid progenitor cells were increased peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute to the T-cell decrease. Further analysis demonstrated that both the organogenesis and homing function of the thymus were seriously impaired. Chd7 might regulate thymus organogenesis through modulating the development of both neural crest cell-derived mesenchyme and pharyngeal endoderm-derived thymic epithelial cells. The expression of foxn1, a central regulator of thymic epithelium, was remarkably down-regulated in the pharyngeal region in chd7-deficient embryos. Moreover, the T-cell reduction in chd7-deficient embryos was partially rescued by overexpressing foxn1, suggesting that restoring thymic epithelium may be a potential therapeutic strategy for treating immunodeficiency in CHARGE syndrome. Collectively, the results indicated that chd7 was critical for thymic development and T-lymphopenia in CHARGE syndrome may be mainly attributed to the defects of thymic organogenesis. The current finding may benefit the diagnosis and therapy of T lymphopenia and immunodeficiency in CHARGE syndrome.

Sema3E is required for migration of cranial neural crest cells in zebrafish: Implications for the pathogenesis of CHARGE syndrome.

CHARGE syndrome is a congenital disorder with multiple malformations in the craniofacial structures, and cardiovascular and genital systems, which are mainly affected by neural crest defects caused by loss-of-function mutations within chromodomain helicase DNA-binding protein 7 (CHD7). However, many patients with CHARGE syndrome test negative for CHD7. Semaphorin 3E (sema3E) is a gene reported to be mutated in patients with CHARGE syndrome. However, its role in the pathogenesis of CHARGE syndrome has not been verified experimentally. Here, we report that the knockdown of sema3E results in severe craniofacial malformations, including small eyes, defective cartilage and an abnormal number of otoliths in zebrafish embryos, which resemble the major features of CHARGE syndrome. Further analysis reveals that the migratory cranial neural crest cells are scattered in the region of the hindbrain, and the postmigratory neural crest cells are reduced in the pharyngeal arches upon sema3E knockdown. Notably, immunostaining and time-lapse imaging analyses of a neural crest cell-labelled transgenic fish line, sox10:EGFP, show that the migration of cranial neural crest cells is severely impaired, and many of these cells are misrouted upon sema3E knockdown. Furthermore, the sox10-expressing cranial neural crest cells are scattered in chd7 homozygous mutants, which phenocopied the phenotype in sema3E morphants. Overexpression of sema3E rescues the phenotype of scattered cranial neural crest cells in chd7 homozygotes, indicating that chd7 may control the expression of sema3E to regulate cranial neural crest cell migration. Collectively, our data demonstrate that sema3E is involved in the pathogenesis of CHARGE syndrome by modulating cranial neural crest cell migration.

Inguinal and Ilio-inguinal Lymphadenectomy in Management of Palpable Melanoma Lymph Node Metastasis: A Long-Term Prospective Evaluation of Morbidity and Quality of Life.

PURPOSE: Prospective data are lacking on long-term morbidity of inguinal lymphadenectomy including the influence of extent of surgery, use of radiotherapy, and patient factors. The aim of this study is to evaluate the effects of these factors on patient outcome, quality of life (QOL), regional symptoms, and limb volumes after inguinal or ilio-inguinal lymphadenectomy for melanoma. METHODS: Analysis of the subgroup of patients with inguinal lymph node field relapse of melanoma, treated by inguinal or ilio-inguinal lymphadenectomy in the ANZMTG/TROG randomized trial of adjuvant radiotherapy versus observation. RESULTS: Sixty-nine patients, 46 having undergone inguinal and 23 ilio-inguinal lymphadenectomy, with median follow-up of 73 months were analyzed. Mean limb volume increased rapidly after surgery (7% by 3 months) and continued to increase for at least another 18 months. Patients with body mass index (BMI) ≥ 25 kg/m2 had greater limb volume increase than normal-weight patients (13.3% versus 6.9%, P = 0.030). QOL improved over the first 18 months, but despite initial improvement, regional symptoms persisted long term. Type of surgery (inguinal or ilio-inguinal lymphadenectomy) had no demonstrably significant effect on limb volume (9.9% versus 13.4%, P = 0.35), QOL (P = 0.68), or regional symptoms (P = 0.65). There was no difference in overall survival between inguinal and ilio-inguinal lymphadenectomy [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.40-1.40, P = 0.43]. CONCLUSIONS: Inguinal lymphadenectomy for melanoma is a potentially morbid procedure with significant increases in limb volume. Patients report reasonable QOL but may have ongoing regional symptoms. Overweight/obesity is associated with poorer QOL, increased limb volume, and regional symptoms.