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Purpose: By recruiting reference population, we aimed to (1): estimate the 25(OH)D threshold that maximally inhibits the PTH, which can be defined as the cutoff value for vitamin D sufficiency; (2) establish the PTH reference interval (RI) in population with sufficient vitamin D., Methods: Study data were retrieved from LIS (Laboratory Information Management System) under literature suggested criteria, and outliers were excluded using Tukey fence method. Locally weighted regression (LOESS) and segmented regression (SR) were conducted to estimate the threshold of 25(OH)D. Multivariate linear regression was performed to evaluate the associations between PTH concentration and variables including 25(OH)D, gender, age, estimated glomerular filtration rate (EGFR), body mass index (BMI), albumin-adjusted serum calcium (aCa), serum phosphate(P), serum magnesium(Mg), and blood collection season. Z test was adopted to evaluate whether the reference interval should be stratified by determinants such as age and gender., Results: A total of 64,979 apparently healthy subjects were recruited in this study, with median (Q1, Q3) 25(OH)D of 45.33 (36.15, 57.50) nmol/L and median (Q1, Q3) PTH of 42.19 (34.24, 52.20) ng/L. The segmented regression determined the 25(OH)D threshold of 55 nmol/L above which PTH would somewhat plateau and of 22 nmol/L below which PTH would rise steeply. Multivariate linear regression suggested that gender, EGFR, and BMI were independently associated with PTH concentrations. The PTH RI was calculated as 22.17-72.72 ng/L for subjects with 25(OH)D ≥ 55 nmol/L with no necessity of stratification according to gender, age, menopausal status nor season., Conclusion: This study reported 25(OH)D thresholds of vitamin D sufficiency at 55 nmol/L and vitamin D deficiency at 22 nmol/L, and consequently established PTH RIs in subjects with sufficient vitamin D for northern China population for the first time., (© 2023. The Author(s).)

The aim was to investigate the association between bisphenol A (BPA), 25-hydroxy vitamin D [25(OH)D], and 1α,25 dihydroxy vitamin D [1,25(OH) 2 D] levels in the cord blood of newborn babies. BPA was measured by high pressure liquid chromatography (HPLC) and vitamin D levels by commercial ELISA or ECLIA kits. BPA and Vitamin D levels were grouped according to tertile values. In the cord blood, the median 25(OH)D level was 14.9 ng/mL (IQR: 8.5-20.8) and median 1,25(OH) 2 D level was 53.3 pg/dL (IQR: 42.3-98.4). 25(OH)D levels were < 20 ng/mL in 76.5% of the babies. BPA was detectable in 72.4% of the cord blood samples; median BPA level was 1.57 ng/mL (IQR: < DL-4.05 ng/mL). Frequencies of vitamin D deficiency and frequencies of cases having the highest tertile active vitamin D levels were similar in groups of BPA tertiles in both univariate and multivariate analysis. In conclusion, both BPA exposure and insufficient vitamin D transfer via cord blood are common in newborns. Bisphenol A levels were not correlated with vitamin D levels in cord blood of healthy mother-fetus pairs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and generally not associated with symptoms of hypercalcemia. High doses of cholecalciferol need to be avoided to protect against vitamin D toxicity and related complications. Strict adherence to the clinical guidelines for treating vitamin D deficiency can ensure safe and effective treatment., Purpose: We observed a tendency to use high doses of cholecalciferol for vitamin D deficiency treatment or vitamin D supplementation. We aimed to determine the biochemical characteristics of patients with high normal and elevated serum 25(OH)D levels., Methods: An online invitation was sent to all tertiary endocrinology clinics in Turkey to complete an online retrospective survey (DeVIT-TOX Survey) for patients diagnosed with high serum 25(OH)D levels (> 88 ng/mL) between January 2019 and December 2019. The patients were evaluated according to the presence of signs and symptoms of hypercalcemia and doses of vitamin D intake, evaluated into the following three groups according to their 25(OH)D levels: group 1, > 150 ng/mL; group 2, 149-100 ng/mL; and group 3, 99-88 ng/mL., Results: A total of 253 patients were included in the final analysis (female/male: 215/38; mean age, 51.5 ± 15.6 years). The average serum 25(OH)D level was 119.9 ± 33 (range, 88-455) ng/mL, and the average serum calcium level was 9.8 ± 0.7 (range, 8.1-13.1) mg/dL. Most (n = 201; 75.4%) patients were asymptomatic despite having high serum 25(OH)D and calcium levels. The serum 25(OH)D level was significantly higher in the symptomatic groups than in the asymptomatic groups (138.6 ± 64 ng/mL vs. 117.7 ± 31 ng/mL, p < 0.05). The most common cause (73.5%) associated with high serum 25(OH)D levels was the inappropriate prescription of a high dose of oral vitamin D (600.000-1.500.000 IU) for treating vitamin D deficiency/insufficiency in a short time (1-3 months). The cut-off value of 25 (OH) D level in patients with hypercalcemia was found to be 89 ng/mL [median 116.5 (89-216)]., Conclusions: High dose of vitamin D intake is associated with a high serum 25 OH D level, without symptoms of hypercalcemia. Inappropriate prescription of vitamin D is the primary cause for elevated 25(OH) D levels and related hypercalcemia. Hypercalcemia may not be observed in every patient at very high 25(OH) D levels. Adherence to the recommendation of guidelines is essential to ensure safe and effective treatment of vitamin D deficiency., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

We investigated the relationship between serum 25(OH)D levels, grip strength, and fall score in elderly osteoporotic women for fall risk assessment. Both low serum 25(OH)D and low grip strength were independently associated with increased fall risk. The serum 25(OH)D cutoff specific to increased fall risk was 14 mg/dL (35 nmol/L)., Purpose: This study aimed to establish a cutoff value of serum 25-hydroxyvitamin D (25(OH)D) for fall assessment and investigate the relationship between serum 25(OH)D, grip strength, and fall score adjusted for age in osteoporotic elderly Japanese women., Methods: This is a cross-sectional study utilizing collected data of osteoporotic elderly (age ≥65 years) female patients. A questionnaire for fall risk assessment was used, in which a score ≥ 6 was determined as increased fall risk. Serum 25(OH)D levels and grip strength were measured, and the cutoff points were calculated by receiver operating curve (ROC) analysis. Logistic regression analysis with age adjustment was conducted for potential risk factors for fall., Results: After applying eligibility criteria, finally, 349 patients were enrolled. The median patient age was 77.0 years, and the mean serum 25(OH)D level was 15.6 ng/mL (36 nmol/L). Based on the ROC analysis, we defined the cutoff values of serum 25(OH)D level and grip strength as 14 ng/mL (35 nmol/L) and 15 kg, respectively. A multivariate analysis adjusted for age was conducted. Low serum 25(OH)D level and grip strength were independent risk factors for ≥6 fall risk scores., Conclusion: Both low serum 25(OH)D level and low grip strength were independently associated with increased fall risk score in osteoporotic elderly women. The appropriate serum 25(OH)D cutoff specific to the increased fall risk group in this population was 14 mg/dL (35 nmol/L). These findings might be used for the identification of patients with high fall risks. These results should be confirmed in other patient groups.

The purpose was to determine if increasing serum 25(OH)D and calcium in postmenopausal women increased skeletal muscle size, strength, balance, and functional task performance while decreasing muscle fatigue. PCSA of the vastus lateralis increased and ascent of stairs time decreased after 6 months of increased serum 25(OH)D., Purpose: The Institute of Medicine recommends ≥ 20 ng/ml of serum 25-hydroxyvitamin D [25(OH)D] for bone and overall health. Serum 25(OH)D levels have been associated with physical performance, postural sway, and falls. The purpose of this study was to determine if increasing postmenopausal women's serum 25(OH)D levels from 20-30 ng/ml to 40-50 ng/ml improved skeletal muscle size, strength, balance, and functional performance while decreasing skeletal muscle fatigue., Methods: Twenty-six post-menopausal women (60-85 years old) with baseline serum 25(OH)D levels between 20 and 30 ng/ml were recruited. Oral over-the-counter (OTC) vitamin D3 and calcium citrate were prescribed to increase subjects' serum 25(OH)D to levels between 40 and 50 ng/ml, serum calcium levels above 9.2 mg/dl, and PTH levels below 60 pg/ml, which were confirmed at 6 and 12 weeks. Outcome measures assessed at baseline and 6 months included muscle physiological cross-sectional area (PCSA), muscle strength, postural balance, time to perform functional tasks, and muscle fatigue. Repeated measures comparisons between baseline and follow-up were performed., Results: Nineteen subjects completed the study. One individual could not afford the time commitment for the repeated measures. Three individuals did not take their vitamin D as recommended. Two subjects were lost to follow-up (lack of interest), and one did not achieve targeted serum 25(OH)D. Vastus lateralis PCSA increased (p = 0.007) and ascent of stair time decreased (p = 0.042) after 6 months of increasing serum 25(OH)D levels from 20-30 ng/ml to 40-50 ng/ml. Isometric strength was unchanged. Anterior-posterior center of pressure (COP) excursion and COP path length decreased (p < 0.1) albeit non-significantly, suggesting balance may improve from increased serum 25(OH)D and calcium citrate levels., Conclusions: Several measures of muscle structure and function were sensitive to elevated serum 25(OH)D and calcium levels indicating that further investigation of this phenomenon in post-menopausal women is warranted.

Objectives: The faecal-oral route is a predominant mode of infectious disease transmission and yet the immunology of the bovine oral cavity is poorly understood. The objectives of this study were to develop an in vitro cell model of bovine salivary gland cells and to characterize the role of vitamin D on the expression of innate immune genes induced by stimulation with bacterial and viral pathogen-associated molecular patterns (PAMPs)., Methods: Submandibular glandular tissue was excised post-mortem, processed, cells isolated and cultured until confluency after which cells were incubated with the active form of vitamin D (1,25(OH)D) for 18 h before stimulation with lipopolysaccharide (LPS μg/ml), lipoteichoic acid (LTA μg/ml) or polyinosinic:polycytidylic acid (poly I:C-20 μg/ml) PAMPs for 6 h and immune gene expression was assessed by Quantitative Real-Time PCR (RT-qPCR)., Results: RT-qPCR analysis of vimentin expression in cells derived from the bovine submandibular gland shows that cultured cells were fibroblast in origin. These cells significantly induce the pro-inflammatory cytokine IL1B, β-defensin and cathelicidin genes but these were not significantly altered in response to 1,25(OH)D. In contrast, 1,25(OH)D significantly up-regulates the expression of the NOS2 gene encoding iNOS in bovine submandibular stromal cells compared to EtOH (vehicle) control and this is a maintained response to all three bacterial and viral ligands. We have developed a new in vitro model to allow detailed investigations of mechanisms to enhance oral immunity in cattle. We show that these cells are fibroblast in nature, immunologically competent and vitamin D responsive. Their vitamin D-mediated enhancement of NOS2 expression warrants further investigation in saliva as a potential mechanism to boost oral immunity against infectious agents.

Background: While bedside assistants play a critical role in many robotic operations, substantial heterogeneity remains in bedside assistant training pathways. As such, this study aimed to develop consensus guidelines for bedside assistant skills required for team members in robotic operations., Methods: We designed a study using the Delphi process to develop consensus guidelines around bedside assistant skills. We generated an initial list of bedside assistant skills from the literature, training materials, and expert input. We selected experts for the Delphi process based on prior scholarship in the area of robotic bedside assistant education and experience facilitating robotic bedside assistant training. For each item, respondents specified which robotic team members should have the skill from a list of "basic" bedside assistants, "advanced" bedside assistants, surgeons, surgical technologists, and circulating nurses. We conducted two rounds of the Delphi process and defined 80% agreement as sufficient for consensus., Results: Fourteen experts participated in two rounds of the Delphi process. By the end of the second round, the group had reached consensus on 253 of 305 items (83%). The group determined that "basic" bedside assistants should have 52 skills and that "advanced" bedside assistants should have 60 skills. The group also determined that surgeons should have 54 skills, surgical technologists should have 25 skills, and circulating nurses should have 17 skills. Experts agreed that all participants should have certain communication skills and basic knowledge of aspects of the robotic system., Conclusions: We developed consensus guidelines on the skills required during robotic surgery by bedside assistants and other team members using the Delphi process. These findings can be used to design training around bedside assistant skills and assess team members to ensure that each team member has the appropriate skills. Hospitals can also use these guidelines to standardize expectations for robotic team members., (© 2024. The Author(s).)

Sunlight generates vitamin D, but there are scant human data from randomised trials on which to base health policy advice about how much sun exposure is necessary to change 25(OH)D concentrations. The purpose of the study was to evaluate the feasibility of using solar ultraviolet (UV) radiation exposure to generate a change in 25(OH)D concentration in a randomised controlled trial (RCT). The intervention tested in this RCT was supervised exposure to one standard erythemal dose (SED; 100 J m-2) of solar UV radiation three days per week for three weeks with approximately 35% of the body surface area not covered by clothing. Thirty-six fair-skinned (skin type II and III) indoor workers from Brisbane, Australia were randomised into either the intervention group (n = 16) or the control group (n = 20); the latter did not receive any supervised sun exposure. We asked both groups to use sunscreen and to minimise time outdoors during the study period. We collected blood samples at baseline, once per week during the three week intervention period, and four weeks after the intervention finished. The cumulative UV radiation exposure over the intervention period measured using polysulphone badges was higher in the intervention group than in the control group (median 8 vs. 4 SEDs, p = 0.14). After three weeks, the mean serum 25(OH)D concentration increased from 60 to 65 nmol l-1 in the intervention group and from 55 to 57 nmol l-1 in the control group. After adjustment for baseline 25(OH)D, the mean change per week during the intervention phase was non-significantly higher in the intervention than in the control group (0.7 vs. 0.3; p = 0.35). This difference was not sustained during the follow-up period. Large field trials are needed to inform policy about how much natural sun exposure is required to raise 25(OH)D concentrations. This pilot identified key issues that need to be considered in the design of such a trial.

The 25-hydroxy vitamin D (25(OH)D) production caused by UVB exposure is usually underestimated as the concurrent degradation of 25(OH)D is not considered. Therefore, the decrease in 25(OH)D was investigated during a 7-week period in winter when ambient UVB is negligible. Twenty-two healthy Danish individuals (113 samples) participated and had a mean and steady maximal 25(OH)D start level of 132 nmol l -1 (range of 68-216 nmol l -1 ) due to long-term UVB treatment prior to this study. In this group with high 25(OH)D start levels, the decrease in 25(OH)D was best described by an exponential model. This suggests a quantitatively larger elimination of 25(OH)D at high 25(OH)D start levels. A linear model (logarithm of 25(OH)D) including personal start levels as intercepts and a slope influenced by gender and the vitamin D receptor gene polymorphism rs2228570 explained 87.8% of the observed variation. The mean half-life was 89 days with a difference in half-life of 120 days between a male with rs2228570 genotype GG (59 days) and a female with rs2228570 genotype AA/AG (179 days). Thus, these two parameters explained a large part of the observed inter-individual variation of 25(OH)D. Furthermore, the decrease was analysed in two groups with medium and low 25(OH)D start levels resulting in longer half-lives of 149 days and 199 days, respectively. The longer half-lives at lower 25(OH)D levels may be caused by storage mobilisation, changed catabolism or increased intestinal absorption.

Deficiency of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and excessive fibroblast growth factor (FGF23) are suggested to be associated with increased mortality in patients with chronic kidney disease (CKD). Generally, 24-hydroxylation has been considered the first step in the degradation pathway of 1,25(OH)(2)D and 25(OH)D. 24,25-dihydroxyvitamin D [24,25(OH)(2)D] was believed to be a degradation product, with no important biological effects. However, some data have accumulated showing that 24,25(OH)(2)D has biological effects on its own. Under conditions of eucalcemia, the synthesis of 24,25(OH)(2)D is increased, and the synthesis of 1,25(OH)(2)D is decreased. In patients with CKD, both high parathyroid hormone levels, which decrease the activity of enzyme CYP24A1 (24-hydroxylase), and high FGF23 levels, which increase the activity of enzyme CYP24A1, were often detected. However, information about 24,25(OH)(2)D levels in these patients is very limited. Whether compensatory changes in levels of FGF23 and 24,25(OH)(2)D in CKD patients are protective or harmful remain unknown issues. Therefore, more studies are needed to identify the nature of the interactions between these molecules and to fully elucidate their clinical significance.

Introduction: Vitamin D deficiencies are well described in general populations and in those with chronic kidney disease (CKD). Although serum 25(OH)D may be a good indicator of vitamin D status in healthy individuals, the hydroxylated product, 1,25(OH)(2)D, essential for important biological functions such as mineral metabolism, bone turnover, regulation of protein synthesis, cell differentiation and proliferation may be a more suitable indicator for individuals with CKD., Methods: We report an observational prospective cohort study of the incidence after 12 months of new isolated 1,25(OH)(2)D and new 25(OH)D deficiency in CKD patients (estimated glomerular filtration rate [eGFR] <60 ml/min), who were vitamin D replete at baseline. All analyses were run in a central laboratory., Results: Of 1,256 patients who completed the study at 12 months, 631 were replete in both 25(OH)D and 1,25(OH)(2)D at baseline; at 12 months, 65% remained replete, 25% developed an isolated 1,25(OH)(2)D deficiency, whereas only 6% developed an isolated 25(OH)D deficiency. Based on the multinomial logistic regression model, factors that were associated with 12-month changes in vitamin D status were diabetes, baseline values of eGFR, albumin and both 25(OH)D and 1,25(OH)(2)D (all p values <0.03). Patients with diabetes, lower albumin, lower eGFR, lower levels of 25(OH)D and 1,25(OH)(2)D at baseline were at increased risk of developing isolated 1,25(OH)(2)D deficiency., Conclusions: The high incidence of new isolated 1,25(OH)(2)D deficiency as compared with new 25(OH)D deficiency, in the presence of 25(OH)D sufficiency, brings into question the value of measuring 25(OH)D levels in CKD. The significance of these findings and implications for replacement strategies require further study.

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by radical esophagectomy is the standard treatment for locally advanced esophageal squamous cell cancer (LA-ESCC). However, various nCRT regimens have been used, and their comparative efficacy and safety remain unclear., Methods: Patients with histologically confirmed LA-ESCC who underwent nCRT followed by radical esophagectomy between January 2016 and February 2022 were enrolled in this study. Of note, 3 different nCRT regimens were retrospectively compared: conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP) (Conv-FP), hypofractionated RT + FP (Hypo-FP), and regimens from the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial (CROSS). The overall survival (OS), pathologic complete response (pCR), toxicity, and treatment compliance rates were analyzed., Results: Among the 600 patients, 225 received Conv-FP, 255 received Hypo-FP, and 120 received the CROSS regimen. The OS rates at 1 year were 78.7%, 83.9%, and 88.1% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). The pCR rates were 30.6%, 33.9%, and 35.0%, respectively (P = .653). The overall incidence of grade 3 toxicities was 10.2%. Hematologic and nonhematologic toxicities of grade ≥ 3 were observed in 8.4% and 11.4%, 0% and 7.6%, and 5.5% and 0.8% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P = .002 and P = .030). Weight loss of > 5% was observed in 44.0%, 51.4%, and 32.5% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). In the multivariate analysis, clinical T stage (P = .004), N stage (P = .012), FP chemotherapy regimen (P = .013), surgical resection (P < .001), hematologic toxicity (P = .001), and weight loss (P = .004) were significantly associated with poor OS., Conclusion: The choice of nCRT regimen did not significantly affect the pCR rates in patients with LA-ESCC. However, the CROSS regimen demonstrated better OS and lower toxicity, suggesting that it may be the optimal treatment option among the groups., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Endoscopic multiple plastic stents are an established first-line treatment for anastomotic biliary stricture (ABS) management after liver transplantation (LT). Fully covered self-expandable metallic stents (FCSEMSs) have recently been used with favorable outcomes, but long-term treatment outcomes remain an issue for ABS. We evaluated the long-term outcomes of FCSEMS for the management of refractory ABS after LT., Methods: We reviewed the prospectively collected and maintained endoscopic retrograde cholangiography database at Asan Medical Center to retrieve consecutive post-LT ABS cases that underwent an endoscopic FCSEMS placement between August 2009 and August 2019 after MPS placement failure., Results: A total of 34 patients were enrolled in this study. Technical success had been achieved in all subjects (100%). The median stent placement duration was 3.1 months (IQR 2.7-6.1). Stricture resolution was achieved in 26 patients (clinical success 76.5%, 95% confidence interval 62-91). Early adverse events developed in 3 patients (8.8%), including distal stent migration. Late adverse events occurred in 9 patients (26.5%), including cholangitis (n = 7, 20.6%) and asymptomatic distal stent migration (n = 2, 5.9%). The median follow-up period was 57.9 months (IQR 51.9-64.3). Stricture recurrence occurred in 3 of 26 patients who achieved clinical success (11.5%)., Conclusions: FCSEMS placement appears to be an effective and advisable intervention for refractory ABS as it can provide persistent stricture improvement over the long-term., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This retrospective study was performed to investigate the survival differences according to the pathologic status after neoadjuvant chemotherapy followed by surgery in esophageal squamous cell carcinoma (ESCC), and to investigate whether current AJCC 8th ypStage can predict survival accurately., Methods: Data of 563 patients who received neoadjuvant therapy and esophagectomy for ESCC between 1994 and 2018 were retrospectively reviewed., Results: The mean age was 62.00 ± 8.01 years, of which 524 (93.1%) were males. The median follow-up period was 29.12 months. A total of 153 (27.1%) patients showed pathologic complete response (pCR) and 92 (16.3%) patients showed pCR of the primary lesion with residual metastatic lymph nodes (ypT0N +). A total of 196 (35%) and 122 (21.6%) patients showed ypT + N + and ypT + N, respectively. The 5-year overall survival (OS) of each group was 75.1% (CR), 42.4% (ypT + N0), 54.9% (ypT0N +), and 26.1% (ypT + N +); CR patients showed better survival than the other groups, and no survival differences were found in the 5-year OS between ypT + N0 and ypT0N + patients (p = 0.811). In ypStage I, there were survival differences between ypT0N0 and ypTis-2N0 patients, and ypT1N0 (ypStage I) and ypT0N1 (ypStageIIIA) showed similar OS (5-year OS in 49.3% vs. 67.1%, p = 0.623)., Conclusions: pCR offers long-term survival in patients; however, survival significantly declines with the presence of residual primary lesion and nodal metastases., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Objectives: To investigate whether the association between SJLsc (sleep-corrected social jetlag) and depressive mood is significant and independent of sleep debt., Methods: Participants from the general adult population were interviewed using structured questionnaires on sleep duration, weekday/weekend sleep schedules, and depressive mood (Patient Health Questionnaire-9). Social jetlag (SJL) was measured by SJLsc and standard SJL (SJLs). SJLs was the absolute difference between mid-sleep time on free days (MSF) and workdays (MSW). For SJLsc, both MSF and MSW were adjusted for average sleep duration across the week according to the direction of sleep debt. Sleep debt was defined by sleep extension on free days. The association of SJL with depression was investigated, and covariates included age, sex, sociodemographic factors, insomnia symptoms, sleep duration, and sleep debt., Results: A total of 1982 individuals (1089 men; age 43.1 ± 14.4 years) were analyzed. SJL was present in 24.6% measured by SJLsc and 51.0% by SJLs. SJLsc and SJLs were significantly associated with depressive mood (r = 0.06, P = 0.02; r = 0.06, P = 0.01, respectively), independent of sleep debt. Sleep debt was also associated with depression (r = 0.07, P < 0.01)., Conclusions: By adopting sleep-corrected formula for SJL, this study found that misaligned and insufficient sleep, at levels occurring in routine social life, can negatively affect mood. Minimizing social jetlag and sleep deprivation may promote individual psychological well-being., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: There has been increased interest in assessing the surgeon learning curve for new skill acquisition. While there is no consensus around the best methodology, one of the most frequently used learning curve assessments in the surgical literature is the cumulative sum curve (CUSUM) of operative time. To demonstrate the limitations of this methodology, we assessed the CUSUM of console time across cohorts of surgeons with differing case acquisition rates while varying the total number of cases used to calculate the CUSUM., Methods: We compared the CUSUM curves of the average console times of surgeons who completed their first 20 robotic-assisted (RAS) cases in 13, 26, 39, and 52 weeks, respectively, for their first 50 and 100 cases, respectively. This analysis was performed for prostatectomy (1094 surgeons), malignant hysterectomy (737 surgeons), and inguinal hernia (1486 surgeons)., Results: In all procedures, the CUSUM curve of the cohort of surgeons who completed their first 20 procedures in 13 weeks demonstrated a lower slope than cohorts of surgeons with slower case acquisition rates. The case number at which the peak of the CUSUM curve occurs uniformly increases when the total number of cases used in generation of the CUSUM chart changes from 50 to 100 cases., Conclusion: The CUSUM analyses of these three procedures suggests that surgeons with fast initial case acquisition rates have less variability in their operative times over the course of their learning curve. The peak of the CUSUM curve, which is often used in surgical learning curve literature to denote "proficiency" is predictably influenced by the total number of procedures evaluated, suggesting that defining the peak as the point at which a surgeon has overcome the learning curve is subject to routine bias. The CUSUM peak, by itself, is an insufficient measure of "conquering the learning curve.", (© 2023. The Author(s).)

Many robotic procedures require active participation by assistants. Most prior work on assistants' effect on outcomes has been limited in procedural focus and scope, with studies reporting differing results. Knowing how assistant experience affects operating room time could inform operating room case scheduling and provide an impetus for additional assistant training. As such, this retrospective cohort study aimed to determine the association between assistant experience and operating room time for 2291 robotic-assisted operations performed from 2016 to 2022 at our institution. Linear regression showed a significant association between the presence of a junior resident and increased case length differential with an increase of 26.9 min (p = 0.01). There were no significant associations between the presence of a senior resident (p = 0.52), presence of a fellow (p = 0.20), or presence of a physician assistant (p = 0.43) and case length differential. The finding of increased operating room time in the presence of a junior resident during robotic cases supports consideration of the adoption of formal assistant training programs for residents to improve efficiency., (© 2023. The Author(s).)

The taxonomic position of strain EF45031 T , isolated from the Neungam Carbonate hot spring, was examined using the polyphasic taxonomic approach. Strain EF45031 T shared the highest percentage of 16S rRNA gene sequence with Brachybacterium nesterenkovii CIP 104813  T (97.7%). The average nucleotide identity (ANI), average amino acid identity (AAI), and digital DNA-DNA hybridization (dDDH) values between strain EF45031 T and the type strains B. nesterenkovii CIP 104813  T and B. phenoliresistens Phenol-A T were 77.0%, 69.15%, 21.9% and 75.73%, 68.81%, 20.5%, respectively. Phylogenomic analysis using an up-to-date bacterial core gene (UBCG) set revealed that strain EF45031 T belonged to the genus Brachybacterium. Growth occurred between 25 and 50 ℃ at pH 6.0-9.0 and could tolerate salinity up to 5% (w/v). Strain had anteiso-C 15:0 and anteiso-C 17:0 as major fatty acids. Menaquinone-7 (MK-7) was the predominant respiratory menaquinone. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, three aminolipids, and two unidentified glycolipids. The cell-wall peptidoglycan contained meso-diaminopimelic acid as a diagnostic diamino acid. The genome comprised 2,663,796 bp, with a G + C content of 70.9%. Stress-responsive periplasmic chaperone/protease coding genes were identified in the genome of EF45031 T and were not detected in other Brachybacterium species. The polyphasic taxonomic properties indicate that the strain represents a novel species within the genus Brachybacterium, for which the name Brachybacterium sillae sp. nov. is proposed. The type strain is EF45031 T (= KCTC 49702  T  = NBRC 115869  T )., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This study aimed to evaluate the effect of photobiomodulation (PBM) for prevention of radiodermatitis in an irradiated mouse model and compare the efficacy of PBM using 633- or 830-nm wavelengths. Irradiated mice were randomly distributed into three groups: A (633 nm), B (830 nm), and C (without PBM). On post-irradiation days 7 and 21, we compared acute damage and recovery in treated skin samples to non-irradiated skin using H&E, Masson's trichrome, anti-CD45 and PCNA immunohistochemistry, and a TUNEL assay. Grade 3 radiodermatitis was evident only in group C. Compared with that in group C, the skin in groups A and B had significantly less epidermal hyperplasia, inflammatory cell infiltration, and thinner dermis on day 7 and less inflammatory cell infiltration, fewer apoptotic cells, and thinner dermis on day 21. However, there was no significant difference between groups A and B. This study indicates PBM could prevent severe radiodermatitis by reducing epidermal and dermal damage, inflammation, and apoptosis. There was no difference in PBM efficacy between the 633- and 830-nm wavelengths.

Simulation is increasingly being used to train surgeons and access technical competency in robotic skills. The construct validity of using simulation performance for high-stakes examinations such as credentialing has not been studied appropriately. There are data on how simulation exercises can differentiate between novice and expert surgeons, but there are limited data to support their use for distinguishing intermediate from competent surgeons. Senior cardiothoracic trainees with limited robotic but significant laparoscopic experience ("intermediate surgeons", IS) and practicing robotic thoracic surgeons ("competent surgeons", CS) participating in a thoracic cadaver robotic course were evaluated on three Da Vinci (Xi) simulations. Scores were separately recorded into components and analyzed by t-test for significant differences between groups. 21 competent and 17 intermediate surgeons participated. Overall scores did not have a statistically significant difference in any exercise between groups. Simulation exercises do not appear to distinguish intermediate from competent surgeon performance of robotic skills. Without better validity data, the use of simulation for credentialing should be thoughtfully considered., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Purpose: 68  Ga-DOTA-TOC uptake in the pancreas uncinate process is often found due to physiologic expression of somatostatin receptors (SSTR). We investigated the association of physiologic 68  Ga-DOTA-TOC uptake in the pancreas uncinate process with blood glucose level., Methods: 68  Ga-DOTA-TOC PET scans acquired from 44 patients (male:female = 20:24, age = 50.8 ± 14.8y [mean ± SD]) were retrospectively analyzed. The blood glucose level (BGL) was examined before 68  Ga-DOTA-TOC injection. Patients diagnosed with diabetes mellitus and patients with BGL over 200 mg/dl were excluded. 68  Ga-DOTA-TOC uptake was measured by the maximum standardized uptake values (SUVmax). Additionally, SSTR-positive volume (SV) in the pancreas uncinate process was measured with two different thresholds: by SUV cutoff of 2.5 (SV 2.5 ) and 40% of SUVmax (SV 40% ). These measurements on 68  Ga-DOTA-TOC PET were correlated with BGL., Results: The mean of SUVmax of the pancreas uncinate process was 6.51 ± 2.04. SV 2.5 was 17.81 ± 7.14 cm 3 , and SV 40% was 18.20 ± 8.83 cm 3 . A significant negative correlation was found between SUVmax of the pancreas uncinate process and BGL ( r  = -0.37, p  = 0.01). The ratio between SUVmax of the pancreas uncinate process and SUVmean of the pancreas body also showed a significance negative correlation with BGL ( r  = -0.40, p  = 0.01). SV 2.5 ( r  = 0.27, p  = 0.07) and SV 40% ( r  = -0.151, p  = 0.32) were not significantly correlated with BGL., Conclusion: Physiologic 68  Ga-DOTA-TOC uptake in the pancreas uncinate process was negatively correlated with BGL. Our results suggested that glycemia could affect physiologic uptake of 68  Ga-DOTA-TOC., Competing Interests: Competing InterestsDongkyu Oh, Hongyoon Choi, Jin Chul Paeng, Keon Wook Kang, and Gi Jeong Cheon declare no conflict of interest., (© Korean Society of Nuclear Medicine 2021.)

Background: Postoperative abdominal fluid collections (PAFCs) are a potentially fatal complication of pancreatobiliary surgery. Endoscopic ultrasound (EUS)-guided drainage has recently been shown to be effective in treating PAFCs of more than 4 weeks old. Little is currently known, however, regarding the EUS-guided drainage of PAFCs of less than 4 weeks. This study assessed the efficacy and safety of the early drainage (< 4 weeks) of PAFCs via EUS guidance., Methods: The data of patients who had undergone EUS-guided PAFC drainage between July 2008 and January 2018 were retrospectively analyzed. Data of EUS-guided PAFC drainage were obtained from prospectively collected EUS database of our institute and reviewed of patients' clinical parameters based on electrical medical record., Results: A total of 48 patients who had undergone EUS-guided PAFC drainage within 4 weeks of pancreatobiliary surgery were enrolled. The indications of procedure included abdominal pain (n = 27), fever (n = 18), leukocytosis (n = 2), and increased size of PAFC during external tube drainage (n = 1). Technical success was achieved in all cases, and the clinical success rate was 95.8% (46/48). Four patients underwent secondary procedures. The median period from surgery to EUS-guide drainage was 14 days (Interquartile range [IQR] 10-16), and median time to resolution was 23.5 days (IQR 8.5-33.8). Adverse events occurred in two cases that were developed intracystic bleeding and were successfully resolved by arterial coil embolization., Conclusions: Early EUS-guided drainage is a technically feasible, effective, and safe method in patients who have developing PAFCs within 4 weeks of pancreatobiliary surgery., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Limited therapy options exist for patients with treatment-refractory metastatic colorectal or anal cancers, prompting investigation into alternative therapies. Immunotherapy in the form of immune checkpoint blockade is one such emerging treatment that has demonstrated promising results in other tumour streams.x This review aims to assess the current use of immune checkpoint blockade in patients with lower gastrointestinal tumours., Patients and Methods: Embase, Medline and Cochrane databases were searched for included studies. Clinical trials published in English and utilising immune checkpoint blockade for primary tumours situated in the lower gastrointestinal tract were included. Databases were searched for studies reporting on at least one of overall survival, progression-free survival or response to therapy., Results: In total, 972 abstracts were screened, with 10 studies included in the final review. Eight trials (833 patients) assessed immune checkpoint blockade in the setting of colorectal cancers. These included pembrolizumab, nivolumab, durvalumab, atezolizumab, tremelimumab and ipilimumab. A total of 20 patients across all studies achieved a complete response, and 111 patients achieved a partial response to treatment. Two trials (62 patients) assessed immune checkpoint blockade in anal cancer, utilising nivolumab and pembrolizumab. Two patients across both studies achieved a complete response, and 11 patients achieved a partial response., Conclusions: A number of patients with advanced lower gastrointestinal tumours achieved a complete response to treatment for what would otherwise be considered palliative disease. Presented data have highlighted that particular patients may benefit from first-line or combination immunotherapy, and thus, further investigation is warranted to individualise treatment., (© 2021. Society of Surgical Oncology.)

Many regulatory RNAs undergo dynamic exchanges that are crucial for their biological functions and NMR spectroscopy is a versatile tool for monitoring dynamic motions of biomolecules. Meaningful information on biomolecular dynamics requires an accurate measurement of relaxation parameters such as longitudinal (R 1 ) rates, transverse (R 2 ) rates and heteronuclear Overhauser effect (hNOE). However, earlier studies have shown that the large 13 C- 13 C interactions complicate analysis of the carbon relaxation parameters. To investigate the effect of 13 C- 13 C interactions on RNA dynamic studies, we performed relaxation measurements on various RNA samples with different labeling patterns and compared these measurements with the computational simulations. For uniformly labeled samples, contributions of the neighboring carbon to R 1 measurements were observed. These contributions increased with increasing magnetic field and overall correlation time ([Formula: see text]) for R 1 rates, necessitating more careful analysis for uniformly labeled large RNAs. In addition, the hNOE measurements were also affected by the adjacent carbon nuclei. Unlike R 1 rates, R 1ρ rates showed relatively good agreement between uniformly- and site-selectively labeled samples, suggesting no dramatic effect from their attached carbon, in agreement with previous observations. Overall, having more accurate rate measurements avoids complex analysis and will be a key for interpreting 13 C relaxation rates for molecular motion that can provide valuable insights into cellular molecular recognition events.

Acute radiodermatitis is one of the major complications when radiation therapy (RT) is delivered to the head and neck region in cases of head and neck cancers or lung cancers with supraclavicular lymph node metastasis. In these cases, high dose of RT is generally used so that acute radiodermatitis is observed in more than 90% of patients, and it negatively affects patients' quality of life. In this pilot study, we evaluated the clinical feasibility of photobiomodulation (PBM) therapy before conducting a randomized trial based on the hypothesis that PBM therapy may reduce the severity of radiodermatitis in participants receiving 60 Gy or higher dose. Patients who were to receive 60 Gy or higher dose in the neck were included in the study. Thirty-three patients received PBM therapy three times a week during RT. The severity of radiodermatitis was evaluated by two dermatologists and a radiation oncologist using the modified Common Terminology Criteria for Adverse Events (CTCAE). Patients were followed up until a week after RT. In all patients, 90.6% of planned PBM schedule was completed. There was no significant side effect of PBM therapy. Thirteen (39%) patients showed wet desquamation (CTCAE grade 2b or higher). Only three (9%) of them showed grade 3 toxicity, which is a favorable result compared with previous studies. This pilot study showed that PBM therapy is safe and feasible in the clinic, and it might reduce the severity of radiodermatitis. A randomized trial should be warranted to prove the efficacy of PBM therapy.

Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by hypercalcemia due to inappropriately high parathyroid hormone secretion. While in the typical, symptomatic form of the disease diagnosis is set easily and standard management is surgical removal of the hyperfunctioning parathyroid (HP), this may not be the case in more subtle forms of PHPT, such as the asymptomatic and the normocalcemic PHPT. Localization of the HP could also be challenging, especially in small-sized adenomas, ectopic lesions or multiglandular disease. An experienced surgical team is essential to achieve curative parathyroidectomy. In this article, we used illustrative clinical vignettes to dissect the approach to the patient with PHPT, from the diagnosis establishment to the suggested investigation to identify classical and non-classical PHPT features and the methodology to locate the abnormal tissue. Accordingly, we elaborated on appropriate management, both surgical and conservative., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Malignant Distal Biliary Obstruction (MBDO) is a common event occurring along the natural history of both pancreatic cancer and cholangiocarcinoma. Epidemiological and biological features make MBDO one of the key elements of the clinical management of patients suffering for of pancreatic cancer or cholangiocarcinoma. The development of dedicated biliary lumen-apposing metal stents (LAMS) is changing the clinical work up of patients with MBDO. i-EUS is an Italian network of clinicians and scientists with a special interest in biliopancreatic endoscopy, EUS in particular., Methods: The scientific methodology was chosen in line with international guidance and in a fashion similar to those applied by broader scientific associations. PICO questions were elaborated and subsequently voted by a broad panel of experts within a simplified Delphi process., Results and Conclusions: The manuscripts describes the results of a consensus conference organized by i-EUS with the aim of providing an evidence based-guidance for the appropriate use of the techniques in patients with MBDO., (© 2024. The Author(s).)

Background: Pancreatic and biliary tract cancers are digestive system tumors with dismal prognosis and limited treatment options. The effectiveness of conventional surgical interventions, radiation therapy, and systemic therapy is restricted in these cases. Furthermore, clinical trials have shown that immunotherapy using immune checkpoint inhibitors has only demonstrated modest clinical results when applied to patients with pancreatobiliary tumors. This highlights the importance of implementing combination immunotherapy approaches or exploring alternative therapeutic strategies to improve treatment outcomes., Materials and Methods: We reviewed the relevant literature on chimeric antigen receptor (CAR)-T cell therapy for pancreatobiliary cancers from PubMed/Medline and ClinicalTrials.gov and retrieved the relevant data accordingly. Attention was additionally given to the examination of grey literature with the aim of obtaining additional details regarding ongoing clinical trials. We mainly focused on abstracts and presentations and e-posters and slides of recent important annual meetings (namely ESMO Immuno-Oncology Congress, ESMO Congress, ASCO Virtual Scientific Program, ASCO Gastrointestinal Cancers Symposium)., Results: CAR-T cell therapy has emerged as a promising and evolving treatment approach for pancreatic and biliary tract cancer. This form of adoptive cell therapy utilizes genetic engineering to modify the expression of specific antibodies on the surface of T cells enabling them to target specific cancer-associated antigens and to induce potent anti-tumor activity. The aim of this review is to provide an updated summary of the available evidence from clinical trials that have explored the application of CAR-T cell therapy in treating pancreatobiliary cancers., Conclusions: While the utilization of CAR-T cell therapy in pancreatobiliary cancers is still in its initial phases with only a limited amount of clinical data available, the field is advancing rapidly, incorporating novel technologies to mitigate potential toxicities and enhance antigen-directed tumor eradication., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background This cross-sectional study investigates the association of fibroblast growth-factor 23 (FGF23) and other bone mineral parameters with iron status and anemia in pediatric chronic kidney disease (CKD). Methods Serum calcium, phosphorus, 25-hydroxyvitamin D (25(OH)D), intact parathormone, c-terminal FGF23, a-Klotho, iron (Fe), ferritin, unsaturated iron-binding capacity, and hemoglobin (Hb) were measured in 53 patients from 5 to 19 years old with GFR 100 ng/mL, TSAT [less than or equal to] 20%) were observed in 32% and 7.5% of patients, respectively. In CKD stages 3-4 (36 patients), lnFGF23 and 25(OH)D were correlated with Fe (rs = - 0.418, p = 0.012 and rs = 0.467, p = 0.005) and TSAT (rs = - 0.357, p = 0.035 and rs = 0.487, p = 0.003) but not to ferritin. In this patient group, lnFGF23 and 25(OH)D were correlated with Hb z-score (rs = - 0.649, p < 0.001 and rs = 0.358, p = 0.035). No correlation was detected between lnKlotho and iron parameters. In CKD stages 3-4, in multivariate backward logistic regression analysis, including bone mineral parameters, CKD stage, patient age, and daily alphacalcidol dose as covariates, lnFGF23 and 25(OH)D were associated with low TS[Alpha][Tau] (15 patients) (OR 6.348, 95% CI 1.106-36.419, and OR 0.619, 95% CI 0.429-0.894, respectively); lnFGF23 was associated with low Hb (10 patients) (OR 5.747, 95% CI 1.270-26.005); while the association between 25(OH)D and low Hb did not reach statistical significance (OR 0.818, 95% CI 0.637-1.050). Conclusions In pediatric CKD stages 3-4, iron deficiency and anemia are associated with increased FGF23, independently of Klotho. Vitamin D deficiency might contribute to iron deficiency in this population. Graphical abstract, Author(s): Vasiliki Karava [sup.1] , John Dotis [sup.1] , Antonia Kondou [sup.1] , Athanasios Christoforidis [sup.2] , Anna Taparkou [sup.3] , Evangelia Farmaki [sup.3] , Marina Economou [sup.4] , Nikoleta [...]

Purpose: Although quantification of amyloid positron emission tomography (PET) is important for evaluating patients with cognitive impairment, its routine clinical use is hampered by complicated preprocessing steps and required MRI. Here, we suggested a one-step quantification based on deep learning using native-space amyloid PET images of different radiotracers acquired from multiple centers., Methods: Amyloid PET data of the Alzheimer Disease Neuroimaging Initiative (ADNI) were used for this study. A training/validation consists of 850 florbetapir PET images. Three hundred sixty-six florbetapir and 89 florbetaben PET images were used as test sets to evaluate the model. Native-space amyloid PET images were used as inputs, and the outputs were standardized uptake value ratios (SUVRs) calculated by the conventional MR-based method., Results: The mean absolute errors (MAEs) of the composite SUVR were 0.040, 0.060, and 0.050 of training/validation and test sets for florbetapir PET and a test set for florbetaben PET, respectively. The agreement of amyloid positivity measured by Cohen's kappa for test sets of florbetapir and florbetaben PET were 0.87 and 0.89, respectively., Conclusion: We suggest a one-step quantification method for amyloid PET via a deep learning model. The model is highly reliable to quantify the amyloid PET regardless of multicenter images and various radiotracers., Competing Interests: Conflict of InterestJi-Young Kim, Hoon Young Suh, Hyun Gee Ryoo, Donkyu Oh, Hongyoon Choi, Jin Chul Paeng, Gi Jeong Cheon, Keon Wook Kang, Dong Soo Lee, and for the Alzheimer’s Disease Neuroimaging Initiative declare that they have no conflict of interest., (© Korean Society of Nuclear Medicine 2019.)

Purpose: In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT., Methods: Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D 3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH) 2 vitamin D (1,25(OH) 2 D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH) 2 D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS)., Results: 70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH) 2 D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH) 2 D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups., Conclusion: The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH) 2 D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

As a bilateral or multilateral international policy, foreign aid has the potential to contribute to economic growth in recipient countries, but the impact on green growth, especially aid flows to the energy sector, is unclear. Existing studies have paid little attention to the actual effects of whether energy aid is effective in raising green total factor productivity (GTFP) in recipient countries. To fill this gap, this study investigates the dynamic impact of energy aid on GTFP in recipient countries using balanced panel data for 92 countries from 2002 to 2019, and the study also examines potential sectoral heterogeneity and impact mechanisms. The results show that energy aid can effectively contribute to improving GTFP in recipient countries, but this scale effect varies significantly by aid type, revealing sectoral heterogeneity in the impact of energy aid. In addition, energy aid can indirectly enhance GTFP in recipient countries by promoting financial development, optimizing energy mix, and improving energy efficiency. Both government quality and human capital have a positive moderating effect on the energy aid-GTFP relationship. These findings reveal an important mechanism for energy aid to contribute to green economic growth and provide theoretical support and a practical basis for the formulation of more targeted aid policies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hypovitaminosis D has been reported to be common in chronic kidney disease (CKD) as well as in proteinuric disorders. We reviewed available evidence to assess clinically relevant effects of low vitamin D status and native vitamin D (NVD) therapy, in pediatric renal diseases. Online medical databases were searched for articles related to vitamin D status, associations of hypovitaminosis D and effects of NVD therapy in kidney disease. Hypovitaminosis D was associated with worse skeletal, cardiovascular, inflammatory, and renal survival outcomes in CKD. Low serum 25 hydroxy-vitamin D (25[OH]D) levels correlated positively with glomerular filtration rate and negatively with serum parathyroid (PTH) levels. However, to date, evidence of benefit of NVD supplementation is restricted mainly to improvements in serum PTH, and biochemical 25[OH]D targets form the basis of clinical practice recommendations for NVD therapy. In nephrotic syndrome (NS) relapse, studies indicate loss of 25[OH]D along with vitamin D binding protein in urine, and serum total 25[OH]D levels are low. Preliminary evidence indicates that free 25[OH]D may be a better guide to the biologically active fraction. NVD therapy in NS does not show consistent results in improving skeletal outcomes and hypercalciuria has been reported when total 25[OH]D levels were considered as indication for therapy. NVD formulations should be regularised, and therapy monitored adequately to avoid adverse effects., Author(s): Sushmita Banerjee [sup.1] , Jayati Sengupta [sup.1] , Surupa Basu [sup.2] Author Affiliations: (1) grid.414710.7, 0000 0004 1801 0469, Department of Pediatric Nephrology, Institute of Child Health, , Kolkata, [...]

We analyzed patterns of care and outcomes for patients with primary central nervous system lymphoma (PCNSL) in this multi-institutional retrospective study. Between January 2000 and December 2011, 220 patients with PCNSL received radiotherapy (RT). Among these patients, 26 patients received RT alone; 179 patients were treated with chemotherapy and radiotherapy; the rest of the patients (N = 15) initially underwent chemotherapy alone, then received RT as a salvage treatment. Most of the patients (N = 188) received methotrexate-based chemotherapy. The median follow up duration was 38 months (range 3-179 months). The median RT dose and whole brain RT (WBRT) dose were 45.0 Gy (range 20.0-59.4) and 30.6 Gy (range 18.0-45.0), respectively. Seventy-seven (35%) patients received WBRT alone, and 143 patients (65%) underwent WBRT plus boost RT. Total RT dose and WBRT dose decreased during the study period. The median survival was 64 months and actuarial 5-year overall survival was 51.4%. In multivariate analysis, age (P < 0.001), ECOG performance status (P = 0.036), deep structure involvement (P = 0.011) and treatment response (P = 0.001) were significant prognosticators. RT combined with chemotherapy is effective modality for treatment of PCNSL. The survival outcome improved in spite of total radiation dose and whole brain RT (WBRT) dose having been decreased over the study period, indicating that low-dose WBRT could be effective.

Background: Despite increases in the performance of pure laparoscopic living donor hepatectomy, variations in the bile duct or portal vein have been regarded as relative contraindications to this technique [1-3]. This report describes a donor with separate right posterior and right anterior hepatic ducts and portal veins who underwent pure laparoscopic living donor right hemihepatectomy, integrated with 3D laparoscopy and indocyanine green (ICG) near-infrared fluorescence cholangiography [1, 4, 5]., Methods: A 50-year-old man offered to donate part of his liver to his older brother, who required a transplant for hepatitis B-associated liver cirrhosis and hepatocellular carcinoma. Donor height was 178.0 cm, body weight was 82.7 kg, and body mass index was 26.1 kg/m 2 . Preoperative computed tomography and magnetic resonance cholangiopancreatography showed that the donor had separate right posterior and right anterior hepatic ducts and portal veins. The entire procedure was performed under 3D laparoscopic view. Following intravenous injections of 0.05 mg/kg ICG, ICG near-infrared fluorescence camera was used to demarcate the exact transection line and determine the optimal bile duct division point., Results: The total operation time was 443 min; the donor required no transfusions and experienced no intraoperative complications. The graft weighed 1146 g with a graft-to-recipient weight ratio of 1.88%. The optimal bile duct division point was identified using ICG fluorescence cholangiography, and the bile duct was divided with good patency without any stricture. The right anterior and posterior portal veins were transected with endostaplers without any torsion. The patient was discharged on postoperative day 8, with no complications., Conclusion: Using a 3D view and ICG fluorescence cholangiography, pure 3D laparoscopic living donor right hemihepatectomy is feasible in a donor with separate right posterior and right anterior hepatic ducts and portal veins.

Establishing specific reference intervals (RIs) of serum 25-hydroxyvitamin D3 [25(OH)D] for children is essential for improving the accuracy of diagnosis and prognosis monitoring of diseases such as rickets and growth retardation. The study including 6,627 healthy children was conducted to establish specific RIs of 25(OH)D for children in Nanning area of China. The results showed that there were statistically significant differences among age, season, and gender of serum 25(OH)D levels, and the age-specific RIs of serum 25(OH)D were 20.3 ~ 53.6 ng/mL for 0 ~ [less than or equal to] 1 year and 18.9 ~ 49.6 ng/mL for 2 ~ [less than or equal to] 3 years. The age-, season-specific RIs of serum 25(OH)D for 4 ~ [less than or equal to] 6 years in spring-summer and autumn-winter were 15.8 ~ 42.6 ng/mL and 15.2 ~ 37.7 ng/mL, respectively. The age-, gender-specific RIs of serum 25(OH)D for 7 ~ [less than or equal to] 18 years for males and females were 12.1 ~ 36.1 ng/mL and 10.8 ~ 35.3 ng/mL, respectively. This study successfully established the RIs of serum 25(OH)D, which may help to improve disease diagnosis and monitoring for children in the Nanning area of China. Keywords: Reference intervals (RIs), 25-hydroxyvitamin D.sub.3 [25(OH)D, Vitamin D, Children, Author(s): Dong-yi Zhou[sup.1], Shang-mou Wei[sup.1], Chun-ling Zhu[sup.1], Yu-hong Wei[sup.1], Xiao-mei Wang[sup.1], Li-ling Yi[sup.1], Si-tao Yang[sup.1] and Qi-liu Peng[sup.1] Introduction Vitamin D is a fat-soluble steroid vitamin that is essential for [...]

Background: Histologic grade of tumor is one of the major prognostic predictors for patients with salivary gland cancer. Because of disease rarity, little is known about the optimal treatment modalities and outcomes in low-grade salivary gland cancers (LGSGC). We tried to identify prognostic factors, and the adequate treatment modalities and outcomes in pathologically confirmed LGSGC patients., Methods: We retrospectively extracted the clinical and pathology data from 179 LGSGC cases from 1995 to 2013. Pathological features, such as extraparenchymal extension, perineural/nerve invasion, lymphovascular invasion/tumor emboli, and resection margin status were redefined for each case. Risk factors for recurrence, extent of surgery, and the role of postoperative radiation therapy were analyzed., Results: Recurrence-free survival and overall survival were 89.6 and 96.6 % at 10 years, respectively. The presence of regional nodal metastasis and positive cancer cells at resection margin were significant unfavorable prognostic factors. Postoperative adjuvant radiation treatment significantly reduced recurrences, particularly in cases with pathology risk factors (perineural invasion, lymphovascular invasion, extraparenchymal extension, or cancer cells at the resection margin), node metastasis, and advanced T-stage tumors. Close surgical margin <5 mm was not a significant risk factor for recurrence, and less-than-total resection of the affected gland did not increase recurrence, if surgery could achieve a cancer cell-free surgical margin., Conclusion: Postoperative radiation clearly benefitted patients with pathology risk factors, node metastasis, and advanced T stage in LGSGC. Meanwhile, the oncological outcomes are very good with surgery alone in cases of pT1-2N0 LGSGC without pathology risk factors.

Background: Whether to administer surgical or non-surgical treatments (radiation or chemoradiation therapies) for the initial management of hypopharyngeal cancer (HPC) remains a topic of debate. Herein, we explored the differences between the two approaches in terms of oncological and functional outcomes in 332 HPC patients., Methods: The primary endpoint was survival probability; secondary outcomes included post-treatment speech and swallowing functions and necessity of additional surgical procedures for salvage or complication management. Cox proportional hazard models using clinical variables were constructed to identify significant factors., Results: The 2- and 5-year overall survival (OS) rates in all patients were 64.9 and 40.9 %, respectively. In early-stage HPC patients (N = 52), initial surgery ± radiation therapy (RT) or RT alone yielded similar oncological (60 % 5-year OS rate) and functional outcomes. As for resectable advanced-stage cancers (N = 177), initial surgery ± RT/chemoradiation therapy (SRC) and initial concurrent chemoradiation therapy (iCRT) resulted in similar 45-50 % 5-year OS rates. After sacrificing the larynx, 60 % of SRC patients recovered their speaking ability through voice prosthesis, which was less than the rate for iCRT patients (76.6 %; p = 0.008). Additional surgical interventions were required in 28.0-28.6 % of patients in both groups; however, 60 % of patients undergoing additional surgery in the iCRT group received multiple (two or more) surgical interventions (p = 0.029)., Conclusions: Our data revealed similar oncological outcomes, but different functional outcomes, between initial surgical and non-surgical treatments for HPC. In resectable advanced-stage HPC, iCRT resulted in better verbal communication outcomes than SRC; however, more iCRT patients required multiple surgical interventions during clinical courses.

Purpose: Non-alcoholic fatty liver disease (NAFLD) and hypovitaminosis D are highly prevalent in people with spinal cord injury (SCI) and could exert an unfavorable influence on cardiovascular profile and rehabilitation outcomes. We aimed to assess the independent association between low 25-hydroxy vitamin D (25(OH)D) levels and NAFLD in people with chronic (> 1 year) SCI., Methods: One hundred seventy-three consecutive patients with chronic SCI (132 men and 41 women) admitted to a rehabilitation program underwent clinical/biochemical evaluations and liver ultrasonography., Results: NAFLD was found in 105 patients (60.7% of the study population). They were significantly older and exhibited a poorer leisure time physical activity (LTPA) and functional independence in activities of daily living, a greater number of comorbidities and a higher prevalence of metabolic syndrome (MetS) and its correlates, including lower HDL and higher values of body mass index (BMI), systolic blood pressure, HOMA-index of insulin resistance and triglycerides. 25(OH)D levels were significantly lower in NAFLD (median: 10.6 ng/ml, range: 2.0-31.0) than in non-NAFLD group (22.5 ng/ml, 4.2-51.6). When all these variables were included in a multiple logistic regression analysis, a significant independent association with NAFLD only persisted for lower 25(OH)D levels, a greater number of comorbidities and a poorer LTPA. The ROC analysis revealed that 25(OH)D levels < 18.25 ng/ml discriminated patients with NAFLD with a sensitivity of 89.0% and a specificity of 73.0% (AUC: 85.7%; 95%CI: 79.6-91.7%). NAFLD was exhibited by 83.9% of patients with 25(OH)D levels < 18.25 ng/ml and by 18% of those with 25(OH)D levels ≥ 18.25 ng/ml (p < 0.0001)., Conclusion: In people with chronic SCI, 25(OH)D levels < 18.25 ng/ml may represent a marker of NAFLD independent of MetS-related features. Further studies are warranted to define the cause-effect relationships of this association., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background Correction of nutritional vitamin deficiency is recommended in children with chronic kidney disease (CKD). The optimal daily dose of vitamin D to achieve or maintain vitamin D sufficiency is unknown. Methods We conducted a phase III, double-blind, randomized trial of two doses of vitamin D.sub.3 in children [greater than or equal to] 9 years of age with CKD stages 3-5 or kidney transplant recipients. Patients were randomized to 1000 IU or 4000 IU of daily vitamin D.sub.3 orally. We measured 25-hydroxvitamin D (25(OH)D) levels at baseline, 3 months and 6 months. The primary efficacy outcome was the percentage of patients who were vitamin D replete (25(OH)D [greater than or equal to] 30 ng/mL) at 6 months. Results Ninety-eight patients were enrolled: 49 randomized into each group. Eighty (81.6%) patients completed the study and were analyzed. Baseline plasma 25(OH)D levels were [greater than or equal to] 30 ng/mL in 12 (35.3%) and 12 (27.3%) patients in the 1000 IU and 4000 IU treatment groups, respectively. At 6 months, plasma 25(OH)D levels were [greater than or equal to] 30 ng/mL in 33.3% (95% CI: 18.0-51.8%) and 74.4% (95% CI: 58.8-86.5%) in the 1000 IU and 4000 IU treatment groups, respectively (p = 0.0008). None of the patients developed vitamin D toxicity or hypercalcemia. Conclusions In children with CKD, 1000 IU of daily vitamin D.sub.3 is unlikely to achieve or maintain a plasma 25(OH)D [greater than or equal to] 30 ng/mL. In children with CKD stages 3-5, a dose of vitamin D.sub.3 4000 IU daily was effective in achieving or maintaining vitamin D sufficiency. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT01909115 Graphical abstract, Author(s): Shahid Nadeem [sup.1] , Vin Tangpricha [sup.2] , Thomas R. Ziegler [sup.3] , James E. Rhodes [sup.4] , Traci Leong [sup.5] , Yijin Xiang [sup.6] , Larry A. Greenbaum [...]

Background: Treatment for patients with N2-positive stage IIIA non-small cell lung cancer has been a controversial issue. The current study evaluated the outcomes in patients treated with trimodality therapy, which consisted of neoadjuvant radiation therapy concurrent with chemotherapy followed by surgical resection, with emphasis on clinical and pathologic nodal status., Methods: We reviewed the records of 355 patients who were treated with trimodality therapy between 1997 and 2011., Results: After completion of neoadjuvant chemoradiation, overall down-staging and complete response rates were 50.4 % (179 patients), and 13.2 % (47 patients), respectively. With median follow-up of 35.3 months, median times of progression-free survival (PFS) and overall survival (OS) were 16.3 months and 45.5 months, respectively. Seventeen patients (4.8 %) died of postoperative complications, and the remaining 338 patients were analyzed on prognostic factors. Old age (p = 0.032), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were found to be the significant prognosticators for worse PFS, and old age (p = 0.013), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were related to worse OS. Clinical N2 status did not influence either OS or PFS: the number of involved stations (single station vs. multi-station; p = 0.187 for PFS; p = 0.492 for OS), and bulk (clinically evident vs. microscopic; p = 0.902 for PFS; p = 0.915 for OS)., Conclusion: ypN stage was the most important prognosticator for both PFS and OS; however, neither initial bulk nor extent of cN2 disease influenced prognosis. Surgery following neoadjuvant chemoradiation should have contributed to improved clinical outcomes regardless of clinical nodal bulk and extent.

Two halophilic archaeal strains, R30(T) and tADL(T), were isolated from an aquaculture farm in Dailing, China, and from Deep Lake, Antarctica, respectively. Both have rod-shaped cells that lyse in distilled water, stain Gram-negative and form red-pigmented colonies. They are neutrophilic, require >120 g/l NaCl and 48-67 g/l MgCl(2) for growth but differ in their optimum growth temperatures (30 °C, tADL(T) vs. 40 °C, R30(T)). The major polar lipids were typical for members of the Archaea but also included a major glycolipid chromatographically identical to sulfated mannosyl glucosyl diether (S-DGD-1). The 16S rRNA gene sequences of the two strains are 97.4 % identical, show most similarity to genes of the family Halobacteriaceae, and cluster together as a distinct clade in phylogenetic tree reconstructions. The rpoB' gene similarity between strains R30(T) and tADL(T) is 92.9 % and less to other halobacteria. Their DNA G + C contents are 62.4-62.9 mol % but DNA-DNA hybridization gives a relatedness of only 44 %. Based on phenotypic, chemotaxonomic and phylogenetic properties, we describe two new species of a novel genus, represented by strain R30(T) (= CGMCC 1.10593(T) = JCM 17270(T)) and strain tADL(T) (= JCM 15066(T) = DSMZ 22187(T)) for which we propose the names Halohasta litorea gen. nov., sp. nov. and Halohasta litchfieldiae sp. nov., respectively.