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A coupled thermomechanical finite element analysis is performed in order to simulate orthogonal cutting of normalized AISI 9310. Damage parameters are optimized to define the behavior of the material subjected to orthogonal cutting. AISI 1045, AISI 4140, and A2024-T351 are selected as precursors to validating the present finite element approach for orthogonal cutting of normalized AISI 9310. The numerical results obtained in this study include the average cutting force, residual stresses and strains, chip morphology, and tool temperature. These results are validated for each material with experimental results found in literature. The current study optimizes the Johnson–Cook damage parameters for steel materials in order to capture physical chip morphology. A correlation analysis is then performed using the validated finite element model for the AISI 9310 material to better understand the effect of specific input parameters such as the damage parameters, coefficient of friction, fracture energy, heat generation fractions and tool velocity on output results such as stresses and strains in the workpiece, chip thickness ratio and tool temperature. This analysis provides input-output relations for a physically reasonable range of input parameters and supports that the damage parameters, coefficient of friction, and fracture energy have a very strong influence on the residual stresses and strains, and the chip morphology. The coefficient of friction has a strong influence of tool temperature. Correlation analysis results can help manufacturers in understanding the nature of residual stresses and distortion, and in choosing optimized process parameters suitable for and applicable to the specific workpiece material. Tool wear that is observed in actual cutting of normalized AISI 9310 is also discussed. This study will benefit the manufacturing industry with the understanding of how specific cutting processing parameters will impact the distortions and residual stresses in the machined AISI 9310 parts.

Background High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/β ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/β ratio for NSCLC treated with SBRT using individual patient data. Materials and methods We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/β ratio based on the observed number of local recurrences and accounting for tumor size. Results A total of 109 local progressions were observed after a median of 17.7 months (range 0.6–76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/β = 12.8 Gy, 14.9 Gy and 12–16 Gy (depending on the prior for α/β), respectively, although with large uncertainties that did not rule out the conventional α/β = 10 Gy. Conclusions Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/β = 10 Gy is not ruled out by our data, larger values in the range 12–16 Gy are more probable, consistent with recent meta-regression analyses.

Vitamin D has been shown to be associated with reduced risk and severity of COVID-19 and exerts regulating effects on all hallmarks of cancer. The goal of this study was to analyze the vitamin D status of a cancer patient cohort from our clinic in the Franconian region, Germany.25-hydroxyvitamin D concentrations were available for 116 patients included in prospective trials in our clinic. Associations of vitamin D with anthropometric and blood parameters were investigated using Kendall's τ correlation coefficients and linear regression.A total of 57 patients (49.1%) were vitamin D deficient (20 ng/mL), and 92.2% did not meet the recommended vitamin D level of 40 ng/mL. There was a strong negative association between vitamin D and leukocyte count (τ = -0.173, p = 0.007) and C-reactive protein concentration (τ = -0.172, p = 0.007). In linear regression, the most important variables for predicting vitamin D levels were (in order of decreasing importance) season, fat mass index, platelet, and leukocyte count.Despite appeals towards medical societies to target widespread vitamin D deficiency in Germany more than 10 years ago, our data indicate that these have been without avail. Low vitamin D levels in cancer patients should be corrected using reasonable sun exposure and supplements.Hintergrund: Es wurde gezeigt, dass Vitamin D mit einem reduzierten Risiko für die Ansteckung mit SARS-CoV-2 und leichteren Verläufen von COVID-19 assoziiert ist; zudem wirkt Vitamin D bei allen kennzeichnenden Merkmalen einer Krebserkrankung mitregulierend. Das Ziel dieser Studie war deshalb, den Vitamin D Status einer Kohorte von Krebspatienten aus unserer Klinik in Unterfranken zu erheben. Methoden: Für 116 Patienten wurde innerhalb prospektiver Studien die 25-Hydroxyvitamin D Konzentration gemessen. Assoziationen zwischen Vitamin D und anthropometrischen sowie Blutparametern wurden mittels Kendall’s Korrelationskoeffizienten τ und linearer Regression untersucht. Ergebnisse: Insgesamt wiesen 57 Patienten (49,1%) einen Vitamin-D Mangel (20 ng/mL) auf, und 92,2% lagen unterhalb des empfohlenen Vitamin D Spiegels von 40 ng/mL. Wir fanden eine starke negative Korrelation zwischen Vitamin D und der Anzahl an Leukozyten (τ = –0.173, p = 0.007) sowie C-reaktivem Protein (τ = –0.172, p = 0.007). Die wichtigsten Variablen zur Vorhersage des Vitamin D Wertes in der linearen Regression waren (der Wichtigkeit nach) die Jahreszeit, der Fettmasseindex, die Thrombozyten- und die Leukozyten-Zahl. Schlussfolgerungen: Trotz dringender Appelle an medizinische Fachgesellschaften vor über 10 Jahren, etwas gegen weitverbreiteten Vitamin D Mangel zu unternehmen, zeigen unsere Daten, dass diesbezüglich immer noch enormer Handlungsbedarf besteht. Niedrige Vitamin D Spiegel von Tumorpatienten sollten mittels vernünftiger Sonnenexposition und Nahrungsergänzungsmitteln behoben werden.

Background and aim Ketogenic diets (KDs) have gained interest as a complementary treatment for cancer patients. Here we present first results of our ongoing KETOCOMP study (NCT02516501) concerning body composition changes among rectal, breast and head & neck cancer (HNC) patients who consumed a KD during curative radiotherapy (RT). Experimental procedure Sixty-one patients eating a non-ketogenic diet were compared to 20 patients on a KD supplemented with 10 g essential amino acids on RT days. Body composition was measured prior to and weekly during RT using 8-electrode bioimpedance analysis. Longitudinal body composition data were analyzed using linear mixed effects models. Results and conclusion Patients on the KD exhibited nutritional ketosis, defined as serum β-hydroxybutyrate levels ≥0.5 mmol/l, in a median of 69.0% of blood measurements (range 0–100%) performed in our clinic. In rectal and breast cancer patients, KD was significantly associated with a loss of 0.5 and 0.4 kg fat mass per week (p = 0.00089 and 8.49 × 10−5, respectively), with no significant changes in fat free and skeletal muscle mass. In HNC patients, concurrent chemotherapy was the strongest predictor of body weight, fat free and skeletal muscle mass loss during RT, while consuming a KD was significantly associated with a gain in these measures. These preliminary results confirm prior reports indicating that KDs are safe to consume during standard-of-care therapy. They also provide an important first indication that KDs with ample amino acid intake could improve body composition during RT in curative cancer patients., Graphical abstract Image 1, Highlights • Consumption of a ketogenic diet (KD) during radio(chemo-)therapy is feasible. • In rectal and breast cancer patients, the KD significantly reduced fat mass. • Fat-free mass and skeletal muscle mass were preserved by the KD. • In head and neck cancer patients a KD influenced body composition opposite to chemotherapy.

There is a growing interest in a particular metabolic state and its influence on cancer therapy: ketosis. Ketosis denotes the physiological rise in ketone bodies that is proportional to fat oxidati...

Background Large variation regarding prescription and dose inhomogeneity exists in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. The aim of this modeling study was to identify which dose metric correlates best with local tumor control probability to make recommendations regarding SBRT prescription. Methods and Materials We combined 2 retrospective databases of patients with non-small cell lung cancer, yielding 1500 SBRT treatments for analysis. Three dose parameters were converted to biologically effective doses (BEDs): (1) the (near-minimum) dose prescribed to the planning target volume (PTV) periphery (yielding BEDmin); (2) the (near-maximum) dose absorbed by 1% of the PTV (yielding BEDmax); and (3) the average between near-minimum and near-maximum doses (yielding BEDave). These BED parameters were then correlated to the risk of local recurrence through Cox regression. Furthermore, BED-based prediction of local recurrence was attempted by logistic regression and fast and frugal trees. Models were compared using the Akaike information criterion. Results There were 1500 treatments in 1434 patients; 117 tumors recurred locally. Actuarial local control rates at 12 and 36 months were 96.8% (95% confidence interval, 95.8%-97.8%) and 89.0% (87.0%-91.1%), respectively. In univariable Cox regression, BEDave was the best predictor of risk of local recurrence, and a model based on BEDmin had substantially less evidential support. In univariable logistic regression, the model based on BEDave also performed best. Multivariable classification using fast and frugal trees revealed BEDmax to be the most important predictor, followed by BEDave. Conclusions BEDave was generally better correlated with tumor control probability than either BEDmax or BEDmin. Because the average between near-minimum and near-maximum doses was highly correlated to the mean gross tumor volume dose, the latter may be used as a prescription target. More emphasis could be placed on achieving sufficiently high mean doses within the gross tumor volume rather than the PTV covering dose, a concept needing further validation.

The shape of the imperfection induced by welding has an influence on the buckling resistance of thin shell structures, and many previous studies have come up with various models to estimate the critical imperfection shape. The aim of the current study is to assess the adequacy of three different approaches available in the literature, which consider that the imperfection wavelength matching the first buckling mode of a perfect tank to be the critical one. The first approach is based on buckling formulae calculated using a linear eigenvalue analysis performed on extensive experimental results of buckling of conical shells. The second approach assumes the critical wavelength, in view of the buckling mode profile detected from finite element analysis, as the distance between the inflection points of the elastic curve of the first buckling mode of a perfect tank. The third approach estimates the critical wavelength as double the distance between maximum and minimum points of the elastic curve. To determine the optimum wavelength that would lead to the minimum buckling capacity of the tank, the current study is conducted numerically by coupling a nonlinear finite element model, developed in house, and a direct search optimization technique. The results obtained from this numerical tool show good agreement with the first and the second approaches, which proves the adequacy of these two approaches in estimating the critical wavelength of the governing buckling mode, while the third approach yields a wavelength that overestimates the buckling capacity of the tank.

Altered glucose metabolism in cancer cells is an almost ubiquitous observation, yet hardly exploited therapeutically. However, ketogenic diets have gained growing attention in recent years as a nontoxic broad-spectrum approach to target this major metabolic difference between normal and cancer cells. Although much research still needs to be done, new knowledge has been gained about the optimal utilization of ketogenic diets for cancer treatment that this review aims to summarize.Although most preclinical studies indicate a therapeutic potential for ketogenic diets in cancer treatment, it is now becoming clear that not all tumors might respond positively. Early clinical trials have investigated ketogenic diets as a monotherapy and - while showing the safety of the approach even in advanced cancer patients - largely failed to prove survival prolonging effects. However, it gradually became clear that the greatest potential for ketogenic diets is as adjuvant treatments combined with pro-oxidative or targeted therapies initiated in early stages of the disease. Beneficial effects on body composition and quality of life have also been found.Ketogenic diets against cancer are worth further exploration, both in the laboratory and clinically. Patients wishing to undertake a ketogenic diet during therapy should receive dietary counselling to avoid common mistakes and optimize compliance. Future research should focus more on important clinical endpoints.

The anterolateral ligament (ALL) is subject of the current debate concerning rotational stability in case of anterior cruciate ligament (ACL) injuries. Today, reliable anatomical and biomechanical evidence for its existence and course is available. Some radiologic studies claim to be able to identify the ALL on standard coronal plane MRI sections. In the experience of the authors, however, ALL identification on standard MRI sequences frequently fails and is prone to errors. The reason for this mainly lies in the fact, that the entire ALL often cannot be identified on a single MRI image. This study aimed to establish an MRI evaluation protocol improving the visualization of the ALL, using multiplanar reformation (MPR) with the goal to be able to evaluate the ALL on one MRI image. A total of 47 knee MRIs performed due to atraumatic knee pain between 2018 and 2019 without any pathology were analyzed. Identification of the ALL was performed twice by an orthopedic surgeon and a radiologist on standard coronal plane and after MPR. For the latter axial and coronal alignment was obtained with the femoral condyles as a reference. Then the coronal plane was adjusted to the course of the ALL with the lateral epicondyle as proximal reference. Visualization of the ALL was rated as “complete” (continuous ligamentous structure with a tibial and femoral insertion visible on one coronal image), “partial” (only parts of the ALL like the tibial insertion were visible) and “not visible”. The distances of its tibial insertion to the bony joint line, Gerdy’s tubercle and the tip of the fibular head were measured. On standard coronal images the ALL was fully visible in 17/47, partially visible in 27/47, and not visible in 3/47 cases. With MPR the ALL was fully visible in 44/47 and not visible in 3/47 cases. The median distance of its tibial insertion to the bony joint line, Gerdy’s tubercle and the tip of the fibular head were 9, 21 and 25 mm, respectively. The inter- (ICC: 0.612; 0.645; 0.757) and intraobserver (ICC: 0.632; 0.823; 0.857) reliability was good to excellent. Complete visualization of the ALL on a single MRI image is critical for its identification and evaluation. Applying multiplanar reformation achieved reliable full-length visualization of the ALL in 94% of cases. The described MPR technique can be applied easily and fast in clinical routine. It is a reliable tool to improve the assessment of the ALL.

Background One of the values determined during the assessment of knee issues is the posterior tibial slope (PTS). A new option for measuring the PTS is the EOS 3D imaging system, which provides anteroposterior (AP) and lateral long leg radiographs (LLRs) using less radiation than a conventional LLR. We investigated the reliability of the EOS 3D imaging system with respect to PTS measurements. Methods We retrospectively searched our radiological database for patients who underwent an EOS scan and a computed tomography (CT) scan of their lower extremities between January and December 2019. Fifty-six knees were included in the study. Medial and lateral PTSs were determined using both modalities. A radiologist and an orthopaedic surgeon each performed all measurements twice and the intraclass correlation (ICC) was calculated to assess inter- and intrarater reliability. The Student t test and Pearson correlation were used to compare the results of both imaging modalities. Results The mean medial PTS was 8.5° (95% confidence interval [CI], 8.1–8.9°) for the EOS system and 7.7° (95% CI, 7.3–8.1°) for CT, and the lateral PTS was 7.4° (95% CI, 6.9–7.9°) for the EOS system, and 7.0° (95% CI, 6.5–7.4°) for CT. Interrater reliability (ICC) with respect to medial and lateral PTSs measured on the EOS (0.880, 0.765) and CT (0.884, 0.887) images was excellent. The intrarater reliability of reader 1 (ICC range, 0.889–0.986) and reader 2 (ICC range, 0.868–0.980) with respect to the same measurements was excellent. Conclusion The PTS measurements from the EOS 3D imaging system are as reliable and reproducible as those from CT, the current gold standard method. We recommend using this system if possible, because it acquires more information (sagittal plane) in a scan than a conventional LLR, while exposing the patient to less radiation. Level of evidence Level III, Retrospective cohort study

Background: COVID-19 vaccines have had expedited reviews without sufficient safety data. We wanted to compare risks and benefits. Method: We calculated the number needed to vaccinate (NNTV) from a large Israeli field study to prevent one death. We accessed the Adverse Drug Reactions (ADR) database of the European Medicines Agency and of the Dutch National Register (lareb.nl) to extract the number of cases reporting severe side effects and the number of cases with fatal side effects. Result: The NNTV is between 200–700 to prevent one case of COVID-19 for the mRNA vaccine marketed by Pfizer, while the NNTV to prevent one death is between 9000 and 50,000 (95% confidence interval), with 16,000 as a point estimate. The number of cases experiencing adverse reactions has been reported to be 700 per 100,000 vaccinations. Currently, we see 16 serious side effects per 100,000 vaccinations, and the number of fatal side effects is at 4.11/100,000 vaccinations. For three deaths prevented by vaccination we have to accept two inflicted by vaccination. Conclusions: This lack of clear benefit should cause governments to rethink their vaccination policy.

Highlights • Re-irradiation of the brain is feasible with an encouraging overall survival. • Treatment related toxicity was low within the reported dose range. • EQD2 cumulative dose distributions were calculated using rigid registration. • Dose-Response-Modelling with logistic regression showed a correlation of the D1cc brain with any grade of acute toxicity., Introduction The use of cranial re-irradiation is growing with improving overall survival and the advent of high-precision radiotherapy techniques. Still the value of re-irradiation needs careful evaluation regarding safety and efficacy. We analyzed dosimetric and clinical data of patients receiving cranial re-irradiation using EQD2 sum plans. Methods and material We retrospectively analyzed the data of 76 patients who received repeated cranial radiotherapy from 02/2013 to 09/2016. 34 patients suffered from recurrent primary brain tumors, 42 from brain metastases. Dosimetric analysis was performed accumulating EQD2 dose distributions based on rigid image registration. Clinical and radiological data was collected at follow-ups including toxicity, local control and overall survival. Results In total 76 patients had at least 2 courses of intracranial radiotherapy. The median accumulated prescription EQD2 dose was 96.5 Gy2 for all radiation courses combined. The median D(0.1 cc) of the brain for patients receiving more than 100 Gy2 was 114 Gy2 with a highest dose of 161.5 Gy2. 74% of patients suffered from low grade (G1–G2) acute toxicity, only two high grade (>G3) toxicities were recorded. Median overall survival from the time of first re-irradiation was 57 weeks (range 4–186 weeks). The median time to local failure for patients with a primary brain tumor was not reached and 24 weeks (range 1–77 weeks) for patients with brain metastases. Conclusion Repeated radiotherapy appears both safe and efficient in patients with recurrent primary or secondary brain tumors with doses to the brain up to 120 Gy2 EQD2, doses below 100 Gy2 for brainstem and doses below 75 Gy2 EQD2 to chiasm and optic nerves.

Vitamin D3 (cholecalciferol) is a secosteroid and prohormone which is metabolized in various tissues to the biologically most active vitamin D hormone 1,25(OH)2D3 (calcitriol). 1,25(OH)2D3 has multiple pleiotropic effects, particularly within the immune system, and is increasingly utilized not only within prophylaxis, but also within therapy of various diseases. In this context, the latest research has revealed clinical benefits of high dose vitamin D3 therapy in autoimmune diseases. The necessity of high doses of vitamin D3 for treatment success can be explained by the concept of an acquired form of vitamin D resistance. Its etiology is based on the one hand on polymorphisms within genes affecting the vitamin D system, causing susceptibility towards developing low vitamin D responsiveness and autoimmune diseases; on the other hand it is based on a blockade of vitamin D receptor signaling, e.g. through pathogen infections. In this paper, we review observational and mechanistic evidence for the acquired vitamin D resistance hypothesis. We particularly focus on its clinical confirmation from our experience of treating multiple sclerosis patients with the so-called Coimbra protocol, in which daily doses up to 1000 I.U. vitamin D3 per kg body weight can be administered safely. Parathyroid hormone levels in serum thereby provide the key information for finding the right dose. We argue that acquired vitamin D resistance provides a plausible pathomechanism for the development of autoimmune diseases, which could be treated using high-dose vitamin D3 therapy.

To report outcome (freedom from local progression: FFLP, overall survival: OS, and toxicity) after stereotactic, palliative, or highly conformal fractionated (> 12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤ 12 fractions, biologically effective dose, (BED10) ≥ 50 Gy), 3DCRT/IMRT (> 12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/Log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). 326 patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT, and Pall-RT in 260, 27, and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%), and melanoma (6.7%). Unadjusted FFLP was higher after SBRT v. Pall-RT (p = 0.026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4%, and 27.7%). OS was longer after SBRT v. other groups (p < 0.05) and increased in patients with locally-controlled metastases in a landmark analysis (p < 0.0001). Toxicity was mostly mild; notably, 4 cases of adrenal insufficiency occurred, 2 of which were likely caused by immunotherapy or tumor progression. RT for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. 1-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway. This article is protected by copyright. All rights reserved.

Breast cancer (BC) patients often ask for a healthy diet. Here, we investigated a healthy standard diet (SD), a low carb diet (LCD), and a ketogenic diet (KD) for BC patients during the rehabilitation phase. KOLIBRI was an open-label non-randomized one-site nutritional intervention trial, combining inpatient and outpatient phases for 20 weeks. Female BC patients (n = 152, mean age 51.7 years) could select their diet. Data collected were: Quality of life (QoL), spiroergometry, body composition, and blood parameters. In total 30, 92, and 30 patients started the KD, LCD, and SD, respectively. Of those, 20, 76, and 25 completed the final examination. Patients rated all diets as feasible in daily life. All groups enhanced QoL, body composition, and physical performance. LCD participants showed the most impressive improvement in QoL aspects. KD participants finished with a very good physical performance and muscle/fat ratio. Despite increased cholesterol levels, KD patients had the best triglyceride/high-density lipoprotein (HDL) ratio and homeostatic model assessment of insulin resistance index (HOMA-IR). Most metabolic parameters significantly improved in the LCD group. SD participants ended with remarkably low cholesterol levels but did not improve triglyceride/HDL or HOMA-IR. In conclusion, both well-defined KDs and LCDs are safe and beneficial for BC patients and can be recommended during the rehabilitation phase.

Evolutionary principles are rarely considered in clinical oncology. We here aimed to test the feasibility and effects of a dietary and physical activity intervention based on evolutionary considerations in an oncological setting. A total of 13 breast cancer patients referred to our clinic for curative radiotherapy were recruited for this pilot study. The women were supposed to undertake a “Paleolithic lifestyle” (PL) intervention consisting of a Paleolithic diet and daily outdoor activity of at least 30 min duration while undergoing radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters were assessed before, during, and at the end of radiotherapy. A control group on an unspecified standard diet (SD) was assigned by propensity score matching. A total of eleven patients completed the study. The majority of patients (64%) reported feeling good or very good during the intervention. The intervention group experienced an average decrease of 0.4 kg body weight (p

The JETSCAPE framework is a modular and versatile Monte Carlo software package for the simulation of high energy nuclear collisions. In this work we present a new tune of JETSCAPE, called PP19, and validate it by comparison to jet-based measurements in p+p collisions, including inclusive single jet cross sections, jet shape observables, fragmentation functions, charged hadron cross sections, and dijet mass cross sections. These observables in p+p collisions provide the baseline for their counterparts in nuclear collisions. Quantifying the level of agreement of JETSCAPE results with p+p data is thus necessary for meaningful applications of JETSCAPE to A+A collisions. The calculations use the JETSCAPE PP19 tune, defined in this paper, based on version 1.0 of the JETSCAPE framework. For the observables discussed in this work calculations using JETSCAPE PP19 agree with data over a wide range of collision energies at a level comparable to standard Monte Carlo codes. These results demonstrate the physics capabilities of the JETSCAPE framework and provide benchmarks for JETSCAPE users.

Background Obesity and low muscle mass are associated with worse outcomes of breast cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in breast cancer patients undergoing radiotherapy. Methods Patients with non-metastasized breast cancer were allocated to either the KD (N = 32) or the SD (N = 31) during radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters and quality of life were assessed before, during, and at the end of radiotherapy. Results A total of 29 KD and 30 SD patients completed the study. During radiotherapy, mean and median fasting BHB concentrations in the KD group were 0.72 and 0.49 mmol/l (range 0.06–4.9) which was significantly higher than those in the SD group (p −16). There was a very small and insignificant increase in body weight and fat mass in the SD group, as well as a decrease of fat free mass. In contrast, patients in the KD group lost body weight and fat free and skeletal muscle mass quickly after diet onset, which for the most part was related to water losses. The KD did not cause further substantial changes in fat free or skeletal muscle mass, but was associated with a gradual decrease of 0.4 kg body weight and fat mass per week (p p = 6.3 × 10−5). Global quality of life remained stable in the SD group but increased in the KD group from a score of 66.7 to 75.0 (p = 0.20). Conclusions In breast cancer patients undergoing curative radiotherapy, a KD based on natural foods is feasible. After initial water losses, the KD tends to reduce body weight and fat mass while preserving fat free and skeletal muscle mass. Trial registration ClinicalTrials.gov identifier: NCT02516501, registered on August 06, 2015.

We here express our concern about a general decree to let patients wear face masks in radiation oncology clinics. We believe that potential risks associated with wearing masks, such as the risk of confounding patients, outweigh any benefits of such a policy for which evidence of protection from COVID-19 is generally weak. For asymptomatic patients, wearing masks in addition to hygiene standards will not provide additional protection of others and should be cautioned against.

Background: Breast Cancer (BC) patients often ask for a healthy diet. Here, we compared three different diets which could support BC patients during the rehabilitation process: a healthy standard diet (SD), a low carb diet (LCD) and a ketogenic diet (KD).Patients and Methods:KOLIBRI was a one-site nutritional intervention trial, combining inpatient and outhouse phases for 20 weeks. Female BC patients (n=152; mean age 51.7 years) could select their diet. Data collected were: quality of life (QoL), spiroergometry, body composition, blood biochemistry. 30, 92 and 30 patients started the KD, LCD and SD, respectively. Of those, 20, 72 and 25 completed the final examination.Results:Patients rated all diets as feasible in daily life. No adverse effects occurred in any diet group. KD offered the highest amount of energy and protein. All groups improved in QoL, body composition and physical performance. KD was superior in improving fatigue, insomnia and physical functioning. KD participants finished with the best physical performance and the highest muscle/fat ratio. Despite their increased cholesterol, KD patients had the best triglyceride/HDL ratio and HOMA-IR. Most metabolic parameters significantly improved in the LCD group. SD participants ended with remarkably low cholesterol levels, but did not improve triglyceride/HDL or HOMA-IR.Conclusions:A well-defined KD and LCD are safe and beneficial for BC. Both diets could thus be recommended for patients wanting to self-support their rehabilitation process.Trial registration IDNCT02092753 Protocol Registration date:02/26/2014Ketogenic Or LOGI Diet In a Breast Cancer Rehabilitation Intervention (KOLIBRI)URL: https://clinicaltrials.gov/ct2/show/NCT02092753?cond=KOLIBRI&draw=2&rank=1

Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices, particularly in a way suitable for large scale adoption, remains a critical challenge. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy-based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser-assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3% &plusmn, 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.

Background Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. Patients and methods This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. Results Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. Conclusions In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis.

Radiation therapy (RT) is often delivered after lumpectomy for women with breast cancer. A common perceived side effect of RT is fatigue, yet its exact effect on activity levels and sleep is unknown. In this study we analyzed the change in activity levels and sleep using an activity tracking device before, during, and after RT for women with early stage breast cancer and ductal carcinoma in situ who underwent adjuvant RT.After institutional review board approval, activity levels were quantified before, during, and after RT with measurements of steps, miles walked, calories burned, and sleep metrics in 10 women fitted with activity trackers. All data were uploaded and tabulated on a secure database. Multivariable linear regressions were used to evaluate changes in these variables over time during the RT course.Median step count was 5047 per day (range, 2741-15,508) and distance traveled was 1.6 miles per day (range, 0.9-5.3). Step count, distance, and calories decreased by an average of 54 steps per day, 0.02 miles per day, and 3 calories per day (median calories 1822; range, 1461-2712) during RT, respectively. These changes were statistically significant (P .001), but not clinically relevant. There was no significant change in sleep (average 6.8 hours per night; range, 5.5-8.3).RT has a minimal effect on activity or sleep in women undergoing treatment for breast cancer. Activity levels varied greatly between patients in a population of women undergoing hypofractionated RT. Because increased activity levels correlate with improved outcomes, further studies evaluating attempts to increase physical activity during as well as after treatment with radiation are warranted.

Purpose/Objective(s) Recent studies suggest improved local control (LC) of early-stage non-small cell lung cancer (NSCLC) treated with SBRT regimens with biologically equivalent dose (BED10) > 150 Gy. It is unclear if this association is histology dependent. Multiple groups have shown lower LC rates after SBRT for squamous cell carcinoma (SCC), compared to non-SCC NSCLC. We compared LC between BEDlow and BEDhigh SBRT schemes, stratified by histology. Materials/Methods As part of an IRB approved collaborative, we retrospectively analyzed 684 patients with cT1-2, cN0, cM0 NSCLC, treated with definitive SBRT to a minimum BED of 100 Gy at five international centers. Patients were grouped into SCC and non-SCC, then divided into BEDhigh (BED10 ≥150 Gy) or BEDlow (BED10 Results Of 684 eligible tumors, 457 were non-SCC and 227 SCC. Median follow-up was 30 months. Of non-SCC patients, 262 (57%) were BEDlow and 195 (43%) BEDhigh. Of SCC patients, 144 (63%) were BEDlow and 83 (37%) BEDhigh. BEDhigh SBRT included those treated with 54 Gy in 3 fractions (54/3). BEDlow included 60/5, 50/5, 48/4, or 60/8. Baseline characteristics, including T-stage and max tumor dimension, were similar between BED groups after matching. MVA including T-stage, tumor grade, and tumor location, showed BEDlow regimens were associated with higher rates of local failure for SCC (HR 9.8, 95% CI 1.9-25.1, P = 0.007), but not for non-SCC (HR 1.2, 95% CI 0.6-2.5, P = 0.6). Three-year LC rates for BEDlow and BEDhigh were 70% and 97%, respectively for SCC, and 91% and 92%, respectively, for non-SCC. Similarly, there were higher rates of failure with BEDlow PTVmean (3 yr LC 94 vs 69%, MVA HR 6.4, 95% CI 1.9-22.2, P = 0.003) and BEDlow GTVmean (3 yr LC 87 vs 68%, MVA HR 7.6, 95% CI 2.7-21.6, P = 0.001) in SCC patients. In non-SCC patients, LC was similar between BED groups for PTVmean (3 yr LC 92% vs 93%, MVA HR 1.1, 95% CI 0.5-2.8, P = 0.8) and GTVmean (3 yr LC 94 vs 90%, MVA HR 0.8, 95% CI 0.3-2.6, P = 0.8). There was a trend of worse survival in BEDlow SCC patients (MVA HR 1.3, 95% CI 0.9-1.9, P = 0.1), but survival was similar in non-SCC patients (MVA HR 1.02, 95% CI 0.8-1.3, P = 0.9). There were no differences in regional recurrence or distant metastases between BED groups in either histology. Conclusion This multi-institutional analysis shows improved LC in early-stage SCC NSCLC treated with SBRT regimens with BED10 > 150 Gy. No difference was observed in LC between BED groups for non-SCC patients. Our results suggest BEDhigh SBRT should be strongly considered for early-stage non-central SCC NSCLC.

Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal-end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices remains a critical challenge, particularly in a way suitable for large scale adoption. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3 ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.

Preclinical data provide evidence for synergism between ketogenic diets (KDs) and other oncological therapies. The aim of this systematic review was to summarize data from clinical studies that have tested KDs along with other treatments used within medical oncology. The PubMed database was searched using the key words "ketogenic" AND ("cancer" OR "glioblastoma"). A secondary search was conducted by screening the reference lists of relevant articles on this topic. Relevant studies for this review were defined as studies in which KDs were used complementary to surgery, radio-, chemo-, or targeted therapy and at least one of the following four outcomes were reported: (i) Overall survival (OS); (ii) progression-free survival (PFS); (iii) local control rate; (iv) body composition changes. Twelve papers reporting on 13 clinical studies were identified. Nine studies were prospective and six had a control group, but only two were randomized. KD prescription varied widely between studies and was described only rudimentarily in most papers. Adverse events attributed to the diet were rare and only minor (grade 1-2) except for one possibly diet-related grade 4 event. Studies reporting body composition changes found beneficial effects of KDs in both overweight and frail patient populations. Beneficial effects of KDs on OS and/or PFS were found in four studies including one randomized controlled trial. Studies in high-grade glioma patients were not sufficiently powered to prove efficacy. Evidence for beneficial effects of KDs during cancer therapy is accumulating, but more high-quality studies are needed to assess the overall strength of evidence.

Purpose To identify frequency, clinical relevance and risk factors for vertebral compression fracture (VCF) after spine stereotactic body radiation therapy (SBRT) with long-term follow up (FU). Methods From 2012 to 2015, 61 lesions (56 patients) were treated within a prospective multicenter phase 2 study (NCT01594892) of SBRT for painful vertebral metastases. Post-SBRT VCF were identified. Anatomical segments, normal and tumor tissue of treated vertebrae were segmented for volumetric analyses. Predictive factors for VCF were identified by logistic regression. Results Median clinical and radiological FU for all patients was 16.2 months (range, 0–68.2) and 7.8 months (range, 0–66.9), respectively. Local metastasis control was observed in 82% of lesions at last imaging FU. Post-SBRT VCF occurred in 21 lesions (34.4%): 16.4% showed a progressive VCF, while a new VCF occurred in 18.0%. 3/56 (5.4%) patients developed painful VCF defined as pain increase by ≥2 on the visual analogue scale (VAS) and 2 (3.6%) patients required surgical stabilization. Pre-SBRT VCF, localization in the thoracic spine, Bilsky score >0, SINS score, pre-SBRT osteolytic volume and metastatic vertebral body (VB) involvement were predictive factors for VCF on univariate analysis. Relative VB involvement, osteolytic volume and pre-SBRT VCF remained in the multivariate logistic regression model that had AUC = 0.930, 83.3% sensitivity and 96.6% specificity. Conclusion Spine SBRT resulted in favorable long-term pain and local metastasis control. Despite post-SBRT VCF being observed after one third of treatments, this was symptomatic in only 5% of patients. Predictive factors for developing VCF were identified which could contribute to better selection of patients for spine SBRT.

INTRODUCTION Studies have consistently identified an increased risk of pancreatic cancer in diabetics, yet the role hyperglycemia may play in predicting prognosis is less clear. This work aims to evaluate the impact of glycemic state and antidiabetics on outcomes after systemic and local treatment for locoregionally advanced pancreatic cancer. MATERIALS AND METHODS This retrospective study consisted of 303 patients with newly diagnosed advanced-stage pancreatic cancer treated from 2004 to 2014. Kaplan-Meier survival analysis method was used to estimate time to event for overall survival, distant metastasis, and locoregional control. Blood glucose values (n=8599) were assessed both as continuous and categorical variables in univariate and multivariable Cox proportional hazard regression models to estimate hazard ratios (HRs) and identify independent prognostic factors. A 6-month conditional landmark analysis excluding patients with

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Colorectal cancer is the fourth-most prominent cause of cancer related fatalities across the globe. Conventional electrocautery techniques used in the resection of colon tissue cause a relatively high degree of collateral damage to the healthy tissues bordering the target sites. Ultrafast infrared lasers offer significantly improved localisation in the ablation of such biological tissues arising from a plasma-mediated ablation mechanism. This improved localisation is two-fold, with lateral confinement and precise depth control being advantageous in minimising thermal necrosis and avoiding bowel perforation respectively. Various laser scanning strategies and optical elements have been investigated, with the intent to exploit the inherent advantages offered from applying photonics to these procedures. Evaluation of the corresponding ablation characteristics was carried out using three-dimensional optical profilometry and histological analysis. If adopted in operating theatres, surgeons could benefit from more control when carrying out resection of neoplasia in the mucosal or submucosal layers of colon tissue, compared to previous electrocautery methods.

Diet is frequently considered as a food regimen focused on weight loss, while it is actually the sum of food consumed by the organism. Western diets, modern lifestyle, sedentary behaviors, smoking habits, and drug consumption have led to a significant reduction of gut microbial diversity, which is linked to many non-communicable diseases (NCDs). The latter kill 40 million people each year, equivalent to more than 70% of all deaths globally. Among NCDs, tumors play a major role, being responsible for 29% of deaths from NCDs. A link between diet, microbiota, and cancer prevention and treatment has recently been unveiled, underlining the importance of a new food culture based on limiting dietary surplus and on preferring healthier foods. Here, we review the effects of some of the most popular “cancer-specific” diets on microbiota composition and their potential impact on cancer prevention and treatment.

Highlights • We provide an external validation of the extracranial prognostic score developed by Nieder et al. • This extracranial score could effectively define the patients with very short survival. • A new combination of extracranial score with DS-GPA-score achieved an even better discrimination, Purpose The aim of our study was an external validation of the extracranial prognostic score predicting survival of patients with brain metastases receiving cranial irradiation on data from a single institution. Materials and methods A retrospective analysis of 524 patients with brain metastases treated with cranial radiotherapy in a single tertiary center was performed. Three predictive scores were calculated and assessed for their ability to discriminate prognostic groups: (i) The Recursive Partitioning Analysis (RPA) score (available for 524 patients); (ii) the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) score (464 patients); (iii) the extracranial score (EC-S) developed by Nieder et al. which is based on serum albumin, lactate dehydrogenase (LDH) and the number of extracranial organs involved (157 patients). Discrimination of each score was assessed by Gönen & Heller’s concordance probability estimate (CPE). The calibration was checked by comparing median survival estimates of each risk group with the corresponding values of the datasets from which the scores were derived. Finally, a multivariable Cox regression model was built by using the least absolute shrinkage and selection operator on a large number of variables including all three scores. Results With a CPE = 0.626 ± 0.022, the EC-S had the best discriminatory power. The EC-S also appeared to be better calibrated and had the best ability to separate patients with a very poor prognosis: patients with combination of low albumin, elevated LDH and more than 1 extracranial organ with metastatic involvement had a median survival time of only 0.6 months (CI95% 0.1–1.1) and a hazard ratio for death of 6.36 (2.67–15.14) compared to patients with no extracranial metastases and normal levels of albumin and LDH. In the multivariable Cox model serum albumin, LDH, treatment modality, DS-GPA and EC-S were retained as prognostic factors. An ad hoc combination of both DS-GPA and EC-S into a new score was possible for 134 patients and indicated a slightly better discrimination (CPE = 0.636 ± 0.023) than either DS-GPA or EC-S alone. Conclusions This study provides an independent validation of the prognostic EC-S which was the best prognostic model for defining the patients who obviously did not benefit from radiation therapy of brain metastases in terms of overall survival. The combination of the EC-S with the established DS-GPA score resulted in a slight increase in discriminatory ability. The new EC-GPA score needs further validation in larger patient cohorts.

Background: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. Methods: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. Results: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. Conclusion: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Background: Chronic stress has become a central problem of our modern society. It appears plausible that our Paleolithic ancestors were more exposed to acutely life-threatening stress stimuli than chronically enduring psychosocial stressors. The aim of this study was to test whether it is possible to reduce physiological and psychological stress parameters by returning to simulated Paleolithic lifestyle conditions. Methods: In total, 15 volunteers undertook a four-day hiking tour simulating hunter-gatherer lifestyle conditions in a National Park. Saliva samples were taken at 5, 6 and 7 pm prior to, during and after the intervention and evaluated for cortisol concentration. Perceived stress was measured by the Perceived Stress Questionnaire. Results: The study was completed by 11 of the subjects. Mean body weight and fat mass decreased significantly during the intervention by 2.3 and 2.2 kg, respectively. There was a marked increase in cortisol levels on the first day of the intervention compared to baseline with a gradual return to baseline levels on the subsequent days. Individual cortisol responses were heterogeneous; in threes subjects, cortisol concentrations generally decreased from 5 to 7 pm, while in four subjects the opposite trend was observed. Conclusions: During this four-day outdoor intervention under simulated Paleolithic conditions, significant changes occurred almost exclusively at the first day of the study. The increase in cortisol levels at this point supports the hypothesis that some individuals respond by an increased release of cortisol as a result of adaptation to new environmental conditions.

Stereotactic body radiotherapy (SBRT) is the guideline-recommended treatment for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC). This study analyzed whether short-term (6 months) death can be predicted reliably to select a subgroup of patients who will not have a benefit from SBRT.A total of 779 patients with early-stage NSCLC who had been treated with cone beam computed tomography-guided SBRT in five institutes and for whom information on overall survival during the first 6 months after treatment was available were included in this analysis. The probability of dying within 6 months after treatment was defined as the end point "early death" and modeled by multivariate logistic regression. Model fitting was performed using the least absolute shrinkage and selection operator method, and model test performance was estimated using double 10-fold cross validation. The variables age, sex, Eastern Cooperative Oncology Group performance status, operability, forced expiratory volume in 1 second, and Charlson comorbidity index were considered for model building.Eastern Cooperative Oncology Group performance status and (to a lesser extent) operability were the most important predictors of early death, whereas the Charlson comorbidity index was associated only with the overall survival time. On the basis of the best expected test performance (area under the curve = 0.699), the risk for early death would be 8.8% (range 8.2%-13.7%) and 4.1% (3.0%-4.3%) for the 10% of patients with the highest and lowest risk, respectively. Overall, predictive performance was too low for clinical application.SBRT should be offered to all patients irrespective of their comorbidities, unless the performance status of the patients and the comorbidities prevent accurate SBRT planning and delivery.

Summary Background We have found that a ketogenic diet (KD) during the course of radiotherapy (RT) was feasible and led to a preservation or favorable changes of body composition. Based on these observations and theoretical considerations, we initiated a study to investigate the impact of a KD or a ketogenic breakfast intervention in patients undergoing RT. Methods All patients presenting for curative RT with age between 18 and 75, body mass index between 18 and 34 kg/m 2 and a histologically confirmed cancer of the breast, colorectum or head and neck region are considered for inclusion. Exclusion criteria are Karnofsky index ® , vitaflo, Bad Homburg, Germany) plus (ii) 5–15 g amino acids (MAP, dr. reinwald healthcare gmbh+co kg, Schwarzenbruck, Germany). If willing to undertake a complete KD for the duration of RT, patients are entered into intervention group 2. Intervention group 2 does not have to fast prior to RT fractions but will be supplemented with MAP analogous to intervention group 1. The control group will not receive dietary advice to follow a KD or reduce carbohydrate intake. The objective is twofold: (i) to test whether the ketogenic interventions are feasibly, as measured by the number of dropouts; (ii) to see whether intervention groups 1 and 2 attain a better preservation of BIA phase angle than the control group. Endpoints Primary endpoints are the feasibility of the interventions (measured through dropout rates), and changes in body weight and composition (measured through BIA). Secondary endpoints are changes in quality of life (EORTC questionnaires) and blood parameters as well as the occurrence and grade of toxicities and grade of regression after surgery in case of colorectal carcinomas. Trial registration Registered under ClinicalTrials.gov Identifier no. NCT00123456 .

Objectives Calorie restriction (CR) >20% has been hypothesized to aid cancer prevention and treatment. Yet, to our knowledge, there is a lack of reported studies in humans describing tolerance, adherence, or efficacy, and unpublished and incomplete dietary studies may indicate lack of tolerability and compliance. The aim of this study was to assess registered clinical trials using CR for cancer treatment and prevention, rates of completion, and published reports to determine whether barriers to publication may be indicative of either negative studies, or incompletion due to unreported compliance issues. Methods Current registered clinical trials assessing CR in cancer prevention and treatment were assessed at clinicaltrials.gov and the International Clinical Trials Registry at the World Health Organization. Assessment of study completion and publication was calculated and compared with methods of CR used, as were rates of inactive and incomplete studies, dormant studies, time of dormancy, type of study, and generalizable conclusions. Results Twenty-nine trials were registered assessing CR in cancer treatment or prevention. Of these studies, 18 met initial criteria, and only 4 had completed and published results. Three of these tested a CR regimen incorporating exercise or intermittent restriction. Target CR ranged from 500 to 1000 kcal/d, with one study aim of 20% CR; no study reported rates of actual calorie intake. The majority of dormant and unpublished studies (69%) used general dietary CR and was without update ranging from 265 to 2518 d. Only one study reported on the side effects of the CR regimen; compliance and adherence to the regimen was described in the four completed studies that reported results. Only two studies were registered as pilot studies testing the feasibility of CR. Conclusions Poor completion and lack of reporting of results is apparent in the majority of studies assessing CR for cancer prevention or treatment. These findings should be considered during the design of future studies assessing dietary strategies for cancer prevention or treatment.

We present a broadband infrared and optical study of the compositionally complex nickel-based superalloy Inconel-718, a common material used in additive manufacturing using the direct metal laser sintering (DMLS) technique. We find a broad, featureless spectral emissivity, which is consistent with dc transport measurements and contextualize the results against literature reports of disordered metals. We show that electronic structure calculations based on first-principles modeling can explain most of the spectral weight distribution and show that the peculiar infrared optical properties in this class of materials can present challenges in accurately reporting remote temperature sensing in DMLS.

To the Editor:We read with interest the work by Perez et al. (1), concluding that omega-3 fatty acids may have an effect on the development of neuropathic pain in a sciatic nerve ligation model. The methodology may be compromised because a thorough analysis of key constituents of fatty acid emulsion

A 91-yr-old man (57 kg, 156 cm, ASA III) received an infraclavicular brachial plexus block for surgery of bursitis of the olecranon. Twenty minutes after infraclavicular injection of 30 mL of mepivacaine 1% (Scandicain®) and 5 min after supplementation of 10 mL of prilocaine 1% (Xylonest®) using an

BACKGROUND The postoperative beneficial effects of thoracic epidural analgesia (TEA) within various clinical pathways are well documented. However, intraoperative data are lacking on the effect of different epidurally administered concentrations of local anesthetics on inhaled anesthetic, fluid and vasopressor requirement, and hemodynamic changes. We performed this study among patients undergoing major upper abdominal surgery under combined TEA and general anesthesia. METHODS Forty-five patients undergoing major upper abdominal surgery were randomly assigned to one of three treatment groups receiving intraoperative TEA with either 10 mL of 0.5% (Group 1) or 0.2% (Group 2) ropivacaine (both with 0.5 microg/mL sufentanil supplement), or 10 mL saline (Group 3) every 60 min. Anesthesia was maintained with desflurane in nitrous oxide (60%) initiated at an age-adapted 1 minimum alveolar concentration (MAC) until incision. Desflurane administration was then titrated to maintain an anesthetic level between 50 and 55, as assessed by continuous Bispectral Index monitoring and the common clinical signs (PRST score). Lack of intraoperative analgesia, as defined by an increase in pulse rate, sweating, and tearing (PRST) score >2 or an increase of mean arterial blood pressure (MAP) >20% of baseline, was treated by readjusting the end-tidal concentration of desflurane toward 1 MAC, and above this level by additional rescue i.v. remifentanil infusion. Hypotension, as defined as a decrease in MAP >20% of baseline, was treated by reducing the end-tidal desflurane concentration to a Bispectral Index level of 50-55 and below that with crystalloid or norepinephrine infusion, depending on central venous pressure. RESULTS End-tidal desflurane concentration could be significantly reduced in Group 1 to 0.7 +/- 0.1 MAC (P < 0.001) and to 0.8 +/- 0.1 MAC (P < 0.001) in Group 2, but not in Group 3. Significant hypotension occurred within 20 min in all patients of Groups 1 and 2 (MAP from 80 +/- 10 to 56 +/- 5) (Group 1), 78 +/- 18 to 58 +/- 7 mm Hg (Group 2), P < 0.01, whereas MAP remained unchanged in Group 3 (74 +/- 12 to 83 +/- 15 mm Hg, P = 0.42). Heart rate did not change significantly over time within any of the groups. Furthermore, groups did not differ significantly regarding i.v. fluid and norepinephrine requirement. Patients in Group 3 received more remifentanil throughout the surgical procedure (7.2 +/- 4.9 mg x kg(-1) x h(-1)) when compared with Group 2 (1.6 +/- 2.2 mg x kg(-1) x h(-1)), P < 0.01. Remifentanil infusion among patients receiving ropivacaine 0.5% was not necessary at any time. CONCLUSION Epidural administration of 0.5% ropivacaine leads to a more pronounced sparing effect on desflurane concentration for an adequate anesthetic depth when compared with a 0.2% concentration of ropivacaine at comparable levels of vasopressor support and i.v. fluid requirement.

The growing interest in the alterations of tumor cell metabolism and their possible therapeutic exploitation also spurred new complementary and integrative approaches such as treating patients with a ketogenic diet (KD). KDs aim at inhibiting glycolytic tumor metabolism and growth, and have therefore been proposed as adjuncts not only to standard-of-care, but also to other therapies targeting tumor metabolism. Here I describe the life and forgotten work of one of the earliest researchers who realized the importance of altered tumor cell metabolism and its possible exploitation through metabolic modifications: Wilhelm Brünings. Brünings was a German natural scientist and physician famous for his innovative contributions to the fields of physiology and otorhinolaryngology. Based on the findings of Otto Warburg and his physiological reasoning he started to experiment with insulin administration and KDs in his patients with head and neck cancers, aiming to maximally lower blood glucose concentrations. He obtained encouraging short-term results, although most tumors became refractory to treatment after several weeks. His pioneering work is worth revisiting, especially for an international readership that may be unaware of his efforts, as hypoglycemic treatments, including the use of insulin injections and KDs, are currently being re-investigated as complementary and integrative cancer treatments. Keywords: Cancer, Hypoglycemia, Insulin, Ketogenic diet, Low carbohydrate diet

To report the development of an ultimately fatal occurrence of Fournier’s gangrene in a rectal cancer patient undergoing neoadjuvant radiotherapy without chemotherapy. A 53-year-old male patient with G2 cT3 cN1a cM0 stage IIIB adenocarcinoma of the lower rectum and several comorbidities including ulcerative colitis was treated with 56 Gy to the primary tumor in 28 fractions because he declined the recommended simultaneous chemotherapy. He was also enrolled in the ketogenic diet arm of our KETOCOMP study, so that prospective measurements of blood parameters, quality of life, and body composition were made. The patient died 6 days after completion of radiotherapy due to septic shock associated with Fournier’s gangrene reaching from the right buttock into the gluteal muscles and descending into the scrotum. In retrospect, there were several signs probably indicating the development of the gangrene: (i) a decline in bioelectrical phase angle; (ii) an accelerated weight and fat-free mass loss starting in the third week of radiotherapy; (iii) an increase in C-reactive protein (CRP) and concurrent drop in high-density lipoprotein (HDL) cholesterol and insulin-like growth factor(IGF)-1 concentrations; and (iv) the occurrence of a sharp pain in the perianal region reported in the fifth week of radiotherapy. Notably, his self-reported quality of life score was the same at the end of as before radiotherapy. This case highlights the occurrence of Fournier’s gangrene as an extremely rare but life-threatening complication during neoadjuvant radiotherapy for rectal cancer which should be refreshed in the awareness of radiation oncologists and radiologists.

Introduction: Epidemiologic data indicate diabetes confers an augmented risk of lung cancer development, yet the relationship between hyperglycemia, metabolic agents, and prognosis is unclear. We analyzed the impact of hyperglycemia, anti-diabetic agents, and statins on outcomes in non-small cell lung cancer (NSCLC) patients undergoing chemoradiation. Method and Materials: In total, data from 170 patients with stage III NSCLC treated at the University of Pittsburgh Medical Center between 2001 and 2014 were obtained for analysis. Kaplan-Meier survival analysis was used to estimate time-to-event for overall survival (OS), disease-free survival, distant metastasis (DM), and loco-regional control (LRC). Blood glucose values (n = 2870), statins, and diabetic medications were assessed both continuously and categorically in univariable and multivariable Cox proportional hazard regression models to estimate hazard ratios and identify prognostic factors. Results: Tumor volume was a negative prognostic factor for OS, disease-free survival, DM, and LRC (p = 0.001). Tumor stage and treatment time were associated with increased all-cause mortality. Any glucose measurement ≥ 130 mg/dl during treatment (2-year estimate 49.9 vs. 65.8%, p = 0.095) was borderline significant for decreased LRC, with similar trends on multivariable analysis (HR 1.636, p = 0.126) and for OS (HR 1.476, p = 0.130). Statin usage was associated with improved 2-year LRC (53.4 vs. 62.4%, p = 0.088) but not with improvements in survival. Other glycemic parameters, comorbid diabetes diagnosis, or anti-diabetic medications were not significantly associated with outcomes. Conclusions: There were trends for blood glucose value over 130 mg/dl and statin nonuse being associated with inferior prognosis for LRC in stage III NSCLC patients; glycemic state, statin usage, and glucose-modulating medications were not associated with survival outcomes in multivariable analysis in this retrospective database.