Changes in serum omega fatty acids on a Mediterranean diet intervention in patients with gingivitis: An exploratory study.

BACKGROUND: Omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) are precursors of pro- and anti-inflammatory lipid mediators. Serum PUFA levels could influence the severity of inflammatory oral diseases, such as gingivitis. OBJECTIVE: The study analyzed serum PUFA levels in a six-week randomized controlled trial in individuals on the Mediterranean diet (MedD), associations with the intake of specific foods, and possible correlations with oral inflammatory parameters. METHODS: Data from 37 study participants on either a MedD (MedDG; n = 18) or a "Western diet" in the control group (CG, n = 19) were analyzed. Dental examinations and serum analyses were performed at two time points, T1 (baseline) and T2 (week 6). Serum PUFA status, adherence to the MedD, and data from a Food Frequency Questionnaire were analyzed. RESULTS: Within the MedDG omega-6 fatty acid levels decreased significantly. In the overall sample, the proportional decrease in sites with bleeding on probing correlated weakly to moderately with the decrease in total omega-6 fatty acid level (Spearman's ρ = 0.274) and the decrease in gingival index correlated moderately with the decrease in linoleic acid level (Spearman's ρ = 0.351). Meat and fast-food consumption correlated positively with levels of various omega-6 fatty acids, whereas nut, fish, and dairy product consumption correlated positively with omega-3 levels. CONCLUSION: Adherence to a MedD was associated with a decrease in serum omega-6 levels, which positively affected the omega-6/omega-3 ratio. The MedD associated reduction in serum omega-6 levels may be a mechanism that favorably affects gingival inflammatory parameters.

Comparison of Diffusion Signal Models for Fiber Tractography in Eloquent Glioma Surgery-Determination of Accuracy Under Awake Craniotomy Conditions.

OBJECTIVE: Fiber tractography (FT) has become an important noninvasive tool to ensure maximal safe tumor resection in eloquent glioma surgery. Intraoperatively applied FT is still predominantly based on diffusion tensor imaging (DTI). However, reconstruction schemes of high angular resolution diffusion imaging data for high-resolution FT (HRFT) are gaining increasing attention. The aim of this prospective study was to compare the accuracy of sophisticated HRFT models compared with DTI-FT. METHODS: Ten patients with eloquent gliomas underwent surgery under awake craniotomy conditions. The localization of acquisition points, representing deteriorations during intraoperative electrostimulation (IOM) and neuropsychological mapping, were documented. The offsets of acquisition points to the respective fiber bundle were calculated. Probabilistic Q-ball imaging (QBI) and constrained spherical deconvolution (CSD)-FT were compared with DTI-FT for the major language-associated fiber bundles (superior longitudinal fasciculus [SLF] II-IV, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus/medial longitudinal fasciculus). RESULTS: Among 186 offset values, 46% were located closer than 10 mm to the estimated fiber bundle (CSD, 36%; DTI, 40% and QBI, 60%). Moreover, only 10 offsets were further away than 30 mm (5%). Lowest mean minimum offsets (SLF, 7.7 ± 7.9 mm; inferior fronto-occipital fasciculus, 12.7 ± 8.3 mm; inferior longitudinal fasciculus/medial longitudinal fasciculus, 17.7 ± 6.7 mm) were found for QBI, indicating a significant advantage compared with CSD or DTI (P < 0.001), respectively. No significant differences were found between CSD-FT and DTI-FT offsets (P = 0.105), albeit for the compound SLF exclusively (P < 0.001). CONCLUSIONS: Comparing HRFT techniques QBI and CSD with DTI, QBI delivered significantly better results with lowest offsets and good correlation to IOM results. Besides, QBI-FT was feasible for neurosurgical preoperative and intraoperative applications. Our findings suggest that a combined approach of QBI-FT and IOM under awake craniotomy is considerable for best preservation of neurological function in the presented setting. Overall, the implementation of selected HRFT models into neuronavigation systems seems to be a promising tool in glioma surgery.

Evaluation of robotic versus open partial pancreatoduodenectomy-study protocol for a randomised controlled pilot trial (EUROPA, DRKS00020407).

BACKGROUND: Partial pancreatoduodenectomy (PD) is the indicated surgical procedure for a wide range of benign and malignant diseases of the pancreatic head and distal bile duct and offers the only potential cure for pancreatic head cancer. The current gold standard, open PD (OPD) performed via laparotomy, is associated with morbidity in around 40% of cases, even at specialised centres. Robotic PD (RPD) might offer a viable alternative to OPD and has been shown to be feasible. Encouraging perioperative results have been reported for RPD in a number of small, non-randomised studies. However, since those studies showed a considerable risk of bias, a thorough comparison of RPD with OPD is warranted. METHODS: The EUROPA (EvalUation of RObotic partial PAncreatoduodenectomy) trial is designed as a randomised controlled unblinded exploratory surgical trial with two parallel study groups. A total of 80 patients scheduled for elective PD will be randomised after giving written informed consent. Patients with borderline or non-resectable carcinoma of the pancreatic head as defined by the National Comprehensive Cancer Network guidelines, distant metastases or an American Society of Anaesthesiologists (ASA) score > III will be excluded. The experimental intervention, RPD, will be compared with the control intervention, OPD. An intraoperative dropout of approximately eight patients per group is expected because they may receive another type of surgical procedure than planned. Overall, 64 patients need to be analysed. The primary endpoint of the trial is overall postoperative morbidity within 90 days after index operation, measured using the Comprehensive Complication Index (CCI). The secondary endpoints include the feasibility of recruitment and assessment of clinical, oncological and safety parameters and quality of life and cost-effectiveness. DISCUSSION: The EUROPA trial is the first randomised controlled trial comparing RPD with OPD. Differences in postoperative morbidity will be evaluated to design a future multicentre confirmatory efficacy trial. TRIAL REGISTRATION: German Clinical Trial Register DRKS00020407 . Registered on 9 March 2020.

Contrast-enhanced ultrasound for determining muscular perfusion after oral intake of L-citrulline, L-arginine, and galloylated epicatechines: A study protocol.

INTRODUCTION: The market for dietary supplements in the sports sector has been growing rapidly for several years, though there is still lacking evidence regarding their claimed benefits. One group is that of nitric oxide increasing supplements, so-called "NO-boosters," which are claimed to improve the supply of oxygen and nutrients to the muscle by enhancing vasodilation.The aim of this study was to investigate 3 of these supplements in healthy male athletes for their muscle perfusion-enhancing potential using contrast-enhanced ultrasound (CEUS). METHODS: This placebo-controlled, double-blind, randomized cross-over trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Three commercial NO enhancing products including 300 mg of the specific green tea extract VASO6 and a combination of 8 g L-citrulline malate and 3 g L-arginine hydrochloride will be examined for their potential to increase muscular perfusion in 30-male athletes between 18 and 40 years and will be compared with a placebo. On each of the 3 appointments CEUS of the dominant biceps muscle will be performed at rest and after a standardized resistance training. Every athlete receives each of the 3 supplements once after a wash-out period of at least 1 week. Perfusion will be quantified via VueBox quantification software. The results of CEUS perfusion measurements will be compared intra- and interindividually and correlated with clinical parameters. DISCUSSION: The results of this study may help to establish CEUS as a suitable imaging modality for the evaluation of potentially vasodilatory drugs in the field of sports. Other supplements could also be evaluated in this way to verify the content of their advertising claims. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), ID: DRKS00016972, registered on 25.03.2019.

Continuous wound infiltration versus epidural analgesia for midline abdominal incisions - a randomized-controlled pilot trial (Painless-Pilot trial; DRKS Number: DRKS00008023).

OBJECTIVES: To test the feasibility of a randomized controlled study design comparing epidural analgesia (EDA) with continuous wound infiltration (CWI) in respect to postoperative complications and mobility to design a future multicentre randomized controlled trial. DESIGN, SETTING, PARTICIPANTS: CWI has been developed to address drawbacks of EDA. Previous studies have established the equivalent analgesic potential of CWI compared to EDA. This is a single centre, non-blinded pilot randomized controlled trial at a tertiary surgical centre. Patients undergoing elective non-colorectal surgery via a midline laparotomy were randomized to EDA or CWI. Endpoints included recruitment, feasibility of assessing postoperative mobility with a pedometer and morbidity. No primary endpoint was defined and all analyses were explorative. INTERVENTIONS: CWI with local anaesthetics (experimental group) vs. thoracic EDA (control). RESULTS: Of 846 patients screened within 14 months, 71 were randomized and 62 (31 per group) included in the intention-to-treat analysis. Mobility was assessed in 44 of 62 patients and revealed no differences within the first 3 postoperative days. Overall morbidity did not differ between the two groups (measured via the comprehensive complication index). Median pain scores at rest were comparable between the two groups, while EDA was superior in pain treatment during movement on the first, but not on the second and third postoperative day. Duration of preoperative induction of anaesthesia was shorter with CWI than with EDA. Of 17 serious adverse events, 3 were potentially related to EDA, while none was related to CWI. CONCLUSION: This trial confirmed the feasibility of a randomized trial design to compare CWI and EDA regarding morbidity. Improvements in the education and training of team members are necessary to improve recruitment. TRIAL REGISTRATION: DRKS00008023.

Acupuncture to improve tolerance of diagnostic esophagogastroduodenoscopy in patients without systemic sedation: results of a single-center, double-blinded, randomized controlled trial (DRKS00000164).

BACKGROUND: Sedation prior to esophagogastroduodenoscopy is widespread and increases patient comfort. However, it demands additional trained personnel, accounts for up to 40 % of total endoscopy costs and impedes rapid hospital discharge. Most patients lose at least one day of work. 98 % of all serious adverse events occurring during esophagogastroduodenoscopy are ascribed to sedation. Acupuncture is reported to be effective as a supportive intervention for gastrointestinal endoscopy, similar to conventional premedication. We investigated whether acupuncture during elective diagnostic esophagogastroduodenoscopy could increase the comfort of patients refusing systemic sedation. METHODS: We performed a single-center, double-blinded, placebo-controlled superiority trial to compare the success rates of elective diagnostic esophagogastroduodenoscopies using real and placebo acupuncture. All patients aged 18 years or older scheduled for elective, diagnostic esophagogastroduodenoscopy who refused systemic sedation were eligible; 354 patients were randomized. The primary endpoint measure was the rate of successful esophagogastroduodenoscopies. The intervention was real or placebo acupuncture before and during esophagogastroduodenoscopy. Successful esophagogastroduodenoscopy was based on a composite score of patient satisfaction with the procedure on a Likert scale as well as quality of examination, as assessed by the examiner. RESULTS: From February 2010 to July 2012, 678 patients were screened; 354 were included in the study. Baseline characteristics of the two groups showed a similar distribution in all but one parameter: more current smokers were allocated to the placebo group. The intention-to-treat analysis included 177 randomized patients in each group. Endoscopy could successfully be performed in 130 patients (73.5 %) in the real acupuncture group and 129 patients (72.9 %) in the placebo group. Willingness to repeat the procedure under the same conditions was 86.9 % in the real acupuncture group and 87.6 % in the placebo acupuncture group. CONCLUSIONS: Esophagogastroduodenoscopy without sedation is safe and can successfully be performed in two-thirds of patients. Patients planned for elective esophagogastroduodenoscopy without sedation do not benefit from acupuncture of the Sinarteria respondens (Rs) 24 Chengjiang middle line, Pericard (Pc) 6 Neiguan bilateral, or Dickdarm (IC) 4 Hegu bilateral, according to traditional Chinese medicine meridian theory. TRIAL REGISTRATION: DRKS00000164 . Registered on 10 December 2009.

Duodenum-preserving pancreatic head resection: 10-year follow-up of a randomized controlled trial comparing the Beger procedure with the Berne modification.

BACKGROUND: Since the introduction of the duodenum-preserving pancreatic head resection for operative treatment of chronic pancreatitis, various modifications of the original Beger procedure have emerged. A randomized controlled trial comparing the Beger procedure and the Berne modification indicated that the latter is an equivalent alternative, but a comparison of the long-term results of both procedures has not yet been published. METHODS: Between December 2002 and January 2005, 65 patients were randomized intraoperatively to the Beger or the Berne procedure. For this 10-year follow-up, patients were contacted by phone and in writing to evaluate patient-relevant outcome parameters. Statistical analysis was made on an intention-to-treat basis. RESULTS: Median follow-up was 129 (111-137) months. Forty of 65 patients were available for follow-up; 11 of the original study cohort had died, and 14 were otherwise lost to follow-up. Quality of life, pain, occupational disability, exocrine and endocrine pancreatic function, endoscopic interventions, and redo operations were comparable in both groups. More than half of the patients were completely free of pain, and the majority in both groups judged that the index operation had improved their quality of life. CONCLUSION: Ten-year follow-up showed no differences in patient-relevant outcome parameters between the Beger and Berne procedures for treatment of chronic pancreatitis. Because short-term results have shown the Berne modification is superior in terms of operation time and duration of hospital stay, it should be preferred whenever possible, depending on the individual surgeon's expertise and the intraoperative findings.

Biochemical markers of bone turnover in patients with spinal metastases after resistance training under radiotherapy--a randomized trial.

BACKGROUND: To compare the effects of resistance training versus passive physical therapy on bone turnover markers (BTM) in the metastatic bone during radiation therapy (RT) in patients with spinal bone metastases. Secondly, to evaluate an association of BTM to local response, skeletal-related events (SRE), and number of metastases. METHODS: In this randomized trial, 60 patients were allocated from September 2011 to March 2013 into one of the two arms: resistance training (Arm A) or passive physical therapy (Arm B) with thirty patients in each arm during RT. Biochemical markers such as pyridinoline (PYD), desoxy-pyridinoline (DPD), bone alkaline phosphatase (BAP), total amino-terminal propeptide of type I collagen (PINP), beta-isomer of carboxy-terminal telopeptide of type I collagen (CTX-I), and cross-linked N-telopeptide of type I collagen (NTX) were analyzed at baseline, and three months after RT. RESULTS: Mean change values of PYD and CTX-I were significantly lower at 3 months after RT (p = 0.035 and p = 0.043) in Arm A. Importantly, all markers decreased in both arms, except of PYD and CTX-I in arm B, although significance was not reached for some biomarkers. In arm A, the local response was significantly higher (p = 0.003) and PINP could be identified as a predictor for survivors (OR 0.968, 95%CI 0.938-0.999, p = 0.043). BAP (OR 0.974, 95%CI 0.950-0.998, p = 0.034) and PINP (OR 1.025, 95%CI 1.001-1.049, p = 0.044) were related with an avoidance of SRE. CONCLUSIONS: In this group of patients with spinal bone metastases, we were able to show that patients with guided resistance training of the paravertebral muscles can influence BTM. PYD and CTX-I decreased significantly in arm A. PINP can be considered as a complementary tool for prediction of local response, and PINP as well as BAP for avoidance of SRE. TRIAL REGISTRATION: Clinical trial identifier NCT 01409720. August 2, 2011.

Long-term durability of alumina ceramic heads in THA.

BACKGROUND: The optimal type of bearing for hip arthroplasty remains a matter of debate. Ceramic-on-polyethylene (CoP) bearings are frequently used in younger and more active patients to reduce wear and increase biocompatibility compared to Metal-on-Polyethylene (MoP) bearings. However, in comparison to metal heads, the fracture risk of ceramic heads is higher. In addition, ceramic head fractures pose a serious complication which often necessitates major revision surgery. To date, there are no long-term data (>20 years of follow-up) reporting fracture rates of the ceramic femoral heads in CoP bearings. The purpose of this research was to investigate long-term CoP fracture rate. METHODS: We evaluated the clinical and radiographic results of 348 cementless THAs treated with 2nd generation Biolox Al2O3 Ceramic-on-Polyethylene (CoP) bearings consecutively implanted between January 1985 and December 1989. The mean age at implantation was 57 years. The patients were followed for a minimum of 20 years. At the final 111 had died, and 5 were lost to follow-up. The cumulative incidence of ceramic head fractures in the long-term was estimated using a competing risk analysis. RESULTS: The cumulative incidence of ceramic head fracture after 22-years was estimated with a competing risk analysis at 0.29% after 22-years (SE = 2.09%; 95% - CI: 0.03-1.5%). The radiographic analysis revealed no impending failures at final follow-up. DISCUSSION/CONCLUSION: The fracture rate of second-generation ceramic heads using a CoP articulation remains very low into the third decade after cementless THA.

Pancreatic Atrophy in Hepatocellular Carcinoma Patients Receiving Long-Term Treatment with Sorafenib.

OBJECTIVE: To date, sorafenib is the only approved systemic therapy for advanced hepatocellular carcinoma (HCC). Pancreatic atrophy has recently been reported in 2 patients as a novel side effect after long-term sorafenib treatment. METHODS: We retrospectively analyzed clinical and radiological data of patients with advanced HCC with long-term treatment of sorafenib (median 279 days, range 153-826 days). Pancreata were semi-manually segmented section by section to calculate the pancreas volumes before and under sorafenib treatment. RESULTS: Sorafenib reduced pancreatic volume in 18/19 (95%) HCC patients with a mean pancreatic volume loss of 25% (p = 0.002). Pancreatic volume loss depended on the dose (r = 0.36) and exposure time of sorafenib (r = 0.35) and was detectable as early as after 3 months of sorafenib treatment and already after a cumulative sorafenib dose of <100 g. Median overall survival was 13.2 months (range 7.8-31.3 months) but did not correlate with sorafenib-induced pancreatic volume reduction (hazard ratio 1.002, 95% confidence interval 0.981-1.060, p = 0.24). CONCLUSION: We could confirm pancreatic atrophy as a novel adverse event of sorafenib therapy in HCC patients, correlating with sorafenib dose and exposure time.

Prevalence of intracardiac thrombi under phenprocoumon, direct oral anticoagulants (dabigatran and rivaroxaban), and bridging therapy in patients with atrial fibrillation and flutter.

Direct oral anticoagulants (DOACs) are effective for stroke prevention in nonvalvular atrial fibrillation (AF). Cardioversion (CV) is frequently performed in patients with AF or flutter. To further explore the safety profile of DOACs in the context of CV, we sought to assess the prevalence of intracardiac thrombi under DOAC therapy in comparison with treatment with vitamin K antagonists. A total of 672 transesophageal echocardiograms performed in 643 patients with a history of nonvalvular AF were analyzed. The median CHA2DS2-VASc score was 4. Cases were stratified according to anticoagulation with dabigatran (n = 79), rivaroxaban (n = 122), phenprocoumon (n = 180), or bridging therapy (n = 287). In a subgroup analysis, only patients receiving phenprocoumon with an international normalized ratio ≥2 on the day of the investigation or on DOAC therapy for ≥3 weeks were considered. The prevalence of intracardiac thrombi under phenprocoumon was significantly higher than under DOACs (phenprocoumon, 17.8%; all DOACs, 3.9%; dabigatran, 3.8%; rivaroxaban, 4.1%) and showed no significant difference to bridging therapy (12.5%). In patients with sufficient short-term anticoagulation, similar differences between DOAC and phenprocoumon groups were observed (phenprocoumon, 18.4%; all DOACs, 3.8%; dabigatran, 0%; rivaroxaban, 6.6%). The influence of anticoagulation medication on thrombus rates was confirmed after adjusting for baseline intergroup differences regarding left atrial size and CHA2DS2-VASc score. In conclusion, the prevalence of intracardiac thrombi was lower under DOAC therapy than under phenprocoumon in this high-risk patient cohort. Safety of CV during DOAC treatment requires further prospective evaluation.

Leukodepletion of autologous whole blood has no impact on perioperative infection rate and length of hospital stay.

BACKGROUND: Several mechanisms have been proposed as possible causes of transfusion-related immunomodulation (TRIM) after allogeneic transfusion. If one of these mechanisms, the release of mediators of immunity and inflammation ("biologic response modifiers"[BRMs]) from disintegrating blood cells during storage of blood products, really causes TRIM, it should in principle also occur after autologous transfusion. As a consequence, prestorage leukoreduction of autologous blood should be able to prevent the clinical consequences of TRIM after autologous transfusion. STUDY DESIGN AND METHODS: This hypothesis was investigated in a multicenter, double-blind, randomized controlled trial. A total of 1089 patients scheduled for total hip arthroplasty and eligible for preoperative autologous blood donation were randomly assigned to receive autologous whole blood (AWB) either unmodified or leukoreduced when transfusion was indicated. RESULTS: Neither the primary study outcome, that is, the overall postoperative infection rate (17.3% vs. 17.6%, p = 0.59), nor several secondary outcomes like median length of hospital stay (14 days vs. 14 days, p = 0.17) were significantly different between groups, whether analyzed according to the intention-to-treat principle or "as treated." CONCLUSION: This trial provides strong evidence, from clinically relevant outcome data, that leukoreduction of AWB does not improve postoperative patient outcome and that the release of BRMs from disintegrating blood cells during storage cannot explain the immunomodulatory effect of blood transfusion.