Robotic-Assisted versus Laparoscopic Surgery for Rectal Cancer: An Analysis of Clinical and Financial Outcomes from a Tertiary Referral Center.

Background: The popularity of robotic-assisted surgery for rectal cancer is increasing, but its superiority over the laparoscopic approach regarding safety, efficacy, and costs has not been well established. Methods: A retrospective single-center study was conducted comparing consecutively performed robotic-assisted and laparoscopic surgeries for rectal cancer between 1 January 2016 and 31 September 2021. In total, 125 adult patients with sporadic rectal adenocarcinoma (distal extent ≤ 15 cm from the anal verge) underwent surgery where 66 were operated on robotically and 59 laparoscopically. Results: Severe postoperative complications occurred less frequently with robotic-assisted compared with laparoscopic surgery, as indicated by Clavien-Dindo classification grades 3b-5 (13.6% vs. 30.5%, p = 0.029). Multiple logistic regression analyses after backward selection revealed that robotic-assisted surgery was associated with a lower rate of total (Clavien-Dindo grades 1-5) (OR = 0.355; 95% CI 0.156-0.808; p = 0.014) and severe postoperative complications (Clavien-Dindo grades 3b-5) (OR = 0.243; 95% CI 0.088-0.643; p = 0.005). Total inpatient costs (median EUR 17.663 [IQR EUR 10.151] vs. median EUR 14.089 [IQR EUR 12.629]; p = 0.018) and surgery costs (median EUR 10.156 [IQR EUR 3.551] vs. median EUR 7.468 [IQR EUR 4.074]; p < 0.0001) were higher for robotic-assisted surgery, resulting in reduced total inpatient profits (median EUR -3.196 [IQR EUR 9.101] vs. median EUR 232 [IQR EUR 6.304]; p = 0.004). Conclusions: In our study, robotic-assisted surgery for rectal cancer resulted in less severe and fewer total postoperative complications. Still, it was associated with higher surgery and inpatient costs. With increasing experience, the operative time may be reduced, and the postoperative recovery may be further accelerated, leading to reduced surgery and total inpatient costs.

Standardized digital solution with surgical procedure manager (SPM®)-an opportunity for maximizing patient safety and efficiency in ileostomy reversal?

Background: Standardization and digitalization are getting more and more essential in surgery. Surgical procedure manager (SPM®) is a freestanding computer serving as a digital supporter in the operating room. SPM® navigates step-by-step through surgery by providing a checklist for each individual step. Methods: This was a single center, retrospective study at the Department for General and Visceral Surgery at Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin. Patients who underwent ileostomy reversal without SPM® in the period of January 2017 until December 2017 were compared to patients who were operated with SPM® in the period of June 2018 until July 2020. Explorative analysis and multiple logistic regression were performed. Results: Overall, 214 patients underwent ileostomy reversal: 95 patients without SPM® vs. 119 patients with SPM®. Ileostomy reversal was performed by head of department/attendings in 34.1%, by fellows in 28.5% and by residents in 37.4%; p = 0.91. Postoperative intraabdominal abscess emerged more often in patients without SPM®: ten (10.5%) patients vs. four (3.4%) patients; p = 0.035. Multiple logistic regression showed a risk reduction for intraabdominal abscess {Odds ratio (OR) 0.19 [95% confidence interval (CI) 0.05-0.71]; p = 0.014} and for bowel perforation [OR 0.09 (95% CI 0.01-0.93); p = 0.043] in the group with use of SPM® in ileostomy reversal. Conclusions: SPM® may reduce postoperative complications in ileostomy reversal such as intraabdominal abscess and bowel perforation. SPM® may contribute to patient safety.

Robotic-Assisted versus Laparoscopic Proctectomy with Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: An Analysis of Clinical and Financial Outcomes from a Tertiary Referral Center.

Background: Robotic-assisted colorectal surgery is gaining popularity, but limited data are available on the safety, efficacy, and cost of robotic-assisted restorative proctectomy with the construction of an ileal pouch and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Methods: A retrospective study was conducted comparing consecutively performed robotic-assisted and laparoscopic proctectomy with IPAA between 1 January 2016 and 31 September 2021. In total, 67 adult patients with medically refractory UC without proven dysplasia or carcinoma underwent surgery: 29 operated robotically and 38 laparoscopically. Results: There were no differences between both groups regarding postoperative complications within 30 days according to Clavien-Dindo classification' grades 1−5 (51.7% vs. 42.1%, p = 0.468) and severe grades 3b−5 (17.2% vs. 10.5%, p = 0.485). Robotic-assisted surgery was associated with an increased urinary tract infection rate (n = 7, 24.1% vs. n = 1, 2.6%; p = 0.010) and longer operative time (346 ± 65 min vs. 281 ± 66 min; p < 0.0001). Surgery costs were higher when operated robotically (median EUR 10.377 [IQR EUR 4.727] vs. median EUR 6.689 [IQR EUR 3.170]; p < 0.0001), resulting in reduced total inpatient profits (median EUR 110 [IQR EUR 4.971] vs. median EUR 2.853 [IQR EUR 5.386]; p = 0.001). Conclusion: Robotic-assisted proctectomy with IPAA can be performed with comparable short-term clinical outcomes to laparoscopy but is associated with a longer duration of surgery and higher surgery costs. As experience increases, some advantages may become evident regarding operative time, postoperative recovery, and length of stay. The robotic procedure might then become cost-efficient.

Impact of Adjuvant Ocular Interventions on the Quality of Life of Patients with Uveal Melanoma after Proton Beam Therapy.

Introduction: Proton beam therapy is an established primary treatment for patients with nonmetastasized uveal melanoma. Adjuvant local interventions, like intravitreal injections or surgery, were shown to improve long-term eye preservation; however, their impact on the patient's quality of life (QOL) remains unknown. Methods: In a post-radiotherapeutic follow-up, we prospectively collected data on QOL, visual acuity, and interventional adjuvant procedures. QOL was measured with QOL-C30 questionnaire and quality of life questionnaire OPT30 at baseline, and at 3 and 12 months after proton therapy. Patients were grouped by the type of adjuvant treatment. The impact on QOL was analyzed by comparing changes in the mean score values and visual acuity for different interventional subgroups, with generalized linear mixed models and Wilcoxon signed-rank tests. Results: We received 108 (100%) and 95 (88.0%) questionnaires at 3 and 12 months post-therapy, respectively. Adjuvant interventions included observation (n = 61, 56.5%), intravitreal injections (n = 17, 15.7%), and an intraocular surgical procedure (n = 30, 27.8%). In the latter group, several QOL items significantly declined after the 3-month adjuvant interval, but they partially recovered at the 12-month follow-up. In all adjuvant-intervention groups, global QOL scores returned to baseline levels at 12 months. Conclusion: Posttreatment adjuvant interventions had no long-lasting effects on QOL in patients with uveal melanoma.

Impact of myopenia and myosteatosis on postoperative outcome and recurrence in Crohn's disease.

PURPOSE: Myopenia and myosteatosis have been proposed to be prognostic factors of surgical outcomes for various diseases, but their exact role in Crohn's disease (CD) is unknown. The aim of this study is to evaluate their impact on anastomotic leakage, CD recurrence, and postoperative complications after ileocecal resection in patients with CD. METHODS: A retrospective analysis of CD patients undergoing ileocecal resection at our tertiary referral center was performed. To assess myopenia, skeletal muscle index (skeletal muscle area normalized for body height) was measured using an established image analysis method at third lumbar vertebra level on MRI cross-sectional images. Muscle signal intensity was measured to assess myosteatosis index. RESULTS: A total of 347 patients were retrospectively analyzed. An adequate abdominal MRI scan within 12 months prior to surgery was available for 223 patients with median follow-up time of 48.8 months (IQR: 20.0-82.9). Anastomotic leakage rate was not associated with myopenia (SMI: p = 0.363) or myosteatosis index (p = 0.821). Patients with Crohn's recurrence had a significantly lower SMI (p = 0.047) in univariable analysis, but SMI was not an independent factor for recurrent anastomotic stenosis in multivariable analysis (OR 0.951, 95% CI 0.840-1.078; p = 0.434). Postoperative complications were not associated with myopenia or myosteatosis. CONCLUSION: Based on the largest cohort of its kind with a long follow-up time, we could provide some data that MRI parameters for myopenia and myosteatosis may not be reliable predictors of postoperative outcome or recurrence in patients with Crohn's disease undergoing ileocecal resection.

90-yttrium-ibritumomab tiuxetan as first-line treatment for follicular lymphoma: updated efficacy and safety results at an extended median follow-up of 9.6 years.

Radioimmunotherapy with 90-yttrium-ibritumomab tiuxetan (90Y-IT) as first-line treatment in patients with follicular lymphoma (FL) demonstrated promising results with a complete remission (CR) rate of 56% and a median progression-free survival (PFS) of 26 months, when initially analyzed after a median follow-up of 30.6 months. The aim of this long-term follow-up was to investigate whether clinical benefits were maintained and new safety signals appeared. Fifty-nine patients, aged ≥ 50 years, with FL grade 1 to 3A in stages II to IV were treated with 90Y-IT as first-line therapy. If CR without evidence of minimal residual disease (MRD), partial response or stable disease was achieved 6 months after treatment, patients were observed without further treatment. Patients with CR but persisting MRD received consolidation therapy with rituximab. The primary endpoint was the clinical response rate. Secondary endpoints were time to progression, safety, and tolerability. After a median follow-up of 9.6 years, median PFS was 3.6 years, and 8-year PFS was 38.3%. Median overall survival (OS) was not reached during the extended follow-up, and 8-year OS amounted to 69.2%. Age 65 years and above or disease progression within 24 months of treatment were significantly associated with shorter OS. An important finding was the lack of new safety signals. In particular, no increase in secondary malignancies or transformation into aggressive lymphoma was observed compared to trials with a similar follow-up. In summary, 90Y-IT as first-line treatment demonstrates a favorable safety profile and long-term clinical activity in a substantial fraction of FL patients in need of therapy. ClinicalTrials.gov Identifier: NCT00772655.

PuraStat in gastrointestinal bleeding: results of a prospective multicentre observational pilot study.

BACKGROUND: A recently developed haemostatic peptide gel for endoscopic application has been introduced to improve the management of gastrointestinal bleeding. The aim of this pilot study was to evaluate the feasibility, safety, efficacy and indication profiles of PuraStat in a clinical setting. METHODS: In this prospective observational multicentre pilot study, patients with acute non-variceal gastrointestinal bleeding (upper and lower) were included. Primary and secondary application of PuraStat was evaluated. Haemoglobin, prothrombin time, platelets and transfusion behaviour were documented before and after haemostasis. The efficacy of PuraStat was assessed during the procedure, at 3 days and 1 week after application. RESULTS: 111 patients with acute gastrointestinal bleeding were recruited into the study. 70 percent (78/111) of the patients had upper gastrointestinal bleeding and 30% (33/111) had lower gastrointestinal bleeding. After primary application of PuraStat, initial haemostatic success was achieved in 94% of patients (74/79, 95% CI 88-99%), and in 75% of the patients when used as a secondary haemostatic product, following failure of established techniques (24/32, 95% CI 59-91%). The therapeutic success rates (absence of rebleeding) after 3 and 7 days were 91% and 87% after primary use, and 87% and 81% in all study patients. Overall rebleeding rate at 30 day follow-up was 16% (18/111). In the 5 patients who finally required surgery (4.5%), PuraStat allowed temporary haemostasis and stabilisation. CONCLUSIONS: PuraStat expanded the therapeutic toolbox available for an effective treatment of gastrointestinal bleeding sources. It could be safely applied and administered without complications as a primary or secondary therapy. PuraStat may additionally serve as a bridge to surgery in order to achieve temporary haemostasis in case of refractory severe bleeding, possibly playing a role in preventing immediate emergency surgery.

Quality of life and treatment-related burden during ocular proton therapy: a prospective trial of 131 patients with uveal melanoma.

BACKGROUND: Proton beam therapy is a well-established treatment option for patients with uveal melanoma (UM). The treatment procedure, in general, includes placing radiopaque clips to ensure exact eye-positioning during radiotherapy, followed by the delivery of proton irradiation. The short-term burden associated with proton therapy in patients with UM has rarely been addressed. In this prospective study, we investigated the physiological and psychological aspects of proton therapy that might affect the well-being of patients during the different stages of treatment. METHODS: During the treatment procedure, we conducted longitudinal assessments of the Quality of life (QOL), organ-specific symptoms, and psychological aspects in patients with UM with three questionnaires (EORTC QLQ-C30, EORTC QLQ-OPT30, and GAD-7). Patients completed questionnaires before clip surgery (T0), before proton therapy (T1), after completing treatment (T2), and three months after treatment completion (T3). We also collected data on tumor characteristics and socio-demographics to identify potential risk factors associated with high treatment burdens. RESULTS: We prospectively included 131 consecutive patients. Questionnaire data showed a significant, temporary decline in global QOL and an increase in eye-related symptoms, as a result of the clip surgery (T0-T1). After treatment completion (T2), global QOL improved gradually, and none of the eye-related symptoms significantly deteriorated over the course of proton therapy. The global QOL returned to baseline levels three months after treatment (T3). We identified baseline anxiety as an independent risk factor for experiencing an acute treatment-related burden. Furthermore, we found interactions between GAD7 and patient sex showing that anxiety had a more pronounced effect on QOL outcome in female patients. CONCLUSION: The short-term treatment-related burden of ocular proton therapy appeared to be largely associated with the preceding clip surgery, rather than the irradiation procedure. We found that anxiety was strongly associated with experiencing QOL issues during the treatment procedure. Our findings could contribute to the development of future strategies for improving the treatment process and psycho-oncologic patient care.

Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE Trial.

Background: Inflammatory markers, such as C-reactive Protein (CRP), Interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha and fibrinogen, are upregulated following acute stroke. Studies have shown associations of these biomarkers with increased mortality, recurrent vascular risk, and poor functional outcome. It is suggested that physical fitness training may play a role in decreasing long-term inflammatory activity and supports tissue recovery. Aim: We investigated the dynamics of selected inflammatory markers in the subacute phase following stroke and determined if fluctuations are associated with functional recovery up to 6 months. Further, we examined whether exposure to aerobic physical fitness training in the subacute phase influenced serum inflammatory markers over time. Methods: This is an exploratory analysis of patients enrolled in the multicenter randomized-controlled PHYS-STROKE trial. Patients within 45 days of stroke onset were randomized to receive either four weeks of aerobic physical fitness training or relaxation sessions. Generalized estimating equation models were used to investigate the dynamics of inflammatory markers and the associations of exposure to fitness training with serum inflammatory markers over time. Multiple logistic regression models were used to explore associations between inflammatory marker levels at baseline and three months after stroke and outcome at 3- or 6-months. Results: Irrespective of the intervention group, high sensitive CRP (hs-CRP), IL-6, and fibrinogen (but not TNF-alpha) were significantly lower at follow-up visits when compared to baseline (p all ≤ 0.01). In our cohort, exposure to aerobic physical fitness training did not influence levels of inflammatory markers over time. In multivariate logistic regression analyses, increased baseline IL-6 and fibrinogen levels were inversely associated with worse outcome at 3 and 6 months. Increased levels of hs-CRP at 3 months after stroke were associated with impaired outcome at 6 months. We found no independent associations of TNF-alpha levels with investigated outcome parameters. Conclusion: Serum markers of inflammation were elevated after stroke and decreased within 6 months. In our cohort, exposure to aerobic physical fitness training did not modify the dynamics of inflammatory markers over time. Elevated IL-6 and fibrinogen levels in early subacute stroke were associated with worse outcome up to 6-months after stroke. Clinical Trial Registration:ClinicalTrials.gov, NCT01953549.

Assessment of Risk Factors for the Occurrence of a High-Output Ileostomy.

Background: Ileostomy is often required in patients undergoing bowel resections for inflammatory bowel diseases (IBD), colorectal cancer, and emergencies. Unfortunately, some patients develop a high-output stoma (HOS). This condition affects homeostasis and may be life threatening. We aimed to identify possible risk factors for the development of HOS. Patients and methods: From 2012 to 2018, 296 patients who underwent ileostomy at Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin were retrospectively analyzed. Emergency operations were included. Diverting ileostomy, end ileostomies and anastomotic stomata with at least part ileum, were examined. HOS was defined as stoma output of more than 1,000 mL per day for more than 3 days. Univariate and multivariable analyses were used to detect potential risk factors for the development of HOS. Results: 41 of 296 patients developed HOS (13.9%). Mortality was 0.3%. In the univariate analysis, age (p < 0.002), diagnosis (Crohn's disease, p = 0.005), arterial hypertension (p = 0.023), surgical procedure (right-sided colectomy, small bowel resection, p < 0.001), open technique (p < 0.002), emergencies (p = 0.014), and anastomotic ileostomy (p < 0.001) were identified as risk factors. In the multivariable logistic regression, older age, diagnosis (Crohn's disease) and surgical procedure (right-sided colectomy, separate ileostomy, small bowel resection) remained significant risk factors. Conclusion: The occurrence of HOS is a relevant problem after ileostomy. The identification of risk factors for a high-output may be helpful for monitoring, early diagnosis and initiation of therapy as well as in the planning of close follow-up care.

Risk factors for upper and lower type prolonged postoperative ileus following surgery for Crohn's disease.

PURPOSE: Prolonged postoperative ileus (PPOI) is common after bowel resections, especially in Crohn's disease (CD). The pathophysiology of PPOI is not fully understood. PPOI could affect only the upper or lower gastrointestinal (GI) tract. The aim of this study was to assess risk factors for diverse types of PPOI, particularly to differentiate PPOI of upper and lower GI tract. METHODS: A retrospective analysis of 163 patients with CD undergoing ileocecal resection from 2015 to 2020 in a single center was performed. PPOI of the upper GI tract was predefined as the presence of vomiting or use of nasogastric tube longer than the third postoperative day. Lower PPOI was predefined as the absence of defecation for more than three days. Independent risk factors were identified by multivariable logistic regression analysis. RESULTS: Overall incidence of PPOI was 42.7%. PPOI of the upper GI tract was observed in 30.7% and lower PPOI in 20.9% of patients. Independent risk factors for upper PPOI included older age, surgery by a resident surgeon, hand-sewn anastomosis, prolonged opioid analgesia, and reoperation, while for lower PPOI included BMI ≤ 25 kg/m2, preoperative anemia, and absence of ileostomy. CONCLUSION: This study identified different risk factors for upper and lower PPOI after ileocecal resection in patients with CD. A differentiated upper/lower type approach should be considered in future research and clinical practice. High-risk patients for each type of PPOI should be closely monitored, and modifiable risk factors, such as preoperative anemia and opioids, should be avoided if possible.

Benefit of a wearable cardioverter defibrillator for detection and therapy of arrhythmias in patients with myocarditis.

AIMS: Myocarditis may lead to malignant arrhythmias and sudden cardiac death. As of today, there are no reliable predictors to identify individuals at risk for these catastrophic events. The aim of this study was to evaluate if a wearable cardioverter defibrillator (WCD) may detect and treat such arrhythmias adequately in the peracute setting of myocarditis. METHODS AND RESULTS: In this observational, retrospective, single centre study, we reviewed patients presenting to the Charité Hospital from 2009 to 2017, who were provided with a WCD for the diagnosis of myocarditis with reduced ejection fraction (<50%) and/or arrhythmias. Amongst 259 patients receiving a WCD, 59 patients (23%) were diagnosed with myocarditis by histology. The mean age was 46 ± 14 years, and 11 patients were women (19%). The mean WCD wearing time was 86 ± 63 days, and the mean daily use was 20 ± 5 h. During that time, two patients (3%) had episodes of sustained ventricular tachycardia (VT; four total) corresponding to a rate of 28 sustained VT episodes per 100 patient-years. Consequently, one of these patients underwent rhythm stabilization through intravenous amiodarone, while the other patient received an implantable cardioverter defibrillator. Two patients (3.4%) were found to have non-sustained VT. CONCLUSIONS: Using a WCD after acute myocarditis led to the detection of sustained VT in 2/59 patients (3%). While a WCD may prevent sudden cardiac death after myocarditis, our data suggest that WCD may have impact on clinical management through monitoring and arrhythmia detection.

Increased proinflammatory cytokines in mesenteric fat in major surgery and Crohn's disease.

BACKGROUND: Proinflammatory cytokines play an important role in abdominal surgery and are often associated with the development of postoperative ileus, especially in Crohn's disease. The aim of this study was to investigate proinflammatory cytokine levels in mesenteric fat in Crohn's disease and patients without Crohn's disease. METHODS: Human mesenteric tissue specimen were divided into 3 patient groups (n = 10 each): minor surgery (laparoscopic cholecystectomy), major surgery (colectomy) in patients without Crohn's disease, and major surgery (colectomy) in patients with Crohn's disease. Levels of interleukin 6, interleukin 1-ß, and tumor necrosis factor α were determined by cytometric bead array, enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. The Kruskal-Wallis and the Mann-Whitney U test were used to compare continuous variables. For categorical variables, the χ2 test or Fisher exact test was used. RESULTS: In minor surgery, cytokines levels of interleukin 6, interleukin 1-ß and Tumor necrosis factor α were low (ie, interleukin 6: 1 pg/mL [0-36], interleukin 1-ß: 0 fg/mL [0-18], tumor necrosis factor α: 157 fg/mL [91-237]) compared with major surgery in patients with and without Crohn's disease. Cytokines were significantly higher in major surgery (ie, interleukin 6: 147 pg/mL [29-347], interleukin 1-ß: 660 fg/mL [0-2580], tumor necrosis factor α: 532 fg/mL [289-1647]; P = .02 and major surgery with CD (cytometric bead array: interleukin 6: 94 pg/mL [24-627], interleukin 1-ß: 708 fg/mL [0-1664], tumor necrosis factor α: 733 fg/mL [209-1,354]; P < .05). Cytokine levels in major surgery with Crohn's disease showed a further increase of interleukin 6 in polymerase chain reaction in comparison to major surgery in patients without Crohn's disease (1.2 vs 4, P = .04). CONCLUSION: Proinflammatory cytokines are increased in the mesenteric fat in major operations compared to minor operations, which indicates local mesenteric inflammation. In Crohn's disease, levels of proinflammatory cytokines are even higher, which may put the patients at risk for postoperative ileus.

Validation of the German Classification of Diverticular Disease (VADIS)-a prospective bicentric observational study.

PURPOSE: The German Classification of Diverticular Disease was introduced a few years ago. The aim of this study was to determine whether Classification of Diverticular Disease enables an exact stratification of different types of diverticular disease in terms of course and treatment. METHODS: This was a prospective, bicentric observational trial. Patients aged ≥ 18 years with diverticular disease were prospectively included. The primary endpoint was the rate of recurrence within 2 year follow-up. Secondary outcome measures were Gastrointestinal Quality of Life Index, Quality of life measured by SF-36, frequency of gastrointestinal complaints, and postoperative complications. RESULTS: A total of 172 patients were included. After conservative management, 40% of patients required surgery for recurrence in type 1b vs. 80% in type 2a/b (p = 0.04). Sixty percent of patients with type 2a (micro-abscess) were in need of surgery for recurrence vs. 100% of patients with type 2b (macro-abscess) (p = 0.11). Patients with type 2a reached 123 ± 15 points in the Gastrointestinal Quality of Life Index compared with 111 ± 14 in type 2b (p = 0.05) and higher scores in the "Mental Component Summary" scale of SF-36 (52 ± 10 vs. 43 ± 13; p = 0.04). Patients with recurrent diverticulitis without complications (type 3b) had less often painful constipation (30% vs. 73%; p = 0.006) when they were operated compared with conservative treatment. CONCLUSION: Differentiation into type 2a and 2b based on abscess size seems reasonable as patients with type 2b required surgery while patients with type 2a may be treated conservatively. Sigmoid colectomy in patients with type 3b seems to have gastrointestinal complaints during long-term follow-up. TRIAL REGISTRATION: https://www.drks.de ID: DRKS00005576.

Operative outcome of hernia repair with synthetic mesh in immunocompromised patients.

BACKGROUND: The safety of synthetic mesh in elective hernia repair in the setting of immunosuppression lacks national and international consensus. The aim of our analysis was to explore the effects of immunosuppression on the rates of wound complications. METHODS: Comparative analysis of immunocompetent and immunocompromised patients with elective mesh repair of inguinal, femoral, primary ventral, incisional or parastomal hernia between January 2001 and December 2013. Immunosuppression included glucocorticoids, biologicals, chemotherapy and chemoradiotherapy. Primary outcome parameter was mesh infection rate. Follow-up questionnaires were completed in written form or by telephone interview. RESULTS: Questionnaire response rate was 59.5% (n = 194) with a median follow-up of 33 (interquartile range: 28-41) months. There were no differences between immunocompromised (n = 40, 20.6%) and immunocompetent patients (n = 154, 79.4%) based on hernia and patient characteristics. Immunosuppression was not associated with the rates of mesh infection (P = 1.000), surgical site infection (SSI, P = 0.330) or re-operation for SSI (P = 0.365), but with higher rates (P = 0.007) and larger odds for hernia recurrence (odds ratio 3.264, 95% confidence interval 1.304-8.172; P = 0.012). Mesh infection also increased the odds for hernia recurrence (odds ratio 11.625; 95% confidence interval 1.754-77.057; P = 0.011). Only in the subset of ventral/incisional hernias, immunocompromised (n = 8, 40%) patients had higher recurrence rates than immunocompetent patients (n = 5, 11.6%; P = 0.017). Patients with SSI reported more frequently moderate to severe dysesthesia at the surgical site (P = 0.013) and would less frequently re-consent to surgery (P = 0.006). CONCLUSION: Immunosuppression does not increase the rate of wound infections after elective hernia repair with synthetic mesh. However, immunosuppression and mesh infection are risk factors for hernia recurrence.

Side effects of proton beam therapy of choroidal melanoma in dependence of the dose to the optic disc and the irradiated length of the optic nerve.

PURPOSE: To analyze the impact of the dose to the optic disc and the irradiated length of the optic nerve on radiation-induced optic neuropathy, radiation-induced retinopathy, iris neovascularization, secondary glaucoma, enucleation, and local tumor control after proton beam therapy (PBT) of choroidal melanoma. METHOD: Retrospective analysis of 1129 patients, who received primary PBT for the treatment of choroidal melanoma with a dose of 60 cobalt gray equivalents (CGE) between 1998 and 2013 at the Helmholtz-Zentrum Berlin, Germany. Kaplan-Meier curves and logrank test have been used for time-to-event analyses. Adjustment for potential confounders was done using multiple Cox regression models with forward and backward selection. RESULTS: We found a significant correlation between the irradiated length of the optic nerve and the dose to the optic disc (correlation coefficient, 0.93). Multivariate Cox regression revealed the dose to the optic disc as an independent predictive risk factor for the development of radiation-induced optic neuropathy (p < 0.001, HR 1.023, 95 CI 1.016-1.029), iris neovascularization (p < 0.001, HR 1.013, 95% CI 1.008-1.019), secondary glaucoma (p < 0.001, HR 1.017, 95% CI: 1.011-1.023) and enucleation (p < 0.001, HR 1.037, 95% CI 1.020-1.053). The irradiated length of the optic nerve was not a statistically independent predictive risk factor in multivariate analysis. CONCLUSION: Our data implicate the predominance of the dose to the optic disc over the irradiated length of the optic nerve regarding radiation-induced optic neuropathy, iris neovascularization, secondary glaucoma, and enucleation.

Association of simple renal cysts and chronic kidney disease with large abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysms (AAA) primarily affect men over 65 years old who often have many other diseases, with similar risk factors and pathobiological mechanisms to AAA. The aim of this study was to assess the prevalence of simple renal cysts (SRC), chronic kidney disease (CKD), and other kidney diseases (e.g. nephrolithiasis) among patients presenting with AAA. METHODS: Two groups of patients (97 AAA and 100 controls), with and without AAA, from the Surgical Clinic Charité, Berlin, Germany, were selected for the study. The control group consisted of patients who were evaluated for a kidney donation (n = 14) and patients who were evaluated for an early detection of a melanoma recurrence (n = 86). The AAA and control groups were matched for age and sex. Medical records were analyzed and computed tomography scans were reviewed for the presence of SRC and nephrolithiasis. RESULTS: SRC (74% vs. 57%; p<0.016) and CKD (30% vs. 8%; p<0.001) were both more common among AAA than control group patients. On multivariate analysis, CKD, but not SRC, showed a strong association with AAA. CONCLUSIONS: Knowledge about pathobiological mechanisms and association between CKD and AAA could provide better diagnostic and therapeutic approaches for these patients.

The effect of iron deficiency on cardiac resynchronization therapy: results from the RIDE-CRT Study.

AIMS: Cardiac resynchronization therapy (CRT) improves functional status, induces reverse left ventricular remodelling, and reduces hospitalization and mortality in patients with symptomatic heart failure, left ventricular systolic dysfunction, and QRS prolongation. However, the impact of iron deficiency on CRT response remains largely unclear. The purpose of the study was to assess the effect of functional and absolute iron deficiency on reverse cardiac remodelling, clinical response, and outcome after CRT implantation. METHODS AND RESULTS: The relation of iron deficiency and cardiac resynchronization therapy response (RIDE-CRT) study is a prospective observational study. We enrolled 77 consecutive CRT recipients (mean age 71.3 ± 10.2 years) with short-term follow-up of 3.3 ± 1.9 months and long-term follow-up of 13.0 ± 3.2 months. Primary endpoints were reverse cardiac remodelling on echocardiography and clinical CRT response, assessed by change in New York Heart Association classification. Echocardiographic CRT response was defined as relative improvement of left ventricular ejection fraction ≥ 20% or left ventricular global longitudinal strain ≥ 20%. Secondary endpoints were hospitalization for heart failure and all-cause mortality (mean follow-up of 29.0 ± 8.4 months). At multivariate analysis, iron deficiency was identified as independent predictor of echocardiographic (hazard ratio 4.97; 95% confidence interval 1.15-21.51; P = 0.03) and clinical non-response to CRT (hazard ratio 4.79; 95% confidence interval 1.30-17.72, P = 0.02). We found a significant linear-by-linear association between CRT response and type of iron deficiency (P = 0.004 for left ventricular ejection fraction improvement, P = 0.02 for left ventricular global longitudinal strain improvement, and P = 0.003 for New York Heart Association response). Iron deficiency was also significantly associated with an increase in all-cause mortality (P = 0.045) but not with heart failure hospitalization. CONCLUSIONS: Iron deficiency is a negative predictor of effective CRT therapy as assessed by reverse cardiac remodelling and clinical response. Assessment of iron substitution might be a relevant treatment target to increase CRT response and outcome in chronic heart failure patients.

Comorbidities Associated with Large Abdominal Aortic Aneurysms.

BACKGROUND: Abdominal aortic aneurysm has become increasingly important owing to demographic changes. Some other diseases, for example, cholecystolithiasis, chronic obstructive pulmonary disease, and hernias, seem to co-occur with abdominal aortic aneurysm. The aim of this retrospective analysis was to identify new comorbidities associated with abdominal aortic aneurysm. METHODS: We compared 100 patients with abdominal aortic aneurysms and 100 control patients. Their preoperative computed tomographic scans were examined by two investigators independently, for the presence of hernias, diverticulosis, and cholecystolithiasis. Medical records were also reviewed. Statistical analysis was performed using univariate analysis and multiple logistic regression analysis. RESULTS: The aneurysm group had a higher frequency of diverticulosis (p = 0.008). There was no significant difference in the occurrence of hernia (p = 0.073) or cholecystolithiasis (p = 1.00). Aneurysm patients had a significantly higher American Society of Anesthesiology score (2.84 vs. 2.63; p = 0.015) and were more likely to have coronary artery disease (p < 0.001), congestive heart failure (p < 0.001), or chronic obstructive pulmonary disease (p < 0.001). Aneurysm patients were more likely to be former (p = 0.034) or current (p = 0.006) smokers and had a significantly higher number of pack years (p < 0.001). Aneurysm patients also had a significantly poorer lung function. In multivariate analysis, the following factors were associated with aneurysms: chronic obstructive pulmonary disease (odds ratio, OR = 12.24; p = 0.002), current smoking (OR = 4.14; p = 0.002), and coronary artery disease (OR = 2.60; p = 0.020). CONCLUSIONS: Our comprehensive analysis identified several comorbidities associated with abdominal aortic aneurysms. These results could help to recognize aneurysms earlier by targeting individuals with these comorbidities for screening.

Long noncoding RNA NEAT1 modulates immune cell functions and is suppressed in early onset myocardial infarction patients.

AIMS: Inflammation is a key driver of atherosclerosis and myocardial infarction (MI), and beyond proteins and microRNAs (miRs), long noncoding RNAs (lncRNAs) have been implicated in inflammation control. To obtain further information on the possible role of lncRNAs in the context of atherosclerosis, we obtained comprehensive transcriptome maps of circulating immune cells (peripheral blood mononuclear cells, PBMCs) of early onset MI patients. One lncRNA significantly suppressed in post-MI patients was further investigated in a murine knockout model. METHODS AND RESULTS: Individual RNA-sequencing (RNA-seq) was conducted on PBMCs from 28 post-MI patients with a history of MI at age ≤50 years and stable disease ≥3 months before study participation, and from 31 healthy individuals without manifest cardiovascular disease or family history of MI as controls. RNA-seq revealed deregulated protein-coding transcripts and lncRNAs in post-MI PBMCs, among which nuclear enriched abundant transcript (NEAT1) was the most highly expressed lncRNA, and the only one significantly suppressed in patients. Multivariate statistical analysis of validation cohorts of 106 post-MI patients and 85 controls indicated that the PBMC NEAT1 levels were influenced (P = 0.001) by post-MI status independent of statin intake, left ventricular ejection fraction, low-density lipoprotein or high-density lipoprotein cholesterol, or age. We investigated NEAT1-/- mice as a model of NEAT1 deficiency to evaluate if NEAT1 depletion may directly and causally alter immune regulation. RNA-seq of NEAT1-/- splenocytes identified disturbed expression and regulation of chemokines/receptors, innate immunity genes, tumour necrosis factor (TNF) and caspases, and increased production of reactive oxygen species (ROS) under baseline conditions. NEAT1-/- spleen displayed anomalous Treg and TH cell differentiation. NEAT1-/- bone marrow-derived macrophages (BMDMs) displayed altered transcriptomes with disturbed chemokine/chemokine receptor expression, increased baseline phagocytosis (P < 0.0001), and attenuated proliferation (P = 0.0013). NEAT1-/- BMDMs responded to LPS with increased (P < 0.0001) ROS production and disturbed phagocytic activity (P = 0.0318). Monocyte-macrophage differentiation was deregulated in NEAT1-/- bone marrow and blood. NEAT1-/- mice displayed aortic wall CD68+ cell infiltration, and there was evidence of myocardial inflammation which could lead to severe and potentially life-threatening structural damage in some of these animals. CONCLUSION: The study indicates distinctive alterations of lncRNA expression in post-MI patient PBMCs. Regarding the monocyte-enriched NEAT1 suppressed in post-MI patients, the data from NEAT1-/- mice identify NEAT1 as a novel lncRNA-type immunoregulator affecting monocyte-macrophage functions and T cell differentiation. NEAT1 is part of a molecular circuit also involving several chemokines and interleukins persistently deregulated post-MI. Individual profiling of this circuit may contribute to identify high-risk patients likely to benefit from immunomodulatory therapies. It also appears reasonable to look for new therapeutic targets within this circuit.