High Resolution Treatment Effects Estimation: Uncovering Effect Heterogeneities with the Modified Causal Forest.

There is great demand for inferring causal effect heterogeneity and for open-source statistical software, which is readily available for practitioners. The mcf package is an open-source Python package that implements Modified Causal Forest (mcf), a causal machine learner. We replicate three well-known studies in the fields of epidemiology, medicine, and labor economics to demonstrate that our mcf package produces aggregate treatment effects, which align with previous results, and in addition, provides novel insights on causal effect heterogeneity. For all resolutions of treatment effects estimation, which can be identified, the mcf package provides inference. We conclude that the mcf constitutes a practical and extensive tool for a modern causal heterogeneous effects analysis.

[Preperitoneal Umbilical Hernia Mesh Plasty (PUMP): Indications, Technique and Results]. / Präperitoneale umbilikale Netzplastik (PUMP): Indikationen, Technik und Resultate.

BACKGROUND: The principle of the preperitoneal umbilical mesh plasty (PUMP) technique is placement of the prosthesis in the extraperitoneal space, posterior to the rectus muscles, followed by ventral fascia closure. Difficulties can arise from preperitoneal dissection, mesh insertion, deployment, and positioning. METHODS: 81 elective patients underwent preperitoneal repair of primary umbilical or epigastric hernias sized from 2 - 4 cm between January 2015 and March 2018 and were prospectively collected in the Herniamed database and retrospectively analysed. The same general technique was applied, but over time three different types of mesh devices were used. The experience from these cases and the gradual change between the implants during the observation period is described in this study. RESULTS: No intraoperative complications were recorded. Postoperative complications occurred in 6 of 81 patients (7.4%) with the need for unplanned re-operation in 3 cases. Seventy-six of 81 patients (93.8%) attended the one year follow-up evaluation. Three of 76 patients (3.9%) suffered recurrence and five patients (6.6%) requires treatment for chronic pain. CONCLUSION: Surgeons must work with the implant that best suits their patients' needs and that also provides good results and adequate working comfort. The PUMP technique performs well for ventral hernias sized between 2 and 4 cm without the need of midline reconstruction due to diastasis of the rectus muscles. It enables a local extraperitoneal mesh augmentation without the risk of intraperitoneal complications. PUMP repair lowers the risk of recurrence in comparison with suture repair without increasing the risk of complications.

Delayed closure of open abdomen in septic patients treated with negative pressure wound therapy and dynamic fascial suture: the long-term follow-up study.

INTRODUCTION: Negative pressure wound therapy (NPWT) is widely used in the treatment of open abdomen (OA). The use of dynamic fascial sutures (DFS) increases the rate of successful delayed closure by reducing fascial lateralization. We recently published a prospective controlled trial including 87 patients undergoing abdominal surgery for secondary peritonitis between 2007 and 2012. Patients were treated with NPWT and DFS for approximation of fascial edges. The present study represents a follow-up assessment of these patients 5-9 years after OA treatment with NPWT and DFS. METHODS: The 39 patients still alive were included in the recent study according to the protocol of our last study in 2013. All patients received a questionnaire regarding long-term complications after OA treatment between 2007 and 2012. Mean follow-up was 5-9 years. Analyzed parameters included pain, the presence of incisional hernia, and subsequent surgical interventions. Results were analyzed quantitatively. RESULTS: One patient had deceased since the last publication in 2013, and hence 38 patients were included in the current study. The median age was 60.9 (25.2-86.1) years, and 17 (44.7%) were females. Overall 56.3% of the original 87 patients had died during the long-term follow-up period. 21 patients (55.3%) answered the questionnaire. Six (28.6%) declared that they suffered from pain in the previous operating field, five (23.8%) at rest, and three (14.3%) during exercise. In five patients (23.8%), pain lasted for more than 3 months. One patient (4.8%) still requires analgesic treatment. Among the 21 patients, seven (33.3%) were found to have incisional hernias. Three hernias (42.9%) were treated by surgery. CONCLUSION: Incisional hernia rates after OA treatment remain high, but are accompanied by little pain. The ideal technique of fascial closure after NPWT should be investigated in further research.

Self-Gripping Meshes for Lichtenstein Repair. Do We Need Additional Suture Fixation?

BACKGROUND: The Lichtenstein repair is a frequently used treatment of inguinal hernias. In recent years, there has been an increasing tendency to apply self-gripping meshes (s.g). In many cases, additional suture of the mesh is carried out; however, it is uncertain what the benefits or potential risks of this actually are. METHODS: The evaluation was undertaken on the basis of the Herniamed register, and covered all unilateral Lichtenstein operations between 01.09.2009 up to 30.09.2013. The analysis only included patients with whom s.g. meshes with resorbable micro hooks had been used (Progrip(®), Covidien) and who had undergone a full 1-year follow-up examination (80.15 %). RESULTS: In total, 2095 patients were suitable for analysis, of which 816 (38.95 %) cases received an additional suture fixation (Fix). With increasing hernia size, more frequent fixation took place (29.97 % of hernias <1.5 cm vs. 46.65 % of hernias >3 cm, p < 0.001). The recurrence rates 1 year after surgery did not show any significant differences (Fix. 0.86 % vs. No Fix. 1.17 %; p = 0.661) with and without fixation, even when being adjusted for covariables. Likewise, no differences were noted in terms of postoperative complications (Fix. 5.15 % vs. No Fix. 5.08 %; p = 1.0). In addition, the numbers of patients needing to be treated after 1 year for chronic pain were also comparable (Fix. 2.33 % vs. No Fix. 2.97 %; p = 0.411). CONCLUSION: Within the group that did not have additional suture fixation of self-gripping meshes (No Fix.), the length of operations was on average 8 min shorter (p < 0.001). No differences could be observed in terms of postoperative complications, treatment requiring chronic pain and recurrence rates.

Changes in the Surgical Management of Parastomal Hernias Over 15 Years: Results of 135 Cases.

BACKGROUND: Over the years, various open and laparoscopic approaches toward the repair of parastomal hernias (PSH) have been described. The variety of published techniques itself can be seen as an indicator for the often low level of satisfaction reached with the surgical procedures. METHODS: From January 1999 to January 2014, we assessed all cases of PSH repair performed at the three participating surgical departments in a retrospective analysis. The results were evaluated with regard to different surgical techniques focusing on complications and recurrences. RESULTS: One hundred and thirty-five individuals could be included in the analysis. They were operated on with eight different surgical techniques. Laparoscopic procedures were carried out in 46.7 % (63/135) of the cases. Median follow-up was 54 months (12-146 months). We found 44 cases of recurrence (32.6 %) and 24 (17.8 %) of the patients experienced perioperative complications and 12 of them needed to return to theater. Fourteen of the 135 patients (10.4 %) were operated as emergency cases which were associated with a mortality of 28.6 % (4/14). In case of elective PSH repair, no mortality occured. CONCLUSION: The results achieved by direct suture or the use of incised flat meshes for the repair of PSH were poor with these procedures having unacceptably high recurrence rates. With regard to the latter ostomy revision through three-dimensional funnel-shaped meshes and the laparoscopic sandwich technique showed the best results. Emergency procedures were linked to a dramatic increase in morbidity and mortality (p < 0.001).

Prevention of subcutaneous seroma formation in open ventral hernia repair using a new low-thrombin fibrin sealant.

BACKGROUND: Seroma formation is a frequent postoperative complication following open ventral hernia repair (OVHR), especially in cases requiring wide subcutaneous dissection (WSD). The aim of this study was to evaluate the effectiveness of a new low-thrombin fibrin sealant for seroma prevention. METHODS: A total of 60 consecutive patients with median incisional hernias who required OVHR with WSD of at least 100 cm(2) were included in the prospective non-randomized study. The fibrin glue group (FG) comprised 30 patients who had undergone OVHR with sublay mesh placement as well as subcutaneous application of low-thrombin fibrin sealant. This cohort of patients was compared with a control group (CG) of 30 consecutive patients who had previously undergone OVHR without prevention of seroma formation with regard to outcome measures such as seroma formations and wound complications. RESULTS: Though the median extent of subcutaneous dead space was larger in the FG than in the CG (229 vs.174 cm(2); p = 0.012), seroma formation occurred in three of the FG versus 16 of the CG patients (p = 0.003). Postoperative wound complications occurred in two of the FG versus nine of the CG patients (p = 0.002). Four patients in the CG and none in the FG required re-operation within 30 days (p < 0.001). CONCLUSION: The use of a new low-thrombin fibrin glue demonstrated a protective effect against formation of seromas and decreased the rate of wound complications in OVHR, with consecutive shorter length of hospital stay (5.8 vs. 10.4 days; p = 0.04).

Relevance of surgery after embolization of gastrointestinal and abdominal hemorrhage.

BACKGROUND: Gastrointestinal and abdominal bleeding can lead to life-threatening situations. Embolization is considered a feasible and safe treatment option. The relevance of surgery has thus diminished in the past. The aim of the present study was to evaluate the role of surgery in the management of patients after embolization. METHODS: We performed a retrospective single-center analysis of outcomes after transarterial embolization of acute abdominal and gastrointestinal hemorrhage between January 2009 and December 2012 at the Sisters of Charity Hospital, Linz. Patients were divided into three groups, as follows: upper gastrointestinal bleeding (UGIB), lower gastrointestinal bleeding (LGIB), and abdominal hemorrhage. RESULTS: Fifty-four patients with 55 bleeding events were included. The bleeding source could be localized angiographically in 80 %, and the primary clinical success rate of embolization was 81.8 % (45/55 cases). Early recurrent bleeding (<30 days) occurred in 18.2 % (10/55) of the patients, and delayed recurrent hemorrhage (>30 days) developed in 3.6 % (2/55). The mean follow-up was 8.4 months, and data were available for 85.2 % (46/54) of the patients. Surgery after embolization was required in 20.4 % of these patients (11/54). Failure to localize the bleeding site was identified as predictive of recurrent bleeding (p = 0.009). More than one embolization effort increased the risk of complications (p = 0.02) and rebleeding (p = 0.07). CONCLUSIONS: Surgery still has an important role after embolization in patients with gastrointestinal and abdominal hemorrhage. One of five patients required surgery in cases of early and delayed rebleeding or because of ischemic complications (2/55 both had ischemic damage of the gallbladder) and bleeding consequences.

Institutions and the resource curse: New insights from causal machine learning.

There is a widely held belief that natural resource rents are a blessing if institutions are strong, but a curse if institutions are weak. We use data from 3,800 Sub-Saharan African districts and apply a causal forest estimator to reassess the relationship between institutions and the effects of resource rents. Consistent with this belief, we document that stronger institutions increase the positive effect of the presence of mining activities on economic development and dampen the negative effect of mining activities on conflict. In contrast, we find that the effects of higher world mineral prices on economic development and conflict in mining districts are non-linear and vary little in institutional quality.

Interleukin-1 receptor-mediated inflammation impairs the heat shock response of human mesothelial cells.

Bioincompatibility of peritoneal dialysis fluids (PDF) limits their use in renal replacement therapy. PDF exposure harms mesothelial cells but induces heat shock proteins (HSP), which are essential for repair and cytoprotection. We searched for cellular pathways that impair the heat shock response in mesothelial cells after PDF-exposure. In a dose-response experiment, increasing PDF-exposure times resulted in rapidly increasing mesothelial cell damage but decreasing HSP expression, confirming impaired heat shock response. Using proteomics and bioinformatics, simultaneously activated apoptosis-related and inflammation-related pathways were identified as candidate mechanisms. Testing the role of sterile inflammation, addition of necrotic cell material to mesothelial cells increased, whereas addition of the interleukin-1 receptor (IL-1R) antagonist anakinra to PDF decreased release of inflammatory cytokines. Addition of anakinra during PDF exposure resulted in cytoprotection and increased chaperone expression. Thus, activation of the IL-1R plays a pivotal role in impairment of the heat shock response of mesothelial cells to PDF. Danger signals from injured cells lead to an elevated level of cytokine release associated with sterile inflammation, which reduces expression of HSP and other cytoprotective chaperones and exacerbates PDF damage. Blocking the IL-1R pathway might be useful in limiting damage during peritoneal dialysis.

Alanyl-glutamine dipeptide restores the cytoprotective stress proteome of mesothelial cells exposed to peritoneal dialysis fluids.

BACKGROUND: Exposure of mesothelial cells to peritoneal dialysis fluids (PDF) results in cytoprotective cellular stress responses (CSR) that counteract PDF-induced damage. In this study, we tested the hypothesis that the CSR may be inadequate in relevant models of peritoneal dialysis (PD) due to insufficient levels of glutamine, resulting in increased vulnerability against PDF cytotoxicity. We particularly investigated the role of alanyl-glutamine (Ala-Gln) dipeptide on the cytoprotective PDF stress proteome. METHODS: Adequacy of CSR was investigated in two human in vitro models (immortalized cell line MeT-5A and mesothelial cells derived from peritoneal effluent of uraemic patients) following exposure to heat-sterilized glucose-based PDF (PD4-Dianeal, Baxter) diluted with medium and, in a comparative proteomics approach, at different levels of glutamine ranging from depletion (0 mM) via physiological (0.7 mM) to pharmacological levels (8 mM administered as Ala-Gln). RESULTS: Despite severe cellular injury, expression of cytoprotective proteins was dampened upon PDF exposure at physiological glutamine levels, indicating an inadequate CSR. Depletion of glutamine aggravated cell injury and further reduced the CSR, whereas addition of Ala-Gln at pharmacological level restored an adequate CSR, decreasing cellular damage in both PDF exposure systems. Ala-Gln specifically stimulated chaperoning activity, and cytoprotective processes were markedly enhanced in the PDF stress proteome. CONCLUSIONS: Taken together, this study demonstrates an inadequate CSR of mesothelial cells following PDF exposure associated with low and physiological levels of glutamine, indicating a new and potentially relevant pathomechanism. Supplementation of PDF with pharmacological doses of Ala-Gln restored the cytoprotective stress proteome, resulting in improved resistance of mesothelial cells to exposure to PDF. Future work will study the clinical relevance of CSR-mediated cytoprotection.

Does leaving welfare improve health? Evidence for Germany.

Using exceptionally rich linked administrative and survey information on German welfare recipients we investigate the health effects of transitions from welfare to employment and of assignments to welfare-to-work programmes. Applying semi-parametric propensity score matching estimators we find that employment substantially increases (mental) health. The positive effects are mainly driven by males and individuals with bad initial health conditions and are largest for males with poor health. In contrast, the effects of welfare-to-work programmes, including subsidised jobs, are ambiguous and statistically insignificant for most outcomes.

Case Report: Adult Right-Sided Bochdalek Hernia Complicated by Intrathoracic Bowel Perforation.

Right-sided Bochdalek hernia is a mostly congenital condition of the diaphragm caused by a persistence of the pleuroperitoneal cavity and a rare disease in adults. As it often presents as an emergent situation, urgent diagnostics and surgical intervention are essential to reduce morbidity and mortality rates. Choosing the right surgical approach (abdominal, thoracic, or a combination of both) can be very challenging for clinicians. Here, we report a case of a 40-year-old woman, who presented with severe abdominal pain and tachypnoea. Imaging revealed a right-sided Bochdalek hernia. Emergency laparotomy was performed followed by reduction of hernia content, right-sided hemicolectomy, and side-to-side anastomosis from the ileum to the transverse colon due to intestinal ischemia and intrathoracic bowel perforation. The post-operative course was complicated by a pleural empyema. Therefore, the patient underwent thoracotomy. One year after surgical repair the patient had no recurrence. Here, we discuss feasible approaches for the surgical management of complicated Bochdalek hernias.

A proteomic view on the role of glucose in peritoneal dialysis.

Peritoneal dialysis is a frequently used mode of renal replacement therapy although peritoneal dialysis fluid (PDF) acts as stressor for mesothelial cells. In this study, stress response to PDF is investigated by a proteomics approach using Met-5A cell cultures closely resembling mesothelial cells. In a previous work, we identified about 100 proteins as significantly enhanced or diminished in abundance after full-PDF stress (90 mM glucose, pH 5.8, and presence of lactate and glucose degradation products (GDPs)) using two-dimensional electrophoresis (2-DE) and MALDI-MS and MS/MS techniques. In this paper, a functional analysis is presented assigning these proteins to glucose associated pathways according to the KEGG database. To establish the stressor role of high glucose concentration, the up/down regulation of proteins populating these pathways were investigated in a fluorescence-difference gel electrophoresis (DIGE) experiment exposing Met-5A cells to nonphysiologically high glucose conditions only. In this glucose-single stress experiment, the fold-change ratios of the investigated glucose-pathway associated proteins were found much lower than observed in the previous full-PDF stress experiments. This finding supports the hypothesis that cellular response to full-PDF stress is not primarily induced by the high glucose concentration, even when focusing on proteins belonging to the glucose associated pathways.

Long-run labour market and health effects of individual sports activities.

This microeconometric study analyzes the effects of individual leisure sports participation on long-term labour market variables, health and subjective well-being indicators for West Germany based on individual data from the German Socio-Economic Panel study (GSOEP) 1984-2006. Econometric problems due to individuals choosing their own level of sports activities are tackled by combining informative data and flexible semiparametric estimation methods with a specific way to use the panel dimension of the data. The paper shows that sports activities have sizeable positive long-term labour market effects in terms of earnings and wages, as well as positive effects on health and subjective well-being.

Evolution of Endoscopic Anterior Component Separation to a Precostal Access with a New Cylindrical Balloon Trocar.

INTRODUCTION: Endoscopic anterior component separation (ECS) techniques facilitate tension-free midline closure of wide ventral hernia defects. We describe a novel approach with a precostal incision and a new cylindrical ballon trocar. MATERIALS AND METHODS: A single-center analysis of 19 patients undergoing ECS between January 1, 2014 and August 2, 2017 was performed with regard to improvement of technique. We currently start with a lateral precostal incision. This access in a low-fat and stable area allows for easy identification of the external oblique muscle with the ribs functioning as dorsal abutment for entering the correct plane between external and internal oblique muscles. Then a trocar is inserted with a cylindrical ballon, thus providing sufficient pneumatic widening of the dissection plane. A second 5-mm port is inserted under direct vision below the 12th rib. From there a unidirectional incision of the external oblique aponeurosis is performed from subcostal to the inguinal ligament. If necessary, the cephalad muscular parts of the external oblique can be transected over several centimeters in both directions starting from the precostal incision. RESULTS: We documented no procedure-related complications apart from two hematomas that required no interventions. Four procedures were carried out on one side and the remaining ones bilaterally. In one case, a conversion to conventional open component separation was required due to extensive scarring after open cholecystectomy. There were no notable abdominal bulgings or lateral hernias during a structured postoperative follow-up period of 1 year postoperatively. DISCUSSION: The technique described offers advantages in terms of determination of the correct entry point for ECS, regardless of abdominal wall conditions and the precostal access allows for unidirectional dissection toward the inguinal ligament with only two trocars in total. The cylindrical shape of the ballon trocar provides adequate widening of the working space and ensures good overview for safe dissection.

Sports and Child Development.

The role of curricular activities for the formation of education, health and behavioural outcomes has been widely studied. Yet, the role of extra-curricular activities has received little attention. This study analyzes the effect of participation in sports clubs-one of the most popular extra-curricular activities among children. We use alternative datasets and flexible semi-parametric estimation methods with a specific way to use the panel dimension of the data to address selection into sports. We find positive and robust effects on children's school performance and peer relations. Crowding out of passive leisure activities can partially explain the effects.

Workplace health promotion and labour market performance of employees.

This paper investigates the average effects of firm-provided workplace health promotion measures on labour market outcomes of the firms' employees. Exploiting linked employer-employee panel data that consist of rich survey-based and administrative information on firms, workers and regions, we apply a flexible propensity score matching approach that controls for selection on observables and time-constant unobserved factors. While the effects of analysing sickness absenteeism appear to be rather limited, our results suggest that health circles/courses increase tenure and job stability across various age groups. A key finding is that health circles/courses strengthen the labour force attachment of elderly employees (51-60), implying potential cost savings for public transfer schemes such as unemployment insurance or early retirement schemes.

Process Design of Aluminum Tailor Heat Treated Blanks.

In many industrials field, especially in the automotive sector, there is a trend toward lightweight constructions in order to reduce the weight and thereby the CO2 and NOx emissions of the products. An auspicious approach within this context is the substitution of conventional deep drawing steel by precipitation hardenable aluminum alloys. However, based on the low formability, the application for complex stamping parts is challenging. Therefore, at the Institute of Manufacturing Technology, an innovative technology to enhance the forming limit of these lightweight materials was invented. The key idea of the so-called Tailor Heat Treated Blanks (THTB) is optimization of the mechanical properties by local heat treatment before the forming operation. An accurate description of material properties is crucial to predict the forming behavior of tailor heat treated blanks by simulation. Therefore, within in this research project, a holistic approach for the design of the THTB process in dependency of the main influencing parameters is presented and discussed in detail. The capability of the approach for the process development of complex forming operations is demonstrated by a comparison of local blank thickness of a tailgate with the corresponding results from simulation.

Magnetic resonance-visible meshes for laparoscopic ventral hernia repair.

BACKGROUND AND OBJECTIVES: We aimed to evaluate the first human use of magnetic resonance-visible implants for intraperitoneal onlay repair of incisional hernias regarding magnetic resonance presentability. METHODS: Ten patients were surgically treated with intraperitoneally positioned superparamagnetic flat meshes. A magnetic resonance investigation with a qualified protocol was performed on postoperative day 1 and at 3 months postoperatively to assess mesh appearance and demarcation. The total magnetic resonance-visible mesh surface area of each implant was calculated and compared with the original physical mesh size to evaluate potential reduction of the functional mesh surfaces. RESULTS: We were able to show a precise mesh demarcation, as well as accurate assessment of the surrounding tissue, in all 10 cases. We documented a significant decrease in the magnetic resonance-visualized total mesh surface area after release of the pneumoperitoneum compared with the original mesh size (mean, 190 cm(2) vs 225 cm(2); mean reduction of mesh area, 35 cm(2); P < .001). At 3 months postoperatively, a further reduction of the surface area due to significant mesh shrinkage could be observed (mean, 182 cm(2) vs 190 cm(2); mean reduction of mesh area, 8 cm(2); P < .001). CONCLUSION: The new method of combining magnetic resonance imaging and meshes that provide enhanced signal capacity through direct integration of iron particles into the polyvinylidene fluoride base material allows for detailed mesh depiction and quantification of structural changes. In addition to a significant early postoperative decrease in effective mesh surface area, a further considerable reduction in size occurred within 3 months after implantation.