Robotic Complete ALPPS (rALPPS)-First German Experiences.

BACKGROUND: ALPPS leads to fast and effective liver hypertrophy. This enables the resection of extended tumors. Conventional ALPPS is associated with high morbidity and mortality. MILS reduces morbidity and the robot adds technical features that make complex procedures safe. MATERIAL AND METHODS: The MD-MILS was screened for patients who underwent rALPPS. Demographic and perioperative data were evaluated retrospectively. Ninety days postoperative morbidity was scored according to the CD classification. The findings were compared with the literature. RESULTS: Since November 2021, five patients have been identified. The mean age and BMI of the patients were 50.0 years and 22.7 kg/m2. In four cases, patients suffered from colorectal liver metastases and, in one case, intrahepatic cholangiocarcinoma. Prior to the first operation, the mean liver volume of the residual left liver was 380.9 mL with a FLR-BWR of 0.677%. Prior to the second operation, the mean volume of the residual liver was 529.8 mL with a FLR-BWR of 0.947%. This was an increase of 41.9% of the residual liver volume. The first and second operations were carried out within 17.8 days. The mean time of the first and second operations was 341.2 min and 440.6 min. The mean hospital stay was 27.2 days. Histopathology showed the largest tumor size of 39 mm in diameter with a mean amount of 4.7 tumors. The mean tumor-free margin was 12.3 mm. One complication CD > 3a occurred. No patient died during the 90-day follow up. CONCLUSION: In the first German series, we demonstrated that rALPPS can be carried out safely with reduced morbidity and mortality in selected patients.

Fatal heat stroke based on foudroyant irreversible multiple organ dysfunction in German summer.

Objectives: Heat stroke is a serious condition that might lead from moderate organ impairment to multiple organ dysfunction syndrome. Appropriate diagnosis-finding, fast initiation of cooling and intensive care are key measures of the initial treatment. Scientific case report based on i) clinical experiences obtained in the clinical management of a particularly rare case and ii) selected references from the medical scientific literature. Case presentation: We present a case of a young and healthy construction worker who suffered from an exertional heat stroke with a body core temperature exceeding 42 °C by previous several hour work at 35 °C ambient temperature. Heat stroke was associated with foudroyant, not reversible multiple organ dysfunction syndrome, in particular, early disturbed coagulation, microcirculatory, liver and respiratory failure, and subsequent fatal outcome despite immediate diagnosis-finding, rapid external cooling and expanded intensive care management. Conclusions: Basic knowledge on an adequate diagnosis(-finding in time) and treatment of heat stroke is important for (almost each) physician in the summertime as well as is essential for the initiation of an appropriate management. Associated high morbidity and mortality rates indicate the need for implementation of standard operation protocols.

Neoadjuvant radiochemotherapy with cisplatin/5-flourouracil or carboplatin/paclitaxel in patients with resectable cancer of the esophagus and the gastroesophageal junction - comparison of postoperative mortality and complications, toxicity, and pathological tumor response.

PURPOSE: In 2012, the CROSS trial implemented a new neoadjuvant radiochemotherapy protocol for patients with locally advanced, resectable cancer of the esophagus prior to scheduled surgery. There are only limited studies comparing the CROSS protocol with a PF-based (cisplatin/5-fluorouracil) nRCT protocol. METHODS: In this retrospective, monocentric analysis, 134 patients suffering from esophageal cancer were included. Those patients received either PF-based nRCT (PF group) or nRCT according to the CROSS protocol (CROSS group) prior to elective en bloc esophagectomy. Perioperative mortality and morbidity, nRCT-related toxicity, and complete pathological regression were compared between both groups. Logistic regression analysis was performed in order to identify independent factors for pathological complete response (pCR). RESULTS: Thirty-day/hospital mortality showed no significant differences between both groups. Postoperative complications ≥ grade 3 according to Clavien-Dindo classification were experienced in 58.8% (PF group) and 47.6% (CROSS group) (p = 0.2) respectively. nRCT-associated toxicity ≥ grade 3 was 30.8% (PF group) and 37.2% (CROSS group) (p = 0.6). There was no significant difference regarding the pCR rate between both groups (23.5% vs. 30.5%; p = 0.6). In multivariate analysis, SCC (OR 7.7; p < 0.01) and an initial grading of G1/G2 (OR 2.8; p = 0.03) were shown to be independent risk factors for higher rates of pCR. CONCLUSION: We conclude that both nRCT protocols are effective and safe. There were no significant differences regarding toxicity, pathological tumor response, and postoperative morbidity and mortality between both groups. Squamous cell carcinoma (SCC) and favorable preoperative tumor grading (G1 and G2) are independent predictors for higher pCR rate in multivariate analysis.

The effect of biofeedback pelvic floor training with ACTICORE1 on urinary incontinence: a multicenter randomized clinical pilot trial.

Background: Pelvic floor training with biofeedback has been shown to significantly reduce symptoms of urinary incontinence. The present study aimed to evaluate the effectiveness of pelvic floor training with the ACTICORE1 biofeedback device, which uses a noninsertable pelvic floor sensor with a digital interface. Materials and methods: A multicenter randomized controlled clinical pilot study in Germany was conducted between October 2021 and January 2022. The intervention group was instructed to use ACTICORE1 for 6 min daily to train the pelvic floor for 12 weeks. The control group was instructed not to do any pelvic floor training. Over 18-year-old men and women with urinary incontinence and an International Consultation on Incontinence Questionnaire score (ICIQ) of ≥5 were included in the study. The primary endpoint was the ICIQ score 12 weeks after enrollment. The secondary endpoints were the ICIQ score and quality of life using the EG-5D-3L questionnaire 4, 8, and 12 weeks after patients' enrollment. Results: A total of 40 individuals with urinary incontinence were recruited for the present study (35 females, 5 males; 40% lost to follow-up). In terms of biometric data, both groups did not differ. At 4, 8, and 12 weeks, the ICIQ scores of those in the ACTICORE1 group decreased from 12.9 to 7.5. The ICIQ score in the control group decreased from 11.0 to 10.5. The intraindividual improvement of patients in the ACTICORE group was statistically significant. Conclusion: Biofeedback training with ACTICORE1 significantly reduces symptoms of urinary incontinence after 12 weeks.

Robot-assisted transthoracic hybrid esophagectomy versus open and laparoscopic hybrid esophagectomy: propensity score matched analysis of short-term outcome.

PURPOSE: Minimally invasive en-bloc esophagectomy is associated with a reduction of postoperative morbidity. This was demonstrated for both total minimally invasive and hybrid esophagectomy. However, little is known about any benefits of robotic assistance compared to the conventional minimally invasive technique, especially in hybrid procedures. METHODS: For this retrospective study, all consecutive patients who had undergone elective esophagectomy with circular stapled intrathoracic anastomosis using the open and the minimally invasive hybrid technique at the University Hospital Magdeburg, from January 2010 to March 2021 were considered for analysis. RESULTS: In total, 137 patients (60.4%) had undergone open esophagectomy. In 45 patients (19.8%), the laparoscopic hybrid technique and in 45 patients (19.8%), the robot-assisted hybrid technique were applied. In propensity score matching analysis comparing the open with the robotic hybrid technique, significant differences were found in favor of the robotic technique (postoperative morbidity, p < 0.01; hospital length of stay, p < 0.01; number of lymph nodes retrieved, p = 0.048). In propensity score matching analysis comparing the laparoscopic with the robotic hybrid technique, a significant reduction of the rate of postoperative delayed gastric emptying (p = 0.02) was found for patients who had undergone robotic esophagectomy. However, the operation time was significantly longer (p < 0.01). CONCLUSIONS: En-bloc esophagectomy using the robotic hybrid technique is associated with a significant reduction of postoperative morbidity and of the hospital length of stay when compared to the open approach. However, when compared to the laparoscopic hybrid technique, only few advantages could be demonstrated.

Survival Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-2).

Introduction: Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-CRLM) was a propensity score matched (PSM) study that reported short-term outcomes of patients with CRLM who met the Milan criteria and underwent either open (OLR), laparoscopic (LLR) or robotic liver resection (RLR). This study, designated as SIMMILR-2, reports the long-term outcomes from that initial study, now referred to as SIMMILR-1. Methods: Data regarding neoadjuvant chemotherapeutic (NC) and neoadjuvant biological (NB) treatments received were collected, and Kaplan−Meier curves reporting the 5-year overall (OS) and recurrence-free survival (RFS) for OLR, LLR and RLR were created for patients who presented with synchronous lesions only, as there was insufficient follow-up for patients with metachronous lesions. Results: A total of 73% of patients received NC and 38% received NB in the OLR group compared to 70% and 28% in the LLR group, respectively (p = 0.5 and p = 0.08). A total of 82% of patients received NC and 40% received NB in the OLR group compared to 86% and 32% in the RLR group, respectively (p > 0.05). A total of 71% of patients received NC and 53% received NB in the LLR group compared to 71% and 47% in the RLR group, respectively (p > 0.05). OS at 5 years was 34.8% after OLR compared to 37.1% after LLR (p = 0.4), 34.3% after OLR compared to 46.9% after RLR (p = 0.4) and 30.3% after LLR compared to 46.9% after RLR (p = 0.9). RFS at 5 years was 12.1% after OLR compared to 20.7% after LLR (p = 0.6), 33.3% after OLR compared to 26.3% after RLR (p = 0.6) and 22.7% after LLR compared to 34.6% after RLR (p = 0.6). Conclusions: When comparing OLR, LLR and RLR, the OS and RFS were all similar after utilization of the Milan criteria and PSM. Biological agents tended to be utilized more in the OLR group when compared to the LLR group, suggesting that highly aggressive tumors are still managed through an open approach.

Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-CRLM).

(1) Background: Here we report on a retrospective study of an international multicentric cohort after minimally invasive liver resection (SIMMILR) of colorectal liver metastases (CRLM) from six centers. (2) Methods: Resections were divided by the approach used: open liver resection (OLR), laparoscopic liver resection (LLR) and robotic liver resection (RLR). Patients with macrovascular invasion, more than three metastases measuring more than 3 cm or a solitary metastasis more than 5 cm were excluded, and any remaining heterogeneity found was further analyzed after propensity score matching (PSM) to decrease any potential bias. (3) Results: Prior to matching, 566 patients underwent OLR, 462 LLR and 36 RLR for CRLM. After PSM, 142 patients were in each group of the OLR vs. LLR group and 22 in the OLR vs. RLR and 21 in the LLR vs. RLR groups. Blood loss, hospital stay, and morbidity rates were all highly statistically significantly increased in the OLR compared to the LLR group, 636 mL vs. 353 mL, 9 vs. 5 days and 25% vs. 6%, respectively (p < 0.001). Only blood loss was significantly decreased when RLR was compared to OLR and LLR, 250 mL vs. 597 mL, and 224 mL vs. 778 mL, p < 0.008 and p < 0.04, respectively. (4) Conclusions: SIMMILR indicates that minimally invasive approaches for CRLM that follow the Milan criteria may have short term advantages. Notably, larger studies with long-term follow-up comparing robotic resections to both OLR and LLR are still needed.

The Effect of an Abdominal Binder on Postoperative Pain After Laparoscopic Incisional Hernia Repair­A Multicenter, Randomized Pilot Trial (ABIHR-I) of the Intraperitoneal Onlay-Mesh Technique.

BACKGROUND: Incisional hernias with apertures measuring less than 7 cm can generally be treated adequately with the laparoscopic intraperitoneal onlay-mesh (IPOM) technique. The wearing of an abdominal binder after surgery is often recommended in order to promote wound healing and prevent recurrent herniation. We carried out a multicenter, randomized pilot trial to evaluate the utility of abdominal binders. METHODS: The trial was conducted from May 2019 to December 2020. Persons with a laparoscopic IPOM procedure for treatment of an incisional hernia were included in the trial and randomized preoperatively (1:1). The patients in the abdominal binder group wore an abdominal binder during the day for 14 days after surgery, while those in the control group wore no binder. The primary endpoint was pain at rest on postoperative days 1, 2, and 14, as measured on a visual analog scale. The secondary endpoints were overall subjective well-being, the rates of wound infection, recurrence, and complications, mobility, and the rate and size of postoperative seromas (on postoperative days 1, 2, and 14). RESULTS: Forty patients were included. Three were excluded because of conversion to an open surgical technique. The biometric and perioperative data of the abdominal binder group (n = 18) and the control group (n = 19) did not differ to any statistically significant extent. The patients in the binder group had significantly less postoperative pain (F [dfn, dfd]) 4.44, 95% confidence interval [1; 35]; p = 0.042).The patients in the binder group also had better overall subjective well-being and a higher rate of postoperative seroma formation, but these differences did not reach statistical significance. There was less limitation of mobility than in the control group; however, this difference also did not attain statistical significance. CONCLUSION: An abdominal binder may reduce pain after incisional hernia repair with the IPOM technique. The postoperative use of analgesic medication was not measured.

Three-Device (3D) Technique for Liver Parenchyma Dissection in Robotic Liver Surgery.

BACKGROUND: The implementation of robotics in liver surgery offers several advantages compared to conventional open and laparoscopic techniques. One major advantage is the enhanced degree of freedom at the tip of the robotic tools compared to laparoscopic instruments. This enables excellent vessel control during inflow and outflow dissection of the liver. Parenchymal transection remains the most challenging part during robotic liver resection because currently available robotic instruments for parenchymal transection have several limitations and there is no standardized technique as of yet. We established a new strategy and share our experience. METHODS: We present a novel technique for the transection of liver parenchyma during robotic surgery, using three devices (3D) simultaneously: monopolar scissors and bipolar Maryland forceps of the robot and laparoscopic-guided waterjet. We collected the perioperative data of twenty-eight patients who underwent this procedure for minor and major liver resections between February 2019 and December 2020 from the Magdeburg Registry of minimally invasive liver surgery (MD-MILS). RESULTS: Twenty-eight patients underwent robotic-assisted 3D parenchyma dissection within the investigation period. Twelve cases of major and sixteen cases of minor hepatectomy for malignant and non-malignant cases were performed. Operative time for major liver resections (≥ 3 liver segments) was 381.7 (SD 80.6) min vs. 252.0 (70.4) min for minor resections (p < 0.01). Intraoperative measured blood loss was 495.8 (SD 508.8) ml for major and 256.3 (170.2) ml for minor liver resections (p = 0.090). The mean postoperative stay was 13.3 (SD 11.1) days for all cases. Liver surgery-related morbidity was 10.7%, no mortalities occurred. We achieved an R0 resection in all malignant cases. CONCLUSIONS: The 3D technique for parenchyma dissection in robotic liver surgery is a safe and feasible procedure. This novel method offers an advanced locally controlled preparation of intrahepatic vessels and bile ducts. The combination of precise extrahepatic vessel handling with the 3D technique of parenchyma dissection is a fundamental step forward to the standardization of robotic liver surgery for teaching purposing and the wider adoption of robotic hepatectomy into routine patient care.

Tumor visualization and fluorescence angiography with indocyanine green (ICG) in laparoscopic and robotic hepatobiliary surgery - valuation of early adopters from Germany.

OBJECTIVES: Indocyanine green (ICG) is a fluorescent dye which was initially used for liver functional assessment. Moreover, it is of value for intraoperative visualization of liver segments and bile ducts or primary and secondary liver tumors. Especially in minimally invasive liver surgery, this is essential to enhance the precision of anatomical guided surgery and oncological quality. As early adopters of ICG implementation into laparoscopic and robotic-assisted liver surgery in Germany, we summarize the current recommendations and share our experiences. METHODS: Actual strategies for ICG application in minimally invasive liver surgery were evaluated and summarized during a review of the literature. Experiences in patients who underwent laparoscopic or robotic-assisted liver surgery with intraoperative ICG staining between 2018 and 2020 from the Magdeburg registry for minimally invasive liver surgery (MD-MILS) were evaluated and the data were analyzed retrospectively. RESULTS: ICG can be used to identify anatomical liver segments by fluorescence angiography via direct or indirect tissue staining. Fluorescence cholangiography visualizes the intra- and extrahepatic bile ducts. Primary and secondary liver tumors can be identified with a sensitivity of 69-100%. For this 0.5 mg/kg body weight ICG must be applicated intravenously 2-14 days prior to surgery. Within the MD-MILS we identified 18 patients which received ICG for intraoperative tumor staining of hepatocellular carcinoma (HCC), cholangiocarcinoma, peritoneal HCC metastases, adenoma, or colorectal liver metastases. The sensitivity for tumor staining was 100%. In 27.8% additional liver tumors were identified by ICG fluorescence. In 39% a false positive signal could be detected. This occurred mainly in cirrhotic livers. CONCLUSIONS: ICG staining is a simple and useful tool to assess individual hepatic anatomy or to detect tumors during minimally invasive liver surgery. It may enhance surgical precision and improve oncological quality. False-positive detection rates of liver tumors can be reduced by respecting the tumor entity and liver functional impairments.

Robotic and laparoscopic liver surgery for colorectal liver metastases: an experience from a German Academic Center.

BACKGROUND: Minimally invasive liver surgery (MILS) in the treatment of colorectal liver metastases (CRLM) is increasing in incidence. The aim of this work was to present our experience by reporting short-term and long-term outcomes after MILS for CRLM with comparative analysis of laparoscopic (LLS) and robotic liver surgery (RLS). METHODS: Twenty-five patients with CRLM, who underwent MILS between May 2012 and March 2020, were selected from our retrospective registry of minimally invasive liver surgery (MD-MILS). Thirteen of these patients underwent LLS and 12 RLS. Short-term and long-term outcomes of both groups were analyzed. RESULTS: Operating time was significantly longer in the RLS vs. the LLS group (342.0 vs. 200.0 min; p = 0.004). There was no significant difference between the laparoscopic vs. the robotic group regarding length of postoperative stay (8.8 days), measured blood loss (430.4 ml), intraoperative blood transfusion, overall morbidity (20.0%), and liver surgery related morbidity (4%). The mean BMI was 27.3 (range from 19.2 to 44.8) kg/m2. The 30-day mortality was 0%. R0 resection was achieved in all patients (100.0%) in RLS vs. 10 patients (76.9%) in LLS. Major resections were carried out in 32.0% of the cases, and 84.0% of the patients showed intra-abdominal adhesions due to previous abdominal surgery. In 24.0% of cases, the tumor was bilobar, the maximum number of tumors removed was 9, and the largest tumor was 8.5 cm in diameter. The 1-, 3- and 5-year overall survival rates were 84, 56.9, and 48.7%, respectively. The 1- and 3-year overall recurrence-free survival rates were 49.6 and 36.2%, respectively, without significant differences between RLS vs. LLS. CONCLUSION: Minimally invasive liver surgery for CRLM is safe and feasible. Minimally invasive resection of multiple lesions and large tumors is also possible. RLS may help to achieve higher rates of R0 resections. High BMI, previous abdominal surgery, and bilobar tumors are not a barrier for MILS. Laparoscopic and robotic liver resections for CRLM provide similar long-term results which are comparable to open techniques.

Comparison of different durations of physical activity restrictions following incisional hernia repair in sublay technique, the 3N6 trial: A prospective clinical trial.

BACKGROUND: Incisional hernias (IH) occur in 4 to 20% of cases following abdominal surgeries, often after laparotomies. In the US, there are 4 to 5 million laparotomies performed per year, which could lead to 400.000 to 1.000.000 IHs. Therefore, this disease accounts as an important social-economic factor. Furthermore, these hernias can lead to bowel incarcerations, chronic pain, and a decrease in quality of life. To guarantee sufficient wound healing and decrease the recurrence rate, physical activity restrictions (PAR) are recommended. The standard recommendations for PAR seem to vary from 0 to 12 weeks, but the evidence remains low due to a lack of clinical trials. Conducting the study at hand, we aim to provide more evidence on this topic. METHODS: The 3N6 trial will be conducted as a national multicenter prospective trial with two study groups (n = 90), where the goal is to find matched pairs within the two groups. Patients who underwent open incisional hernia repair (IHR) in sublay technique will be enrolled. A patient in the 3-week PAR group will be matched to a patient in the 6-week PAR group based on heavy lifting, male gender, BMI > 30, and large hernia >7 cm. The primary endpoint is the duration of sick leave that patients require to return to work, by comparing PAR of 6 weeks with PAR of 3 weeks. The secondary endpoints are the recurrence rate, seroma formation, and chronic pain one year after surgery and postoperative complications within 30 days using Clavien-Dindo-classification. DISSEMINATION: The findings will be published in a peer-reviewed journal. We may also present the findings at local and/or national conferences.

Patient reported outcome following incisional hernia repair: A survey on 163 patients at two maximum care hospitals.

INTRODUCTION: Incisional hernias of the abdominal wall are frequent complications after laparotomy (9-20%) and often need incisional hernia repair (IHR). In order to ensure wound healing and to therefore prevent postoperative short and long term morbidity carrying an abdominal binder (AB) and physical rest is frequently advised. However, there is a lack of evidence concerning clinical effects regarding these recommendations. Hence, we conducted a survey to analyze the patient reported outcome following IHR. METHODS: From December 2017 to May 2018, we conducted a survey among 270 patients who underwent open and laparoscopic IHR at two maximum care hospitals. They were interviewed about their type of operation, postoperative treatment, recommendations, and outcome. RESULTS: 163 patients replied to the questionnaire. The average age was 63.2 ±â€¯12 years. 74 patients were female and 89 were male. 32.6% of the patients reported an AB-induced immobility and 71.2% reported that the AB reduced pain after IHR. A prolonged period of physical rest and the use of an AB had no statistical significance on postoperative morbidity. CONCLUSIONS: Due to our findings we assume that the AB may induce immobility and reduce postoperative pain. A prolonged period of physical rest and wearing an AB does not seem to have an impact on the postoperative outcome following IHR. Therefore, a shortened duration of physical rest and wearing an AB following IHR should be taken under consideration. To reveal more evidence on this topic further clinical trials are essential.

[Roux-Y-Gastric Bypass for Morbid Obesity in Adolescents: Is it as Safe and Effective as in Obese Adults?] / Der Roux-Y-Magenbypass zur Therapie der Adipositas bei Jugendlichen: Analyse des Gewichtsverlaufs und des Einflusses auf Komorbiditäten im Vergleich zu adipösen Erwachsenen.

BACKGROUND: Obesity is one of the major challenges of the 21st century. There is also an increasing incidence of obesity in adolescents. Bariatric surgery has been proven safe and effective in obese adults. In adolescents, these operations are still subject to controversy. Current evidence is limited regarding its safety and outcome in this age group. METHODS: Within the German Bariatric Surgery Registry, data from obese patients that underwent bariatric procedures in Germany are prospectively registered. The current analysis includes all adolescent and adult subjects that underwent primary Roux-Y-gastric bypass (RYGB) surgery from 2005 to 2014. RESULTS: Overall, 370 adolescents (≤ 21 years) and 16,840 obese adults were enrolled. In 2014, RYGB was the second most common bariatric procedure in Germany. In the adolescent group, initial BMI was higher (49.2 vs. 47.9 kg/m2, p < 0.01); the proportion of associated comorbidities was lower (67.8 vs. 87.4%, p < 0.01). Operation time (104.9 vs. 113.0 min, p < 0.01) and hospital stay (5.2 vs. 5.9 days; p < 0.01) differed significantly between both groups. The leakage rate in adults was 1.6%; none of the adolescents experienced a postoperative anastomotic leak (p = 0.04). No mortalities were reported in adolescents; the mortality rate in adults was 0.2%. The mean percentage of excess weight loss (% EWL) did not differ between both groups at 12 (69.9 vs. 68.2%; p = 0.97) and 24 months (72.6 vs. 72.1% p = 1.0). The remission rate for hypertension was higher in the adolescent group. CONCLUSION: RYGB can be performed in obese adolescents with lower morbidity and mortality. Despite all limitations of a multicentre registry and the low follow-up rate, the results show that weight change and resolution of comorbidities in the short term were at least comparable to those achieved in adults. The evaluation of safety and efficiency in the long run should now be in the focus of future studies.

Microbial production of glutathione.

Glutathione (GSH) is a non-coding tripeptide thiol with several important regulative and protective functions in eukaryotes and in most prokaryotes. The primary function of GSH is to maintain the redox potential of the cell, which is directly connected to GSH concentration, and to prevent cellular damages caused by reactive oxygen species or toxic heavy metals. Due to its antioxidant character, it is widely used in pharmaceutical, cosmetic and food industry. There have been different strategies to optimize GSH yield and productivity in bacteria and yeasts by means of metabolic and evolutionary engineering, media optimization and bioprocess engineering. The fed-batch procedure with yeasts of the genera Saccharomyces and Candida is still common method for industrial production. However, for an economic bioprocess production of GSH key factors like media costs, strain performance and process scalability are essential. Beside the extraction and purification of GSH as bulk product, GSH-enriched yeast cells are used for food and beverage applications, as well. This review outlines current applications of microbially produced GSH and illustrates current developments and strategies for its production.

A physical description of the adhesion and aggregation of platelets.

The early stages of clot formation in blood vessels involve platelet adhesion-aggregation. Although these mechanisms have been extensively studied, gaps in their understanding still persist. We have performed detailed in vitro experiments, using the well-known Impact-R device, and developed a numerical model to better describe and understand this phenomenon. Unlike previous studies, we took into account the differential role of pre-activated and non-activated platelets, as well as the three-dimensional nature of the aggregation process. Our investigation reveals that blood albumin is a major parameter limiting platelet aggregate formation in our experiment. Simulations are in very good agreement with observations and provide quantitative estimates of the adhesion and aggregation rates that are hard to measure experimentally. They also provide a value of the effective diffusion of platelets in blood subject to the shear rate produced by the Impact-R.

Systematic development of a two-stage fed-batch process for lipid accumulation in Rhodotorula glutinis.

The application of oleaginous yeast cells as feed supplement, for instance in aqua culture, can be a meaningful alternative for fish meal and oil additives. Therefore, a two-stage fed-batch process split into growth and lipogenesis phase was systematically developed to enrich the oleaginous yeast Rhodotorula glutinis Rh-00301 with high amounts of lipids at industrial relevant biomasses. Thereby, the different carbon sources glucose, sucrose and glycerol were investigated concerning their abilities to serve as a suited raw material for growth and/or lipid accumulation. With the background of economic efficiency C/N ratios of 40, 50 and 70 were investigated as well. It became apparent that glycerol is an improper carbon source most likely because of the passive diffusion of this compound caused by absence of active transporters. The opposite was observed for sucrose, which is the main carbon source in molasses. Finally, an industrially applicable process was successfully established that ensures biomasses of 106±2gL-1 combined with an attractive lipid content of 63±6% and a high lipid-substrate yield (YL/S) of 0.18±0.02gg-1 in a short period of time (84h). Furthermore, during these studies a non-negligible formation of the by-product glycerol was detected. This characteristic of R. glutinis is discussed related to other oleaginous yeasts, where glycerol formation is absent. Nevertheless, due to modifications in the feeding procedure, the formation of glycerol could have been reduced but not avoided.

Medium optimization based on yeast's elemental composition for glutathione production in Saccharomyces cerevisiae.

The production of glutathione (GSH) or GSH enriched yeast is still in the focus of research driven by a high industrial interest. In this study, an optimal growth rate for GSH production via Saccharomyces cerevisiae Sa-07346 was investigated. To further improve the fermentation process in a way that it is independent of lots, the influence of different WMIX medium compositions on biomass and GSH production was studied. Thereby, the fermentation medium was adjusted based on yeast's elemental composition. The resulting chemically defined fermentation medium led to high cell densities in fed-batches. Therefore, it has the potential to be applied successfully for other high cell density yeast fermentation processes. As cysteine is the key component for GSH production, different cysteine addition strategies were studied and finally, a continuous cysteine feeding was applied in the late stage of fermentation. Thereby, a GSH concentration of 1459 ± 57 mg/l was reached by continuously feeding cysteine, which meant an increase to 253% compared to the control without cysteine addition (577 mg/l GSH).