DIALAPP: a prospective validation of a new diagnostic algorithm for acute appendicitis.

PURPOSE: The management of patients with suspected appendicitis remains a challenge in daily clinical practice, and the optimal management algorithm is still being debated. Negative appendectomy rates (NAR) continue to range between 10 and 15%. This prospective study evaluated the accuracy of a diagnostic pathway in acute appendicitis using clinical risk stratification (Alvarado score), routine ultrasonography, gynecology consult for females, and selected CT after clinical reassessment. METHODS: Patients presenting with suspected appendicitis between November 2015 and September 2017 from age 18 years and above were included. Decision-making followed a clear management pathway. Patients were followed up for 6 months after discharge. The hypothesis was that the algorithm can reduce the NAR to a value of under 10%. RESULTS: A total of 183 patients were included. In 65 of 69 appendectomies, acute appendicitis was confirmed by histopathology, corresponding to a NAR of 5.8%. Notably, all 4 NAR appendectomies had other pathologies of the appendix. The perforation rate was 24.6%. Only 36 patients (19.7%) received a CT scan. The follow-up rate after 30 days achieved 69%, including no patients with missed appendicitis. The sensitivity and specificity of the diagnostic pathway was 100% and 96.6%, respectively. The potential saving in costs can be as much as 19.8 million €/100,000 cases presenting with the suspicion of appendicitis. CONCLUSION: The risk-stratified diagnostic algorithm yields a high diagnostic accuracy for patients with suspicion of appendicitis. Its implementation can safely reduce the NAR, simultaneously minimizing the use of CT scans and optimizing healthcare-related costs in the treatment of acute appendicitis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02627781 (December 2015).

Cotreatment with sorafenib and oleanolic acid induces reactive oxygen species-dependent and mitochondrial-mediated apoptotic cell death in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common liver malignancy, and the lack of effective chemotherapies underlines the need for novel therapeutic approaches for this disease. Recently, we discovered a novel synergistic induction of cell death by combining sorafenib, the only routinely used palliative chemotherapeutic agent, and the triterpenoid oleanolic acid (OA). However, the underlying mechanisms of action have remained obscure. Here, we report that sorafenib and OA acted in concert to trigger mitochondria-mediated apoptotic cell death, which is dependent on reactive oxygen species (ROS). Sorafenib/OA cotreatment significantly increased ROS production, which was prevented by the ROS scavengers α-tocopherol and MnTBAP. Importantly, rescue experiments showed that ROS were required for sorafenib/OA-induced apoptosis as ROS scavengers protected HCC cells against cell death. In addition, sorafenib and OA cotreatment cooperated to decrease myeloid cell leukaemia-1 expression and to activate Bak, two events that were prevented by ROS scavengers. Bak activation was accompanied by the loss of mitochondrial membrane potential, followed by PARP cleavage, DNA fragmentation and, finally, apoptotic cell death in HCC cells. By providing new insights into the molecular regulation of sorafenib/OA-mediated and ROS-dependent cell death, our study contributes toward the development of novel treatment strategies to overcome sorafenib resistance in HCC.

Antibiotic-treated acute appendicitis-reception in social media.

PURPOSE: Social media, especially Twitter®, is becoming increasingly important for medical topics. Systematic analyses of the content of these tweets are rare. To date, no analysis of the reception of antibiotic/non-operative-treated acute appendicitis on Twitter® has been performed. METHODS: Tweets with the content "appendicitis," "appendix," and "appendectomy" from December 31, 2010, to September 27, 2017, were recorded. Further analysis was performed by secondary search strings related to antibiotic-treated acute appendicitis. Subsequent systematic analysis of content, author groups, and followers was performed. RESULTS: Out of 22,962 analyzed tweets, 3400 were applicable on all search strings, and 349 dealt meaningfully with antibiotic-treated acute appendicitis. 47.9% of the tweets were published by individuals, of which non-surgical consultants comprised the largest group. The tweets published by organizations and institutions were mostly published by publishing platforms. Half of the tweets were neutral, with an overall positive trend for antibiotic-treated acute appendicitis, but significant differences were noted among the authors. The number of followers showed a wide range, with an considerable numeric impact. CONCLUSION: The scientific discussion of antibiotic-treated acute appendicitis is reflected on Twitter®. Overall, antibiotic-treated acute appendicitis is presented in a neutral and differentiated manner on Twitter®, but this picture is exclusively derived from assessment of a variety of tweets. Individual tweets are partially undifferentiated in content and misrepresent antibiotic-treated acute appendicitis. In addition, content and intentions are significantly author dependent. Scientists should therefore use Twitter® to make sound medical information heard. If this policy is not implemented, the importance of inadequate and incorrect information transfer is indirectly increased.

Influence of the recipient body mass index on the outcomes after kidney transplantation.

PURPOSE: The relationship between the body mass index (BMI) of kidney transplant recipients and outcomes after kidney transplantation (KT) is not fully understood and remains controversial. We studied the influence of BMI on clinically relevant outcomes in kidney transplant recipients. METHODS: In this retrospective single-centre study, all patients who underwent kidney transplantation at our institution between January 2007 and December 2012 were included. Demographic data and BMI were correlated with the clinical course of the disease, rejection rates, delayed graft function rates, and graft and patient survival. RESULTS: During the study period, 384 single KTs (130 women and 254 men) were performed. Seventeen percent of the transplants were transplanted within the Eurotransplant Senior Programme (ESP). Most of the transplants were performed using organs that were obtained from donors after brain death (DBD), and living donor kidney transplants were performed in 22.4% of all transplants. The median BMI of the recipients was 25.9 kg/m2. Additionally, 13.5% of the recipients had a BMI of 30-34.9 kg/m2 and 3.9% had a BMI >35 kg/m2. A BMI >30 kg/m2 was significantly associated with primary non-function of the kidney (p = 0.047), delayed graft function (p = 0.008), and a higher rate of loss of graft function (p = 0.015). The glomerular filtration rate 12 months after KT was significantly lower in recipients with a BMI >30 kg/m2. Multivariate analysis revealed that recipient BMI, among other factors, was an independent risk factor for delayed graft function and graft survival. Patients with a BMI >30 kg/m2 had an almost four times higher risk for surgical site infection than did recipients with a lower BMI. CONCLUSIONS: Increased BMI at kidney transplantation is a predictor of adverse outcomes, including delayed graft function. These findings demonstrate the importance of the careful selection of patients and pre-transplant weight reduction, although the role of weight reduction for improving graft function is not clear.

The meteorological influence on seasonal alterations in the course of acute appendicitis.

BACKGROUND: Several diseases, including acute appendicitis (AA), have been known to undergo seasonal variations. Changes in the incidence and course of AA are attributed to seasonal weather differences, but this connection remains unproven. METHODS: In this retrospective, single-center analysis, we analyzed daily meteorological data over an 8-year period. A connection of day-by-day meteorological data with 680 consecutive appendectomies was performed. Patients' characteristics, intraoperative findings, and outcome parameters were analyzed. Seasons were classified meteorologically as 3-month periods (winter, spring, summer, and autumn). RESULTS: Nonambient temperature (unusual warm or cold weather) is correlated with a higher rate of complicated (gangrenous or perforated) AA (P = 0.018). In summer and winter, days with nonambient temperatures were more frequent (P < 0.0001). A higher rate of complicated AA was seen during summer and winter (P = 0.009). In addition, patients operated on in summer and accordingly after warm days suffer more complications (P < 0.0001), especially more superficial surgical site infections (P < 0.048). CONCLUSIONS: The concordant observation of more complicated AA and complications after AA with meteorological data and calendric seasonal variations makes it most likely that temperature is a cofactor in complicated AA and contributes to the seasonal variations in AA. Although an increase in the microbiome of the skin during warm seasons might explain the increase in surgical site infection, the functional connection between warmer temperatures and AA complications remains unclear.

Bad bacteria in acute appendicitis: rare but relevant.

PURPOSE: Bacterial infections are a factor for morbidity in patients with acute appendicitis (AA). The spreading of multidrug-resistant (MDR) bacteria is a significant problem in surgery, and the most relevant MDR pathogens are summarized as Enterobacteriaceae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococci (ESKAPE) bacteria. Data regarding the species and distribution of bacteria in AA are available, but information about the resistances and their relevance is deficient. METHODS: In this retrospective study, we analyzed microbiological swabs of patients with AA. The outcome parameters of patients after laparoscopic appendectomy were analyzed against microbiological results, including antibiotic resistance testing. Positive swabs were compared with bacteria cultivated after alternative abdominal emergency surgery (AES). RESULTS: In total, 584 patients with AA were included and had a mean age of 35.5 years. In 216 patients (36.9%), a swab was taken, and in 128 (59.3%) swabs, bacteria could be cultivated. The most frequent organisms were Escherichia coli, Bacteroides species, and Pseudomonas. In 9.4% of the positive AA swabs, MDR germs were cultivated, and all of them were ESKAPE pathogens. Patients with MDR bacteria in AA suffered more infectious complications (p = 0.006) and needed longer hospitalizations (p < 0.009). In AES, aside from appendicitis, a different spectrum containing more MDR bacteria was cultivated (5.9 vs. 20.9%; p < 0.0001). CONCLUSIONS: Although they occur less frequently in appendectomy compared to emergency surgeries for other abdominal diseases, MDR bacteria are traceable in this common disease and contribute to additional morbidity.

Role of CD15 expression in dysplastic and neoplastic tissue of the bile duct - a potential novel tool for differential diagnosis of indeterminate biliary stricture.

BACKGROUND AND AIMS: CD15 is expressed by various cancer types; among these are intrahepatic and perihilar cholangiocarcinoma (CCA). The aim of this study was to elucidate CD15 expression in distal CCA as well as in dysplastic biliary tissue and to determine its prognostic significance. METHODS AND RESULTS: Tissue samples from patients with intrahepatic (iCCA, n = 22), perihilar (pCCA, n = 7) and distal CCA (dCCA, n = 15), who underwent surgical resection in the period from 2010 to 2015 were evaluated for CD15 expression. Tissue of synchronous lymph node metastasis (n = 13), CCA-associated dysplasia (n = 20), dysplasia in intraductal biopsies (n = 10) and benign proliferations (n = 12), as well as inflammatory biliary lesions (n = 28) and non-inflammatory bile ducts (n = 23), were evaluated equally for CD15 expression. CD15 was found to be expressed highly in iCCA (81.8%), pCCA (85.7%), dCCA (73.3%), CCA-associated dysplasia (70.0%), dysplasia in intraductal biopsies (100%) and metastatic tissue (84.6%). CD15 expression was negative in 58 of 64 benign bile duct alterations resulting in an overall sensitivity and specificity of CD15 in CCA of 80.7 and 90.6% patients, respectively. CD15 expression was correlated significantly with a decreased overall survival in patients with CD15-positive CCA associated dysplasia (P = 0.003). However, CD15 expression in the invasive tumour component was not correlated with clinical outcome. CONCLUSION: CD15 is a sensitive and specific marker for intraepithelial and invasive neoplasias of the bile duct. Therefore, it can be helpful in the delineation of dysplastic and neoplastic biliary cells from non-neoplastic tissue, which frequently causes a diagnostic problem in indeterminate biliary stricture.

A possible role of microRNAs as predictive markers for the recurrence of hepatocellular carcinoma after liver transplantation.

With favourable 5-year survival rates up to 75%, liver transplantation (LT) is the treatment of choice for hepatocellular carcinoma (HCC). Nonetheless, tumour recurrence after LT remains a challenge. The aim of this retrospective study was to develop a predictive score for tumour recurrence after LT by combining clinical parameters with HCC biomarkers (microRNA). A microRNA (miRNA) microarray analysis was used to compare miRNA expression patterns in tissue samples of 40 patients with and without HCC recurrence after LT. In a screening cohort (n = 18), the miRNA analysis identified significant differences in the expression of 13 miRNAs in patients with tumour recurrence. Using the most significant miRNAs in this screening cohort, we could develop a predictive score, which combined the expression levels of miR-214, miR-3187 and the Milan criteria, and we could define low- and high-risk groups for tumour recurrence and death. The above score was evaluated in a second and independent cohort (n = 22). In contrast to the Milan criteria alone, this score was significantly associated with tumour recurrence. Our analysis indicated that the use of a specific miRNA expression pattern in combination with a limited tumour burden as defined by the Milan criteria may lead to a more accurate prediction of tumour recurrence.

Education in thyroid surgery: a matched-pair analysis comparing residents and board-certified surgeons.

PURPOSE: Resident participation in operative procedures is mandatory in educational residency programs but remains controversial, especially in the context of patient safety. This study compared the surgical quality and outcomes of thyroidectomies performed by surgical residents (RESs) and board-certified surgeons (BCSs). METHODS: This retrospective matched-pair study included patients undergoing thyroidectomies for multinodular goiter, Grave's disease and early-stage thyroid cancer that were performed by a RES with BCS supervision between 2006 and 2014. The intraoperative and postoperative course, complication rates and handling of the recurrent laryngeal nerve (RLN) and parathyroid glands were analyzed. RESULTS: In total, 112 thyroidectomies that were performed by a RES fulfilled the inclusion criteria and were matched 1:1 with BCS patients. We included 88 hemithyroidectomies, 80 subtotal thyroidectomies and 56 total thyroidectomies. No significant differences in the handling of the RLN or parathyroid glands, the rates of postoperative RLN palsies or the rates of hypocalcaemia were found. No intraoperative complications led to the replacement of the RES as the surgeon-in-charge. Three RES and two BCS patients experienced postoperative haemorrhages (p = 0.205), and three surgical site infections (p = 1.000) occurred in each group. The mean operative time and the length of stay did not differ significantly between the two groups. CONCLUSIONS: Major aspects of patient safety in thyroid surgery are not affected by resident participation. Thyroidectomies performed by RES are not significantly longer and reveal no differences in length of stay or complication rates. The economic burden of resident involvement is modest.

The use of purse-string skin closure in loop ileostomy reversals leads to lower wound infection rates--a single high-volume centre experience.

PURPOSE: Wound infections affect not only the individual patient but lead to an increase in medical costs. After ileostomy reversal, surgical site infections are a common problem. The objective of the study was to compare the infection rates of purse-string and conventional skin closure techniques in a high volume setting. METHODS: Patients undergoing ileostomy reversal at the Goethe University Hospital between January 2009 and August 2012 were retrospectively analysed regarding surgical site infections and associated risk factors. Patients received either conventional skin closure (running, interrupted or stapled suturing; group C) or subcuticular purse-string suture (group PS). RESULTS: In total, 114 patients have been analysed. Conventional wound closure was performed in 81 patients and 33 patients received purse-string skin closure. The groups did not differ regarding age, gender, indication for ileostomy, previous chemotherapy, and operation time. Median hospital stay was 7 days (3-34) in group PS and 8 (3-53) in group C (p = 0.15). Wound infections only occurred in groups C (n = 10, 12 %) compared to group PS (n = 0; 0 %; p = 0.034), and the wound closure technique was the only significant factor associated with surgical site infection. Surgery performed by a resident under supervision was not a risk factor for complications compared to the procedure done by a senior surgeon (p = 0.73). CONCLUSION: This study reveals an advantage of the purse-string skin closure technique in ileostomy reversals analysing a large cohort of patients. Therefore, we recommend the use of the purse-string skin closure in ileostomy reversals as one way to lower wound infection rates.

Appendicitis-the balance between cost effectiveness and safety remains challenging.

PURPOSE: The diagnosis of acute appendicitis remains a challenge in daily clinical practice. The aim of the present study was to determine clinical criteria for a careful and cost-effective integration of computed tomography (CT) scans in the clinical pathway for the diagnosis of acute appendicitis. METHODS: In this retrospective study, we analyzed all patients who were admitted to our hospital with suspected appendicitis (2008-2011). We included all patients who had an appendectomy with or without preoperative CT. Furthermore, we analyzed all patients who received a CT because of suspected appendicitis but did not have an appendectomy. RESULTS: A total of 367 patients were included in this study. A CT was performed in 35 % of the patients with suspected appendicitis. Women had a significantly higher rate of negative appendectomy (NA) (16.5 %) than men (5.3 %). The frequency of NA was 5.7 % in the group of patients who were imaged, whereas it was 11.8 % (p = 0.075) among those who were not imaged. Thereby, CT scans helped to reduce total hospital expenses (1,317.44 (no CT scan) to 675.85 (CT scan and no operation). Furthermore, CT scans can be avoided in men with normal white blood cell counts who should be observed if not operated immediately. CONCLUSION: CT can be effectively applied for the diagnosis of acute appendicitis. We propose a diagnostic algorithm which helps to simultaneously avoid unnecessary operations and radiation exposure.

[Sustainable waste management in general surgical operations]. / Nachhaltiges Abfallmanagement bei allgemeinchirurgischen Operationen.

BACKGROUND AND OBJECTIVE OF THE STUDY: Hospitals, especially surgical departments, are among the largest producers of waste in Germany. Data on waste management in the operating room (OR) are largely lacking. The aim of this study was to assess and discuss the possibilities of reducing waste and recovering recyclable materials in general surgery against the background of current practice. METHODOLOGY: Surgical departments throughout Germany were surveyed on waste management. First, the theoretical waste separation possibilities for laparoscopic appendectomy were determined. Subsequently, a simple system for the separation of recyclables was established and practically tested in 35 operations. These were compared with 35 appendectomies without separation. RESULTS: Only 25.7% of hospitals perform waste separation. Theoretically, 20.7% of waste can be recycled, in practice up to 18.9%. Paper, cardboard and plastics, especially polyethylene terephthalate (PET) and high-density polyethylene (HDPE) were separated. This leads to a significant reduction in residual waste without extending the operation time. DISCUSSION: Separation of recyclables can contribute to more sustainable waste management in the OR. High-value recyclables can be recycled and the residual waste mass can be significantly reduced. This is possible without special effort and does not delay the processes in the OR. The opportunities for this have hardly been used in Germany to date.

Cognitive profile of kidney transplant patients and impact of deceased vs. living donor transplantation.

BACKGROUND: It is important to learn more about the prevalence, severity and characteristics (i.e., which cognitive abilities are especially affected) of cognitive impairment in kidney transplant patients. Furthermore, the impact of living vs. deceased donor renal transplantation on cognitive outcome in this patient group needs further studies. METHODS: Fifty-nine patients (43 men, age 55 ± 13 years) who received a deceased donor or living donor kidney transplant, completed a comprehensive neuropsychological test assessment. Neuropsychological tests explored the cognitive domains of verbal and visual memory, attention, and executive functions. RESULTS: Fifteen percent  of the patients had mild, 25% moderate, and 15% severe cognitive impairment. The level of domain-specific cognitive deficit differed between verbal memory, attention, and executive functions (χ2(2) = 7.11, p = 0.029). On average, patients showed the highest deficit in executive functions, and the lowest deficit in verbal memory. Patients who received a kidney graft from a deceased donor were more likely to have a cognitive impairment than those who received a kidney graft from a living donor (OR = 3.03, 95% CI [0.99,9.32], Wald χ2(1) = 3.74, p = 0.053). This effect was independent of time on dialysis as well as of creatinine levels, or creatinine clearance. CONCLUSIONS: Our results show that in kidney transplant patients with cognitive impairment, the cognitive domain of executive functions is the most affected one. This might be detrimental for quality of life. The fact that patients who received living donor kidneys seem to do better in terms of cognition than patients with deceased donor kidneys deserves more attention in future research.

Partial spleen resection with a radiofrequency needle device--a pilot study.

INTRODUCTION: Total splenectomy leads to an immunocompromised state, with an increased lifetime risk of infection. The lifetime risk of developing overwhelming postsplenectomy infection is 5 %, with a mortality rate of approximately 50 %. In addition to vaccination and antibiotic prophylaxis, partial splenectomy is believed to improve patient safety. METHODS: We performed partial splenectomy in seven patients using a radiofrequency (RF) technique with Habib® needles. In seven patients, an open access partial splenectomy was performed. In three patients, a partial splenectomy was performed simultaneously with intraabdominal tumour resection. In two patients, the upper pole of the spleen was removed due to tumours of the spleen. In one patient, a large symptomatic splenic cyst was resected and in another patient, a partial splenectomy was performed due to trauma. RF was applied using Habib® needles (AngioDynamics, Manchester, GA, 31816, USA). RESULTS: The partial splenectomy procedures were easy and safe in all seven patients. The RF application with the Habib® needles led to primary haemostasis. The blood loss was less than 50 ml in all cases. After a minimum follow-up of 1 year, there were no cases of infections or other adverse events related to the previous partial splenectomy. CONCLUSION: In our experience, partial splenectomy with Habib® needles is easy to perform and safe for the patient. Thus, radiofrequency resection is a good alternative to total splenectomy in many patients and reduces the risk of postsplenectomy infections.

Cartilage tissue engineering of nasal septal chondrocyte-macroaggregates in human demineralized bone matrix.

Tissue Engineering is an important method for generating cartilage tissue with isolated autologous cells and the support of biomaterials. In contrast to various gel-like biomaterials, human demineralized bone matrix (DBM) guarantees some biomechanical stability for an application in biomechanically loaded regions. The present study combined for the first time the method of seeding chondrocyte-macroaggregates in DBM for the purpose of cartilage tissue engineering. After isolating human nasal chondrocytes and creating a three-dimensional macroaggregate arrangement, the DBM was cultivated in vitro with the macroaggregates. The interaction of the cells within the DBM was analyzed with respect to cell differentiation and the inhibitory effects of chondrocyte proliferation. In contrast to chondrocyte-macroaggregates in the cell-DBM constructs, morphologically modified cells expressing type I collagen dominated. The redifferentiation of chondrocytes, characterized by the expression of type II collagen, was only found in low amounts in the cell-DBM constructs. Furthermore, caspase 3, a marker for apoptosis, was detected in the chondrocyte-DBM constructs. In another experimental setting, the vitality of chondrocytes as related to culture time and the amount of DBM was analyzed with the BrdU assay. Higher amounts of DBM tended to result in significantly higher proliferation rates of the cells within the first 48 h. After 96 h, the vitality decreased in a dose-dependent fashion. In conclusion, this study provides the proof of concept of chondrocyte-macroaggregates with DBM as an interesting method for the tissue engineering of cartilage. The as-yet insufficient redifferentiation of the chondrocytes and the sporadic initiation of apoptosis will require further investigations.

Robotic operations in urgent general surgery: a systematic review.

Robotically assisted operations are the state of the art in laparoscopic general surgery. They are established predominantly for elective operations. Since laparoscopy is widely used in urgent general surgery, the significance of robotic assistance in urgent operations is of interest. Currently, there are few data on robotic-assisted operations in urgent surgery. The aim of this study was to collect and classify the existing studies. A two-stage, PRISMA-compliant literature search of PubMed and the Cochrane Library was conducted. We analyzed all articles on robotic surgery associated with urgent general surgery resp. acute surgical diseases of the abdomen. Gynecological and urological diseases so as vascular surgery, except mesenterial ischemia, were excluded. Studies and case reports/series published between 1980 and 2021 were eligible for inclusion. In addition to a descriptive synopsis, various outcome parameters were systematically recorded. Fifty-two studies of operations for acute appendicitis and cholecystitis, hernias and acute conditions of the gastrointestinal tract were included. The level of evidence is low. Surgical robots in the narrow sense and robotic camera mounts were used. All narrow-sense robots are nonautonomous systems; in 82%, the Da Vinci® system was used. The most frequently published emergency operations were urgent cholecystectomies (30 studies, 703 patients) followed by incarcerated hernias (9 studies, 199 patients). Feasibility of robotic operations was demonstrated for all indications. Neither robotic-specific problems nor extensive complication rates were reported. Various urgent operations in general surgery can be performed robotically without increased risk. The available data do not allow a final evidence-based assessment.

New Perianal Sepsis Risk Score Predicts Outcome of Elderly Patients with Perianal Abscesses.

Antibiotic therapy following surgical perianal abscess drainage is debated, but may be necessary for high-risk patients. Frailty has been shown to increase the risk of unfavorable outcomes in elderly surgical patients. This study aims to identify high-risk patients by retrospectively analyzing a single-center cohort and using a pretherapeutic score to predict the need for postoperative antibiotics and extended nursing care following perianal abscess drainage surgery. The perianal sepsis risk score was developed through univariable and multivariable analysis. Internal validation was assessed using the area under receiver-operating characteristic curve. Elderly, especially frail patients exhibited more severe perianal disease, higher frequency of antibiotic therapy, longer hospitalization, poorer clinical outcomes. Multivariable analysis revealed that scores in the 5-item modified frailty index, severity of local infection, and preoperative laboratory markers of infection independently predicted the need for prolonged hospitalization and anti-infective therapy after abscess drainage surgery. These factors were combined into the perianal sepsis risk score, which demonstrated better predictive accuracy for prolonged hospitalization and antibiotic therapy compared with chronological age or frailty status alone. Geriatric assessments are becoming increasingly important in clinical practice. The perianal sepsis risk score identifies high-risk patients before surgery, enabling early initiation of antibiotic therapy and allocation of additional nursing resources.

Activation of endothelial NO synthase and P2X7 receptor modification mediates the cholinergic control of ATP-induced interleukin-1ß release by mononuclear phagocytes.

Objective: The pro-inflammatory cytokine interleukin-1ß (IL-1ß) plays a central role in host defense against infections. High systemic IL-1ß levels, however, promote the pathogenesis of inflammatory disorders. Therefore, mechanisms controlling IL-1ß release are of substantial clinical interest. Recently, we identified a cholinergic mechanism inhibiting the ATP-mediated IL-1ß release by human monocytes via nicotinic acetylcholine receptor (nAChR) subunits α7, α9 and/or α10. We also discovered novel nAChR agonists that trigger this inhibitory function in monocytic cells without eliciting ionotropic functions at conventional nAChRs. Here, we investigate the ion flux-independent signaling pathway that links nAChR activation to the inhibition of the ATP-sensitive P2X7 receptor (P2X7R). Methods: Different human and murine mononuclear phagocytes were primed with lipopolysaccharide and stimulated with the P2X7R agonist BzATP in the presence or absence of nAChR agonists, endothelial NO synthase (eNOS) inhibitors, and NO donors. IL-1ß was measured in cell culture supernatants. Patch-clamp and intracellular Ca2+ imaging experiments were performed on HEK cells overexpressing human P2X7R or P2X7R with point mutations at cysteine residues in the cytoplasmic C-terminal domain. Results: The inhibitory effect of nAChR agonists on the BzATP-induced IL-1ß release was reversed in the presence of eNOS inhibitors (L-NIO, L-NAME) as well as in U937 cells after silencing of eNOS expression. In peripheral blood mononuclear leukocytes from eNOS gene-deficient mice, the inhibitory effect of nAChR agonists was absent, suggesting that nAChRs signal via eNOS to inhibit the BzATP-induced IL-1ß release. Moreover, NO donors (SNAP, S-nitroso-N-acetyl-DL-penicillamine; SIN-1) inhibited the BzATP-induced IL-1ß release by mononuclear phagocytes. The BzATP-induced ionotropic activity of the P2X7R was abolished in the presence of SIN-1 in both, Xenopus laevis oocytes and HEK cells over-expressing the human P2X7R. This inhibitory effect of SIN-1 was absent in HEK cells expressing P2X7R, in which C377 was mutated to alanine, indicating the importance of C377 for the regulation of the P2X7R function by protein modification. Conclusion: We provide first evidence that ion flux-independent, metabotropic signaling of monocytic nAChRs involves eNOS activation and P2X7R modification, resulting in an inhibition of ATP signaling and ATP-mediated IL-1ß release. This signaling pathway might be an interesting target for the treatment of inflammatory disorders.

Posthepatectomy liver failure.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most serious complications after liver resection and is still reported in up to 8% after liver resection. AIMS: To provide an overview about the current status of risk analysis and definition of PHLF. Prevention and treatment is also discussed. METHODS: A literature review was carried out on PubMed using the terms 'liver failure', 'posthepatectomy' and 'liver surgery' to search relevant papers. DISCUSSION: PHLF remains a serious problem in patients undergoing major liver resection. Adequate preoperative risk assessment and an optimal postoperative treatment are essential for PHLF prevention.

Frailty in elderly patients with acute appendicitis.

PURPOSE: Acute appendicitis in the elderly is becoming increasingly recognized for its often severe course. For various elective and urgent operations in older patients, frailty is a risk factor for poor outcomes. However, there is a lack of data on frailty in elderly patients with acute appendicitis. METHODS: Patients over 65 years old who underwent surgery for acute appendicitis in three hospitals between January 2015 and September 2020 were assessed with the Hospital Frailty Risk Score (HFRS) and the modified Frailty Index (mFI). Outcomes of interest, including morbidity, mortality, and length of stay, were recorded. RESULTS: While frailty can be measured with both tests, the mFI has better applicability and takes significantly less time to implement compared to the HFRS (21.6 s vs. 80.3 s, p < 0.0001) while providing the same information value. Patients who exhibited frailty according to either assessment had a significantly higher rate of milder (OR 5.85/2.87, p < 0.0001/0.009) and serious (OR 4.92/3.61, p < 0.011/0.029) complications, more admissions to the intensive care unit (OR 5.16/7.36, p < 0.0001), and an almost doubled length of stay (12.7 days vs. 6.6 days, p < 0.005). Up to 31% of these patients required institutional care after discharge, which is significantly more than those without frailty (p < 0.0001). Furthermore, the mortality rate in frail patients was significantly elevated to 17%, compared to less than 1% in non-frail patients (p = 0.018). CONCLUSION: In elderly patients, frailty is a significant risk factor for negative outcomes. Frailty can be assessed more quickly and reliably with the mFI compared to the HFRS.