The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses ...depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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•SARS-CoV-2 uses the SARS-CoV receptor ACE2 for host cell entry•The spike protein of SARS-CoV-2 is primed by TMPRSS2•Antibodies against SARS-CoV spike may offer some protection against SARS-CoV-2
The emerging SARS-coronavirus 2 (SARS-CoV-2) threatens public health. Hoffmann and coworkers show that SARS-CoV-2 infection depends on the host cell factors ACE2 and TMPRSS2 and can be blocked by a clinically proven protease inhibitor. These findings might help to establish options for prevention and treatment.
Isolated human primary hepatocytes are an essential in vitro model for basic and clinical research. For successful application as a model, isolated hepatocytes need to have a good viability and be ...available in sufficient yield. Therefore, this study aims to identify donor characteristics, intra-operative factors, tissue processing and cell isolation parameters that affect the viability and yield of human hepatocytes. Remnant liver pieces from tissue designated as surgical waste were collected from 1034 donors with informed consent. Human hepatocytes were isolated by a two-step collagenase perfusion technique with modifications and hepatocyte yield and viability were subsequently determined. The accompanying patient data was collected and entered into a database. Univariate analyses found that the viability and the yield of hepatocytes were affected by many of the variables examined. Multivariate analyses were then carried out to confirm the factors that have a significant relationship with the viability and the yield. It was found that the viability of hepatocytes was significantly decreased by the presence of fibrosis, liver fat and with increasing gamma-glutamyltranspeptidase activity and bilirubin content. Yield was significantly decreased by the presence of liver fat, septal fibrosis, with increasing aspartate aminotransferase activity, cold ischemia times and weight of perfused liver. However, yield was significantly increased by chemotherapy treatment. In conclusion, this study determined the variables that have a significant effect on the viability and the yield of isolated human hepatocytes. These variables have been used to generate an algorithm that can calculate projected viability and yield of isolated human hepatocytes. In this way, projected viability can be determined even before isolation of hepatocytes, so that donors that result in high viability and yield can be identified. Further, if the viability and yield of the isolated hepatocytes is lower than expected, this will highlight a methodological problem that can be addressed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite constant improvements in diagnostic as well as interventional and surgical techniques, acute mesenteric ischemia (AMI) remains a life-threatening emergency with high mortality rates. The time ...to diagnosis of AMI is the most important predictor of patients' outcome; therefore, prompt diagnosis and intervention are essential to reduce mortality in patients with AMI. The present review was performed to analyze potential risk factors and to help find ways to improve the outcome of patients with AMI.
Whereas AMI only applies to approximately 1% of all patients with an "acute abdomen," its incidence is rising up to 10% in patients >70 years of age. The initial clinical stage of AMI is characterized by a sudden onset of strong abdominal pain followed by a painless interval. Depending on the extent of disease, the symptoms of nonocclusive mesenteric ischemia (NOMI) and patients with a venous thrombosis can be very different from those of acute occlusive ischemia. Biphasic contrast-enhanced CT represents the gold standard for the diagnosis of arterial and venous occlusion. In case of a central occlusion of the superior mesenteric artery or signs of peritonitis, immediate surgery should be performed. If major bowel resection becomes necessary, critical residual intestinal length limits must be kept in mind. Endovascular techniques for arterial occlusion have taken on a much greater importance today. For stable patients with NOMI, interventional catheter angiography is recommended because it enables diagnosis and treatment with selective application of vasodilators. Depending on its degree, interventional treatment with a transhepatic catheter lysis should be considered for acute and chronic portal vein thrombosis.
The prompt and targeted use of the appropriate diagnostics and interventions appears to be the only way to reduce the persistently high mortality rates for AMI.
Background The need for adjuvant chemotherapy after resection of ampullary cancer (PapCa) remains undefined. Recent data suggest that a different epithelial origin of PapCa might be associated with ...different tumor biology. The aim of the present study was to assess the clinical value of morphologic and immunohistochemic subclassification of PapCa into intestinal-type (IT) and pancreaticobiliary-type (PT) to predict chemotherapy response and overall survival (OS). Methods Via a prospective database, 112 PapCa were identified, of which 95 could be included in the present study. Those were compared with 206 matching patients with periampullary pancreatic cancer (ie, pancreatic ductal adenocarcinoma, PDAC). IT and PT PapCa were classified morphologically, and tissue microarray was prepared with immunohistochemistry for CK7, CK20, MUC2, CDX2, ß-Catenin, and Villin. Multivariate survival analysis was performed. Results OS of PT patients was less compared with IT patients (25 vs 98 months; P < .001), whereas it was comparable with patients with PDAC (25 vs 14 months; P = .123). PT patients receiving adjuvant gemcitabine chemotherapy featured improved OS (32 vs 13 months; P = .013), whereas gemcitabine tended to be associated with decreased OS in IT patients (35 vs 112 months; P = .193). Besides histopathologic classification, expression of CK7 and MUC2 were important prognostic variables. PT patients with CK7-positivity or MUC2-negativity were segregated into an even poorer prognostic group. Conclusion PapCa is not a separate tumor entity. We demonstrate important differences between IT-PapCa and PT-PapCa not only in long-term survival but also in response to adjuvant gemcitabine. Tumor biology and clinical course of PT tumors resemble those of PDAC. PT tumors should therefore be treated like PDAC.
BACKGROUND:Perioperative allogeneic red blood cell transfusion has been conclusively shown to be associated with adverse oncologic outcomes after resection of nonmetastatic colorectal adenocarcinoma.
...OBJECTIVE:The aim of the study was to identify risk factors for a perioperative transfusion and to assess the effects of transfusion on survival after curative-intended resection of hepatic metastases in patients featuring stage IV colorectal cancer.
DESIGN:This was an observational study with a retrospective analysis of a prospective data collection.
SETTING:The study was conducted at a tertiary care center.
PATIENTS:A total of 292 patients undergoing curative-intended liver resection for colorectal liver metastases were included in the study.
MAIN OUTCOME MEASURES:Univariate and multivariate analyses were performed identifying factors influencing transfusion, recurrence-free survival, and overall survival.
RESULTS:A total of 106 patients (36%) received allogeneic red blood cells. Female sex (p = 0.00004), preoperative anemia (p = 0.001), major intraoperative blood loss (p < 0.00001), and major postoperative complications (p = 0.02) were independently associated with the necessity of transfusion. Median recurrence-free and overall survival were 58 months. Allogeneic red blood cell transfusion was significantly associated with reduced recurrence-free survival (32 vs 72 months; p = 0.008). It was reduced further by administration of >2 units (27 months; p = 0.02). Overall survival was not significantly influenced by transfusion (48 vs 63 months; p = 0.08). When multivariately adjusted for major intraoperative blood loss and factors univariately associated, namely comorbidities, tumor load, and positive resection margins, transfusion was an independent predictor for reduced recurrence-free survival (p = 0.03).
LIMITATIONS:These include the retrospective and observational design, as well as the impossibility to prove causality of the association between transfusion and poor outcome.
CONCLUSIONS:In patients undergoing liver resection for colorectal liver metastases, perioperative transfusion is independently associated with earlier disease recurrence. This emphasizes appropriate blood management measures, including the conservative correction of preoperative anemia, the use of low transfusion triggers, and the minimization of intraoperative blood loss.
Endoscopic vacuum therapy for the treatment of rectal anastomotic leak has been shown to be effective and safe. The majority of patients are treated after fecal diversion to avoid further septic ...complications.
To report the effectiveness of endoscopic vacuum therapy for rectal anastomotic leak without diversion compared to secondary stoma creation.
Retrospective cohort analysis.
University hospital, single-center.
Patients undergoing sigmoid or rectal resection without fecal diversion during primary surgery who were treated with endoscopic vacuum therapy for clinically relevant anastomotic leak.
Treatment success (sepsis control, granulation and closure of the leak cavity, and no subsequent interventional or surgical procedure required); treatment duration; complications associated with endoscopic vacuum therapy; outpatient treatment; and restoration of intestinal continuity in diverted patients.
Fifty-seven patients were included. In 20 patients (35%), endoscopic vacuum therapy was initiated without secondary diversion since the leak was extraperitoneal, and the sponge could be placed into the leak cavity with an adequate seal toward the lumen. In 18 patients (90%), this approach was successful. None of these patients required subsequent diversion in the further course of their disease. In two patients, secondary diversion was necessary due to treatment failure. Balloon dilatation for luminal stenosis was required in two patients. When comparing patient and treatment characteristics of patients with and without a stoma, including treatment success and duration, no significant differences were found. Restoration of intestinal continuity was achieved in 69% of diverted patients.
Unrandomized, retrospective study design; confounding factors of treatment assignment; low patient numbers and short follow-up of diverted patients; and low statistical power.
In this single-institution study, endoscopic vacuum therapy for rectal anastomotic leak was successful in 90% of patients without diversion with regard to sepsis control, granulation of the leak cavity, avoidance of surgery, and long-term stoma-free survival. See Video Abstract at http://links.lww.com/DCR/B737.TERAPIA ENDOSCÓPICA POR ASPIRACIÓN AL VACÍO EN CASOS DE FUGA ANASTOMÓTICA RECTO-CÓLICA IZQUIERDA SIN OSTOMÍA DE PROTECCIÓNANTECEDENTES:Se ha demostrado que la terapia endoscópica por aspiración al vacío en casos de fuga anastomótica recto-cólica izquierda en el tratamiento de la fuga anastomótica rectal es eficaz y segura. La mayoría de los casos beneficiaron del tratamiento después de la confeción de un ostomía de protección para evitar más complicaciones sépticas.OBJETIVO:Demostrar la efectividad de la terapia endoscópica por aspiración al vacío en casos de fuga anastomótica recto-cólica izquierda sin ostomía de protección comparada con los casos que tuvieron la creación de una ostomía secundaria.DISEÑO:Análisis de cohortes de tipo retrospectivo.AJUSTE:Hospital universitario, unicéntrico.PACIENTES:Aquellos pacientes sometidos a una resección sigmoidea o rectal sin ostomía de protección durante una cirugía primaria, y que fueron tratados con terapia endoscópica por aspiración al vacío en caso de fuga anastomótica clínicamente relevante.PRINCIPALES MEDIDAS DE RESULTADO:Tratamiento exitoso (control de la sepsis, granulación y cierre de la cavidad de la fuga, sin requerir procedimiento quirúrgico o intervención ulteterior); duración del tratamiento; complicaciones asociadas con la terapia endoscópica por aspiración al vacío; tratamiento ambulatorio; restablecimiento de la continuidad intestinal en los pacientes portadores de ostomía.RESULTADOS:Se incluyeron 57 pacientes. En 20 pacientes (35%), se inició la terapia endoscópica por aspiración al vacío sin derivación secundaria, ya que la fuga era extraperitoneal y la esponja podía colocarse en la cavidad de la fuga con un sellado adecuado hacia el lumen. En 18 pacientes (90%), este enfoque fue exitoso. Ninguno de estos pacientes requirió una derivación posterior durante la evolución de la enfermedad. En dos pacientes, fue necesaria una derivación secundaria debido al fracaso del tratamiento. Se requirió dilatación con balón por estenosis luminal en dos pacientes. Al comparar las características de los pacientes y del tratamiento con y sin ostomía, incluido el éxito y la duración del tratamiento, no se encontraron diferencias significativas. El restablecimiento de la continuidad intestinal se logró en el 69% de los pacientes derivados.LIMITACIONES:Diseño de estudio retrospectivo no aleatorio; factores de confusión en la asignación del tratamiento; escaso número de pacientes y seguimiento a corto plazo de los pacientes ostomizados; bajo poder estadístico.CONCLUSIÓN:En este estudio de una sola institución, la terapia al vacío por vía endoscópica en casos de fuga anastomótica rectal fue exitosa en el 90% de los pacientes sin derivación con respecto al control de la sepsis, granulación de la cavidad de la fuga, como se evitó la cirugía y la sobrevida sin ostomía a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B737. (Traducción-Dr. Xavier Delgadillo).
Summary Background Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery, and triclosan-coated sutures were developed to reduce their ...occurrence. The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure, compared with non-coated PDS II sutures, in the prevention of surgical site infections. Methods This multicentre, randomised controlled group-sequential superiority trial was done in 24 German hospitals. Adult patients (aged ≥18 years) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion. Exclusion criteria were impaired mental state, language problems, and participation in another intervention trial that interfered with the intervention or outcome of this trial. A central web-based randomisation tool was used to randomly assign eligible participants by permuted block randomisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures (PDS Plus) or uncoated sutures (PDS II) for abdominal fascia closure. The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation. Patients, surgeons, and the outcome assessors were masked to group assignment. Interim and final analyses were by modified intention to treat. This trial is registered with the German Clinical Trials Register, number DRKS00000390. Findings Between April 7, 2010, and Oct 19, 2012, 1224 patients were randomly assigned to intervention groups (607 to PDS Plus, and 617 to PDS II), of whom 1185 (587 PDS Plus and 598 PDS II) were analysed by intention to treat. The study groups were well balanced in terms of patient and procedure characteristics. The occurrence of surgical site infections did not differ between the PDS Plus group (87 14·8% of 587) and the PDS II group (96 16·1% of 598; OR 0·91, 95% CI 0·66–1·25; p=0·64). Serious adverse events also did not differ between the groups—146 of 583 (25·0%) patients treated with PDS Plus had at least one serious adverse event, compared with 138 of 602 (22·9%) patients treated with PDS II; p=0·39). Interpretation Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy. Innovative, multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections. Funding Johnson & Johnson Medical Limited.
To assess the perioperative and long-term outcome following pulmonary resection in patients with metachronous metastasis of pancreatic ductal adenocarcinoma (PDAC).
Most patients with PDAC relapse or ...develop tumor spread to secondary organs. Currently, it remains unclear how to proceed with pulmonary metastasis in the metachronous setting. In particular, the role of surgery remains controversial.
Data of patients with pulmonary metachronous metastasis after PDAC collected from 2003 to 2015 in databases of two high-volume pancreatic cancer centers were retrospectively analyzed. Clinical and pathological aspects of primary PDAC as well as the perioperative and long-term outcome following pulmonary metastasectomy (PM) was evaluated, respectively. Patients with synchronous liver metastasis or metastasis to other secondary organs were excluded. Univariate survival analysis was performed.
We identified 15 patients undergoing pulmonary resection for suspected metastasis after primary pancreatic resection. Operative and histopathologic evaluation revealed resectable pancreatic pulmonary metastasis in 11 patients (73.3%). The median disease-free survival (DFS) and overall survival (OS) after PM diagnosis was 18 months and 26 months, respectively. The median time to metachronous metastasis (TMM) was 17 months 3–64 months. Perioperative morbidity was low with only one readmission (8.3%). There was no perioperative mortality. Patients who developed pulmonary metastasis later than 17 months after primary surgery showed better OS compared to those who did earlier (32.2 vs. 14.75 months, p = 0.025). In addition, patients with high-grade tumors had worse survival (12.4 vs. 31 months, p = 0.02). Elevated serum CEA levels or CA 19-9 levels were also not associated with shortened OS.
This study suggests that pulmonary metastasectomy after PDAC is safe and effective. Patients with extended DFS after primary pancreatic surgery as well as favorable tumor grading seem to particularly benefit from pulmonary surgery.
•Total pulmonary metastasectomy of metachronic disease after PDAC is safe with little perioperative morbidity and mortality.•Extended DFS after primary pancreatic surgery favors benefits from pulmonary surgery.•Low grade pancreatic tumors are more likely to profit from pulmonary metastasectomy.
Background
Evidence for endoscopic vacuum therapy (EVT) for colorectal defects is still based on small patient series from various institutions, employing different treatment algorithms and methods. ...As EVT was invented at our institution 20 years ago, the aim was to report the efficacy and safety of EVT for colorectal defects as well as to analyze factors associated with efficacy, therapy duration, and outpatient treatment.
Methods
Cohort study with analysis of prospectively collected data of patients receiving EVT for colorectal defects at a tertiary referral center in Germany (
n
= 281).
Results
The majority of patients had malignant disease (83%) and an American Society of Anesthesiologists classification of III/IV (81%). Most frequent indications for EVT were anastomotic leakage after sigmoid or rectal resection (67%) followed by rectal stump leakage (20%). EVT was successful in 256 out of 281 patients (91%). EVT following multi-visceral resection (
P
= 0.037) and recent surgical revision after primary surgery (
P
= 0.009) were risk factors for EVT failure. EVT-associated adverse events occurred in 27 patients (10%). Median treatment duration was 25 days. Previous chemo-radiation (
P
= 0.006) was associated with a significant longer duration of EVT. Outpatient treatment was conducted in 49% of patients with a median hospital stay reduction of 15 days and 98% treatment success. Younger patient age (
P
= 0.044) was associated with the possibility of outpatient treatment. Restoration of intestinal continuity was achieved in 60% of patients where technically possible with a 12-month rate of 52%.
Conclusions
In patients with colorectal defects, EVT appears to be a safe and effective, minimally invasive option for in- and outpatient treatment.
BACKGROUND:Patients with permanent end ileostomy are at high risk for detrimental stomal effects on their quality of life. However, little is known about the long-term quality of life of these ...patients.
OBJECTIVE:The purpose of this study was to assess long-term quality of life in patients with permanent end ileostomy.
DATA SOURCES:Registration at the German self-help organization ILCO was used for this study.
STUDY SELECTION:Selection included a cross-sectional survey of 1434 patients with permanent end ileostomy.
MAIN OUTCOME MEASURES:Quality of life was assessed using the Medical Outcomes Study Short Form 36, including physical and mental component summary scores, the Gastrointestinal Quality of Life Index, and the Cleveland Global Quality of Life Index. Multivariate risk factor analysis was performed.
RESULTS:A total of 783 responders were included. Indications for ileostomy included ulcerative colitis (44%), Crohn’s disease (38%), and colorectal cancer (7%). Adverse effects on daily life because of stoma were reported by 72% of participants. Quality of life was significantly impaired compared with the general population on all of the summary scores and several subscales (physical component summary44.6 ± 10.4 (mean ± SD) vs 50.2 ± 10.2, p < 0.001; mental component summary47.5 ± 10.7 vs 51.5 ± 10.2, p < 0.001; Gastrointestinal Quality of Life Index94.4 ± 16.4 vs 126.0, p < 0.001). Stoma care problems affecting quality of life were reported by 63% of respondents. These included parastomal hernia (p < 0.001), stenosis (p = 0.003), and prolapse (p = 0.008). Vitamin B12, iron, and zinc deficiencies were also associated with diminished quality of life; in particular, vitamin B12 deficiency was associated with reduced mental and emotional quality of life.
LIMITATIONS:Not all patients undergoing ileostomy in Germany are registered at ILCO, and there were many nonresponders. In addition, the inherent limitations of cross-sectional studies should be considered, including the response–shift phenomenon.
CONCLUSIONS:Quality of life was markedly impaired in patients with permanent end ileostomy as compared with the general population. The main reasons were stoma-associated morbidity and nutritional deficiency syndromes. These findings highlight the importance of prevention, screening, and adequate treatment.
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