Changes over time in the course of advanced pancreatic cancer treatment with systemic chemotherapy: a pooled analysis of five clinical trials from two decades of the German AIO study group.

BACKGROUND: Over the past two decades, our group has conducted five multicenter trials focusing on first-line systemic therapy for patients with advanced pancreatic cancer. The current pooled analysis was designed to evaluate prognosis over time and the impact of clinical characteristics on survival. PATIENTS AND METHODS: Individual patient data were derived from five prospective, controlled, multicenter trials conducted by the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO): 'Gem/Cis', 'Ro96', 'RC57', 'ACCEPT' and 'RASH', which recruited patients between December 1997 and January 2017. RESULTS: Overall, 912 patients were included. The median overall survival (OS) for all assessable patients was 7.1 months. OS significantly improved over time, with a median OS of 8.6 months for patients treated from 2012 to 2017 compared with 7.0 months from 1997 to 2006 [hazard ratio (HR) 1.06; P < 0.004]. Eastern Cooperative Oncology Group performance status (HR 1.48; P < 0.001), use of second-line treatment (HR 1.51; P < 0.001), and Union for International Cancer Control (UICC) stage (III versus IV) (HR 1.34, P = 0.002) had a significant impact on OS. By contrast, no influence of age and gender on OS was detectable. Comparing combination therapy with single-agent chemotherapy did not demonstrate a survival benefit, nor did regimens containing epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as afatinib or erlotinib, compared with chemotherapy-only arms. Patients with early-onset pancreatic cancer (age at study entry of ≤50 years, n = 102) had a similar OS compared with those >50 years (7.1 versus 7.0 months; HR 1.13; P = 0.273). The use of a platinum-containing regimen was not associated with better outcomes in patients with early-onset pancreatic cancer. CONCLUSIONS: Within this selected group of patients treated within prospective clinical trials, survival has shown improvement over two decades. This effect is likely attributable to the availability of more effective combination therapies and treatment lines, rather than to any specific regimen, such as those containing EGFR-TKIs. In addition, concerning age and sex subgroups, the dataset did not provide evidence for distinct clinical behavior.

Overexpression of VEGFα as a biomarker of endothelial dysfunction in aortic tissue of α-GAL-Tg/KO mice and its upregulation in the serum of patients with Fabry's disease.

Introduction: Fabry's disease is an X-linked lysosomal storage disorder caused by reduced activity of α-galactosidase A (GAL), leading to premature death on account of renal, cardiac, and vascular organ failure. Accumulation of the GAL substrate globotriaosylceramide (Gb3) in endothelial and smooth muscle cells is associated with early vascular cell damage, suggesting endothelial dysfunction as a driver of cardiorenal organ failure. Here, we studied the vascular expression of the key angiogenic factors, VEGFα and its antagonist angiostatin, in Fabry α-GAL-Tg/KO mice and determined circulating VEGFα and angiostatin serum levels in patients with Fabry's disease and healthy controls. Methods: Cryopreserved aortic vessels from six α-GAL-Tg/KO and six wild-type (WT) mice were obtained and VEGFα and angiostatin levels were determined by performing Western blot analysis. VEGFα expression was visualized by an immunohistochemical staining of paraffin aortic rings. In addition, VEGFα and angiostatin serum levels were measured by using an enzyme-linked immunosorbent assay in 48 patients with genetically verified Fabry's disease (50% male) and 22 healthy controls and correlated with disease severity markers such as lyso-Gb3, albuminuria, NTproBNP, high-sensitive troponin T (hsTNT), and myocardial wall thickness. Results: It was found that there was a significant increase in VEGFα protein expression (1.66 ± 0.35 vs. 0.62 ± 0.16, p = 0.0009) and a decrease in angiostatin expression (0.024 ± 0.007 vs. 0.053 ± 0.02, p = 0.038) in aortic lysates from α-GAL-Tg/KO compared with that from WT mice. Immunohistochemical staining revealed an adventitial VEGFα signal in α-GAL-Tg/KO mice, whereas no VEGFα signal could be detected in WT mice aortas. No differences in aortic angiostatin expression between α-GAL-Tg/KO- and WT mice could be visualized. The serum levels of VEGFα were significantly upregulated in patients with Fabry's disease compared with that in healthy controls (708.5 ± 426.3 vs. 458.5 ± 181.5 pg/ml, p = 0.048) and positively associated with albuminuria (r = 0.82, p < 0.0001) and elevated NTproBNP (r = 0.87, p < 0.0001) and hsTNT values (r = 0.41, p = 0.048) in male patients with Fabry's disease. For angiostatin, no significant difference was found between patients with Fabry's disease and healthy controls (747.6 ± 390.3 vs. 858.8 ± 599.3 pg/ml). Discussion: In conclusion, an overexpression of VEGFα and downregulation of its counter player angiostatin in aortic tissue of α-GAL-Tg/KO mice support the hypothesis of an underlying vasculopathy in Fabry's disease. Elevated VEGFα serum levels were also observed in patients with Fabry's disease and were positively associated with elevated markers of organ manifestation in males. These findings suggest that angiogenetic markers, such as VEGFα, may be potentially useful biomarkers for the detection of endothelial dysfunction in classical Fabry's disease.

High vaccination coverage and infection rate result in a robust SARS-CoV-2-specific immunity in the majority of liver cirrhosis and transplant patients: A single-center cross-sectional study.

BACKGROUND: In the third year of the SARS-CoV-2 pandemic, little is known about the vaccine- and infection-induced immune response in liver transplant recipients (LTR) and liver cirrhosis patients (LCP). OBJECTIVE: This cross-sectional study assessed the vaccination coverage, infection rate, and the resulting humoral and cellular SARS-CoV-2-specific immune responses in a cohort of LTR and LCP at the University Medical Center Hamburg-Eppendorf, Germany between March and May 2023. METHODS: Clinical and laboratory data from 244 consecutive patients (160 LTR and 84 LCP) were collected via chart review and a patient survey. Immune responses were determined via standard spike(S)- and nucleocapsid-protein serology and a spike-specific Interferon-gamma release assay (IGRA). RESULTS: On average, LTR and LCP were vaccinated 3.7 and 3.3 times, respectively and 59.4% of patients received ≥4 vaccinations. Altogether, 68.1% (109/160) of LTR and 70.2% (59/84) of LCP experienced a SARS-CoV-2 infection. Most infections occurred during the Omicron wave in 2022 after an average of 3.0 vaccinations. Overall, the hospitalization rate was low (<6%) in both groups. An average of 4.3 antigen contacts by vaccination and/or infection resulted in a seroconversion rate of 98.4%. However, 17.5% (28/160) of LTR and 8.3% (7/84) of LCP demonstrated only low anti-S titers (<1000 AU/ml), and 24.6% (16/65) of LTR and 20.4% (10/59) of LCP had negative or low IGRA responses. Patients with hybrid immunity (vaccination plus infection) elicited significantly higher anti-S titers compared with uninfected patients with the same number of spike antigen contacts. A total of 22.2% of patients refused additional booster vaccinations. CONCLUSION: By spring 2023, high vaccination coverage and infection rate have resulted in a robust, mostly hybrid, humoral and cellular immune response in most LTR and LCP. However, booster vaccinations with vaccines covering new variants seem advisable, especially in patients with low immune responses and risk factors for severe disease.

[The clinical importance of the critical view of safety in laparoscopic cholecystectomy]. / Die klinische Bedeutung des "critical view of safety" in der laparoskopischen Gallenblasenchirurgie.

BACKGROUND: Injury of the bile duct during cholecystectomy (CHE) is a severe complication. The critical view of safety (CVS) can help to reduce the frequency of this complication during laparoscopic CHE. So far, no scoring of CVS images with a grading system is available. METHOD: The CVS images of 534 patients with laparoscopic CHE could be structurally analyzed and assessed with marks from 1 (very good) to 5 (insufficient). The CVS mark was correlated with the perioperative course. Additionally, the perioperative course of patients after laparoscopic CHE with and without a CVS image was investigated. RESULTS: In 534 patients 1 or more CVS images could be analyzed. The average CVS mark was 1.9, whereby 280 patients (52.4%) had a 1, 126 patients (23.6%) a 2, 114 (21.3%) a 3 and 14 patients (2.6%) a 4 or 5. Younger patients with elective laparoscopic CHE had CVS images significantly more frequently (p ≤ 0.04). The statistical examination with Pearson's χ2-test and the F­test (ANOVA) showed a significant correlation between improving CVS marks and reduction of surgery time (p < 0.01) and the hospitalization time (p < 0.01). For senior physicians the quota of CVS images ranged from 71% to 92% and the average marks from 1.5 to 2.2. The marks for the CVS images were significantly better for female than male patients (1.8 vs. 2.1, p < 0.01). DISCUSSION: There was a relatively broad distribution of marks for CVS images. Injuries of the bile duct can be avoided with a high degree of certainty with marks 1­2 for the CVS image. The CVS is not always adequately visualized in laparoscopic CHE.

[The COVID-19 pandemic had significant impact on duration of surgery and hospitalization time for patients after cholecystectomy]. / Die Auswirkungen der COVID-19 Pandemie führten zu signifikanten Veränderungen der Operations- und Liegezeiten bei Patienten nach Cholezystektomie.

BACKGROUND: The COVID-19 pandemic made substantial changes in medical care necessary. The aims of this study were to find out what influence the pandemic had on the perioperative course in patients with cholecystectomy (CHE) and to highlight possible residual consequences. METHOD: From 1 July 2018 to 31 December 2021 a total of 735 patients with CHE were analyzed. Up to 21 March 2020 patients were assigned to the regular patient group (Reg, n = 430), patients after this date (first lockdown 22 March 2020) to the Cov19 patient group (Cov19, n = 305) and the 2 groups were compared. RESULTS: The average age of all patients was 59 years and 63% were women. The average length of hospitalization (KrVD, time period between surgery and discharge) was 4.4 days. The patient groups Reg and Cov19 did not differ with respect to age, gender or KrVD. The total number of CHEs carried out was reduced by 21.4% in the Cov19 group. This affected elective and emergency CHE to the same extent. The length of surgery significantly increased in the Cov19 group from 64 min (SD 34 min) to 71 min (SD 38 min). The number of short and long hospital stays (KrVD 2 or >4 days) significantly increased in the Cov19 group from 4 % to 20 % (short stay, p < 0.01) and from 23 % to 27 % (long stay, p < 0.01). This was particularly observed for patients >70 years old with an increase in long stays from 43 % to 56 % in the Cov19 group. CONCLUSION: The COVID-19 pandemic led to a clear reduction in CHE both for elective and emergency interventions. Furthermore, a significant lengthening of the surgery and hospitalization times could be observed for older patients. The residual consequences of the pandemic could be shortened hospitalization times after uncomplicated CHE and more interventional treatment procedures in complex cases.

[After inconspicuous elective laparoscopic cholecystectomy patients can be discharged without control of laboratory parameters]. / Patienten* nach unauffälliger elektiver laparoskopischer Cholezystektomie können ohne Laborwertkontrollen entlassen werden ­ Ergebnisse einer prospektiven Studie.

BACKGROUND: The importance of postoperative control of laboratory parameters after elective laparoscopic cholecystectomy (lap-CHE) is controversial. The aim of this prospective study was to find out whether patients can be safely discharged following an inconspicuous perioperative course after lap-CHE without control of the laboratory parameters. METHOD: All patients with a lap-CHE from September 2020 to March 2022 were screened and included in the study after providing informed consent. The course was followed in a structured way with a scoring system (value 3-15 points) and questionnaire. A score of ≤ 9 reflected an inconspicuous perioperative course. Approval was obtained from the ethics committee of Heidelberg University (S-026/2020). RESULTS: A total of 275 patients who underwent gall bladder surgery were documented of which 220 (80%) patients underwent an elective lap-CHE and 56 (25%) of the patients were included in the study. Of the patients 51 with a score of ≤ 9 were discharged without providing a blood sample. The average age of the patients was 50.8 years, the average duration of hospital stay was 2.6 days and 40 out of 51 (78.4%) patients could be postoperatively questioned. None of the patients suffered from relevant complications after being discharged. Out of 40 patients 27 (67.5) visited a general practitioner again postoperatively and 4 were readmitted as inpatients due to other operations and an endoscopic intervention. All patients were satisfied with the course of surgery. CONCLUSION: Patients with an inconspicuous course after elective lap-CHE (score ≤ 9 points) can be discharged without a postoperative control of laboratory parameters.

Nasal polyp load determines the recovery of olfaction after surgery for chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is typically accompanied by impairment of olfaction. Despite of this, until today the efficacy of endonasal sinus surgery (ESS) in terms of olfactory function is still unclear. So far it is known that patients with nasal polyps are most likely to experience post-operative recovery. Within the present study we investigated the sense of smell and other parameters of impairment in CRS before and after ESS in relation to the degree of nasal polyposis, determined with the nasal endoscopic Lildholdt-score. METHODS: Patients with different degrees of severity of nasal polyposis were included. Olfactory function was assessed for odor thresholds [T], odor discrimination [D] and odor identification [I] and the changes of these parameters were investigated postoperatively. RESULTS: For 72 patients baseline measures were available and in 47 patients, postoperative changes were described. There was a correlation between olfactory scores and nasal anatomy/polyposis scores (Lildholdt scores, Lund-Mackay CT score), rated nasal health, and nasal quality of life (sinonasal outcome test). Three months after surgery the average TDI-Score improved by 3.1 points with 30% of patients showing significant clinical improvement. Patients with severe polyposis (Lildholdt score of 5 or 6) benefited most in terms of olfaction. Other significant prognostic indicators of a postoperative increase of olfactory scores included younger age, low pre-operative TDI-scores and high CT-scores. CONCLUSIONS: This study shows that not only the presence of polyps in CRS, but also the degree of nasal polyposis - measured by a grading system - predicts the results in olfactory test results. Additionally, the degree of recovery of olfaction after ESS seems to be most relevant in patients with high polyp scores.

Randomized controlled trial of robotic-assisted versus conventional laparoscopic fundoplication: 12 years follow-up.

AIMS: Numerous reports have addressed the feasibility and safety of robotic-assisted (RALF) and conventional laparoscopic fundoplication (CLF). Long-term follow-up after direct comparison of these two minimally invasive approaches is scarce. The aim of the present study was to assess long-term disease-specific symptoms and quality of life (QOL) in patients with gastroesophageal reflux disease (GERD) treated with RALF or CLF after 12 years in the randomized ROLAF trial. METHODS: In the ROLAF trial 40 patients with GERD were randomized to RALF (n = 20) or CLF (n = 20) between August 2004 and December 2005. At 12 years after surgery, all patients were invited to complete the standardized Gastrointestinal Symptom Rating Scale (GSRS) and the Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD). Failure of treatment was assessed according to Lundell score. RESULTS: The GSRS score was similar for RALF (n = 15) and CLF (n = 15) at 12 years´ follow-up (2.1 ± 0.7 vs. 2.2 ± 1.3, p = 0.740). There was no difference in QOLRAD score (RALF 6.4 ± 1.2; CLF 6.4 ± 1.5, p = 0.656) and the QOLRAD score sub items. Long-term failure of treatment according to the definition by Lundell was not different between RALF and CLF [46% (6/13) vs. 33% (4/12), p = 0.806]. CONCLUSION: In accordance with previous short-term outcome studies, the long-term results 12 years after surgery showed no difference between RALF and CLF regarding postoperative symptoms, QOL and failure of treatment. Relief of symptoms and patient satisfaction were high after both procedures on the long-term. REGISTRATION NUMBER: DRKS00014690 ( https://www.drks.de ).

Whole-body [18F]-FDG-PET/MRI for staging of pediatric non-Hodgkin lymphoma: first results from a single-center evaluation.

AIM: In 2015, the revised International Pediatric Non-Hodgkin Lymphoma Staging System was published. It mentions [18F]-FDG-PET/MRI as the latest method to perform whole-body imaging. However, supporting data are pending. Our aim was to investigate the performance of whole-body [18F]-FDG-PET/MRI in pediatric non-Hodgkin lymphoma patients by using a limited number of MRI sequences. MATERIALS AND METHODS: Ten pediatric patients with histologically proven non-Hodgkin lymphoma underwent whole-body [18F]-FDG-PET/MRI at staging. The retrospective analysis included three steps: First, [18F]-FDG-PET and MR scans were evaluated separately by a nuclear medicine physician and a pediatric radiologist. Nineteen nodal and two extranodal regions as well as six organs were checked for involvement. Second, discrepant findings were reviewed together in order to reach consensus. Third, [18F]-FDG-PET/MRI findings were correlated with the results of other clinical investigations. RESULTS: Of the 190 lymph node regions evaluated, four were rated controversial. Consensus was reached by considering metabolic, functional and morphologic information combined. Concordantly, [18F]-FDG-PET and MRI detected Waldeyer's ring involvement in two patients whose Waldeyer's ring was negative on clinical assessment. In four patients MRI showed pleural effusion. However, in only two of them an increased glucose metabolism as a reliable sign of pleural involvement was detectable. In six patients [18F]-FDG-PET and MRI detected skeletal lesions although bone marrow biopsy was positive in only one of them. CONCLUSION: Despite the small number of cases evaluated, whole-body [18F]-FDG-PET turned out to be a valuable tool for staging of pediatric non-Hodgkin lymphoma.

[Which patient needs controls of laboratory values after elective laparoscopic cholecystectomy?-Can a score help?] / Welcher Patient benötigt Laborwertkontrollen nach elektiver laparoskopischer Cholezystektomie? ­ Kann ein Score helfen?

BACKGROUND: Laparoscopic cholecystectomy is nearly exclusively carried out as an inpatient operation in Germany. The aim of the study was to evaluate for which patients postoperative laboratory control values are necessary. METHODS: This retrospective analysis included 100 patients who underwent elective laparoscopic cholecystectomy. A scoring and data collection sheet was developed, which enables a risk stratification. Using the scoring system patients can achieve between 3 and 15 points. RESULTS: In total 100 patients were included in the study. Of the patients 64 (group 1) had between 3 and 8 points, 29 patients (group 2) between 9 and 11 points and 7 patients (group 3) between 12 and 15 points. In comparison to group 1 the C­reactive protein values as well as the duration of hospital stay were significantly increased in group 2 and group 3 (p > 0.05). In group1 a total of 60 patients (93.7%) were discharged regularly on postoperative days 1-3. In group 2 there were 17 patients (58.6%) who could be discharged with unremarkable blood values and in group 3 there were 3 patients (42.8%). In the total collective hospital discharge without a laboratory control of blood values would have been justified in 80% of the patients. CONCLUSION: A postoperative control of laboratory blood values is not routinely necessary for patients after elective laparoscopic cholecystectomy with a score <9 points.

Hiperpigmentación cutánea y melanoniquia provocada por hidroxicloroquina: primer caso reportado en Chile / The First Case of Skin Hyperpigmentation and Melanonychia Due to Hydroxychloroquine in Chile

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Development of a cost-effective automated platform to produce human liver spheroids for basic and applied research.

Liver disease represents an increasing cause of global morbidity and mortality. Currently, liver transplant is the only treatment curative for end-stage liver disease. Donor organs cannot meet the demand and therefore scalable treatments and new disease models are required to improve clinical intervention. Pluripotent stem cells represent a renewable source of human tissue. Recent advances in three-dimensional cell culture have provided the field with more complex systems that better mimic liver physiology and function. Despite these improvements, current cell-based models are variable in performance and expensive to manufacture at scale. This is due, in part, to the use of poorly defined or cross-species materials within the process, severely affecting technology translation. To address this issue, we have developed an automated and economical platform to produce liver tissue at scale for modelling disease and small molecule screening. Stem cell derived liver spheres were formed by combining hepatic progenitors with endothelial cells and stellate cells, in the ratios found within the liver. The resulting tissue permitted the study of human liver biology 'in the dish' and could be scaled for screening. In summary, we have developed an automated differentiation system that permits reliable self-assembly of human liver tissue for biomedical application. Going forward we believe that this technology will not only serve as anin vitroresource, and may have an important role to play in supporting failing liver function in humans.

Size-dependent influence of NOx on the growth rates of organic aerosol particles.

Atmospheric new-particle formation (NPF) affects climate by contributing to a large fraction of the cloud condensation nuclei (CCN). Highly oxygenated organic molecules (HOMs) drive the early particle growth and therefore substantially influence the survival of newly formed particles to CCN. Nitrogen oxide (NOx) is known to suppress the NPF driven by HOMs, but the underlying mechanism remains largely unclear. Here, we examine the response of particle growth to the changes of HOM formation caused by NOx. We show that NOx suppresses particle growth in general, but the suppression is rather nonuniform and size dependent, which can be quantitatively explained by the shifted HOM volatility after adding NOx. By illustrating how NOx affects the early growth of new particles, a critical step of CCN formation, our results help provide a refined assessment of the potential climatic effects caused by the diverse changes of NOx level in forest regions around the globe.

Health status of free-ranging ring-necked pheasant chicks (Phasianus colchicus) in North-Western Germany.

Being a typical ground-breeding bird of the agricultural landscape in Germany, the pheasant has experienced a strong and persistent population decline with a hitherto unexplained cause. Contributing factors to the ongoing negative trend, such as the effects of pesticides, diseases, predation, increase in traffic and reduced fallow periods, are currently being controversially discussed. In the present study, 62 free-ranging pheasant chicks were caught within a two-year period in three federal states of Germany; Lower Saxony, North Rhine-Westphalia and Schleswig-Holstein. The pheasant chicks were divided into three age groups to detect differences in their development and physical constitution. In addition, pathomorphological, parasitological, virological, bacteriological and toxicological investigations were performed. The younger chicks were emaciated, while the older chicks were of moderate to good nutritional status. However, the latter age group was limited to a maximum of three chicks per hen, while the youngest age class comprised up to ten chicks. The majority of chicks suffered from dermatitis of the periocular and caudal region of the head (57-94%) of unknown origin. In addition, intestinal enteritis (100%), pneumonia (26%), hepatitis (24%), perineuritis (6%), tracheitis (24%), muscle degeneration (1%) and myositis (1%) were found. In 78% of the cases, various Mycoplasma spp. were isolated. Mycoplasma gallisepticum (MG) was not detected using an MG-specific PCR. Parasitic infections included Philopteridae (55%), Coccidia (48%), Heterakis/Ascaridia spp. (8%) and Syngamus trachea (13%). A total of 8% of the chicks were Avian metapneumovirus (AMPV) positive using RT-PCR, 16% positive for infectious bronchitis virus (IBV) using RT-PCR, and 2% positive for haemorrhagic enteritis virus (HEV) using PCR. All samples tested for avian encephalomyelitis virus (AEV), infectious bursal disease virus (IBDV) or infectious laryngotracheitis virus (ILTV) were negative. The pool samples of the ten chicks were negative for all acid, alkaline-free and derivative substances, while two out of three samples tested were positive for the herbicide glyphosate. Pheasant chick deaths may often have been triggered by poor nutritional status, probably in association with inflammatory changes in various tissues and organs as well as bacterial and parasitic pathogens. Theses impacts may have played a major role in the decline in pheasant populations.

Consensus on definition and severity grading of lymphatic complications after kidney transplantation.

BACKGROUND: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy. METHODS: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres. RESULTS: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention. CONCLUSION: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.

ANTECEDENTES: La incidencia de complicaciones linfáticas tras el trasplante renal (post-kidney-transplantation lymphatic, PKTL) varía considerablemente en la literatura. Esto se debe en parte a que no se ha establecido una definición universalmente aceptada. Este estudio tuvo como objetivo proponer una definición aceptable para las complicaciones PKTL y un sistema de clasificación de la gravedad basado en la estrategia de tratamiento. MÉTODOS: Se realizó una búsqueda sistemática de la literatura relevante en MEDLINE y Web of Science. Se logró un consenso para la definición y la clasificación de gravedad de las PKTL entre veinte centros de trasplante de alto volumen. RESULTADOS: En 32 de los 87 estudios incluidos se definía la linforrea/linfocele. Sesenta y tres artículos describían como se trataban las PKTL, pero ninguno calificó la gravedad de las mismas. La definición propuesta para la linforrea fue la de un débito diario superior a 50 ml de líquido (no orina, sangre o pus) a través del drenaje o del orificio cutáneo tras su retirada, más allá del 7º día postoperatorio del trasplante renal. La definición propuesta para linfocele fue la de una colección de líquido de tamaño variable adyacente al riñón trasplantado, tras haber descartado un urinoma, hematoma o absceso. Las PKTL de grado A fueron aquellas con escaso impacto o que no requirieron tratamiento invasivo; las PKTL de grado B fueron aquellas que precisaron intervención no quirúrgica y las PKTL de grado C aquellas en que fue necesaria la reintervención quirúrgica. CONCLUSIÓN: Se propone una definición clara y una clasificación de gravedad basada en la estrategia de tratamiento de las PKTLs. La definición propuesta y el sistema de calificación en 3 grados son razonables, sencillos y fáciles de comprender, y servirán para estandarizar los resultados de las PKTL y facilitar las comparaciones entre los diferentes estudios.

[Patient blood management : Medical concept for increasing patient safety]. / Patient Blood Management : Medizinisches Konzept zur Steigerung der Patientensicherheit.

Patient blood management (PBM) is a multidisciplinary evidence-based treatment model. Aims are to provide treatment of pre-existing or recently occureed deficits in blood volume and of substances that are important for erythropoiesis in patients, as well as the targeted administration of cellular and non-cellular blood products within reasonable and scientifically proven limits. The overall goal is therefore a safe therapy and complication-free course of the disease. PBM follows a strategy based on three pillars, which encompasses the aspects of optimization of anemia and hemoglobin, the handling of bleeding and the use of patient-related resources.

Learning Curves of Laparoscopic Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in Bariatric Surgery: a Systematic Review and Introduction of a Standardization.

BACKGROUND: The most commonly performed bariatric procedures are laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (LSG). Impact of learning curves on operative outcome has been well shown, but the necessary learning curves have not been clearly defined. This study provides a systematic review of the literature and proposes a standardization of phases of learning curves for RYGB and LSG. METHODS: A systematic literature search was performed using PubMed, Web of Science, and CENTRAL databases. All studies specifying a number or range of approaches to characterize the learning curve for RYGB and LSG were selected. RESULTS: A total of 28 publications related to learning curves for 27,770 performed bariatric surgeries were included. Parameters used to determine the learning curve were operative time, complications, conversions, length of stay, and blood loss. Learning curve range was 30-500 (RYGB) and 30-200 operations (LSG) according to different definitions and respective phases of learning curves. Learning phases described the number of procedures necessary to achieve predefined skill levels, such as competency, proficiency, and mastery. CONCLUSIONS: Definitions of learning curves for bariatric surgery are heterogeneous. Introduction of the three skill phases competency, proficiency, and mastery is proposed to provide a standardized definition using multiple outcome variables to enable better comparison in the future. These levels are reached after 30-70, 70-150, and up to 500 RYGB, and after 30-50, 60-100, and 100-200 LSG. Training curricula, previous laparoscopic experience, and high procedure volume are hallmarks for successful outcomes during the learning curve.