Gas Chromatography-Mass Spectrometry Detection of Thymoquinone in Oil and Serum for Clinical Pharmacokinetic Studies.

Thymoquinone (TQ) is the primary component of Nigella sativa L. (NS) oil, which is renowned for its potent hepatoprotective effects attributed to its antioxidant, anti-fibrotic, anti-inflammatory, anti-carcinogenic, and both anti- and pro-apoptotic properties. The aim of this work was to establish a method of measuring TQ in serum in order to investigate the pharmacokinetics of TQ prior to a targeted therapeutic application. In the first step, a gas chromatography-mass spectrometry method for the detection and quantification of TQ in an oily matrix was established and validated according to European Medicines Agency (EMA) criteria. For the assessment of the clinical application, TQ concentrations in 19 oil preparations were determined. Second, two serum samples were spiked with TQ to determine the TQ concentration after deproteinization using toluene. Third, one healthy volunteer ingested 1 g and another one 3 g of a highly concentrated NS oil 30 and 60 min prior to blood sampling for the determination of serum TQ level. After the successful establishment and validation of the measurement method, the highest concentration of TQ (36.56 g/L) was found for a bottled NS oil product (No. 1). Since a capsule is more suitable for oral administration, the product with the third highest TQ concentration (No. 3: 24.39 g/L) was used for all further tests. In the serum samples spiked with TQ, the TQ concentration was reliably detectable in a range between 5 and 10 µg/mL. After oral intake of NS oil (No. 3), however, TQ and/or its derivatives were not detectable in human serum. This discrepancy in detecting TQ after spiking serum or following oral ingestion may be attributed to the instability of TQ in biomatrices as well as its strong protein binding properties. A pharmacokinetics study was therefore not viable. Studies on isotopically labeled TQ in an animal model are necessary to study the pharmacokinetics of TQ using alternative modalities.

Solitary colorectal liver metastasis: overview of treatment strategies and role of prognostic factors.

The following is an overview of the treatment strategies and the prognostic factors to consider in the therapeutic choice of patients characterized by solitary colorectal liver metastasis. Liver resection is the only potential curative option; nevertheless, only 25% of the patients are considered to be eligible for surgery. To expand the potentially resectable pool of patients, surgeons developed multidisciplinary techniques like portal vein embolization, two-stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy. Moreover, mini-invasive surgery is gaining support, since it offers lower post-operative complication rates and shorter hospital stay with no differences in long-term outcomes. In case of unresectable disease, various techniques of local ablation have been developed. Radiofrequency ablation is the most commonly used form of thermal ablation: it is widely used for unresectable patients and is trying to find its role in patients with small resectable metastasis. The identification of prognostic factors is crucial in the choice of the treatment strategy. Previous works that focused on patients with solitary colorectal liver metastasis obtained trustable negative predictive factors such as presence of lymph-node metastasis in the primary tumour, synchronous metastasis, R status, right-sided primary colon tumor, and additional presence of extrahepatic tumour lesion. Even the time factor could turn into a predictor of tumour biology as well as further clinical course, and could be helpful to discern patients with worse prognosis.

Ligation of the middle hepatic vein to increase hypertrophy induction during the ALPPS procedure.

PURPOSE: Here, we analyse the technical modification of the ALPPS procedure, ligating the middle hepatic vein during the first step of the operation to enhance remnant liver hypertrophy. METHODS: In 20 of 37 ALPPS procedures, the middle hepatic vein was ligated during the first step. Hypertrophy of the functional remnant liver volume was assessed in addition to postoperative courses. RESULTS: Volumetric analysis showed a significant volume increase, especially for patients with colorectal metastases. Pre-existing liver parenchyma damage (odds ratio = 0.717, p = 0.017) and preoperative chemotherapy were found to be significant predictors (odds ratio = 0.803, p = 0.045) of higher morbidity and mortality. In addition, a survival benefit for maintenance of middle hepatic vein was shown. CONCLUSION: This technical modification of the ALPPS procedure can accentuate future liver remnant volume hypertrophy. The higher morbidity and mortality observed are most likely associated with pre-existing parenchymal damage within this group.

[A glimpse into the future: smart technologies and enhanced recovery after surgery (ERAS)]. / Blick in die Zukunft: smarte Technologien und ERAS ("enhanced recovery after surgery").

Smart technologies facilitate our daily life in many respects, e.g. by rendering travel safer. In medicine, however, they have so far hardly been used, even though the demographic changes with an aging population in small or single households warrant an urgent change of our traditional care structures. Furthermore, patients are more demanding and better informed than they were a few decades ago. Enhanced recovery after surgery (ERAS) focusses on good prehabilitation as well as fast rehabilitation and therefore represents, even almost 20 years after the first publication, a modern and evidence-based treatment concept. Nevertheless, it is still not comprehensively implemented nationwide. The reasons for this may be concerns regarding an early discharge. In addition, there is often a gap in care care between discharge from hospital and start of the follow-up rehabilitation. In order to improve acceptance of the ERAS concept, to fulfil the patients' needs for better information while decreasing the workload of the medical staff and to close the gap in care after discharge from hospital, integrating ERAS into the concept of a smart hospital with subsequent transition into a temporary smart home is an appealing idea. With the use of an individually configurated online learning platform, a large part of the information flow can be transferred from the outpatient clinic to the pre-outpatient area (i.e. the patient's home). Consequently, patients will be better prepared for their first contact with the hospital. After a short stay in hospital the patient is then discharged into the serviced apartments of the smart quarter, where a stress-free recovery in a home-like environment is possible. The further rehabilitation is undertaken there under virtual guidance, following individualized schedules on demand.

[Living related liver transplantation]. / Lebertransplantation durch Lebendspende.

Liver transplantation has become established as a standard procedure in the treatment of end-stage liver diseases. Despite intense efforts by all parties involved up to the amendment of the German Transplantation Act, the lack of suitable donor organs was still one of the limiting factors of this therapeutic procedure. One way out of this problem is to make so-called marginal organs usable, e.g. with the help of machine perfusion or by utilizing living liver donation, which are used in some countries for more than 90% of organ donations. In general, there is no difference in the indications for liver transplantation between a (partial) organ obtained by post-mortem or living donation. Before any living donation, a thorough evaluation of the donor is carried out in order to minimize postoperative morbidity as far as possible. Technically the partial liver donation is based on the oncological liver resection, while the partial liver transplantation is a further development of split liver transplantation after post-mortem liver donation. In specialized centers comparable or even better results can nowadays be achieved using living liver donation instead of post-mortem donation.

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.

[Intraoperative completion diagnostics in open vascular surgery]. / Intraoperative Diagnostik in der offenen Gefäßchirurgie.

Intraoperative imaging diagnostics during open vascular surgical procedures aim to enhance diagnostic certainty during the operation, ensure quality control documentation and reduce avoidable complications; however, the evidence for the various diagnostic imaging procedures with respect to improvement of perioperative outcome is not confirmed for carotid endarterectomy or for infrainguinal bypass surgery. Nevertheless, an intraoperative diagnostic control is principally recommended. The advantage of intraoperative imaging is confirmed and essential for the surgical reconstruction of bypass occlusions and acute thromboembolic occlusions.

[Benign liver tumors : Diagnostics and treatment]. / Benigne Lebertumoren : Diagnostik und Behandlung.

Benign liver tumors are often detected during routine ultrasound examinations or as an incidental finding in radiological imaging. Only very few benign liver tumors are at risk of becoming malignant. In the majority of cases the differentiation from malignant tumors is currently carried out using imaging procedures. In a few cases of diagnostic uncertainty, a transcutaneous liver biopsy can lead to clarification. If the suspicion of malignancy is substantiated or this cannot be excluded with absolute certainty, the tumor should be removed by partial liver resection.

[Prerehabilitation in frail patients : Frailty as a risk factor]. / Prärehabilitation gebrechlicher Patienten : "Frailty" als Risikofaktor.

The German population is aging in accordance with the worldwide trend; however, in comparison to most other industrial countries the number of disease-free years of life gained by patients is significantly lower in Germany. Subsequently, the number of hospitalizations and necessary surgical treatment for older and especially frail patients is significantly increasing. Several frailty scoring systems have been published with the aim of improving the assessment of the perioperative risk for these patients; however, these systems for risk assessment have not yet become clinical routine in surgery and therefore this group of frail patients remains underdiagnosed in the field of surgery. Frail patients in particular often need individualized treatment or the adaptation of standard of perioperative care. It has already been clearly shown that frail patients have a markedly higher incidence for certain risk factors (e.g. postoperative delirium, hypovolemia, pharmacological side effects and drug interactions). Additionally, malnutrition is common at the time of hospital admission in up to 70% of this patient group. If not recognized and treated accordingly all these risk factors lead to a compromised rehabilitation, higher complication rates, a prolonged length of hospital stay and a higher mortality. Special preoperative risk assessment scores, which highlight physical, psychological and social evaluation should be widely implemented in surgical departments. A standardized risk assessment embedded in evidence-based prerehabilitation programs and implemented in geriatric surgery centers can help to improve the outcome in this group of fragile patients.