Indication of Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer (Gastripec, Gastrichip)

Background: Gastric cancer (GC) is associated with a poor prognosis mostly due to peritoneal metastasis, which will develop in time during the patient's disease history. To prevent and treat peritoneal metastasis, different kinds of treatment regimens have been described. Summary: In this review, we addressed two main topics - prophylaxis and treatment of peritoneal metastasis in GC. Prevention should be directed towards diminishing cancer cell spillage and reducing adherence of cancer cells to the abdominal cavity. Postoperative washing of the abdomen with or without chemotherapy and additional heat are herein discussed. Key Messages: Treatment of existing peritoneal metastasis is effective in patients with limited disease and tumour spread. Cytoreductive surgery including resection of peritoneal metastasis followed directly with hyperthermic intraperitoneal chemotherapy can increase overall survival and progression-free survival in selected patients. Drugs, duration and time schedules of intraperitoneal chemotherapy are reviewed and presented. Intraperitoneal chemotherapy seems to improve the prognosis of patients with GC and peritoneal metastasis after complete resection of both primary and metastatic tumours

Sodium Thiosulfate Reduces Acute Kidney Injury in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy with Cisplatin: A Single-Center Observational Study

Background: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) represents a multimodal treatment concept for patients with peritoneal surface malignancies. The use of intraperitoneal cisplatin (CDDP) is associated with a risk of acute kidney injury (AKI). The aim of this study is to evaluate the protective effect of perioperative sodium thiosulfate (STS) administration on kidney function in patients undergoing CRS and CDDP-based HIPEC. Patients and Methods: We retrospectively analyzed clinical data of all patients who underwent CRS and CDDP-based HIPEC at our hospital between March 2017 and August 2020. Patients were stratified according to the use of sodium thiosulfate (STS vs. no STS). We compared kidney function and clinical outcome parameters between both groups and determined risk factors for postoperative AKI on univariate and multivariate analysis. AKI was classified according to acute kidney injury network (AKIN) criteria. Results: Of 238 patients who underwent CRS and CDDP-based HIPEC, 46 patients received STS and 192 patients did not. There were no significant differences in baseline characteristics. In patients who received STS, a lower incidence (6.5% vs. 30.7%; p = 0.001) and severity of AKI (p = 0.009) were observed. On multivariate analysis, the use of STS (OR 0.089, p = 0.001) remained an independent kidney-protective factor, while arterial hypertension (OR 5.283, p < 0.001) and elevated preoperative urea serum level (OR 5.278, p = 0.032) were predictors for postoperative AKI. Conclusions: The present data suggest that STS protects patients from AKI caused by CRS and CDDP-based HIPEC. Further prospective studies are needed to validate the benefit of STS among kidney-protective strategies

Molekulare Mechanismen des kolorektales Karzinom: MACC1 und das neuartige IER2-Gene

Background Colorectal cancer (CRC) remains a clinical challenge as the third most common cause of cancer-related morbidity worldwide. The gene Metastasis-associated in colon cancer 1 (MACC1) is a key mediator of tumor progression and metastasis formation as well as a prognostic biomarker for CRC and more than 20 other solid cancer types. Higher MACC1 expression is associated with metachronous metastasis. Immediate Early Response 2 (IER2) is a novel player in the biology of metastasis. Previous studies have linked IER2 expression with enhanced metastatic capabilities, contributing to worse overall survival in different cancer entities. Concomitant upregulated mRNA expression of MACC1 and IER2 has been associated with worse overall survival in metastatic CRC patients, possibly identifying a population at high risk for metachronous metastatic disease. This dissertation addresses the question of a possible MACC1-driven IER2 regulation and the consequent metastasis formation. Methods We analyzed in silico mRNA expression profiles and predictive binding motifs for MACC1 and IER2. We made use of RT-qPCR, Western blot, co-Immunoprecipitation, clonogenic and proliferation assays to further understand the mechanisms behind a possible synergy among both genes. Furthermore, we used the CRISPR-Cas9 system for the creation of an IER2 knockout cell line. Results Cumulative survival for patients with a higher expression of IER2 and MACC1 genes was significantly worse. In silico, both a positive correlation between MACC1 and IER2 mRNA expression and a predicted SH3-mediated protein-protein interaction were found. Furthermore, overexpression of IER2 enhances colony formation in vitro, and silencing IER2 significantly hinders cellular proliferation. 13 Conclusion MACC1, an established marker for metastatic disease, and IER2, a novel biomarker, may play an important synergetic role to confer enhanced proliferative and clone formation capabilities to cancer cells. From a clinical standpoint, the synergism between them undeniably translates into worst patient survival outcomes.Einleitung Das kolorektales Karzinom bleibt eine klinische Herausforderung, da es weltweit die dritthäufigste Ursache für krebsbedingte Morbidität ist. Das Gen Metastasis-associated in colon cancer 1 (MACC1) ist ein wichtiger Vermittler der Tumorprogression und Metastasenbildung und ein prognostischer Biomarker für Darmkrebs und mehr als 20 andere solide Krebsarten. Eine höhere MACC1-Expression wird mit metachroner Metastasierung in Verbindung gebracht. Immediate Early Response 2 (IER2) ist ein neuer Akteur in der Biologie der Metastasierung. Frühere Studien haben die IER2- Expression mit einer erhöhten Metastasierungsfähigkeit in Verbindung gebracht, die bei verschiedenen Krebsarten zu einem schlechteren Gesamtüberleben beiträgt. Die gleichzeitige hochregulierte mRNA-Expression von MACC1 und IER2 wurde mit einer schlechteren Gesamtüberlebenszeit bei metastasierenden Darmkrebspatienten in Verbindung gebracht, was auf eine Risikopopulation für metachrone metastatische Erkrankungen hindeuten könnte. In dieser Dissertation soll die Frage nach einer möglichen MACC1-gesteuerten IER2-Regulierung und der daraus folgenden Metastasenbildung untersucht werden. Methoden Wir analysierten in silico mRNA-Expressionsprofile und prädiktive Bindungsmotive für MACC1 und IER2. Wir nutzten RT-qPCR, Western Blot, Co-Immunopräzipitation, klonogene- und Proliferationsassays, um die Mechanismen hinter einer möglichen Synergie zwischen beiden Genen besser zu verstehen. Außerdem verwendeten wir das CRISPR-Cas9-System zur Herstellung einer IER2-Knockout-Zelllinie. Ergebnisse Das kumulative Überleben von Patienten mit einer höheren Expression der Gene IER2 und MACC1 war signifikant schlechter. In silico wurde sowohl eine positive Korrelation zwischen der mRNA-Expression von MACC1 und IER2 als auch eine vorhergesagte SH3-vermittelte Protein-Protein-Interaktion gefunden. Darüber hinaus gewährleistet die 15 Überexpression von IER2 eine höhere in vitro Koloniebildungsfähigkeit, und das Silencing von IER2 hemmt die zelluläre Proliferation erheblich. Fazit MACC1, ein etablierter Marker für metastatische Erkrankungen, und IER2, ein neuartiger Biomarker, spielen möglicherweise eine wichtige synergetische Rolle, indem sie den Krebszellen eine erhöhte Fähigkeit zur Proliferation und Klonbildung verleihen. Aus klinischer Sicht führt die Synergie zwischen beiden zweifellos zu schlechteren Überlebensaussichten für die Patienten

Cause and Long-Term Outcome of Cardiac Tamponade

Cardiac tamponade is a life-threatening condition, whose current specific cause and outcome are unknown. Our purpose was to analyze it. We performed a retrospective observational study with prospective follow-up data including 136 consecutive patients admitted with diagnosis of cardiac tamponade, from 2003 to 2013. We thoroughly recorded variables as clinical features, drainage/pericardiocentesis, fluid characteristics, and long-term events (new cardiac tamponade ± death). The median age was 65 ± 17 years (55% men). In the baseline characteristics, 70% were no smokers, 12% were on anticoagulation, and 13 had suffered a previous myocardial infarction. In the preceding month, 15 patients had undergone a cardiac catheterization, 5 cardiac surgery, and 5 pacemaker insertion. Fever was observed in 16% of patients and 21% displayed other inflammatory symptoms. In 81% of patients, pericardiocentesis was needed. The fluid was hemorrhagic or a transudate in the majority, with positive cytology in 15% and bacteria in 3.7%. Main causes were malignancy (32%), infection (24%), idiopathic (16%), iatrogenic (15%), postmyocardial infarction (7%), uremic (4%), and other causes (2%). After a maximum follow-up of 10.4 years, cardiac tamponade recurred in 10% of the cases (62% in the neoplastic group) and the 48% of patients died (89% in the neoplastic cohort). In conclusion, most cardiac tamponades are due to malignancy, having this specific cause a poorer outcome, probably as a manifestation of an advanced disease. The rest of causes, after an aggressive intensive management, have a good prognosis, especially the iatrogenicEl taponamiento cardíaco es una afección potencialmente mortal, cuya causa específica y desenlace actuales se desconocen. Nuestro propósito fue analizarla. Se realizó un estudio retrospectivo con seguimiento prospectivo de 136 pacientes consecutivos ingresados con diagnóstico de taponamiento cardíaco entre 2003 y 2013. Se registraron exhaustivamente variables como características clínicas, pericardiocentesis, características del líquido y eventos a largo plazo (nuevo taponamiento cardiaco - muerte). La edad media fue de 65 años (55% hombres). En las características basales, el 70% no eran fumadores, el 12% estaban anticoagulados y 13 habían sufrido un infarto de miocardio previo. En el mes anterior, 15 pacientes habían sido sometidos a un cateterismo cardíaco, 5 a cirugía cardíaca y 5 a inserción de marcapasos. Se observó fiebre en el 16% de los pacientes y el 21% presentaba otros síntomas inflamatorios. En el 81% de los pacientes fue necesaria una pericardiocentesis. El líquido era hemorrágico o un trasudado en la mayoría, con citología positiva en el 15% y bacterias en el 3,7%. Las principales causas fueron malignidad (32%), infección (24%), idiopática (16%), iatrogénica (15%), postinfarto de miocardio (7%), urémica (4%) y otras causas (2%).Tras un seguimiento máximo de 10,4 años, el taponamiento cardiaco recidivó en el 10% de los casos (62% en el grupo neoplásico) y el 48% de los pacientes fallecieron (89% en la cohorte neoplásica). Conclusiones: nuestro estudio pone de manifiesto que la mayoría de los taponamientos cardiacos, al menos en nuestro entorno, se deben a neoplasia, teniendo esta causa específica un peor pronóstico, probablemente como manifestación de una enfermedad avanzada. El resto de causas, tras un manejo intensivo agresivo, mediante pericardiocentesis evacuadora, tienen un buen pronóstico, especialmente las iatrogénicas.Depto. de MedicinaFac. de MedicinaTRUEpu

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort

CatedresBackground: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women

COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization