Palliation with a multimodality treatment including hypoxic pelvic perfusion for unresectable recurrent rectal cancer: outcomes based on a retrospective study

Patients with unresectable recurrent rectal cancer that progresses after systemic chemotherapy and radiotherapy are candidates for palliation with hypoxic pelvic perfusion (HPP). The aim of this observational retrospective study was to evaluate if a multimodality treatment including HPP and targeted-therapy may be useful to prolong clinical responses and survival of these patients. From a cohort of 77 patients with unresectable recurrent rectal cancer in progression after standard treatments and submitted to HPP, 21 patients underwent repeat HPP using mitomycin C (MMC) at the dose of 25 mg/m2. After the last HPP, 7 patients received a targeted-therapy with cetuximab according to overexpression of epidermal growth factor receptor in recurrence cancer cells. The median overall survival of these 21 patients from the diagnosis of unresectable recurrent rectal cancer was 23 months (iqr 18-24). After the first HPP, the median survival of the 21 patients until death or end of follow-up was 10 months (iqr 9-13). The 1-year and 2-year survival rates were 71.4%, and 4.8%, respectively. From the first HPP, age\u2009>\u200960 years, a recurrence shrinkage of at least 30% (partial response), and the addition of a post-HPP targeted-therapy with cetuximab significantly affected survival (P\u2009<\u20090.04). In conclusion, repeated MMC-HPP followed by targeted-therapy seems to be an effective palliative treatment for patients with unresectable recurrent rectal cancer in progression after systemic chemotherapy and radiation but the results of this study have to be confirmed by a larger phase III trial

Short- and Long-Term, 11–22 Years, Results after Laparoscopic Nissen Fundoplication in Obese versus Nonobese Patients

Background. Some studies suggest that obesity is associated with a poor outcome after Laparoscopic Nissen Fundoplication (LNF), whereas others have not replicated these findings. The effect of body mass index (BMI) on the short- and long-term results of LNF is investigated. Methods. Inclusion criteria were only patients who undergone a LNF with at least 11-year follow-up data available, patients with preoperative weight and height data available for calculation of BMI (Kg/m2), and patients with a BMI up to a maximum of 34.9. Results. 201 patients met the inclusion criteria: 43 (21.4%) had a normal BMI, 89 (44.2%) were overweight, and 69 (34.4%) were obese. The operation was significantly longer in obese patients; the use of drains and graft was less in the normal BMI group (p<0.0001). The hospital stay, conversion (6,4%), and intraoperative and early postoperative complications were not influenced by BMI. Conclusions. BMI does not influence short-term outcomes following LNF, but long-term control of reflux in obese patients is worse than in normal weight subjects

A Prospective Study of Intraarterial Infusion Chemotherapy in Advanced WT BRAF Melanoma Patients.

ABSTRACT Background Treatment strategies for advanced cutaneous melanoma (CM) patients, resistant or not treatable with novel target and immunotherapeutic drugs, remain a significant challenge, particularly for patients with unresectable stage IIIC/D disease localized to inferior limbs and pelvis, for whom specific outcomes are rarely considered. Materials and methods This is a prospective study of multidisciplinary treatments, including locoregional melphalan chemotherapy, in 62 BRAF wild-type CM patients with locoregional metastases in the inferior limbs and pelvis, including inguinal regions. Patients were either in progression following or ineligible for, or not treatable with novel immunotherapy. For exclusively inferior limb-localised disease, patients received locoregional melphalan chemotherapy performed by hyperthermic isolated limb perfusion (n = 19) or isolated limb infusion (n = 19), and for synchronous lesions localised to inferior limbs and pelvis, received hypoxic pelvic and limb perfusion (n = 24). Additional multidisciplinary therapy included local, locoregional and systemic treatments and the primary endpoint was tumour response. Results The objective response rate following first cycle of locoregional chemotherapy was 37.1% at 3 mo and median progression-free survival was 4-mo, with 12.9% procedure-related complications, 30.6% low-grade haematological toxicity and 11.3% severe limb toxic tissue reactions. Multivariate logistic regression showed that the odds of response were significantly higher for patients ≤ 75 y of age and for patients with locoregional metastases exclusively located in the inferior limbs. Conclusion In this subgroup of CM patients with BRAF wild-type status, locoregional metastases localized to inferior limbs and pelvis, in progression following or ineligible for immunotherapy, melphalan locoregional chemotherapy demonstrated a safe and effective profile. Trial Registration ClinicalTrials.gov Identifier NCT01920516; date of trial registration: August 6, 2013

Blood Transfusions and Adverse Events after Colorectal Surgery: A Propensity-Score-Matched Analysis of a Hen-Egg Issue

Blood transfusions are considered a risk factor for adverse outcomes after colorectal surgery. However, it is still unclear if they are the cause (the hen) or the consequence (the egg) of adverse events. A prospective database of 4529 colorectal resections gathered over a 12-month period in 76 Italian surgical units (the iCral3 study), reporting patient-, disease-, and procedure-related variables, together with 60-day adverse events, was retrospectively analyzed identifying a subgroup of 304 cases (6.7%) that received intra- and/or postoperative blood transfusions (IPBTs). The endpoints considered were overall and major morbidity (OM and MM, respectively), anastomotic leakage (AL), and mortality (M) rates. After the exclusion of 336 patients who underwent neo-adjuvant treatments, 4193 (92.6%) cases were analyzed through a 1:1 propensity score matching model including 22 covariates. Two well-balanced groups of 275 patients each were obtained: group A, presence of IPBT, and group B, absence of IPBT. Group A vs. group B showed a significantly higher risk of overall morbidity (154 (56%) vs. 84 (31%) events; OR 3.07; 95%CI 2.13-4.43; p = 0.001), major morbidity (59 (21%) vs. 13 (4.7%) events; OR 6.06; 95%CI 3.17-11.6; p = 0.001), and anastomotic leakage (31 (11.3%) vs. 8 (2.9%) events; OR 4.72; 95%CI 2.09-10.66; p = 0.0002). No significant difference was recorded between the two groups concerning the risk of mortality. The original subpopulation of 304 patients that received IPBT was further analyzed considering three variables: appropriateness of BT according to liberal transfusion thresholds, BT following any hemorrhagic and/or major adverse event, and major adverse event following BT without any previous hemorrhagic adverse event. Inappropriate BT was administered in more than a quarter of cases, without any significant influence on any endpoint. The majority of BT was administered after a hemorrhagic or a major adverse event, with significantly higher rates of MM and AL. Finally, a major adverse event followed BT in a minority (4.3%) of cases, with significantly higher MM, AL, and M rates. In conclusion, although the majority of IPBT was administered with the consequence of hemorrhage and/or major adverse events (the egg), after adjustment accounting for 22 covariates, IPBT still resulted in a definite source of a higher risk of major morbidity and anastomotic leakage rates after colorectal surgery (the hen), calling urgent attention to the implementation of patient blood management programs

Plasma Cystatin C correlates with plasma NfL levels and predicts disease progression in Parkinson's disease

INTRODUCTION: Previous studies reported increased plasma levels of Cystatin C (Cys-C) in Parkinson's disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration and clinical progression in a longitudinal study. METHODS: Plasma Cys-C, high-sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6) and Neurofilament Light Chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration and peripheral inflammation. RESULTS: Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at two years of follow-up independently from the peripheral inflammatory profile. CONCLUSIONS: Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases

Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance

The growing global epidemic of obesity and type 2 diabetes mellitus has de-termined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the West-ern world and a leading cause of liver transplan-tation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close as-sociation between insulin resistance (IR), dys-biosis, and steatosis. However, all the mecha-nisms that lead to impaired permeability, inflam- mation, and fibrosis have not been fully clari- fied. Recently, new possible treatment modali- ties have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (poly -phenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NA-FLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the thera-peutic strategies currently in use

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Orientation de l'attention visuelle en volley-ball

L'étude des processus mentaux impliqués dans la prestation sportive représente un terrain de recherche de grande importance. En effet, à travers lui, est possible d'un coté, de déterminer les éléments "non explicites" du geste athlétique qui concourent à la réussite d'une épreuve de haut niveau, et de l'autre, à en évaluer les modalités d'utilisation de la part des athlètes. Ces connaissances peuvent ensuite être traduites dans le cadre de l'application en développant des méthodologies d'entraînement opportunes, consacrées à l'amélioration de la performance. Dans les disciplines sportives où la variabilité élevée des composantes ambiantes impose à l'athlète d'opérer des choix dans des limites de temps très réduites, comme dans le cas du volley-ball, la capacité d'utiliser au mieux ses propres ressources attentionnelles peut se révéler décisive. Dans la phase de prise d'informations du milieu environnant, l'athlète doit être en mesure d'optimiser l'opération d'orientation de l'attention visuelle sur des éléments réellement utiles à la performance. De cette façon, il sera capable de réduire les temps et les coûts mentaux nécessaires à la production d'une réponse motice efficace. Dans ce travail, après avoir affronté les problématiques relatives à l'attention, et analysé ensuite les principales études faites sur l'attention visuelle tant dans le cadre psychologique général que sportif, nous présentons certaines expérimentations effectuées sur des joueurs de volley-ball de différents niveaux de performances. Les principaux résultats indiquent que ces athlètes, indépendamment de leur niveau de performance, présentent des caractéristiques particulières qui les distinguent des sujets non sportifs ainsi que des athlètes qui pratiquent des disciplines comparables sur le plan de l'utilisation des ressources attentionnelles. Cela indique qu'il n'est pas toujours possible d'étendre à d'autres les résultats obtenus sur une population sportive particulière, mais que chaque discipline sportive doit être explorée en tenant compte des spécificités qui la caractérisent.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF