Infections

All Conditions

Symptoms and General Pathology

Wounds and Injuries

Communicable Diseases

Surgical Wound Infection

Surgical Wound

Wound Infection

Disease Attributes

Postoperative Complications

Anti-Infective Agents

All Drugs and Chemicals

Vancomycin

Anti-Bacterial Agents

Clindamycin

Clindamycin palmitate

Clindamycin phosphate

Cefuroxime

Cefuroxime axetil

Cephalosporins

Antibiotics, Antitubercular

Gentamicins

The standard prophylaxis consists of one to three intravenous doses of cefuroxime 1.5 g intravenously; or cefuroxim 3g if obesity \> 120 kg or a BMI \> 35 kg/m2; or vancomycin 1 g or clindamycin 600 mg in case of intolerance to cephalosporins

In patients alrady under current therapuetic antibiotic therapy, continuation of that therapuetic antibiotic regimen

Additional single-shot perioperative antibiotic prophylaxis with Broad-spectrum prophylaxis: vancomycin 1 g \& gentamicin 5 mg/kg.

One to three intravenous doses of cefuroxime 1.5 g intravenously; or 3g if obesity; or vancomycin 1 g or clindamycin 600 mg; if allergy. Continuation of eventual current therapeutic antibiotc regimens for any infection

Standard antibiotic prophylaxis

Ilker Uçkay, Professor

Mazda Farshad, Professor

The perioperative antibiotic prophylaxis is evidence-based in orthopedic surgery. While its duration ranges from a single dose to three doses throughout the world, the choice of the prophylactic agents is undisputed. Worldwide, the surgeons use 1st or 2nd-generation cephalosporins (or vancomycin in some cases).

However, there are particular clinical situation with a high risk of antibiotic-resistant surgical site infections (SSI); independently of the duration of adminis-tered prophylaxis. These resistant SSI's occur in contaminated wounds, or during surgery under current therapeutic antibiotics, and base on "selection" by antibiotics used for therapy or for prophylaxis.

The perioperative antibiotic prophylaxis is evidence-based for the majority of orthopedic surgeries. While the debate of its duration and timing (single-dose versus triple-dose; before or after the intraoperative microbiological sampling) may continue, no clinicians doubt on the efficiency of the recommended prophylactic agents; that are mostly 1st or 2nd-generation cephalosporins, co-amoxiclav or other exceptional agents in cases of (pseudo)-allergy. However. and traditionally, up to the half of all detected pathogens of orthopedic SSI's are not covered by the prior prophylactic regimens: e.g. SSIs due to methicillin-resistant cocci or non-fermenting Gram-negative rods in orthopedic surgery.

Additionally, orthopedic surgeons operating selected patient populations (neoplasms, open fractures, postoperative wound dehiscence9, diabetic foot infections or already infected body sites) experience a high risk of prophylactic-resistant pathogens, or pathogens resistant to current therapeutic antibiotics regimens. At least 10% of all new intraoperative tissue samples, during iterative surgical debridement, yield (new) pathogens unknown to the clinicians.

This is due to selection by prophylactic or therapeutic antibiotics, which only kill the previously detected pathogens, but left over newly introduced contaminants, remnant parts of partially-diagnosed polymicrobial infections; ultimately leading to a new SSIs occurring during therapy for the first infection at the orthopedic site. This selection is unpredictable involving both Gram-positive skin pathogens as well as (multi) resistant Gram-negative rods.From a microbiological point of view, only a maximal Gram-negative coverage, alongside with a large Gram-negative coverage, would cover these selections.

The literature is in-existing how to prevent these selections. Most clinicians just continue with the standard prophylactic recommendation, or the current thera-peutic antibiotic regimen. Theoretically, clinicians cannot exclude that these selected patient populations eventually might profit from a broad-spectrum prophylaxis.

The BAPTIST trials only concern the perioperative antibiotic prophylaxis in selected situations of orthopedic surgery: tumor surgery, debridement for postoperative dehiscent wounds, debridement under antibiotics, open fractures, skin colonization with multidrug-resistant bacteria, plus, as a control; spine surgery in selected multimorbid patients. The investigators alternately randomize the standard prophylaxis (or by continuing the current antibiotic treatment) to the additional broad-spectrum single-shot of vancomycin 1g IV \& single-shot of gentamicin 5 mg/kg intravenously; before an eventual intraoperative sampling. End-of-Treatment (EOT) and/or Test-of-Cure (TOC) occur latest at the 6-week's surgical control visit. The rest of the hospital stay, treatment, the use of negative-pressure vacuum therapy, other interventions, local antibiotic therapies; therapies or procedure are at the discretion of the treating clinicians.

The investogators will randomize surgical interventions defined by the inclusion criteria in a prospective-alternating scheme (1:1) according to the scheduled position in the operating theatres. The anesthetists (or the nurses at the hospitalization units) the will administer the standard prophylaxis (or the therapeutic antibiotics) alone, or with the addition of the single-shot broad-spectrum prophylaxis regimen composed of vancomycin and gentamicin. In case of clinical suspicion of infection or massive contamination, the surgeons will perform at least three microbiological intraoperative tissue samples. Each surgery counts as an independent event. If a patient is debrided several times, he/she can have different prophylaxis regimens during each of the interventions. After the prophylactic regimen, the clinicians are free to continue with a targeted or empirical therapeutic antibiotic regimen. The antibiotic therapy per se is not an objective of this current trials.

The treatment period includes the following daily study visits:

* Visit 1 - Enrollment (Day 1)
* EOT (end of microbiological cultures) - Day 14 (+/- 3 days)
* TOC (clinical surgical control) - Day 42 (+/- 14 days)
* Follow-up (telephone) for implant-related surgery - 1 year (+/- 2 months)

At enrollment (Day 1), the investigator will prescribe the preoperative antibiotic prophylaxis based on instructions provided in the protocol according to the patient's randomization. Patients will be randomized in the ratio 1:1 into the investigational group (broad-spectrum prophylaxis) and the control group (usual prophylaxis). Each patient can be included several times with one episode for each surgical interven-tion in the operating theatre. The initial consent form is valid during 1 month and will be renewed in case of another inclusion following a delay of 1 month after the initial signature of the patient.

The microbiologists culturing the pathogens of eventual surgical site infections are blinded to the prior prophylaxis during the index surgery

Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Surgery

Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Sur-gery - the Prospective-randomized, Microbiologist-blinded, Stratified, Superiority Trials - BAPTIST Trials

The investigators might share anonomyzed key elements (data) upon scientific request to the corresponding person

Assessment of SSI at the clinical controls according to clinical criteria in the literature (pus, discharge, pain, inflammation, several deep tissue microbiological cultures

Assessments of antibiotic resistance of pathogens according to standard susceptibilty testing in the Microbiological Laboratory

Unplanned revision surgery in the operating theatre for any reasons

Asssesment in the medical files. Have therapeutic antibiotics been changed according to new intraoperative bacterial culture findings

If there is therapeutic antibiotc treatment necessary, the investigators assess the drugs, the adverse events and the global costs related to the antibiotc treatment. The costs are the global (overall) hospitalizations costs in Swiss Francs.

Assessment of all nosocomial and community-acquired infections ocrruging in the immediate postoperative period and relate them to prior perioperative antibiotic prophylaxis

Assessment of the impact of the priorantibiotic prophylaxis on the body colonization with multiresistant bacteria of concern for infection control

Balgrist University Hospital

Neoplasms

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Recurrence

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

Liver Extracts

Transplanted patients with HCC in LATAM from 2005-2011

Transplanted patients with HCC in France from 2003-2005

Transplanted patients with HCC in Italy from 2005-2011

Liver transplantation for patients with hepatocellular carcinoma

Liver transplantation

Federico Piñero, MD, MSCE

Christophe Duvoux, MD

Background \& Aim: Presence of microvascular invasion (mvi) in the explanted liver defines a higher risk of recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT). The aim of this study is to evaluate pre LT selection models of HCC recurrence specifically in patients without mvi in the explanted liver.

Methods: Three multicenter cohorts are going to be included: a Latin American, a French and an Italian cohort of consecutive adult patients with HCC a first LT performed during two different periods: 2005-2011 and 2012-2016. AFP model is going to be compared against Milan and San Francisco criteria according to each models accuracy and prediction of HCC recurrence among patients without microvascular invasion in the explanted liver considering these candidates as "Low-risk patients". Multivariate Cox regression analysis, with hazard ratios (HR) and 95% confidence intervals (CI) for 5-year recurrence is going to be done with Competing Risk Regression analysis and corresponding Subhazard Ratios (SHR).

Introduction Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a catastrophic event, with limited therapeutics and poor survival \[1\]. Prior to 1990s, transplantation for HCC was a limited option with high recurrence and poor recipient survival, largely because of a lack of accurate selection of transplant candidates and a late diagnosis.

The Milan criteria have remained as the gold standard selection criteria, with post-transplant 5-year recurrence less than 15% and 5-year survival over 70% \[2\]. These criteria do not contemplate a relevant histological variable and a risk marker of recurrence, microvascular invasion (mvi). Presence of mvi in the explanted liver has been identified as an independent variable related to recurrence that categorizes patients with low and high risk of HCC recurrence \[3\]. That is why other selection criteria, beyond Milan criteria, have tried to find pre-transplant surrogate markers of mvi or other related risk factors for recurrence \[4-6\].

Serum alpha-fetoprotein (AFP) is a marker of renewed interest as a selection criterion, which has been identified as an independent risk variable associated with recurrence and as a surrogate marker of mvi \[4,5,7,8\]. Evaluation of mvi before LT by a tumor biopsy has many caveats; on the one hand, the risk of tumor seeding, bleeding and other complications and on the other hand, the absence of it does not exclude of its presence in the explanted liver analysis.

Consequently, while it is known that the presence of mvi defines a greater risk, its absence generates uncertainty regarding the risk of recurrence in this population. The Up-to 7 criteria showed that the occurrence of mvi at any size and tumor number was paralleled by a significant lower patient survival and higher recurrence \[3\]. However, the Metroticket calculator excluded important pre transplant variables such as serum AFP and tumor treatment or progression while on the waitlist \[9\]. A recently predicting model, the RETREAT score, showed that when considering pre and post transplant variables, the AFP at different cut-offs, presence of mvi and the sum of the largest tumor diameter and tumor number were associated with HCC recurrence \[7\]. While it has been published earlier in Italian and French cohorts that the prevalence of mvi is 24% \[4,11\], in another Latin American validation cohort of the AFP model the prevalence of mvi was 22.2% \[10\].

Our objective therefore, is to evaluate the AFP model against Milan and San Francisco criteria (UCSF) in the prediction of HCC recurrence and patient survival specifically in patients without mvi in the explanted liver and evaluate if the AFP model can assure and identify good candidates for LT that are beyond Milan and UCSF in this subgroup of patients.

Patients and Methods Study design, setting and participating centers This study is going to include three multicenter cohorts of consecutive adult patients (\>17 years of age) who underwent a first LT between January 1 2005 and December 31 2016 \[4,10,11\]. Participating centers will appoint a study coordinator responsible for data collection. In cases of conflicting or missing data, central revision and resubmission were requested. All the requested variables are going to be included in a written CRF.

Eligibility criteria and study variables Criteria for inclusion required patients to be adult cirrhotic or non-cirrhotic recipients with confirmed HCC in the explanted liver. Patients are going to be excluded if: 1) other tumors than HCC are confirmed in the explanted liver, or 2) there are missing relevant information; 3) extrahepatic or macrovascular tumor invasion were observed during pre transplant evaluation or in the explanted liver 4) incidental HCC, 5) had a previous liver transplant and 6) patients with microvascular invasion in the explanted liver (this latter criteria is going to be assessed for the final inclusion criteria).

Recipient characteristics, pre-transplant tumor characteristics and serum α-fetoprotein (AFP) levels are going to be recorded at listing and at last pre-LT evaluation. Subjects with HCC diagnosis prior to transplant based on imaging criteria are going to be classified according to Milan (MC) and University of California San Francisco (UCSF) \[12\] and the AFP model \[4\], depending on size and number of lesions detected on pre-LT computerized tomography (CT) or magnetic resonance images (MRI) and on serum pre-LT AFP levels ng/ml including the following cut-offs values ≤100 ng/ml, 101-1000 ng/ml, and \>1000 ng/ml \[4\].

Tumor treatment before transplantation is going to be recorded (date and type of treatments performed) including trans-arterial chemoembolization (TACE), radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) and liver resection (LR).

Explanted liver findings will include macroscopic and microscopic evaluation of each nodule, number and diameter (cm) of each, presence of mvi, and degree of tumor differentiation according to Edmonson-Steiner grading system. Nodules of largest diameter are going to be identified as the major nodule. Necrotic nodules are going to be also measured including necrotic and viable tumor diameter. Finally, Milan and Up-to seven criteria are going to also be applied to the explanted liver specimen.

Study end-points Primary end-points analyzed are going to be 5-year patient survival and HCC recurrence. Recurrence is going to be determined on the basis of imaging criteria plus serum AFP or by biopsy. Time to recurrence (TTR) is going to be calculated considering it a robust clinical outcome measure and calculated as the time in months elapsed between transplantation and diagnosis of recurrence.

Secondary aims include the development of tumor progression while on the waitlist according to RECIST 1.1 criteria.

Statistical Analysis Categorical data were compared using Fisher's exact test or Chi-Square (Χ2) test (2-tailed). Continuous variables were compared with Student's T test or Wilcoxon rank-sum test according to their distribution, respectively. First of all, in order to evaluate if microvascular invasion in the explant is an independent risk variable for recurrence, a multivariate Cox regression analysis, with hazard ratios (HR) and 95% confidence intervals (95% CI) for identifying explanted liver risk variables for 5-year recurrence is going to be carried out evaluating potential confounding variables. After calculation of each adjusted HR separately in each overall cohort (French, Italian and LATAM), cumulative incidence of recurrence by a competing risk regression analysis with death is going to be compared among patients with or without mvi ("high" and "low" risk patients, respectively).

Second, after evaluating the effect of mvi as a selection criteria of "low" and "high" risk patients, the following analysis is going to be done after excluding patients with mvi in each cohort in order to evaluate the performance of the AFP model in these "low-risk" patients.

A multivariate Cox regression analysis (HR, 95% CI) is going to be done in order to identify the effect of each pre-LT model on prediction of HCC 5-year recurrence adjusted with potential confounding variables. Variables with a P value \<0.05 after the univariate analysis are going to be included in the multivariate model, generated by stepwise forward elimination evaluating P values (Wald test) and considering adjusted HR with confounding variables (\>20% of change in crude HR). For each multivariate model, 1 variable per 10 events were included. Adjustment of each final model is going to be evaluated with proportional hazards through graphic and statistical evaluation (Schoenfeld residual test). Calibration is going to be assessed by comparison of observed and predicted curves and evaluation of the goodness of fit of the model by Harrell's c-statistic index.

Finally, a competing risk analysis with death and recurrence is going to be done with calculation of subharzard ratios (SHR) and 95% CI. Kaplan Meier survival curves were compared using the log-rank test (Mantel-Cox). Collected data were analyzed with STATA 10.0.

Agenda.

1. Collection and analysis of data: until 1-January-2018.
2. Full statistical analysis and overall results: until 1-January to February-2019.
3. Submission of overall results to all co-authors included in the 3 cohorts: March 2019.
4. Manuscript, figures and tables done: March 2019.

AFP Model and Liver Transplantation.

Evaluation of the AFP Model in Predicting Recurrence of Hepatocellular Carcinoma After Liver Transplantation in Patients Without Microvascular Invasion.

Cox regression multivariable adjusted models, HR (95% CI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Surgery	NCT05502380	Surgical Site I... Microbial Colon... Antibiotic Resi...	Standard antibi...	18 Years -	Balgrist University Hospital
AFP Model and Liver Transplantation.	NCT03775863	Liver Carcinoma Liver Transplan...	Liver transplan...	-	Austral University, Argentina
AFP Model and Liver Transplantation.	NCT03775863	Liver Carcinoma Liver Transplan...	Liver transplan...	-	Austral University, Argentina
Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Surgery	NCT05502380	Surgical Site I... Microbial Colon... Antibiotic Resi...	Standard antibi...	18 Years -	Balgrist University Hospital

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Spots Global Cancer Trial Database for selection

Every month we try and update this database with for selection cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for selection cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.