Protocolization of multicenter clinical studies in the digital era. Is useful data centralization by a data-manager?

INTRODUCTION: In multicenter studies, the protocolization of data is a critical phase that can generate biases.The objective is to analyze the concordance and reliability of the data obtained in a clinical multicenter study between the protocolization in the center of origin and the centralized protocolization of the data by a data -manager. METHODS: National multicenter clinical study about an infrequent carcinoma. A double protocolization of the data is carried out: (a) center of origin; and (b) centralized by a data manager: The concordance between the data is analyzed for the global data and for the two groups of the project: (a) study group (Familiar carcinoma, 30 researchers protocolize); (b) control group (Sporadic carcinoma, 4 people protocolize). Interobserver variability is evaluated using Cohen's kappa coefficient. RESULTS: The study includes a total of 689 patients with carcinoma, 252 in the study group and 437 in the control group. Regarding the concordance analysis of the tumor stage, 2.5% of disagreements were observed and the concordance between people who protocolize was near perfect (Kappa = 0.931). Regarding the evaluation of the recurrence risk, disagreements occurred in 7% of the cases and the concordance was near perfect (Kappa = 0.819). Regarding the sonography evaluation (TIRADS), the disagreements were 6.9% and the concordance was near perfect (Kappa = 0.922). Also, 4.6% of transcription errors were detected. CONCLUSIONS: In multicenter clinical studies, the centralized data protocolization o by a data-manager seems to present similar results to the direct protocolization in the database in the center of origin.

Lower limb cutaneous melanoma surgery: location matters.

The anatomical location of cutaneous melanoma is a relevant independent prognostic factor in melanoma. The aim of the study is to know the prognosis of lower limb cutaneous melanoma related to their location within the limb, regardless of the histological type, and if there are any other influencing variables. A real-world data observational study was developed. The lesions were divided depending on the location of the melanoma (thigh, leg and foot). Bivariate and multivariate analysis were performed, and melanoma-specific survival and disease-free survival rates were calculated. When these analysis were done, the results showed that, in melanomas of the lower limb, location on the foot presented a lower melanoma-specific survival rate compared to more proximal locations, and only the anatomical location presents statistical significance to discriminate cases with a higher mortality risk and a lower disease-free survival rate among distal melanomas (mainly on the foot). In conclusion, this study confirms that a more distal location of lower limb cutaneous melanoma is a relevant prognostic factor.Trial registration number NCT04625491 retrospectively registered.

[Influence of the lockdown due to COVID-19 on weight-loss results during the first year after sleeve gastrectomy]. / Influencia del confinamiento por COVID-19 en los resultados ponderales durante el primer año tras la gastrectomía vertical.

INTRODUCTION: COVID-19 pandemic has lead to lockdown of population in many countries. In Spain, the state of alarm was established from March 15 to June 20, 2020. Usually this fact decreased people's mobility and physical activity, in addition to producing or exacerbating psychological disorders. Our aim was to determine the influence that this condition had over the short-term ponderal results of patients undergoing laparoscopic vertical gastrectomy from May 2019 to May 2020. METHODS: Case-control study for comparing the percentage of excess weight lost (%EWL) and the percentage of total weight lost (%TWL) of patients that underwent a VG during the last year, so they were affected by lockdown in April and part of March 2020 (group 1), to the %EWL and %TWL of a control group (group 2), obtained from our previous series. RESULTS: The mean %EWL in group 1 is 47,37 ± 18,59 and in group 2 is 51,13 ± 17,59, being p = 0,438. Meanwhile, the mean %TWL in group 1 is 21,14 ± 8,17 and in group 2 is 24,67 ± 8,01, with p = 0,115. CONCLUSIONS: Population lockdown by COVID-19 did not get worse short-term results of vertical gastrectomy. More studies with a larger number of patients are necessary to draw firm conclusions.

Clinical value of baseline 18F-FDG PET/CT in soft tissue sarcomas.

BACKGROUND: The use of 18F-FDG Positron emission tomography/Computed tomography (PET/CT) in the initial staging of many cancers is clearly established. Most soft tissue sarcoma (STS) has a high affinity for 18F-FDG, which is why 18F-FDG PET/CT has been proposed as a non-invasive method, useful in diagnosis and follow-up. The standardized uptake value values (SUV), the volume-based metabolic parameters MTV (metabolic tumor volume), and TLG (total lesion glycolysis) determine tumor viability and provide its total volume and the total activity of metabolically active tumor cells. The histological grade is the most important predictor of metastases and mortality associated with STS, and a significant relationship between the metabolic parameters of 18F-FDG PET/CT and the histological grade has been described. METHODS: A retrospective study was conducted on STS patients, who had histological grade according to the FNCLCC (Fédération Nationale des Centres de Lutte Contre Le Cancer) criteria, as well as a baseline PET/CT. SUV (SUVmax, SUVmean, and SUVpeak), MTV, and TLG were quantified. A T-student test was performed to establish the relationship between the metabolic biomarkers and the histological grade. Their usefulness as predictors of the histological grade was verified using receiver operator characteristic (ROC) curves. A survival function study was performed using the Kaplan-Meier method. To assess the prognostic utility of the metabolic biomarkers we use the Log-Rank method. RESULTS: The SUV values were useful to discriminate high-grade STS. We found a significant relationship between the histological grade and the SUV values. SUVmax, SUVpeak, MTV, and TLG were predictors of overall survival (OS). There were no significant differences in the OS for the SUVmean, or in the disease-free survival (DFS) for SUVmax, SUVmean, SUVpeak, MTV, and TLG. CONCLUSIONS: The SUVmax, SUVmean, and SUVpeak values correlate with the HG and are useful to discriminate high-grade from low-grade STS. Patients with high SUVmax, SUVpeak, MTV, and TLG have a significantly lower OS.

Cavity shaving for invasive breast cancer conservative surgery: Reduced specimen volume and margin positive rates.

INTRODUCTION: The cavity shaving (CS) technique was described in breast conserving surgery to reduce the rate of reoperation avoiding the need for intraoperative margin analysis. This study assesses differences in the rates of involvement of the surgical margin (requiring further surgery) and volume of surgical specimens, depending on the use or not of this technique. MATERIAL AND METHODS: A retrospective cohort study was conducted in patients with breast carcinoma who underwent breast conserving surgery between 2013 and 2019. They were divided into two groups depending on whether the cavity shaving technique was used or not. Primary outcomes of the study included presence of final margin involvement, requiring need for further surgery, and the volume of excised tissue comparing the study groups. RESULTS: A total of 202 cases were included: 92 in the control group and 110 in the cavity shaving group. Significant differences were found regarding involvement of the final margin (19.57% control group vs. 4.55% cavity shaving group; p = 0.010). The volume of additional surgical specimens were significantly greater in the traditional technique group than in the shaving technique (46.43 vs 13.32 cm3; p = 0.01) as was total specimen volume (143.40 vs 100.63 cm3; p = 0.022). CONCLUSIONS: CS can reduce the positive margin and re-excision rates without larger-volume resections and should therefore be considered a routine technique in BCS for early-stage breast cancer.

Influence of the lockdown due to COVID-19 on weight-loss results during the first year after sleeve gastrectomy.

INTRODUCTION: COVID-19 pandemic has lead to lockdown of population in many countries. In Spain, the state of alarm was established from March 15 to June 20, 2020. Usually this fact decreased people's mobility and physical activity, in addition to producing or exacerbating psychological disorders. Our aim was to determine the influence that this condition had over the short-term ponderal results of patients undergoing laparoscopic vertical gastrectomy from May 2019 to May 2020. METHODS: Case-control study for comparing the percentage of excess weight lost (%EWL) and the percentage of total weight lost (%TWL) of patients that underwent a VG during the last year, so they were affected by lockdown in April and part of March 2020 (group 1), to the %EWL and %TWL of a control group (group 2), obtained from our previous series. RESULTS: The mean %EWL in group 1 is 47.37±18.59 and in group 2 is 51.13±17.59, being P=.438. Meanwhile, the mean %TWL in group 1 is 21.14±8.17 and in group 2 is 24.67±8.01, with P=.115. CONCLUSIONS: Population lockdown by COVID-19 did not get worse short-term results of vertical gastrectomy. More studies with a larger number of patients are necessary to draw firm conclusions.

Relationship between the polyp detection rate and the post-colonoscopy colorectal cancer rate.

AIM: the adenoma detection rate is the quality indicator of colonoscopy that is most closely related to the development of interval colorectal cancer or post-colonoscopy colorectal cancer. However, the recording of this indicator in different units of gastrointestinal endoscopy is obstructed due to the large consumption of resources required for its calculation. Several alternatives have been proposed, such as the polyp detection rate. The objective of this study was to evaluate the relationship between the polyp detection rate and its influence on post-colonoscopy colorectal cancer rate. PATIENTS AND METHODS: in this study, 12,482 colonoscopies conducted by 14 endoscopists were analyzed. The polyp detection rate was calculated for each endoscopist. Endoscopists were grouped into quartiles (Q1, Q2, Q3, and Q4), from lowest to highest polyp detection rate, in order to evaluate whether there were any differences in the development of post-colonoscopy colorectal cancer. RESULTS: the lowest polyp detection rate was 20.66% and the highest was 52.16%, with a median of 32.78 and a standard deviation of ± 8.54. A strong and positive association between polyp endoscopy diagnosis and adenoma histopathology result was observed and a linear regression was performed. A significantly higher post-colonoscopy colorectal cancer rate was observed in the group of endoscopists with a lower polyp detection rate (p < 0.02). CONCLUSION: polyp detection rate is a valuable quality indicator of colonoscopy and its calculation is much simpler than that of the adenoma detection rate. In our study, the prevalence of post-colonoscopy colorectal cancer was inversely and significantly related to the endoscopists' polyp detection rate.

A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF.

BACKGROUND: The production of anti-drug antibodies (ADAs) against IgG monoclonal antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Since receptors for the Fc portion of IgG (FCGRs) are involved in the degradation of IgG complexes, we hypothesised that a polymorphism in FCGR3A (V158F; rs396991) gene could be involved in anti-TNF ADA generation and treatment resistance. MATERIAL AND METHODS: A cohort of 103 IBD patients (80 CD, 23 UC) were genotyped and serum level of both anti-TNFs (infliximab or adalimumab) and ADA against them were measured. RESULTS: No significant differences were observed between ADA occurrence or V158F genotype and type of disease or the kind of anti-TNF administrated. Interestingly, VV genotype correlated with patients producing ADA (VV: 37.5% vs. FV: 10.6% or FF: 5%; p=0.004) and was an independent predictor of this event after multivariate analysis. Moreover, VV genotype also correlated with those patients receiving anti-TNF dose intensification (p=0.03). CONCLUSION: FCGR3A V158F polymorphism seems to be associated with ADA production against mAbs and it could be taken into account when considering the dose and type of anti-TNF in IBD patients.

Acoustic radiation force impulse imaging for detection of liver fibrosis in overweight and obese children.

Background Acoustic radiation force impulse (ARFI) is a non-invasive alternative to a liver biopsy for the evaluation of liver fibrosis (LF). Purpose To investigate the potential usefulness of acoustic radiation force impulse ARFI for detecting LF in overweight and obese children Material and Methods A cross-sectional study was conducted in 148 schoolchildren. A diagnosis of non-alcoholic fatty liver disease (NAFLD) and LF was based on ultrasound (US) and ARFI shear wave velocity (SWV). Results The laboratory parameters were normal in all the children. NAFLD was observed in 50 children (33.8%). The median SWV was 1.18 ± 0.28 m/s. Differences between ARFI categories and hepatic steatosis grades were observed (χ2 = 43.38, P = 0.0005). No fibrosis or insignificant fibrosis (SWV ≤ 1.60 m/s) was detected in 137 children (92.5%), and significant fibrosis (SWV > 1.60 m/s) in 11 children (7.5%), nine of whom had normal US or mild steatosis. Conclusion The present study is the first to evaluate the utility of the ARFI technique for detecting LF in overweight and obese children. The results of the study suggest that children with normal laboratory parameters such as normal liver ultrasound or mild steatosis may present with significant LF.

A Comparison of Genicular Nerve Treatment Using Either Radiofrequency or Analgesic Block with Corticosteroid for Pain after a Total Knee Arthroplasty: A Double-Blind, Randomized Clinical Study.

BACKGROUND: Knee osteoarthritis is a disease that affects a third of the population over 65 years of age, and it is increasingly becoming a motive for consultation and a source of pain and disability. The gold standard surgical treatment is a total knee arthroplasty; however, 15% to 30% of patients who have undergone surgery continue to experience pain and functional limitation. METHODS: A double-blind, randomized clinical study compared neurolysis using traditional radiofrequency (RF) to local anesthetic and corticosteroid block of the superolateral, superomedial, and inferomedial branches of the knee genicular nerves in patients who had total knee arthroplasty but still experience pain. RESULTS: Twenty-eight patients, 14 on each treatment arm, were followed for over a 1-year period. A reduction in pain and significant joint function improvement during the first 3 to 6 months was shown, with similar results using both techniques. No adverse effects were noted. An improvement in both disability and quality of life was observed, as well as a reduction in the need for analgesics in both treatment groups. CONCLUSIONS: Further clinical trials need to be undertaken, with a larger sample size, in order to demonstrate the efficacy of this technique and to detect the possible appearance of any long-term adverse effects.

Tumoral load quantification of positive sentinel lymph nodes in breast cancer to predict more than two involved nodes.

AIM: One-Step Nucleic Acid Amplification (OSNA) can detect isolated tumour loads in axillary lymph nodes of breast cancer patients. We investigated the predictability of the non-sentinel lymph node (SLN) metastatic involvement (MI) based on the OSNA SLN assessment in surgical invasive breast cancer. METHODS: We studied surgical breast invasive carcinoma patients, not taking neoadjuvant chemotherapy, having SLN positive by OSNA and having received axillary lymphadenectomy. Age, basic histopathological, immunohistochemical, SLN biopsy and lymphadenectomy data were compared between patients with or without MI of more than 2 non-SLN in both univariate and multivariate analyses. The discriminating capacity of the multivariate model was characterized by the ROC AUC. RESULTS: 726 patients from 23 centers in Spain aged 55.3 ± 12.2 years were analysed. The univariate analysis comparing patients with or without MI of more than 2 non-SLN detected statistically significant differences in primary tumour size, multifocality, presence of lymphovascular infiltration, positive proliferation index with ki67, immunophenotype and logTTL (Tumour Total Load). The multivariate logistic analyses (OR (95% CI)) confirmed multifocality (2.16 (1.13-4.13), p = 0.019), lymphovascular infiltration (4.36 (2.43-7.82), p < 0.001) and logTTL (1.22 (1.10-1.35), p < 0.001) as independent predictors, and exhibit an AUC (95% CI) of 0.78 (0.72-0.83) with an overall fit (Hosmer-Lemeshow test) of 0.359. A change in the slope of both sensitivity and specificity is observed at about 10,000 copies/µL, without relevant changes in the Negative Predictive Values. CONCLUSIONS: Using OSNA technique, the MI of more than 2 non-SLN can be reliably predicted.

Pharmacoepidemiological study of drug-drug interactions in onco-hematological pediatric patients.

BACKGROUND: Onco-hematological patients are particularly susceptible to drug-drug interactions (DDIs) because they often undergo multiple combined treatments. Some studies have analyzed the frequency of DDIs in adult patients with cancer; however, the prevalence of DDIs in children, and especially among pediatric cancer patients, remains unknown. OBJECTIVE: To determine the prevalence of DDIs in treatment sheets comparing two commonly used drug interaction databases, to describe the most common clinically relevant DDIs (CR-DDIs) and to investigate the risk factors associated with them. SETTING: An onco-hematological pediatric unit from a tertiary hospital in Spain. METHOD: A prospective, observational and descriptive study was carried out from November 2012 to February 2013. Twice a week, every patient's treatment sheet was collected. Each medication list was screened through two databases: Thomson Micromedex™ and Drug Interaction Facts™. All identified DDIs were graded by their level of severity. Summary statistics were used to describe patient and disease characteristics, most often prescribed drugs, and frequency, types and classification of CR-DDIs. Multivariate analysis was used to identify risk factors associated with CRDDIs. MAIN OUTCOME MEASURE: Prevalence of CR-DDIs was measured as percentage. RESULTS: A total of 506 potential DDIs were detected in 150 treatment sheets. The prevalence of CR-DDIs by Micromedex database and Drug Interaction Facts database were 44.7 and 51.3% respectively. Amikacin, azole antifungals, antiemetics and cyclosporine were the most frequent drugs involved in CR-DDIs. In multivariate analysis, the main risk factor associated with increased odds for CR-DDIs was a higher number of drugs. CONCLUSION: The frequency of potential DDIs was related to a higher number of drugs, being immunosuppressant and azole antifungal agents the most commonly involved drugs. The lack of agreement between different databases enhances the complexity to detect drug interactions in clinical practice.