Asynchronous electronic consultation between primary care and specialized care proved effective for continuum of care for viraemic hepatitis C patients / La consulta electrónica asíncrona entre atención primaria y atención especializada resultó eficaz para la continuidad de la atención a los pacientes con hepatitis C virémica

Introduction: It has been proposed that primary care diagnose and treat hepatitis C virus (HCV) infection. However, a care circuit between primary and specialized care based on electronic consultation (EC) can be just as efficient in the micro-elimination of HCV. It is proposed to study characteristics and predictive factors of continuity of care in a circuit between primary and specialized care. Methods: From February/2018 to December/2019, all EC between primary and specialized care were evaluated and those due to HCV were identified. Variables for regression analysis and to identify predictors of completing the care cascade were recorded. Results: From 8098 EC, 138 were performed by 89 (29%) general practitioners over 118 patients (median 50.8 years; 74.6% men) and were related to HCV (1.9%). Ninety-two patients (78%) were diagnosed>6 months ago, and 26.3% met criteria for late presentation. Overall, 105 patients required assessment by the hepatologist, 82% (n=86) presented for the appointment, of which 67.6% (n=71) were viraemic, 98.6% of known. Finally, 61.9% (n=65) started treatment. Late-presenting status was identified as an independent predictor to complete the care cascade (OR 1.93, CI 1.71–1.99, p<0.001). Conclusion: Communication pathway between Primary and Specialized Care based on EC is effective in avoiding significant losses of viraemic patients. However, the referral rate is very low, high in late-stage diagnoses, heterogeneous, and low in new diagnoses. Therefore, early detection strategies for HCV infection in primary care are urgently needed.(AU)

Introducción: Se ha propuesto que atención primaria diagnostique y trate la infección por virus de la hepatitis C (VHC). Sin embargo, un circuito asistencial entre atención primaria y especializada basado en la consulta electrónica (CE) puede ser igual de eficiente en la microeliminación del VHC. Se propone estudiar características y factores predictivos de la continuidad asistencial en un circuito entre atención primaria y especializada. Métodos: Desde febrero/2018 y diciembre/2019 se evaluaron todas las CE entre atención primaria y especializada, y se identificaron aquellas por VHC. Se registraron variables para análisis de regresión e identificar factores predictores de completar cascada de atención. Resultados: De un total de 8.098 CE, 138 realizadas por 89 (29%) médicos generales de 118 pacientes (mediana de 50,8 años; 74,6% varones) fueron por VHC (1,9%). Noventa y dos pacientes (78%) fueron diagnosticados hace más de 6 meses), y el 26,3% cumplía criterios de presentación tardía. En total, 105 pacientes requirieron valoración por el hepatólogo. El 82% (n=86) se presentaron a la cita, de los cuales el 67,6% (n=71) eran virémicos, el 98,6% de los conocidos. Finalmente, el 61,9% (n=65) inició tratamiento. El estado de presentación tardía se identificó como un factor predictivo independiente para completar la cascada de atención (OR: 1,93; IC 95%: 1,71-1,99; p<0,001). Conclusión: La comunicación entre atención primaria y especializada basada en la CE es eficaz para evitar pérdidas significativas de pacientes virémicos. Sin embargo, la tasa de derivación es muy baja, elevada en diagnósticos en fase tardía, heterogénea y escasa en nuevos diagnósticos. Por tanto, se necesitan con urgencia, estrategias de detección precoz de infección por VHC en atención primaria.(AU)

Nonsentinel Axillary Lymph Node Status in Clinically Node-Negative Early Breast Cancer After Primary Systemic Therapy and Positive Sentinel Lymph Node: A Predictive Model Proposal.

BACKGROUND: In clinically node-negative (cN0) early stage breast cancer (EBC) undergoing primary systemic treatment (PST), post-treatment positive sentinel lymph node (SLN+) directs axillary lymph node dissection (ALND), with uncertain impacts on outcomes and increased morbidities. PATIENTS AND METHODS: We conducted an observational study on imaging-confirmed cN0 EBC, who underwent PST and breast surgery that resulted in SLN+ and underwent ALND. The association among baseline/postsurgical clinic-pathological factors and positive nonsentinel additional axillary lymph nodes (non-SLN+) was analyzed with logistic regression. LASSO regression (LR) identified variables to include in a predictive score of non-SLN+ (ALND-predict). The accuracy and calibration were assessed, an optimal cut-point was then identified, and in silico validation with bootstrap was undertaken. RESULTS: Non-SLN+ were detected in 22.2% cases after ALND. Only progesterone receptor (PR) levels and macrometastatic SLN+ were independently associated to non-SLN+. LR identified PR, Ki67, and type and number of SLN+ as the most efficient covariates. The ALND-predict score was built based on their LR coefficients, showing an area under the curve (AUC) of 0.83 and an optimal cut-off of 63, with a negative predictive value (NPV) of 0.925. Continuous and dichotomic scores had a good fit (p = 0.876 and p = 1.00, respectively) and were independently associated to non-SLN+ [adjusted odds ratio (aOR): 1.06, p = 0.002 and aOR: 23.77, p < 0.001, respectively]. After 5000 bootstrap-adjusted retesting, the estimated bias-corrected and accelerated 95%CI included the aOR. CONCLUSIONS: In cN0 EBC with post-PST SLN+, non-SLN+ at ALND are infrequent (~22%) and independently associated to PR levels and macrometastatic SLN. ALND-predict multiparametric score accurately predicted absence of non-SLN involvement, identifying most patients who could be safely spared unnecessary ALND. Prospective validation is required.

Effect of Fractional Carbon Dioxide vs Sham Laser on Sexual Function in Survivors of Breast Cancer Receiving Aromatase Inhibitors for Genitourinary Syndrome of Menopause: The LIGHT Randomized Clinical Trial.

Importance: Survivors of breast cancer present more severe symptoms of genitourinary syndrome of menopause (GSM) than patients without history of breast cancer. Recently, new treatments, such as vaginal laser therapy, have appeared, but evidence of their efficacy remains scarce. Objective: To assess the safety and efficacy of carbon dioxide (CO2) vs sham vaginal laser therapy after 6 months of follow-up in survivors of breast cancer with GSM receiving aromatase inhibitors. Design, Setting, and Participants: This prospective double-blind sham-controlled randomized clinical trial with two parallel study groups was performed during October 2020 to March 2022 in a tertiary referral hospital. Survivors of breast cancer using aromatase inhibitors were assessed for eligibility, and eligible patients were randomized into the 2 treatment groups. Follow-up was conducted at 6 months. Data were analyzed in July 2022. Interventions: All patients from both groups were instructed to use the first-line treatment (FLT) based on nonhormonal moisturizers and vaginal vibrator stimulation. Patients for each group were allocated to 5 monthly sessions of fractional CO2 laser therapy (CLT) or sham laser therapy (SLT). Main Outcomes and Measures: The primary outcome was sexual function, evaluated through Female Sexual Function Index (FSFI) score. Other subjective measures of efficacy included a visual analog scale of dyspareunia, vaginal pH, a Vaginal Health Index, quality of life (assessed via Short-Form 12), and body image (assessed with the Spanish Body Image Scale). Objective measures of efficacy included vaginal maturation index, vaginal epithelial elasticity (measured in Pascals) and vaginal epithelial thickness (measured in millimeters). Measures were assessed before and after the intervention. Tolerance (measured on a Likert scale), adverse effects, and estradiol levels were recorded. Results: Among 211 survivors of breast cancer assessed, 84 women were deemed eligible and 72 women (mean [SD] age, 52.6 [8.3] years) were randomized to CLT (35 participants) or SLT (37 participants) and analyzed. There were no statistically significant differences between groups at baseline. At 6 months, both groups showed improvement in FSFI (mean [SD] score at baseline vs 6 months: CLT, 14.8 [8.8] points vs 20.0 [9.5] points; SLT, 15.6 [7.0] points vs 23.5 [6.5] points), but there was no significant difference between CLT and SLT groups in the improvement of sexual function evaluated through the FSFI test overall (mean [SD] difference, 5.2 [1.5] points vs 7.9 [1.2] points; P = .15) or after excluding women who were not sexually active (mean [SD] difference, 2.9 [1.4] points vs 5.5 [1.1] points; P = .15). There were also no differences between improvement of the 2 groups at 6 months of follow-up in the other assessed subjective outcomes, including dyspareunia (mean [SD] difference, -4.3 [3.4] vs -4.5 [2.3]; P = .73), Vaginal Health Index (mean [SD] difference, 3.3 [4.1] vs 5.0 [4.5]; P = .17), body image (mean [SD] difference, -3.7 [4.5] vs -2.7 [4.8]; P = .35), and quality of life (mean [SD] difference, -0.3 [3.6] vs -0.7 [3.2]; P = .39). Similarly, there were no differences in improvements in objective outcomes, including vaginal pH (mean [SD] difference, -0.6 [0.9] vs -0.8 [1.2]; P = .29), vaginal maturation index (mean [SD] difference, 10.2 [17.4] vs 14.4 [17.1]; P = .15), vaginal epithelial thickness (mean [SD] difference, 0.021 [0.014] mm vs 0.013 [0.012] mm; P = .30), vaginal epithelial elasticity (mean [SD] difference, -1373 [3197] Pascals vs -2103 [3771] Pascals; P = .64). There were significant improvements in the overall analysis regardless of group in many outcomes. The 2 interventions were well tolerated, but tolerance was significantly lower in the CLT group than the SLT group (mean [SD] Likert scale score, 3.3 [1.3] vs 4.1 [1.0]; P = .007). No differences were observed in complications or serum estradiol levels. Conclusions and Relevance: In this randomized clinical trial, vaginal laser treatment was found to be safe after 6 months of follow-up, but no statistically significant differences in efficacy were observed between CLT and SLT. Trial Registration: ClinicalTrials.gov identifier: NCT04619485.

Asynchronous electronic consultation between primary care and specialized care proved effective for continuum of care for viraemic hepatitis C patients.

INTRODUCTION: It has been proposed that primary care diagnose and treat hepatitis C virus (HCV) infection. However, a care circuit between primary and specialized care based on electronic consultation (EC) can be just as efficient in the micro-elimination of HCV. It is proposed to study characteristics and predictive factors of continuity of care in a circuit between primary and specialized care. METHODS: From February/2018 to December/2019, all EC between primary and specialized care were evaluated and those due to HCV were identified. Variables for regression analysis and to identify predictors of completing the care cascade were recorded. RESULTS: From 8098 EC, 138 were performed by 89 (29%) general practitioners over 118 patients (median 50.8 years; 74.6% men) and were related to HCV (1.9%). Ninety-two patients (78%) were diagnosed>6 months ago, and 26.3% met criteria for late presentation. Overall, 105 patients required assessment by the hepatologist, 82% (n=86) presented for the appointment, of which 67.6% (n=71) were viraemic, 98.6% of known. Finally, 61.9% (n=65) started treatment. Late-presenting status was identified as an independent predictor to complete the care cascade (OR 1.93, CI 1.71-1.99, p<0.001). CONCLUSION: Communication pathway between Primary and Specialized Care based on EC is effective in avoiding significant losses of viraemic patients. However, the referral rate is very low, high in late-stage diagnoses, heterogeneous, and low in new diagnoses. Therefore, early detection strategies for HCV infection in primary care are urgently needed.

Vaginal laser therapy for genitourinary syndrome of menopause - systematic review.

BACKGROUND: Genitourinary syndrome of menopause (GSM) can have a great impact on the quality of life (QOL), and affects between 53.8% and 90% of postmenopausal women. The literature suggests that vaginal laser therapy could be an effective treatment for GSM symptoms, but its efficacy and safety have not been established and international societies do not endorse its use. Despite that, there has been an increase in the use of vaginal laser therapy globally over the last decade. OBJECTIVE: The objective of this review is to evaluate the literature which assesses the efficacy and safety of the vaginal laser therapy in the treatment of GSM. METHODS: A comprehensive literature search was conducted electronically using Embase and PubMed to retrieve studies assessing evidence for the efficacy and safety of vaginal laser therapy for GSM or vulvovaginal atrophy up to June 2021. RESULTS: A total of 64 studies were finally included in the review. There were 10 controlled intervention studies, 7 observational cohort and cross-sectional studies and 47 before-after studies without a control group. CONCLUSION: Vaginal laser seems to improve scores on the Visual Analogue Scale (VAS), Female Sexual Function Index (FSFI) and Vaginal Health Index (VHI) in GSM over the short term. Safety outcomes are underreported and short-term. Further well-designed clinical trials with sham-laser control groups and evaluating objective variables are needed to provide the best evidence on efficacy.

Genitourinary Syndrome of Menopause Assessment Tools.

New therapeutic options are being considered to treat genitourinary syndrome of menopause (GSM), such as vaginal laser, ospemifene, or prasterone, but there is no explicit agreement in the scientific community for its use. Some concerns have arisen on how to evaluate the improvement of GSM symptoms. In 2003, the FDA suggested possible end points for this purpose: change in severity of symptoms, change in vaginal pH, and change in vaginal maturation index (VMI). Contrarily, the most common assessment tools used to quantify severity and improvement of GSM nowadays are the visual analog scale of GSM symptoms, the vaginal health index, and the female sexual function index. In our opinion, subjective and objective variables to evaluate GSM can be differentiated, and not many of the considered objective outcomes are used in the recent literature assessing GSM. There is the possibility that some therapies present only subjective improvement, giving place to a possible placebo effect that is not being evaluated. To conclude, there is a demand to evaluate whether vaginal pH and VMI are enough to assess objectively GSM changes or new objective approaches should be audited.

An Enhanced High-Volume Preparation for Colonoscopy Is Not Better Than a Conventional Low-Volume One in Patients at Risk of Poor Bowel Cleansing: A Randomized Controlled Trial.

Objective: We tested the hypothesis that an enhanced bowel preparation strategy (EBS) improves colonic cleansing in patients at high risk for inadequate bowel cleansing (HRI). Methods: This prospective randomized clinical trial included consecutive HRI patients referred for outpatient colonoscopy between February and October 2019. HRI was considered if patients scored >1.225 according to a previously validated bowel-cleansing predictive score. HRI patients were randomized (1:1) to a low-volume conventional bowel cleansing strategy (CBS) (1-day low residue diet (LRD) plus 2 L of polyethylene glycol (PEG) plus ascorbic acid) or to an EBS (3-day LRD plus 10 mg oral bisacodyl plus 4 L PEG). The Boston Bowel Preparation Scale (BBPS) was used to assess the quality of cleanliness. Intention-to-treat (ITT) and per protocol (PP) analyses were performed. A sample size of 130 patients per group was estimated to reach a 15% difference in favor of EBP. Results: A total of 253 HRI patients were included (mean age 69.8 ± 9.5 years, 51.8% women). No statistically significant differences were found in the BBPS scale between the two groups in the ITT analysis (CBS 76.8% vs. EBS 79.7%, P = 0.58) or PP analysis (CBS 78% vs. EBS 84.3%, P = 0.21), risk difference 2.9% (95% CI-7.26 to 39.16) in the ITT analysis, or risk difference 6.3% (95% CI-3.48 to 16.08) in PP analysis. No differences in preparation tolerance, compliance, adverse effects, or colonoscopy findings were found. Conclusion: EBS is not superior to CBS in hard-to-prepare patients. (EUDRACT: 2017-000787-15, NCT03830489). Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03830489.

Increasing the low residue diet to 3 days does not improve the bowel cleansing in hard to prepare patients: Post hoc analysis of a randomized controlled trial.

BACKGROUND: Recent evidence suggests that the number of low residue diet (LRD) days does not influence the bowel cleansing quality in non-selected patients. However, there are not data in the subgroup of patients with risk factors of inadequate bowel cleansing. OBJECTIVE: The aim of this study was to assess whether a 3-day LRD improved the bowel cleansing quality in patients with risk factors of poor bowel cleansing. PATIENTS AND METHODS: Post hoc analysis of a randomized controlled trial carried out between December 2017 and March 2018 in a tertiary care hospital. Patients with high risk of poor bowel cleansing were selected following a validated score. The patients were randomized to the 1-day LRD or 3-day LRD groups. All patients received a 2-L split-dose of polyethylene glycol plus ascorbic acid. Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted for the main outcome. RESULTS: 135 patients (1-day LRD group=67, 3-day LRD=68) were included. The rate of adequate cleansing quality was not significantly different between the groups in the ITT analysis: 76.1%, 95% CI: [64.6-84.8] vs. 79.4%, 95% CI: [68.2-87.4]; odds ratio (OR) 1.2, 95% CI [0.54-2.73]) or in the PP analysis: 77.3%, 95% CI: [65.7-85.8] vs. 80.3%, 95% CI: [69.0-88.3]; OR 1.2, 95% CI [0.52-2.77]). Compliance with the diet or cleansing solution, satisfaction or difficulties with the LRD and the polyp/adenoma detection rates were not significantly different. CONCLUSION: Our results suggest that 1-day LRD is not inferior to 3-day LRD in patients with risk factors of inadequate bowel cleansing.

Genitourinary Syndrome of Menopause: Current Treatment Options in Breast Cancer Survivors - Systematic Review.

Breast cancer survivors (BCS) usually receive treatments which lead to persistent oestrogen suppression, which may cause atrophic vaginitis in a large proportion of these women. The most effective treatments for vulvovaginal atrophy (VVA) are based on local oestrogen therapy. However, these treatments are restricted in BCS due to the controversy over their use in women who had hormone-dependent tumours. Therefore, it is common to find untreated symptoms that affect sexual function and quality of life in BCS, thereby leading to the discontinuation of anti-oestrogenic treatments. This systematic review aims to discuss the current treatment options available for the genitourinary syndrome of menopause (GSM) in BCS. A comprehensive literature search was conducted electronically using Embase and PubMed to retrieve studies assessing treatment options for GSM or VVA in BCS up to April 2020. Studies evaluating treatments in different BCS cohorts were excluded. A total of 29 studies were finally included in the review. Non-hormonal treatments are the first-line treatment for VVA, but when these are not effective for symptom relief, other options can be considered, such as local oestrogen, erbium laser or CO2 laser and local androgens. The present data suggest that these therapies are effective for VVA in BCS; however, safety remains controversial and a major concern with all of these treatments.

COVID-19 and raising the value of care.

In this opinion piece, we argue the current pandemic is shining a light on caregiving as critical work that is under-valued and under-paid. We call upon national lawmakers to raise the value of care work. Doing so would also make progress in solving another national crisis: closing the gender wage gap. We explore how the gender wage gap is driven primarily by the fact that men and women sort into different work, with women being over-represented in work where they care for others and in work that allows them to care for their families.

Impact of a 1-day versus 3-day low-residue diet on bowel cleansing quality before colonoscopy: a randomized controlled trial.

BACKGROUND: The aim of this study was to assess whether a 3-day low-residue diet (LRD) improved bowel cleansing quality compared with a 1-day LRD regimen. METHODS: Consecutive patients scheduled for outpatient colonoscopy were randomized to the 1-day LRD or 3-day LRD groups. All patients received a 2-L split-dose of polyethylene glycol plus ascorbic acid. The primary outcome was bowel cleansing quality as evaluated using the Boston Bowel Preparation Scale (BBPS) (adequate cleansing ≥ 2 points per segment). Secondary outcomes were adherence to and level of satisfaction with the LRD, difficulty following the dietary recommendations, and willingness to repeat the same LRD in the future. Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted for the primary outcome. A superiority analysis was performed to demonstrate that a 3-day LRD regimen was superior to a 1-day LRD regimen with a margin of 10 %. RESULTS: 390 patients (1-day LRD group = 196, 3-day LRD = 194) were included. The cleansing quality was not significantly different between the groups: ITT analysis 82.7 % (95 % confidence interval [CI] 77.4 to 88.0) vs. 85.6 % (95 %CI 80.7 to 90.5), with odds ratio (OR) 1.2 (95 %CI 0.72 to 2.15); PP analysis 85.0 % (95 %CI 79.9 to 90.1) vs. 88.6 % (95 %CI 84.0 to 93.2), with OR 1.4 (95 %CI 0.88 to 2.52). No differences were found regarding adherence to the diet or cleansing solution, satisfaction or difficulty with the LRD, and the polyp/adenoma detection rates. CONCLUSION: 3-day LRD did not offer advantages over 1-day LRD in preparation for colonoscopy.

Sodium enhances indium-gallium interdiffusion in copper indium gallium diselenide photovoltaic absorbers.

Copper indium gallium diselenide-based technology provides the most efficient solar energy conversion among all thin-film photovoltaic devices. This is possible due to engineered gallium depth gradients and alkali extrinsic doping. Sodium is well known to impede interdiffusion of indium and gallium in polycrystalline Cu(In,Ga)Se2 films, thus influencing the gallium depth distribution. Here, however, sodium is shown to have the opposite effect in monocrystalline gallium-free CuInSe2 grown on GaAs substrates. Gallium in-diffusion from the substrates is enhanced when sodium is incorporated into the film, leading to Cu(In,Ga)Se2 and Cu(In,Ga)3Se5 phase formation. These results show that sodium does not decrease per se indium and gallium interdiffusion. Instead, it is suggested that sodium promotes indium and gallium intragrain diffusion, while it hinders intergrain diffusion by segregating at grain boundaries. The deeper understanding of dopant-mediated atomic diffusion mechanisms should lead to more effective chemical and electrical passivation strategies, and more efficient solar cells.

Risk factors for inadequate bowel preparation: a validated predictive score.

Background and study aim Inadequate bowel cleansing negatively affects the efficiency of colonoscopy in routine clinical practice. The aim of this study was to design and validate a predictive model for inadequate bowel cleanliness. Patients and methods The model was built from 667 consecutive outpatients (development cohort) who were prospectively scheduled for colonoscopy between June and September 2014. The validation cohort included 409 outpatients who underwent colonoscopy between October and December 2014. Cleansing was evaluated using the Boston Bowel Preparation Scale (BBPS). Bowel preparation was administered on the same day as the examination. Results In the development cohort, BBPS was adequate in 541 patients (81.1 %). At multivariate analysis, antidepressants (odds ratio [OR] 4.25, 95 % confidence interval [CI] 1.91 - 9.47), co-morbidity (OR 3.35, 95 %CI 2.16 - 5.18), constipation (OR 2.09, 95 %CI 1.29 - 3.40), and abdominal/pelvic surgery (OR 1.60, 95 %CI 1.03 - 2.47) were independent predictors for inadequate cleansing. The model built with these variables showed an area under the curve of 0.72 in the development cohort and 0.70 in the validation cohort. A cutoff of 1.225 predicted inadequate bowel preparation with a sensitivity, specificity, positive predictive value, and negative predictive value of 60.3 % (95 %CI 51.6 - 68.4), 75.4 % (95 %CI 71.6 - 78.9), 36.4 % (95 %CI 30.1 - 43.1), and 89.1 % (95 %CI 85.9 - 91.6) in the development cohort, and 50.0 % (95 %CI 38.1 - 61.9), 80.0 % (95 %CI 75.3 - 84.2), 35.7 % (95 %CI 26.4 - 45.6), and 87.9 % (95 %CI 83.7 - 91.3) in the validation cohort. Conclusion A simple score may assist the clinician in predicting which patients are at high risk of inadequate bowel cleanliness. This may guide changes in bowel preparation strategy accordingly.

Comparison of Two Intensive Bowel Cleansing Regimens in Patients With Previous Poor Bowel Preparation: A Randomized Controlled Study.

OBJECTIVES: Inadequate bowel cleansing is a major burden for endoscopy units. The aim of this study was to compare two intensive bowel cleansing regimens in patients with previous colonoscopy with inadequate bowel preparation. METHODS: Patients with inadequate cleansing at index colonoscopy were randomized to 4-L split-dose polyethylene-glycol (PEG) regimen vs. 2-L split-dose PEG plus ascorbic acid (PEG+Asc) regimen. All individuals underwent a 3-day low-residue diet and received 10 mg of bisacodyl, the day before colonoscopy. Cleansing was considered to be adequate if the Boston Bowel Preparation Scale scored ≥2 at each colonic segment. A non-inferiority analysis was performed to demonstrate that colonic cleansing with 2-L PEG+Asc was not inferior to 4-l PEG, considering a non-inferiority margin of 10%. RESULTS: Adequate bowel cleansing was significantly higher in patients assigned to 4-L PEG regimen (n=127) vs. those randomized to 2-L PEG+Asc regimen (n=129) by intention-to-treat analysis (81.1 vs. 67.4%, odds ratio (OR) 2.07, 95% confidence interval (CI) (1.163-3.689)) and by per-protocol analysis (86.6 vs. 71.7%, OR: 2.55, 95% CI: (1.316-4.922)). The study was terminated for futility after the interim analysis, because the 95% CI of the difference of proportions was 3.13-24.27% in the intention-to-treat analysis and 3.33-26.47% in the per-protocol analysis, confirming the superiority of 4-L PEG preparation. CONCLUSIONS: After 3-day low-residue diet and oral bisacodyl before colonoscopy, colon cleansing with 4-L split-dose PEG was superior to 2-L split-dose PEG+Asc in patients with previous inadequate cleansing. (EUDRACT: 2013-002506-31, NCT02073552).

Plasma matrix metalloproteinase 9 as an early surrogate biomarker of advanced colorectal neoplasia / Metaloproteinasa 9 como biomarcador plasmático de neoplasia colorrectal avanzada

INTRODUCTION: Matrix metalloproteinases (MMPs) are overexpressed at different stages of colorectal carcinogenesis and could serve as early surrogate biomarkers of colorectal neoplasia. OBJECTIVE: To assess the utility of plasma MMP2 and MMP9 levels in the detection of advanced colorectal neoplasia and their correlation with tissue levels. METHODS: We analysed blood and tissue samples from patients with non-advanced adenomas (n = 25), advanced adenomas (n = 25), colorectal cancer (n = 25) and healthy controls (n = 75). Plasma and tissue gelatinase levels were determined by Luminex XMAP technology and gelatin zymography. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimum cut-off for the detection of advanced colorectal neoplasia. RESULTS: Plasma MMP2 levels were similar between groups whatever the type of lesion. Plasma MMP9 levels were significantly higher in patients with neoplastic lesions than in healthy controls (median 292.3 ng/ml vs. 139.08 ng/ml, P < 0.001). MMP9 levels were also higher in colorectal cancer than in non-advanced adenomas (median 314.6 ng/ml vs. 274.3 ng/ml, P = 0.03). There was a significant correlation between plasma and tissue levels of MMP9 (r =0.5, P < 0.001). The plasma MMP9 cut-off range with the highest diagnostic accuracy was between 173 ng/ml and 204 ng/ml (AUC = 0.80 [95% CI: 0.72-0.86], P < 0.001; sensitivity, 80-86% and specificity, 57-67%). CONCLUSION: Plasma MMP9 could be a surrogate biomarker for the early detection of advanced colorectal neoplasia, although its diagnostic performance could be increased by combination with other biomarkers

INTRODUCCIÓN: Las metaloproteinasas (MMP) son proteínas que se sobreexpresan en diferentes etapas de la carcinogénesis colorrectal y podrían ser biomarcadores de neoplasia colorrectal. OBJETIVO: Evaluar la utilidad de MMP2 y MMP9 en plasma para detectar neoplasia colorrectal avanzada y su correlación con los niveles tisulares. MÉTODOS: Se analizaron muestras de sangre y tejido en pacientes con adenomas no avanzados (n = 25), adenomas avanzados (n = 25), cáncer colorrectal (n = determinaron mediante tecnología xMAP Luminex y zimografía con gelatina. Se utilizaron curvas ROC para calcular el punto de corte óptimo para neoplasia colorrectal avanzada. RESULTADOS: Los niveles de MMP2 fueron similares en las distintas lesiones. Los niveles de MMP9 fueron significativamente superiores en los pacientes con lesiones neoplásicas comparados con controles sanos (mediana de 292,3 ng/ml vs. 139,08 ng/ml; p < 0,001). Los niveles de MMP9 fueron más altos en los cánceres colorrectales que en adenomas no avanzados (mediana de 314,6 ng/ml vs. 274,3 ng/ml; p = 0,03). Se observó correlación entre los niveles plasmáticos y tisulares de MMP9 (r = 0,5; p < 0,001). El rango de MMP9 plasma con mayor precisión diagnóstica fue 173-204 ng/ml (AUC = 0,80 [IC 95%: 0,72-0,86], p < 0,001; sensibilidad 80-86% y especificidad 57-67%). CONCLUSIÓN: Los niveles en plasma de MMP9 podrían ser un biomarcador útil para detectar neoplasia colorrectal avanzada. La combinación con otros biomarcadores podría aumentar su rendimiento diagnóstico

Plasma matrix metalloproteinase 9 as an early surrogate biomarker of advanced colorectal neoplasia.

INTRODUCTION: Matrix metalloproteinases (MMPs) are overexpressed at different stages of colorectal carcinogenesis and could serve as early surrogate biomarkers of colorectal neoplasia. OBJECTIVE: To assess the utility of plasma MMP2 and MMP9 levels in the detection of advanced colorectal neoplasia and their correlation with tissue levels. METHODS: We analysed blood and tissue samples from patients with non-advanced adenomas (n=25), advanced adenomas (n=25), colorectal cancer (n=25) and healthy controls (n=75). Plasma and tissue gelatinase levels were determined by Luminex XMAP technology and gelatin zymography. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimum cut-off for the detection of advanced colorectal neoplasia. RESULTS: Plasma MMP2 levels were similar between groups whatever the type of lesion. Plasma MMP9 levels were significantly higher in patients with neoplastic lesions than in healthy controls (median 292.3ng/ml vs. 139.08ng/ml, P<0.001). MMP9 levels were also higher in colorectal cancer than in non-advanced adenomas (median 314.6ng/ml vs. 274.3ng/ml, P=0.03). There was a significant correlation between plasma and tissue levels of MMP9 (r=0.5, P<0.001). The plasma MMP9 cut-off range with the highest diagnostic accuracy was between 173ng/ml and 204ng/ml (AUC=0.80 [95% CI: 0.72-0.86], P<0.001; sensitivity, 80-86% and specificity, 57-67%). CONCLUSION: Plasma MMP9 could be a surrogate biomarker for the early detection of advanced colorectal neoplasia, although its diagnostic performance could be increased by combination with other biomarkers.

Oncogenic human papillomavirus-infected immature metaplastic cells and cervical neoplasia.

Persistent cervical high-risk human papillomavirus (HR-HPV) infection results in high-grade cervical intraepithelial neoplasia (CIN2/3) and cervical carcinoma. The susceptibility of the cervix to HPV carcinogenesis and the importance of HPV18 in cervical carcinoma despite relative infrequency in CIN2/3 could be linked to HR-HPV infection of immature metaplasia (IM) at the squamocolumnar junction. Atypical IM (AIM) is an equivocal category used to describe changes in IM suggestive of high-grade neoplasia, which causes diagnostic and management problems. We used laser capture microscopy combined with polymerase chain reaction in 24 women with HPV18, HPV16, or other HPV infections on cytologic analysis and a cervical loop electrosurgical excision procedure to locate HR-HPV in cervical tissue. HPV18-positive AIM and CIN2/3 were present in 7/12 cases with HPV18 on cytologic analysis. In 2 cases with HPV18 and other HPV types, HPV18 was only present in AIM and not in CIN2/3. HPV16-positive AIM was present in 3/7 and HPV16-positive CIN2/3 in 5/7 cases with HPV16. No cases had HPV16 AIM without CIN2/3. Other HR-HPV-positive AIM and CIN2/3 cases were present, respectively, in 1/6 and 5/6 cases positive for HR-HPV types other than HPV16/18. In a subset, 94% HPV18 AIM regions showed CK17 and p16 positivity, and 41% were CK7 positive. CIN2/3 and AIM with other HR-HPVs showed similar patterns. AIM was a particular feature of HPV18 infection in women with CIN2/3. HR-HPV infection of CK7/17-positive AIM expressing p16 was particularly seen for HPV18 with and without classical CIN2/3 and should be regarded as a high-grade precancer.