Predictors Of Treatment Failure Research Articles

A deep-learning-based prognostic nomogram integrating microscopic digital pathology and macroscopic magnetic resonance images in nasopharyngeal carcinoma: a multi-cohort study.

Background:To explore the prognostic value of radiomics-based and digital pathology-based imaging biomarkers from macroscopic magnetic resonance imaging (MRI) and microscopic whole-slide images for patients with nasopharyngeal carcinoma (NPC).Methods:We recruited 220 NPC patients and divided them into training (n = 132), internal test (n = 44), and external test (n = 44) cohorts. The primary endpoint was failure-free survival (FFS). Radiomic features were extracted from pretreatment MRI and selected and integrated into a radiomic signature. The histopathological signature was extracted from whole-slide images of biopsy specimens using an end-to-end deep-learning method. Incorporating two signatures and independent clinical factors, a multi-scale nomogram was constructed. We also tested the correlation between the key imaging features and genetic alternations in an independent cohort of 16 patients (biological test cohort).Results:Both radiomic and histopathologic signatures presented significant associations with treatment failure in the three cohorts (C-index: 0.689–0.779, all p < 0.050). The multi-scale nomogram showed a consistent significant improvement for predicting treatment failure compared with the clinical model in the training (C-index: 0.817 versus 0.730, p < 0.050), internal test (C-index: 0.828 versus 0.602, p < 0.050) and external test (C-index: 0.834 versus 0.679, p < 0.050) cohorts. Furthermore, patients were stratified successfully into two groups with distinguishable prognosis (log-rank p < 0.0010) using our nomogram. We also found that two texture features were related to the genetic alternations of chromatin remodeling pathways in another independent cohort.Conclusion:The multi-scale imaging features showed a complementary value in prognostic prediction and may improve individualized treatment in NPC.

Sofosbuvir-containing regimens are safe and effective in the treatment of HCV patients with moderate to severe renal impairment.

This study aimed to assess the safety and efficacy of sofosbuvir (SOF)-based regimens in patients with moderate to severe renal impairment; a subject which has been questioned by many investigators with conflicting results. This is a real-life multicentre retrospective cohort study on 4944 chronic Hepatitis C virus (HCV) patients with chronic kidney disease (CKD) (eGFR <60mL/min/1.73m2 ) who received SOF-based therapy in specialized treatment centres affiliated to the National Committee for the Control of Viral Hepatitis in Egypt. The efficacy and safety of SOF-based regimens was assessed. Week 12 virological response rates were 97.5%, 96.7%, 85.7% and 80% in the total cohort, patients with eGFR <30mL/min/1.73m2 , patients with associated hepatic decompensation and patients on dialysis respectively. Various treatment regimens did not statistically affect the response rates. Treatment experience, cirrhosis and diabetes were predictors of treatment failure on multivariate analysis. Serious adverse events occurred in 0.1% of cases. Forty patients (0.8%) discontinued treatment. Sofosbuvir-based regimens are effective and safe for treating patients with chronic HCV and moderate to severe CKD, and in those with associated hepatic decompensation.

Supplemental Material for Predicting Treatment Failure in Regular Care Internet-Delivered Cognitive Behavior Therapy for Depression and Anxiety Using Only Weekly Symptom Measures

Supplemental Material for Predicting Treatment Failure in Regular Care Internet-Delivered Cognitive Behavior Therapy for Depression and Anxiety Using Only Weekly Symptom Measures

Determinants of first line antiretroviral therapy treatment failure among adult patients on ART at central Ethiopia: un-matched case control study

BackgroundIn 2018 in Ethiopia, magnitude of human immunodeficiency virus Acquired Immunodeficiency Syndrome treatment failure was 15.9% and currently the number of patient receiving second line antiretroviral therapy (ART) is more increasing than those taking first line ART. Little is known about the predictors of treatment failure in the study area. Therefore; more factors that can be risk for first line ART failure have to identified to make the patients stay on first line ART for long times. Consequently, the aim of this study was to identify determinants of first line ART treatment failure among patients on ART at St. Luke referral hospital and Tulubolo General Hospital, 2019.MethodsA 1:2 un-matched case-control study was conducted among adult patients on active follow up. One new group variables was formed as group 1 for cases and group 0 for controls and then data was entered in to Epi data version 3 and exported to STATA SE version 14 for analysis. From binary logistic regression variables with p value ≤0.25 were a candidate for multiple logistic regression. At the end variables with a p-value ≤0.05 were considered as statistically significant.ResultA total of 350 (117 cases and 233 controls) patients were participated in the study. Starting ART after 2 years of being confirmed HIV positive (AOR = 3.82 95% CI 1.37,10.6), nevirapine (NVP) based initial ART (AOR = 2.77,95%CI 1.22,6.28) having history of lost to follow up (AOR 3.66,95%CI 1.44,9.27) and base line opportunistic infection (AOR = 1.97,95%CI 1.06,3.63), staying on first line ART for greater than 5 years (AOR = 3.42,95%CI 1.63,7.19) and CD4 less than100cell/ul (AOR = 2.72,95%CI 1.46,5.07) were independent determinants of first line ART treatment failure.ConclusionLost to follow up, staying on first line ART for greater than 5 years, presence of opportunistic infections, NVP based NNRT, late initiation of ART are determinant factors for first line ART treatment failure. The concerned bodies have to focus and act on those identified factors to maintain the patient on first line ART.

Rate and Predictors of Treatment Failure among Pediatric Population Taking Highly Active Antiretroviral Therapy in Ethiopia

The global scaling up of treatment and care for people living with Human Immunodeficiency Virus has led to a 43% decline in new HIV pediatric infections since 2003, with 330,000 newly infected children in 2011.

Use of HBsAg quantification in the natural history and treatment of chronic hepatitis B.

In patients with chronic hepatitis B (CHB) infection, it is important to monitor the natural history, assess treatment response, and predict the risk of liver-related complications. Quantification of serum hepatitis B surface antigen (HBsAg) has gained wide interests since the last decade. It is secreted from hepatocytes in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative phases of the disease, and can be transcribed and translated from different sources of viral genome [ccc DNA or integrated hepatitis B virus (HBV) DNA]. In untreated patients, it declines slowly through the natural course and remains stable for a long time after HBeAg seroconversion. In patients treated with nucleos(t)ide analogues (NA), it also declines very slowly, even though serum hepatitis B DNA has been rendered negative. Low serum HBsAg may predict either spontaneous or treatment-induced HBsAg seroclearance, and potentially selects out HBeAg-negative patients who can safely stop NA. High serum HBsAg is associated with high risk of hepatocellular carcinoma in untreated population, and predicts treatment failure in patients receiving pegylated interferon. These potential roles of HBsAg quantification are applicable to selected populations only. There is also a need for novel markers to study the effect of emerging antiviral therapies targeting various parts of the HBV cycle to reflect their distinct mechanistic effects. Several agents measuring HBsAg levels have shown rapid and significant decline. Ongoing studies are required to demonstrate the sustainability of HBsAg suppression by these novel agents.

Critical analysis of urethroplasty for male anterior urethral stricture: a single-center experience.

Urethroplasty is the most effective treatment method for anterior urethral strictures, which constitute an important health concern for males. This study aims to investigate factors that may predict treatment failure following urethroplasty for anterior urethral strictures and evaluate outcomes of different urethroplasty techniques. This retrospective study utilized univariate and multivariate analyses to identify factors affecting treatment success following different urethroplasty techniques performed by a single surgeon on male patients with anterior urethral strictures. Surgical outcomes of different urethroplasty techniques were evaluated individually. Urethroplasty procedures performed on 244 patients with a mean age of 54years and a mean stricture length of 4.7cm produced a success rate of 79.1%. Multivariate analyses identified stricture length and number of previous internal urethrotomy procedures as factors predicting urethroplasty success (HR 1.265, 95% CI 1.129-1.416, p < 0.001 and HR 1.188, 95% CI 1.038-1.361, p = 0.013, respectively). The eight surgical techniques used by the surgeon produced success rates that varied between 50% and 86.2%. Urethroplasty can offer satisfactory outcomes for anterior urethral strictures. Accordingly, a longer stricture length and greater number of previous internal urethrotomy procedures were associated with greater risk for urethroplasty failure. Moreover, urethroplasty techniques must be selected based on multifactorial evaluation and performed at experienced centers.

Patterns and Predictors of Relapse Following Radical Chemoradiation Therapy Delivered Using Intensity Modulated Radiation Therapy With a Simultaneous Integrated Boost in Anal Squamous Cell Carcinoma

PurposeOur purpose was to describe the patterns and predictors of treatment failure in patients receiving definitive chemoradiation therapy (CRT) for anal squamous cell carcinoma (ASCC), delivered using intensity modulated radiation therapy (IMRT).Methods and MaterialsOur study was a retrospective cohort analysis of consecutive patients treated with curative intent for ASCC using CRT delivered with a standardized IMRT technique in 5 UK cancer centers. Patients were included from the start of UK IMRT guidance from February 2013 to October 31, 2017. Collected data included baseline demographics, treatment details, tumor control, sites of relapse, and overall survival. Statistical analysis to calculate outcomes and predictive factors for outcome measures were performed using SPSS and R.ResultsThe medical records of 385 consecutive patients were analyzed. Median follow-up was 24.0 months. Within 6 months of completing CRT, 86.7% of patients achieved a complete response. Three-year disease-free survival and overall survival were 75.6% and 85.6%, respectively. Of all relapses, 83.4% occurred at the site of primary disease. There were 2 isolated relapses in regional nodes not involved at outset. Predictive factors for cancer recurrence included male sex, high N-stage, and failure to complete radiation therapy as planned.ConclusionsThe treatment results compare favorably to published outcomes from similar cohorts using 3-dimensional conformal CRT. The observed patterns of failure support the current UK IMRT voluming guidelines and dose levels, highlighting our prophylactic nodal dose as sufficient to prevent isolated regional relapse in uninvolved nodes. Further investigation of strategies to optimize CR should remain a priority in ASCC because the site of primary disease remains the overwhelming site of relapse.

Intraoperative human papillomavirus testing: earlier prediction of treatment failure.

Intraoperative human papillomavirus testing: earlier prediction of treatment failure.

1222 Conservative Management of Cesarean Scar Pregnancies with Systemic Multidose Methotrexate: Predictors of Treatment Failure and Reproductive Outcomes

Study Objective The role of conservative management of CSP has been previously reported with conflicting results reported. In this retrospective study, we aimed to further evaluate its role and better delineate the subsequent reproductive outcomes Design A retrospective cohort study. Setting A large university hospital (Hadassah Medical Center Hospitals, Israel, Jerusalem) between November 2014 to April 2017 Patients or Participants All patients diagnosed with a CSP and treated by intention of conservative management with systemic methotrexate (MTX). Interventions A comparison of maternal and gestation characteristics was performed between treatment success and failure groups Measurements and Main Results Thirty seven cases of CSP were encountered. Overall, 29/37 (78.3%) were treated by systemic injection of MTX while the other 21.7% had combined systemic and local (i.e. intra-sac) MTX treatment. Invasive intervention was needed in 5 (13.5%) cases (failure group). Cases who were converted to surgical treatment had higher number of previous cesarean deliveries (median 4 vs. 2, p=0.002). In logistic regression modeling, the number of prior cesarean deliveries in the past was the only factor found independently associated with conversion to surgical management Odds Ratio 2.02, 95 % Confidence Interval 1.03,3.94. Majority of future pregnancies had term pregnancy with one preterm delivery due to severe intrauterine growth restriction Conclusion Systemic MTX therapy is a safe and effective strategy for the treatment of CSP with favorable subsequent reproductive results and a low conversion rate for surgical management. Patients with high order of previous cesarean deliveries should be considered for early surgical treatment rather than a medical one.

435P - Mature treatment results of 120 cases of acoustic neuroma treated with cyberknife at a single institution

BackgroundStereotactic radiosurgery (SRS) is a noninvasive alternative to microsurgery in the management of acoustic neuromas. Single fraction Gamma Knife SRS of acoustic neuromas results in high rates of local control (85-97 %). CyberKnife (CK) Robotic SRS is an alternative technique delivering the same quality SRS but with the benefits of a frameless treatment system allowing for fractionated treatment. The body of evidence in its use for acoustic neuromas is less robust. We present mature outcomes of a large cohort of patients treated with CK at a single institution. MethodsThis study consisted of 120 acoustic neuroma patients treated with CK from Sept 2010 until March 2016. Patients with complete hearing loss were treated with a single 12Gy fraction (6 Pts). Those with hearing preservation or moderate to large tumors were treated with 18Gy in 3 fractions (114pts). Follow-up T2 axial MRIs (0.50mm slice) were analyzed to evaluate rates of tumor control and incidence of pseudo-progression. To obtain volumetric response data, MRI images were contoured on PACs imaging station using Aquarius Net version 4.4.13 by a single radiation oncologist. ResultsPatients range in age from 15 to 91 (mean 58). The median follow up time was 60 months. Mean tumor size was 2.8cm3 (Range 0.1-30). Progression occurred in 4 patients (local control rate of 97%). Pseudo-progression was seen in 17 cases. For patients with pseudo-progression mean time to the maximum imaged tumor volume post treatment was 5 months (Range of 3 to 12 months) with an average volume increase of 11% (Max 31%). Mean time to subsequent regression to pre-treatment size was 15 months (Range of 10-23) No pseudo-progression led to subsequent local recurrence. There were low rates of late toxicity. One patient who progressed suffered CN VII palsy prior to salvage surgery. All other patients had preserved CNV and CNVII function and there was no case of brain stem necrosis. ConclusionsCyberknife offered high rates of durable local control (97 %) for acoustic neuromas with low rates of toxicity. Pseudo-progression was seen in 14% of patients and was not a predictor for treatment failure. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureS. Malone: Honoraria (self): Janssen; Honoraria (self): Astellas; Travel / Accommodation / Expenses: TerSera; Honoraria (self): AstraZeneca; Honoraria (self): AMGEN; Travel / Accommodation / Expenses: Sanofi; Honoraria (self): Abbvie; Honoraria (self): Bayer. All other authors have declared no conflicts of interest.

Posttreatment squamous cell carcinoma antigen predicts treatment failure in patients with cervical squamous cell carcinoma treated with concurrent chemoradiotherapy

ObjectiveTo analyze the association between posttreatment squamous cell carcinoma antigen (SCC Ag) and treatment failure in patients with cervical SCC treated with concurrent chemoradiotherapy (CCRT). MethodsWe reviewed patients with cervical SCC who were treated with definitive radiotherapy or CCRT between June 2012 and May 2015 at our institute. A receiver operating characteristic (ROC) curve was used to analyze the cutoff value of posttreatment SCC Ag in predicting treatment failure. Log-rank tests and Cox proportional hazards models were used to identify whether posttreatment SCC Ag was significant in predicting disease-free survival (DFS). ResultsA total of 559 patients were included in this study. With the ROC curve, the optimal cutoff posttreatment SCC Ag level was 1.8 ng/mL (sensitivity 27.1%, specificity 96.6%). A posttreatment SCC Ag level ≥ 1.8 ng/mL was observed in 47 patients. The multivariate analysis showed that posttreatment SCC Ag (hazard ratio 5.10; 95% confidence interval, 3.31–7.88; p < 0.001) was an independent prognostic factor of DFS. The 3-year overall survival (OS), DFS, local control, and distant control rates of patients with posttreatment SCC Ag < 1.8 ng/mL and ≥1.8 ng/mL were 90.7% and 46.4% (p < 0.001), 84.8% and 31.9% (p < 0.001), 81.4% and 69.5% (p < 0.001), and 90.4% and 54.1% (p < 0.001), respectively. ConclusionPatients with posttreatment SCC Ag ≥ 1.8 ng/mL suffer due to a high rate of treatment failure and poor survival.

Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research.

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.

Le test HPV dans le dépistage et le suivi des patientes présentant une lésion histologique de haut grade du col utérin

ObjectivesTo evaluate the value of high-risk HPV (HR HPV) testing in screening and post-treatment follow-up of high-grade squamous intraepithelial cervical lesions (HSIL). MethodsA systematic review of the literature from 2000 to 2019 was conducted including the following keywords: “human papilloma virus”, “HPV testing”, “cervical squamous intraepithelial lesion”, “cervical cancer”. ResultNumerous recent randomized studies and meta-analyzes have concordant results in favor of HR HPV superiority over cervical smear in the screening and post-treatment monitoring of HSIL. In screening, the sensitivity of the HR HPV tests is 63% to 98% whereas that of the cervical smear is only 38% to 65% for the detection of HSIL+ (HSIL and invasive cancers). A negative HR HPV test is associated with less than 5% risk of LIEHG+at 6 years. In addition, after removal of a LIEHG, HR HPV tests have a sensitivity>90% and specificity>80% to predict treatment failure. After surgicale exision, a negative HR HPV test is associated with a risk of failure<2% (negative predictive value of 98%), and 12–25% if it is positive. ConclusionsHR HPV tests are effective, allowing early detection of LIEHG+ identification of low-risk women in case of negative test, and a prediction of the risk of failure after treatment.

Randomized Controlled Trial on Adjunctive Lavage for Severe Peritonitis.

Background:In severe peritoneal dialysis (PD)-related peritonitis, patients' response to antibiotic can be poor. We postulated that adjunctive lavage may improve the outcome in severe cases by enhancing the removal of bacteria and inflammatory cells from the peritoneum.Methods:Severe PD peritonitis was defined as poor clinical response to empirical cefazolin/ceftazidime and a PD effluent (PDE) leukocyte count > 1,090/mm3 on day 3. Enrolled patients were randomized into either the lavage group (n = 20) or control group (n = 20). In the lavage group, continuous lavage by an automated PD machine from day 3 to 5 or 6 was performed, whereas the usual PD schedule was maintained in the control group. The primary outcome was treatment success. Post hoc analysis was also performed to compare the outcome between subgroups with different severity.Results:Baseline parameters were similar in the lavage and control groups, including PDE leukocyte count on day 3 (4,871/mm3 vs 4,143/mm3, p = 0.46). Treatment success rates were high in both groups (75% vs 70%, p = 0.72). C-reactive protein (CRP) on day 3 was found to be the only predictor of treatment failure and was used to stratify all patients into tertiles of severity. Whilst a significant decline in treatment success was evident across the tertiles of increasing CRP in the control group (100% vs 85.7% vs 28.6%, p = 0.005), treatment success was relatively maintained in the lavage group (85.7% vs 71.4% vs 66.7%, p = 0.43).Conclusions:Adjunctive lavage did not improve the overall outcome, although it may be beneficial for the more severe peritonitis patients who have high CRP.

Posttreatment Squamous Cell Carcinoma Antigen in Predicting Treatment Failure for Patients with Cervical Squamous Cell Carcinoma Treated with Concurrent Chemoradiotherapy

To analyze the association between posttreatment squamous cell carcinoma (SCC) antigen and treatment failure for patients with cervical SCC and treated with concurrent chemoradiotherapy (CCRT). We reviewed patients with cervical SCC and treated with definitive CCRT between June 2012 and May 2015 in our institute. A dose of 50.4Gy in 28 fractions was delivered to the pelvic with intensity modulated radiation therapy. With high-dose-rate brachytherapy, 30-36Gy in 5-7 fractions was prescribed to point A. The first line regimen of concurrent chemotherapy was cisplatin weekly. Posttreatment SCC antigen level was checked at 20 to 60 days after the completion of CCRT. A receiver operating characteristic (ROC) curve was performed to analyze the cutoff point of pretreatment and posttreatment SCC Ag in predicting treatment failure. Log-rank test and Cox’s proportional hazard model were used to identify whether pretreatment and posttreatment SCC Ag was significant in predicting disease-free survival (DFS). A total of 559 patients were included in this study. With ROC curve, the optimal cut-off points of pretreatment and posttreatment SCC antigen level were 8.6ng/ml (sensitivity 54.2%, specificity 65.8%) and 1.8 ng/ml (sensitivity 27.1%, specificity 96.6%). Posttreatment SCC antigen level ≥ 1.8ng/ml was observed in 47 patients. Multivariate analysis showed that posttreatment SCC Ag (hazard ratio 5.10, 95% confidence interval 3.31-7.88, p<0.001) was an independent prognostic factor of DFS. However, pretreatment SCC Ag was not significant in predicting DFS. The 3-year overall survival, DFS, local control and distant control rates of patients with posttreatment SCC antigen <1.8 ng/ml and ≥ 1.8 ng/ml were 90.7% and 46.4% (p<0.001), 84.8% and 31.9% (p<0.001), 81.4% and 69.5% (p<0.001), 90.4% and 54.1% (p<0.001), respectively. Cervical SCC patients with posttreatment SCC antigen ≥ 1.8ng/ml experienced high risk of treatment failure and poor survival. Consolidation therapy or extensive follow-up should be considered for these patients.

Incomplete excision of cervical intraepithelial neoplasia as a predictor of the risk of recurrent disease—a 16-year follow-up study

Women treated for high-grade cervical intraepithelial neoplasia (grade 2 or 3) are at elevated risk for developing cervical cancer. Suggested factors identifying women at highest risk for recurrence post-therapeutically include incomplete lesion excision, lesion location, size and severity, older age, treatment modality, and presence of high-risk human papilloma virus after treatment. This question has been intensively investigated over decades, but there is still substantial debate as to which of these factors or combination of factors most accurately predict treatment failure. In this study, we examine the long-term risk of residual/recurrent high-grade cervical intraepithelial neoplasia among women previously treated for cervical intraepithelial neoplasia 2/3 and how this varies according to margin status (considering also location), as well as comorbidity (conditions assumed to interact with high-risk human papilloma virus acquisition and/or cervical intraepithelial neoplasia progression), posttreatment presence of high-risk human papilloma virus, and other factors. This prospective study included 991 women with histopathologically confirmed cervical intraepithelial neoplasia 2/3 who underwent conization in 2000-2007. Information on the primary histopathologic finding, treatment modality, comorbidity, age, and high-risk human papilloma virus status during follow-up, and residual/recurrent high-grade cervical intraepithelial neoplasia was obtained from the Swedish National Cervical Screening Registry and medical records. Cumulative incidence of residual/recurrent high-grade cervical intraepithelial neoplasia was plotted on Kaplan-Meier curves, with determinants assessed by Cox regression. During a median of 10 years and maximum of 16 years offollow-up, 111 patients were diagnosed with residual/recurrent high-grade cervical intraepithelial neoplasia or worse. Women with positive/uncertain margins had a higher risk of residual/recurrent high-grade cervical intraepithelial neoplasia or worse than women with negative margins, adjusting for potential confounders (hazard ratio, 2.67; 95% confidence interval, 1.81-3.93). The risk of residual/recurrent high-grade cervical intraepithelial neoplasia or worse varied by anatomical localization of the margins (endocervical: hazard ratio, 2.72; 95% confidence interval, 1.67-4.41) and both endo- and ectocervical (hazard ratio, 4.98; 95% confidence interval, 2.85-8.71). The risk did not increase significantly when only ectocervical margins were positive or uncertain. The presence of comorbidity (autoimmune disease, human immunodeficiency viral infection, hepatitis B and/or C, malignancy, diabetes, genetic disorder, and/or organ transplant) was also a significant independent predictor of residual/recurrent high-grade cervical intraepithelial neoplasia or worse. In women with positive high-risk human papilloma virus findings during follow-up, the hazard ratio of positive/uncertain margins for recurrent/residual high-grade cervical intraepithelial neoplasia or worse increased significantly compared to that in women with positive high-risk human papilloma virus findings but negative margins. Patients with incompletely excised cervical intraepithelial neoplasia 2/3 are at increased risk for residual/recurrent high-grade cervical intraepithelial neoplasia or worse. Margin status combined with high-risk human papilloma virus results and consideration of comorbidity may increase the accuracy for predicting treatment failure.

Real-life effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients with previous DAA failure

Sofosbuvir/velpatasivr/voxilaprevir (SOF/VEL/VOX) is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs), however real-life data are limited. The aim of this study was to assess the effectiveness and safety of SOF/VEL/VOX in a real-life setting. All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13 kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment. A total of 179 patients were included: median age 57 (18-88) years, 74% males, median HCV-RNA 1,081,817 (482-25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, 1a 24%, 1nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12 weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (p = 0.005) and hepatocellular carcinoma (p = 0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%). SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting. This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure.

Efficacy of direct-acting antivirals: UK real-world data from a well-characterised predominantly cirrhotic HCV cohort.

Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C virus (HCV) infection. We describe UK real-world DAA experience. Individuals commencing HCV treatment containing a DAA regimen (Mar 2014-Nov 2016), participating in the National HCV Research UK (HCVRUK) Cohort Study were recruited from 33 UK HCV centers. The data were prospectively entered at sites onto a centralised database. The data were reported as median (Q1-Q3). Of the 1448 treated patients, 1054 (73%) were males, the median age being 54 years (47-60), 900 (62%) being genotype 1 and 455 (31%) genotype 3. The majority, 887 (61%) had cirrhosis, and 590 (41%) were treatment-experienced. DAA regimens utilised: genotype1 sofosbuvir (SOF)/Ledipasvir/±Ribavirin (625/900, 69%) and Ombitasvir/Paritaprevir/Dasabuvir/±RBV (220/900, 24%), and in genotype 3 SOF/Daclatasvir + RBV (256/455, 56%) and SOF/pegylated interferon/RBV (157/455, 35%). Overall, 1321 (91%) achieved sustained virological response (SVR12), genotype 1 vs 3, 93% vs 87%, P < .001. Prior treatment, presence of cirrhosis and treatment regimen did not impact SVR12. Predictors of treatment failure were genotype 3 infection, OR, 2.015 (95% CI: 1.279-3.176, P = .003), and male sex, OR, 1.878 (95% CI: 1.071-3.291, P = .028). Of those with hepatic decompensation at baseline (n = 39), 51% (n = 20) recompensated post-treatment, lower baseline serum creatinine being associated with recompensation (P = .029). There were two liver-related deaths, both having decompensated disease. This real-world UK data, comprising of a predominantly cirrhotic HCV genotype 1/3 cohort, confirms DAA efficacy with an overall 91% SVR12, with 51% recompensating post-treatment. Genotype 3 infection was a predictor of treatment failure.

WITHDRAWN: TREATMENT FAILURE AND EMPIRIC ANTIBIOTIC CHOICE FOR HOSPITALIZED PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA: Β-LACTAM/Β-LACTAMASE INHIBITOR COMBINED WITH MACROLID OR FLUOROQUINOLONE ALONE?

Background&#x0D; A considerable percentage of empirical antibiotic treatment fails in hospitalized patients with community-acquired pneumonia (CAP). β-lactams and macrolid (BLM) combination or respiratory fluoroquinolones (FQ) are the most frequently used in these patients. The aim of the present study is to compare the treatment failure (TF) rates in BLM and FQ treatment and to analyze the predictive factors of TF.&#x0D; Method&#x0D; Hospitalized patients who were initially treated with either BLM or FQ were included retrospectively and treatment results of the two regimens were compared.&#x0D; Results&#x0D; Of the 144 patients included in the study, the mean age was 67±16 and 102 (71%) were male. Each group constituted of 72 patients. Antibiotic selection did not alter TF rates, length of stay (LOS) and 30-day mortality. Baseline higher levels of leucocytes, neutrophils to lymphocytes ratio (NLR), C-reactive protein (CRP), BUN/albumin, lactate dehydrogenase/aspartat aminotransferase (LDH/AST) levels and pneumonia severity index (PSI) scores were detected as predictors of TF.&#x0D; Conclusion&#x0D; Empirical treatments with either BLM or FQ do not correlate with TF, LOS and 30-day mortality. NLR, BUN/albumin and LDH/AST may suggest TF. These inexpensive and easily-reachable parameters have the potential as predictors of the treatment outcome in CAP.&#x0D; &#x0D; Notices of retraction&#x0D; Akyil, F. T., Bekir, S. A., Gungor, A., Akyuz, K., Kose, N., Turker, H., Akyil, M., &amp; Sevim, T. (2019). TREATMENT FAILURE AND EMPIRIC ANTIBIOTIC CHOICE FOR HOSPITALIZED PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA: Β-LACTAM/Β-LACTAMASE INHIBITOR COMBINED WITH MACROLID OR FLUOROQUINOLONE ALONE?. International Journal of Research -GRANTHAALAYAH, 7(7), 360-369. https://doi.org/10.29121/granthaalayah.v7.i7.2019.778&#x0D; Article retracted by : EditorReason(s) for retraction : Author's conflicts of interest