Predictors Of Treatment Failure Research Articles

Predictors of Treatment Failure Following De-escalation to a Fluoroquinolone in Culture-Negative Nosocomial Pneumonia.

Background: Little evidence exists for de-escalation of nosocomial pneumonia therapy without positive cultures. Objective: The purpose of this study was to identify potential predictors of treatment failure following de-escalation to a fluoroquinolone in culture-negative nosocomial pneumonia. Methods: The study involved a single-center, retrospective cohort of patients admitted with diagnosis of nosocomial pneumonia and positive chest radiography who received at least 24 hours of fluoroquinolone monotherapy following at least 24 hours of appropriate empirical antibiotics. Treatment failure was defined using a composite of all-cause death within 30 days of discharge, treatment re-escalation, or readmission for pneumonia within 30 days of discharge. The Cox proportional hazards model was used to analyze predictors of treatment failure. Duration of empirical antibiotics and significant univariable exploratory predictors were included in multivariable analysis. Results: Of 164 patients, 23 (14%) failed de-escalation. Duration of empirical antibiotics (68.5 ± 32.1 vs 65.8 ± 35 hours) was not associated with treatment failure in univariable (Hazard Ratio [HR] = 1.002 [95% CI = 0.991-1.013]) or multivariable analyses (HR = 1.003 [95% CI = 0.991-1.015]). Significant exploratory predictors on univariable analysis included active cancer, intensive care unit (ICU) admission at empirical initiation, APACHE II score, and steroid use ≥20-mg prednisone equivalent. ICU admission at empirical initiation (HR = 2.439 [95% CI = 1.048-5.676]) and steroid use ≥20-mg prednisone equivalent (HR = 2.946 [95% CI = 1.281-6.772]) were associated with treatment failure on multivariable analysis. Conclusion and Relevance: Duration of empirical antibiotics does not appear to influence failure of de-escalation to fluoroquinolone monotherapy in culture-negative nosocomial pneumonia.

Hemigland Cryoablation of Localized Low, Intermediate and High Risk Prostate Cancer: Oncologic and Functional Outcomes at 5 Years.

We evaluated 5-year oncologic and functional outcomes of hemigland cryoablation of localized prostate cancer. We reviewed the records of 160 consecutive men who underwent hemigland cryoablation of localized prostate cancer. Recurrent and/or residual clinically significant prostate cancer was defined as Grade Group 2 or greater on followup biopsy. A prostate specific antigen nadir plus 2 ng/ml according to the Phoenix criteria was used to define biochemical failure. Radical treatment was defined as any whole gland therapy. Treatment failure was defined as any radical and/or whole gland treatment, systemic therapy initiation, metastasis or prostate cancer specific mortality. The study primary end point was treatment failure-free survival. The secondary end points were survival free of biochemical failure, clinically significant prostate cancer and radical treatment. Followup biopsy and functional outcomes were also evaluated. Statistical analysis included the Kaplan-Meier method, and univariate and multivariable Cox and logistic regression with significance considered at p <0.05. Median patient age was 67 years, baseline prostate specific antigen was 6.3 ng/ml and followup was 40 months. A total of 131 patients (82%) had D'Amico intermediate (66%) or high risk (16%) prostate cancer. At 5 years the treatment failure-free survival rate was 85%, the biochemical failure-free survival rate was 62% and the survival rate free of clinically significant prostate cancer was 89%. Higher baseline prostate specific antigen independently predicted treatment failure (p <0.001), biochemical failure (p=0.048), recurrence and radical treatment (p <0.01). Grade Group 3 or greater independently predicted treatment failure (p=0.04). The metastasis-free survival rate was 100% at 5 years. Pad-free continence and potency (erections sufficient for intercourse) were retained in 97% and 73% of patients, respectively. There was no rectal fistula or mortality. Hemigland cryoablation of localized prostate cancer provides effective midterm oncologic outcomes with good continence and potency. Patients with higher baseline prostate specific antigen are at increased risk for biochemical failure, recurrent cancer and treatment failure.

Factors Associated with Treatment Failure and Radiosurgery-Related Edema in WHO Grade 1 and 2 Meningioma Patients Receiving Gamma Knife Radiosurgery

Before the advent of radiosurgery, neurosurgical treatment of meningiomas typically involved gross total resection of the mass whenever surgery was deemed possible. Over the past 4 decades, though, Gamma Knife radiosurgery (GKRS) has proved to be an effective, minimally invasive means to control the growth of these tumors. However, the variables associated with treatment failure (regrowth or clinical progression) after GKRS and GKRS-related complications, such as cerebral edema, are less well understood. We retrospectively collected data between 2009 and 2018 for patients who underwent GKRS for meningiomas. After data collection, we performed univariate and multivariable modeling of the factors that predict treatment failure and cerebral edema after GKRS. Hazard ratios (HR) and P values were determined for these variables. Fifty-two patients were included our analysis. The majority of patients were female (38/52,73%), and nearly all patients presented with a suspected or confirmed World Health Organization grade 1 meningioma (48/52, 92%). The median tumor volume was 3.49 cc (range, 0.22-20.11 cc). Evidence of meningioma progression after treatment developed in 5 patients (10%), with a median time to continued tumor growth of 5.9 months (range, 2.7-18.3 months). In multivariable analysis, patients in whom treatment failed were more likely to be male (HR= 8.42, P= 0.045) and to present with larger tumor volumes (HR=1.27, P= 0.011). In addition, 5 patients (10%) experienced treatment-related cerebral edema. On univariate analysis, patients who experienced cerebral edema were more likely present with larger tumors (HR= 1.16, P= 0.028). Increasing meningioma size and male gender predispose to meningioma progression after treatment with GKRS. Increasing tumor size also predicts the development of postradiosurgery cerebral edema.

What Are the Predictors of Treatment Failure in Patients Who Have Undergone Two-Stage Exchange for Infected Total Ankle Arthroplasty (TAA)?

Predictors for treatment failure in patients undergoing 2-stage exchange for infected total ankle arthroplasty (TAA) include compromised soft tissues (eg, sinus tract and exposed hardware), significant bone involvement/osteomyelitis, and insufficient timing of antibiotic course before reimplantation. Moderate. Agree: 100%, Disagree: 0%, Abstain: 0% (Unanimous, Strongest Consensus).

Abstract 2300: Validation of highly sensitive ctDNA assays for ESR1 resistance mutations with the NGS TargetSelectorTM enrichment technology

Abstract Background: Acquired resistance to anti-hormonal therapy is a common reason for treatment failure in advanced and metastatic breast cancer (mBRC). Mutations in the ESR1 gene, encoding the estrogen receptor (ER) protein, are often associated with this drug resistance. Accurate and timely ESR1 mutation detection may enable early identification of progression and prediction of treatment failure. In contrast to using difficult and painful tissue biopsies, “liquid biopsy” offers a non-invasive and systemic approach to identify solid tumor mutations in peripheral blood by assessing circulating tumor DNA (ctDNA). Biocept has developed the highly sensitive TargetSelectorTM NGS assay to detect low frequency mutant alleles in ctDNA using a patented blocker that suppresses excess WT alleles, while still allowing amplification of tumor derived mutant sequences. Here, we focus on a five-codon ESR1 mutation hotspot that imparts tumor cell resistance to anti-hormonal therapy in mBRC. Methods: The TargetSelectorTM assay applies a specific blocker on a short stretch of target DNA (up to 13 bp). The ESR1 assay consists of two blockers in the region of codons 534-538 of the ESR1 gene. We validated the TargetSelectorTM assays by spiking low level g-block DNA fragments (IDT Inc.) carrying point mutations for each of the targeted ESR1 sites, into human placental DNA. Mutant sequences were enriched via PCR and mutations were subsequently confirmed on the Illumina MiSeq down to a limit of detection (LOD) of 0.01-0.05% minor allele frequency (MAF). For ctDNA testing, whole blood was collected in Biocept CEE-SureTM Blood Collection tubes, and total nucleic acid extraction from plasma was performed on the QIAsymphony. Results: In total, we tested &amp;gt;600 samples for ESR1 TargetSelectorTM ctDNA assays, with ESR1 WT as the background reference. The assay shows &amp;gt;99% analytical sensitivity (at 0.05% MAF) and &amp;gt;97% analytical specificity. Based on practical and theoretical estimates and using ddPCR as an orthogonal verification method, the ESR1assays demonstrate single mutant copy detection for most tested positions, and in all cases showed an LOD of at least 0.05% (5 mutant copies in a background of 10,000 WT copies). Samples tested from 20 healthy donors (40 tests in total) showed high clinical specificity, indicating the test is competent for use in a CLIA certified, CAP accredited laboratory setting. Conclusions: Biocept’s TargetSelectorTM ctDNA assays are validated both analytically and clinically, showing single mutant copy detection and LOD at 0.05% or better in a background of excess WT DNA. Implementation of the Illumina MiSeq platform into our TargetSelectorTM assays leads to higher sample throughput, greater sensitivity and a faster turnaround time than Sanger sequencing. These factors enable a sensitive and efficient test crucial for guiding treatment decisions and patient care. Citation Format: Shan-Fu Wu, Lyle J. Arnold, Jolly Shrivastava, Jason C. Poole. Validation of highly sensitive ctDNA assays for ESR1 resistance mutations with the NGS TargetSelectorTM enrichment technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2300.

Highlights of This Issue

Treatment options are limited for breast cancer patients with central nervous system (CNS) metastasis. The combination of capecitabine and lapatinib, at conventional doses, has activity against HER2-positive breast cancer brain metastases; however, few patients respond, especially long-term. In this study, Morikawa and colleagues evaluated the safety and toxicities associated with intermittent high dose lapatinib alternating with intermittent fixed dose capecitabine in HER2-positive breast cancer patients with CNS metastasis. This regimen resulted in manageable toxicity and promising efficacy and will inform future phase II/III trials.Hypoxia is a negative prognostic feature in nearly all cancer types and predicts treatment failure. Validated, widely available tests are lacking for clinical use. Salem and colleagues provide the first-in-human evidence that oxygen-enhanced MRI (OE-MRI) can track changes in hypoxia that are induced by radiotherapy. OE-MRI was well-tolerated in patients with non-small cell lung cancer, and radiotherapy-induced hypoxia modification was detected. OE-MRI has potential to select patients for hypoxia-modification, track therapeutic efficacy, and identify tumors that may fail immunotherapy.Immunotherapy has been ineffective for patients with pancreatic ductal adenocarcinoma (PDA). In this study, Seo and colleagues demonstrate that CD8+ T cells are often present in PDA, but are localized to the stroma, rather than immediately adjacent to cancer cells. Using slice culture live microscopy from primary PDA tumors, the authors demonstrate that inhibition of the CXCR4 chemokine receptor led to the migration of clonally expanded CD8+ T cells to the cancer cell-rich regions of the tumors. Subsequent PD-1 blockade activated effective cancer cell killing. These results provide a new basis for the rational selection of combination immunotherapy for PDA, a disease with limited treatment options.Relapse remains a major issue for patients with multiple myeloma due to the presence of minimal residual disease (MRD) posttherapy. Bispecific T cell-engager antibody therapy has been effective in the elimination of MRD in other hematological malignancies. Zuch de Zafra and colleagues describe AMG 424, a novel bispecific T-cell–recruiting antibody targeted at CD3 and CD38, the multiple myeloma surface cell marker. AMG 424 effectively killed CD38-positive cells in vitro and showed antitumor activity in mouse and nonhuman primate models. AMG 424 is a promising candidate for multiple myeloma patients and is currently in clinical development.

The WORC Index and Predicting Treatment Failure in Patients Undergoing Primary Arthroscopic Rotator Cuff Repair.

Background:Rotator cuff tears are common injuries that are reliably treated with arthroscopic repair, producing good to excellent results. The Western Ontario Rotator Cuff (WORC) index is a validated disease-specific instrument used to assess patient outcomes; however, no study to date has correlated WORC index with treatment failure.Purpose:To evaluate the WORC index as a predictor for successful treatment in arthroscopic rotator cuff repair. An additional purpose was to identify patient and tear characteristics associated with risk of treatment failure.Study Design:Case-control study; Level of evidence, 3.Methods:This study reviewed a total of 500 patients who underwent arthroscopic rotator cuff repair with a minimum of 2-year follow-up. Patient charts were reviewed for treatment failures, defined as persistent or recurrent shoulder pain or weakness, leading to further workup and identification of a failure to heal or recurrent tear by magnetic resonance imaging. Patient demographic and comorbidity data were gathered and correlated with risk of failure. All patients completed WORC questionnaires, and scores were correlated with risk of treatment failure.Results:There were 28 (5.6%) treatment failures at a median 28 weeks (SD, 42 weeks) postoperatively. Patients claiming workers’ compensation were 3.21 times more likely (odds ratio; P = .018) to fail treatment. Posterior interval tears (those including infraspinatus) were 3.14 times more likely (P = .01) to fail than anterior interval tears. Tear size was associated with treatment failure; the odds of failure was 3.24 for a 2-tendon tear and 5.83 for a 3-tendon tear (P = .03). Tears involving the nondominant arm were associated with an increased risk of failure by a factor of 3.04 (95% CI, 1.01-9.11; P = .047). A WORC score ≥80 was associated with a 95% probability of treatment success at 1 year.Conclusion:After arthroscopic rotator cuff repair, patients with WORC scores ≥80 at 1 year have a 95% probability of successful treatment and likely do not benefit from continued follow-up visits. Furthermore, several risk factors were identified that may influence outcomes after rotator cuff repair, including workers’ compensation, location of tear, tear size, and hand dominance.

Positive Blood Cultures Decrease the Treatment Success in Acute Hematogenous Periprosthetic Joint Infection Treated With Debridement, Antibiotics, and Implant Retention

BackgroundThe influence of positive blood cultures on surgical outcome of acute hematogenous periprosthetic joint infection (PJI) treated by debridement, antibiotics, and implant retention (DAIR) remains unknown. This study evaluated the influence of positive blood cultures on the treatment success of DAIR in patients with acute hematogenous PJI. MethodsA retrospective chart review on 49 patients with blood culture data for acute hematogenous PJI was performed from 2005 to 2016 at a single institution. All patients were treated by DAIR and had a minimum follow-up of 1 year. Treatment success was defined by the Delphi criteria. Multivariate logistic regression analysis was performed to identify variables associated with positive blood culture and treatment success. Kaplan-Meier survivorship curves and log-rank tests were used for analysis. ResultsOverall, 44.9% (22/49) of blood cultures obtained yielded positive growth. Elevated Elixhauser comorbidity index was a significant risk factor associated with positive blood (adjusted odds ratio [OR], 1.65; 95% confidence interval [CI], 1.13-2.40; P = .049). A positive blood culture was the only significant factor predicting treatment failure in acute hematogenous PJI (OR, 3.94; 95% CI, 1.18-13.1; P = .026) after adjusting for confounding variables. Kaplan-Meier survivorship for infection-free implant survivorship was 53.1% (95% CI, 38.3%-65.8%) at 1 year for all patients, 66.7% (95% CI, 45.7%-81.1%) for patients with negative blood cultures, and 36.4% (95% CI, 17.2%-55.7%) for patients with positive blood cultures (P = .037). ConclusionThe presence of positive blood cultures is associated with decreased treatment success of DAIR for acute hematogenous PJI. Patients with more comorbidities may need to be treated more aggressively for a favorable outcome.

An image-based deep learning framework for individualising radiotherapy dose: a retrospective analysis of outcome prediction

Radiotherapy continues to be delivered uniformly without consideration of individual tumor characteristics. To advance toward more precise treatments in radiotherapy, we queried the lung computed tomography (CT)-derived feature space to identify radiation sensitivity parameters that can predict treatment failure and hence guide the individualization of radiotherapy dose. We used a cohort-based registry of 849 patients with cancer in the lung treated with high dose radiotherapy using stereotactic body radiotherapy. We input pre-therapy lung CT images into a multi-task deep neural network, Deep Profiler, to generate an image fingerprint that primarily predicts time to event treatment outcomes and secondarily approximates classical radiomic features. We validated our findings in an independent study population (n = 95). Deep Profiler was combined with clinical variables to derive iGray, an individualized dose that estimates treatment failure probability to be <5%. Radiation treatments in patients with high Deep Profiler scores fail at a significantly higher rate than in those with low scores. The 3-year cumulative incidences of local failure were 20.3% (95% CI: 16.0-24.9) and 5.7% (95% CI: 3.5-8.8), respectively. Deep Profiler independently predicted local failure (hazard ratio 1.65, 95% 1.02-2.66, p = 0.04). Models that included Deep Profiler and clinical variables predicted treatment failures with a concordance index of 0.72 (95% CI: 0.67-0.77), a significant improvement compared to classical radiomics or clinical variables alone (p = <0.001 and <0.001, respectively). Deep Profiler performed well in an external study population (n = 95), accurately predicting treatment failures across diverse clinical settings and CT scanner types (concordance index = 0.77 [95% CI: 0.69-0.92]). iGray had a wide dose range (21.1-277 Gy, BED), suggested dose reductions in 23.3% of patients and can be safely delivered in the majority of cases. Our results indicate that there are image-distinct subpopulations that have differential sensitivity to radiotherapy. The image-based deep learning framework proposed herein is the first opportunity to use medical images to individualize radiotherapy dose.

Effect of aneurysm morphologic parameters on occlusion rates following pipeline embolization

ObjectiveTreatment failures with the use of Pipeline Embolization Device (PED) continue to be observed in up to 18% of patients in large case series. Adjunctive coiling and layering of multiple devices have been shown to improve occlusion rates; however, the optimal treatment strategy with the use of PED has not been established. The purpose of this study is to identify morphological characteristics predictive of treatment failure after PED. Patient and methodsA case control design was used to evaluate the association of aneurysm morphologic parameters with failure after PED placement. Retrospective analysis of patients undergoing PED for elective aneurysm treatment between 2014 and 2017 was performed. Patients who underwent PED placement with at least 12 months follow-up using conventional cerebral angiography were included for further review. Results84 patients met inclusion criteria for further analysis. ten patients (11.9%) experienced treatment failure defined by retained flow within the aneurysm and of those eight patients (9.5%) required additional retreatment. On multivariate analysis decreasing aspect ratio and increasing neck width were significant parameters that predicted treatment failure. ConclusionAneurysms with small aspect ratio and large neck width may be more likely to experience treatment failure after PED embolization. This subset of aneurysms may therefore benefit from adjunctive coiling to improve occlusion rates. Future prospective studies are needed to validate these findings.

Salivary HPV DNA informs locoregional disease status in advanced HPV-associated oropharyngeal cancer

ObjectivesQuantifying tumor DNA in tissue and circulating in blood permits high-quality molecular monitoring to detect and track cancer progression. Evaluating tumor DNA in both blood and saliva in human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) could provide a non-invasive and clinically actionable method for real-time disease detection. MethodsWe previously validated an ultrasensitive droplet-digital (dd)PCR assay targeting the dominant high-risk HPV subtypes causally linked to OPC. Here we enrolled an observational cohort to evaluate the predictive and prognostic potential of paired plasma-salivary tumor DNA among 21 patients with advanced HPV+OPC. ResultsIn patients with recurrent, persistent locoregional (LR) disease, median baseline normalized salivary HPV DNA was 10.9 copies/ng total DNA, nearly 20x higher compared with those with distant disease only (p = 0.01). A cutoff of 5 copies/ng yielded 87% sensitivity and 67% specificity for accurately predicting LR disease. Total tumor burden among those with LR disease strongly correlated with salivary HPV DNA levels (R = 0.83, p = 0.02). The rise and fall of salivary HPV DNA predicted treatment failure and response, respectively, in all patients with LR disease, and predated imaging findings. Among paired salivary-plasma (cell-free) cfDNA samples, only higher plasma HPV cfDNA levels were associated with poor outcomes (p < 0.01), suggesting that each bodily fluid provides unique information about HPV disease status. ConclusionsSalivary HPV DNA provides valuable information about tumor burden and predicts treatment response in advanced HPV+OPC. Paired blood-saliva samples could be used to monitor HPV DNA with broad applications to inform diagnosis, prognosis, and surveillance in HPV-associated diseases.

Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia.

Outcomes for patients with chronic myeloid leukemia (CML) have substantially improved due to advances in drug development and rational treatment intervention strategies. Despite these significant advances there are still unanswered questions on patient management regarding how to more reliably predict treatment failure at the time of diagnosis and how to select frontline tyrosine kinase inhibitor (TKI) therapy for optimal outcome. The BCR-ABL1 transcript level at diagnosis has no established prognostic impact and cannot guide frontline TKI selection. BCR-ABL1 mutations are detected in ~50% of TKI resistant patients but are rarely responsible for primary resistance. Other resistance mechanisms are largely uncharacterized and there are no other routine molecular testing strategies to facilitate the evaluation and further stratification of TKI resistance. Advances in next-generation sequencing technology has aided the management of a growing number of other malignancies, enabling the incorporation of somatic mutation profiles in diagnosis, classification, and prognostication. A largely unexplored area in CML research is whether expanded genomic analysis at diagnosis, resistance, and disease transformation can enhance patient management decisions, as has occurred for other cancers. The aim of this article is to review publications that reported mutated cancer-associated genes in CML patients at various disease phases. We discuss the frequency and type of such variants at initial diagnosis and at the time of treatment failure and transformation. Current limitations in the evaluation of mutants and recommendations for future reporting are outlined. The collective evaluation of mutational studies over more than a decade suggests a limited set of cancer-associated genes are indeed recurrently mutated in CML and some at a relatively high frequency. Genomic studies have the potential to lay the foundation for improved diagnostic risk classification according to clinical and genomic risk, and to enable more precise early identification of TKI resistance.

Nonsurgical Management of Interstitial Pregnancies: Feasibility and Predictors of Treatment Failure

To describe the management of interstitial pregnancies in a tertiary medical center, identify factors associated with treatment failure, and report subsequent pregnancy outcome. Retrospective cohort study. Department of Gynecology in a tertiary medical center. All women who were admitted to and treated for interstitial pregnancy at our center between 2011 and 2019. The women were originally assigned to undergo expectant, medical, or surgical treatment. The women's background and clinical data were compared according to initial treatment modality. Nonsurgical (expectant and medical) management outcomes were analyzed to identify risk factors for treatment failure. Subsequent pregnancy outcomes were described separately. Thirty-seven cases of interstitial pregnancy were identified. There were high rates of pregnancy achieved by in vitro fertilization (45.9%) and a history of ipsilateral salpingectomy (43.2%) among these patients. At presentation, the mean age of the study cohort was 34.76 years, and the median β-human chorionic gonadotropin level was 3853.0, and median gestational age was 7.0, respectively. The nonsurgical management success rate was 70.0%. Uterine rupture occurred during treatment in 5 cases (16.6%). Gestational sac diameter significantly affected treatment failure (p = .03), and a diameter >20 mm was observed in all cases of failed non-surgical treatment. Data on future fertility was available for 21 (58.3%) women: 13 (61.9%) had a subsequent pregnancy, 1 of which was a recurrent interstitial pregnancy. The median interpregnancy interval was 8.1 months, and all but 3 pregnancies reached third trimester and resulted in a live birth, with an overall cesarean delivery rate of 61.5%. None of the subsequent pregnancies were complicated by uterine rupture, and no serious adverse outcomes were noted in any of the subsequent intrauterine pregnancies that reached third trimester. Successful nonsurgical management of an interstitial pregnancy is feasible, although appropriate selection of cases is advised. A large gestational sac is a risk factor for treatment failure and should prompt surgical intervention. Subsequent pregnancies can generally be considered safe and with a favorable outcome.

Impact of body mass index on success, complications and failure of extracorporeal shock wave lithotripsy

Introduction: Extracorporeal shock wave lithotripsy (ESWL) is known as the most common method in treating urinary stones (70%) and is a selective method to treat small urinary stones (&lt;2-2.5 cm). General opinion is that the success rate of ESWL in obese patients is low and risk of complications is high. Objectives: The aim of this study was to evaluate the impact of body mass index (BMI) and the stone-to-skin distance on success, complications and failure of ESWL. Patients and Methods: In this study, 222 patients who referred to lithotripsy clinic of Kashani hospital of Shahrekord to break stones with diameters of 5 to 20 mm participated in the study. Their urinary stones were in kidneys, lower calyces, upper calyces, pelvis or proximal ureter and were divided into two equal groups of BMI &gt;25 kg/m2 and BMI &lt;25 kg/m2 . Assessing the position and diameter of the stones was based on radiographic findings such as sonography and CT scan. Regarding success, failure and complications of lithotripsy, two groups were compared. Results: Around 105 and 117 patients out of 222 subjects, were respectively assigned in BMI&gt;25 kg/ m2 and BMI &lt;25 kg/m2 groups. The failure and success of both groups were statistically significant (P=0.023). In terms of treatment outcomes, difference between two groups was high in low skinto-stone distance (SSD). Logistic regression showed that both BMI and SSD are effective factors in treating the stone while SSD was more effective (P=0.004) than BMI (P=0.023) since SSD&gt;7.5 cm predicts treatment failure. Conclusion: BMI and SSD are effective factors on the outcome of ESWL. Higher BMI and SSD&gt; 7.5 cm are effective factors on treatment failure.

Outcomes and predictors of treatment failure following two-stage total joint arthroplasty with articulating spacers for evolutive septic arthritis

BackgroundThe treatment strategy for evolutive septic arthritis (SA) with coexistent degenerative joint disease is not well established. The purposes of this study were to 1) investigate treatment outcome and potential risk factors of treatment failure in patients with evolutive SA following two-stage procedure, including insertion of an antibiotic-loaded spacer at the first stage and subsequent implantation of a new prosthesis; and 2) determine the performance of serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Interleukin-6 (IL-6) in predicting persisting infection at second-stage procedure.MethodsWe retrospectively reviewed 74 patients with evolutive SA of hips and knees who underwent a two-stage TJA between 2008 and 2015. The treatment success was defined according to the modified Delphi criteria and Kaplan-Meier survivorship curves were constructed to determine treatment success. A Cox regression model was performed to identify risk factors for treatment failure. Receiver operating characteristic (ROC) curves were generated to determine the prognostic value of ESR, CRP, and IL-6 in predicting persistent infection before second-stage prostheses implantation.ResultsOverall, the treatment success rate was 93% for hips and 100% for knees after the first-stage surgery. The treatment success rate was 89% for hips and 84% for knees after second-stage prosthesis implantation with a mean follow-up of 4.7 (range, 2.2 to 10.8) years. Older age (Hazard ratio [HR] [per 10-year increase], 1.20; 95% confidential interval [CI], 1.11 to 1.62), higher preoperative CRP level (HR [per 1-mg/dL increase], 1.15; 95% CI, 1.04 to 1.28) and resistant organism (HR, 13.96; 95% CI, 3.29 to 19.20) were associated with an increased risk of treatment failure. All serologic tests presented limited values in predicting persisting infection, with the area under ROC curve of ESR, CRP, IL-6 and combination of the three markers was 57.8, 61.6, 60.3, and 62.1%, respectively.ConclusionsTwo-stage TJA is an adequate management of infection control in patients with evolutive SA. The three potential risk factors (old age, high preoperative CRP, and resistant organism profile) may predict treatment failure following a two-stage procedure for evolutive SA. Additionally, serum ESR, CRP, and IL-6 had no benefit in predicting persisting infection before second-stage prostheses implantation. These findings may be useful when treating patients with evolutive SA.

Early prediction of treatment failure in severe community-acquired pneumonia: The PRoFeSs score

PurposeTo identify a single/panel of biomarkers and to provide a point score that, after 48 h of treatment, could early predict treatment failure at fifth day of Intensive Care Unit (ICU) stay in severe community-acquired pneumonia (SCAP) patients. Materials and methodsSingle-center, prospective cohort study of 107 ICU patients with SCAP. Primary outcome included death or absence of improvement in Sequential Organ Failure Assessment score by ≥2 points within 5 days of treatment. Biomarkers were evaluated within 12 h of first antibiotic dose (D1) and 48 h after the first assessment (D3). ResultsA model based on Charlson's score and a panel of biomarkers (procalcitonin on D1 and D3, B-natriuretic peptide on D1, D-dimer and lactate on D3) had good discrimination for primary outcome in both derivation (AUC 0.82) and validation (AUC 0.76) samples and was well calibrated (X2 = 0.98; df = 1; p = .32). A point score system (PRoFeSs score) built on the estimates of regression coefficients presented good discrimination (AUC 0.81; 95% Confidence Interval 0.72–0.89) for primary outcome. ConclusionsIn SCAP, a combination of biomarkers measured at admission and 48 h later may early predict treatment failure. PRoFeSs score may recognize patients with poor short-term prognosis.

Conservative management of Caesarean scar pregnancies with systemic multidose methotrexate: predictors of treatment failure and reproductive outcomes.

Caesarean scar pregnancy (CSP) is an increasing concern in modern obstetrics. Early diagnosis and management are of utmost importance. The optimal management approach for CSP is not well established, with various treatment modalities reported. The role of conservative management of CSP has been previously reported, with conflicting results. This study aimed to further evaluate its role and better delineate the subsequent reproductive outcomes. A retrospective cohort study including all patients diagnosed with a CSP and treated by intention of conservative management with systemic methotrexate (MTX). Maternal and gestation characteristics were compared between treatment success and failure groups. Thirty-six cases of CSP were encountered. Overall, 29/36 (80.6%) were treated by systemic injection of MTX while the other 19.4% had combined systemic and local (i.e. intra-sac) MTX treatment. Invasive intervention was needed in five (13.9%) cases (failure group). Among those successfully treated with MTX, the median time to resolution was 22 (interquartile range 13-37) days. Cases who were converted to surgical treatment had a higher number of previous Caesarean deliveries (median 4 versus 2, P=0.002). In logistic regression modelling, the number of previous Caesarean deliveries was the only factor independently associated with conversion to surgical management (odds ratio 2.02, 95% confidence interval 1.03-3.94). The majority of future pregnancies ended at term pregnancy with only one preterm delivery due to severe intrauterine growth restriction. Systemic MTX therapy is a safe and effective strategy for the treatment of CSP, with favourable subsequent reproductive results and a low conversion rate to surgical management.

Incidence and predictors of treatment failure among children on first-line antiretroviral therapy in Amhara Region Referral Hospitals, northwest Ethiopia 2018: A retrospective study.

BackgroundHuman immunodeficiency virus (HIV) infection is a major public health concern globally, especially in sub-Saharan African countries. Even though determining the incidence of treatment failure and its predictor is a crucial step to reduce the problem, there is limited information indicating the incidence and predictors of treatment failure among children in Ethiopia. Therefore, this study was conducted to assess the incidence and predictors of treatment failure among children on first-line antiretroviral therapy (ART) in Amhara Region referral hospitals, Northwest Ethiopia.MethodsAn institution-based retrospective follow-up study was conducted from January 30, 2011, to January 30, 2018. A total of 402 children on first-line antiretroviral therapy were selected with a simple random sampling method in Amhara Region Referral Hospitals, Northwest Ethiopia. Data were extracted by reviewing patients’ ART intake and follow-up forms using pretested and structured checklists. The collected data were entered into Epidata Version 4.2 and analysis was done using STATA Version 13. Bivariable and multivariable Cox proportional hazards regression models were fitted to identify predictors of treatment failure.ResultsA total of 402 records of children on antiretroviral therapy (ART) were reviewed and treatment failures rate within the follow-up period were 12.19% (95% CI: 8.5, 15.88). This study also found that the overall incidence density rate was 3.77% per 100 person-years observation. Virologic failure accounts 48.98% followed by immunologic (28.57%) and mixed failures (22.44%). Poor ART adherence (AHR: 4.6, 95%CI: 1.61, 13.20), drug regimens, AZT-3TC-NVP (AHR: 5.2, 95%CI: 1.9, 14.26), and AZT-3TC-EFV (AHR: 6.26, 95% CI: 1.88, 20.87), Children whose both parent were died (AHR: 2.8, 95%CI: 1.07, 7.37) and world health organization (WHO) clinical stage-4 (AHR: 2.95, 95%CI: 1.04, 8.366) were found to be predictors for treatment failure among children.ConclusionThe proportion of treatment failure among children on first-line ART in Amhara Region referral hospitals, Northwest Ethiopia was found to be high. Nearly half of the children experienced Virologic failure. Poor ART adherence, children whose parents`died without parents, WHO clinical stage-4 at baseline and type of regimen patients took were found to be predictors of first-line ART treatment failure. Therefore, expanding access to routine viral load, CD4 and clinical monitoring is mandatory to detect and early intervene of treatment failures’ to improve outcomes for children on ART. Patient caregivers or parents should strictly support children on medication adherence. Training to health professionals should be given time-based on revised guidelines, and follow up of treatment outcome should be monitored nationally to take the appropriate intervention.

Mo1898 – Evaluation of Body Mass Index and Other Predictors of Treatment Failure in Ulcerative Colitis Patients Being Treated with Vedolizumab

Mo1898 – Evaluation of Body Mass Index and Other Predictors of Treatment Failure in Ulcerative Colitis Patients Being Treated with Vedolizumab

The Association of Cognitive Impairment with Peritoneal Dialysis-Related Peritonitis.

Background:Research on the association between cognitive impairment (CI) and peritoneal dialysis (PD)-related peritonitis is limited. Therefore, we investigated whether CI contributed to the risk of PD-related peritonitis.Methods:This prospective cohort study enrolled 458 patients from 5 PD centers between 1 March 2013, and 30 November 2013, and continued until 31 May 2016. We used the Modified Mini-Mental State Examination (3MS) to assess general cognition, the Trail-Making Test to assess executive function, and subtests of the Battery for the Assessment of Neuropsychological Status to assess immediate and delayed memory, visuospatial skills, and language ability. Patients were assigned to CI and non-CI groups based on their 3MS scores. The first episode of peritonitis was the primary endpoint event. Treatment failure of peritonitis was defined as peritonitis-associated death or transfer to hemodialysis. We used competing risk models to analyze the association between CI and the risk of peritonitis. The association of CI with treatment failure after peritonitis was analyzed using logistic regression models.Results:Ninety-four first episodes of peritonitis were recorded during a median follow-up of 31.4 months, 18.1% of which led to treatment failure. No significant group differences were observed for the occurrence, distribution of pathogenic bacteria, or outcomes of first-episode peritonitis. Immediate memory dysfunction was independently associated with a higher risk of PD-related peritonitis (hazard ratio [HR] 1.736, 95% confidence interval [CI] 1.064 - 2.834, p < 0.05), adjusting for confounders.Conclusions:Immediate memory dysfunction was a significant, independent predictor of PD-related peritonitis. Neither general nor specific domains of CI predicted treatment failure of peritonitis.