Ensemble Algorithm for Risk Prediction of Clinical Failure After Anterior Cruciate Ligament Reconstruction.

Background: Patient-specific risk profiles of clinical failure after anterior cruciate ligament reconstruction (ACLR) are meaningful for preoperative surgical planning and postoperative rehabilitation guidance. Purpose: To create an ensemble algorithm machine learning (ML) model and ML-based web-based tool that can predict the patient-specific risk of clinical failure after ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 432 patients (mean age, 26.8 ± 8.4 years; 74.1% male) who underwent anatomic double-bundle ACLR with hamstring tendon autograft between January 2010 and February 2019. The primary outcome was the probability of clinical failure at a minimum 2-year follow-up. The authors included 24 independent variables for feature selection and model development. The data set was split randomly into training sets (75%) and test sets (25%). Models were built using 4 ML algorithms: extreme gradient boosting, random forest, light gradient boosting machine, and adaptive boosting. In addition, a weighted-average voting (WAV) ensemble model was constructed using the ensemble-voting technique to predict clinical failure after ACLR. Concordance (area under the receiver operating characteristic curve [AUC]), calibration, and decision curve analysis were used to evaluate predictive performances of the 5 models. Results: Clinical failure occurred in 73 of the 432 patients (16.9%). The 8 most important predictors for clinical failure were follow-up period, high-grade preoperative knee laxity, time from injury to ACLR, participation in competitive sports, posterior tibial slope, graft diameter, age at surgery, and medial meniscus resection. The WAV ensemble algorithm achieved the best predictive performance based on concordance (AUC, 0.9139), calibration (calibration intercept, -0.1806; calibration slope, 1.2794; Brier score, 0.0888), and decision curve analysis (greatest net benefits) and was used to develop an web-based application to predict a patient's clinical failure risk of ACLR. Conclusion: The WAV ensemble algorithm was able to accurately predict patient-specific risk of clinical failure after ACLR. Clinicians and patients can use the web-based application during preoperative consultation to understand individual prediction outcomes.

The State of Intermediate Clinical Endpoints as Surrogates for Overall Survival in Prostate Cancer in 2024.

In the past, selection of intermediate clinical endpoints (ICEs) in prostate cancer (PCa) trials largely depended on qualitative assessments; however, the advancing quality of research necessitates a robust correlation with overall survival (OS). This review summarises the results from several high-quality meta-analyses that explored the validity of ICEs as surrogates for OS. We found strong evidence that metastasis-free survival can serve as an ICE in localized PCa. In advanced disease, valid ICEs were identified only within the context of metastatic hormone-sensitive PCa, including radiological and clinical progression-free survival; however, concerns remain regarding their use owing to the limited generalisability of the data used to validate their surrogacy. PATIENT SUMMARY: Intermediate clinical endpoints can reduce the costs of trials and allow earlier introduction of new treatment methods. This article summarises results from studies verifying the validity of these endpoints as surrogates for overall survival.

Clinical efficacy of cefiderocol-based regimens in patients with carbapenem-resistant Acinetobacter baumannii infections: A systematic review with meta-analysis.

OBJECTIVES: To perform a systematic review with meta-analysis to assess the clinical efficacy of cefiderocol-based regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections. METHODS: Two authors independently searched PubMed-MEDLINE, Scopus, and Cochrane databases, from inception to 02 July 2023, for randomised controlled trials (RCTs) or observational studies comparing clinical efficacy of cefiderocol-based vs. non-cefiderocol-based regimens in patients with CRAB infections. Data were extracted by the two authors independently, and the quality of included studies was independently assessed using ROB 2.0 or ROBINS-I tools. Primary outcome was mortality rate. Meta-analysis was performed by pooling odds ratios (ORs) retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity. RESULTS: A total of 530 articles were screened, and 6 studies (1 RCT and 5 observational; N=561; 247 cefiderocol-based vs. 314 non-cefiderocol-based regimens) were included. Cefiderocol did not significantly reduce in-hospital mortality compared to alternative therapies (predominantly colistin-based), but the confidence intervals around the effect estimate included clinically important benefit (N=5; OR 0.64; 95%CI 0.40-1.04; I2=57.5%). When only observational studies providing adjustment for confounders were considered, a lower risk of mortality was found in patients treated with cefiderocol-based regimens (N=4; OR 0.53; 95%CI 0.39-0.71; I2=0.0%). CONCLUSIONS: Cefiderocol-based regimens were associated with a significantly lower risk of mortality in patients with CRAB infections in observational studies providing proper adjustment for confounders.

Outcome of patients with carbapenem-resistant Acinetobacter baumannii infections treated with cefiderocol: A multicenter observational study.

BACKGROUND: No clear evidence supports the use of cefiderocol as first line treatment in A. baumannii infections. METHODS: We conducted an observational retrospective/prospective multicenter study including all patients> 18 years with carbapenem-resistant A. baumannii (CRAB) infections treated with cefiderocol, from June 12021 to October 30 2022. Primary endpoint was 30-day mortality, secondary end-points the clinical and microbiological response at 7 days and at the end of treatment. Furthermore, we compared the clinical and microbiological outcomes among patients who received cefiderocol in monotherapy or in combination. RESULTS: Thirty-eight patients with forty episodes of infection were included [mean age 65 years (SD+16.3), 75% males, 90% with hospital-acquired infections and 70% showing sepsis or septic shock]. The most common infections included unknown source or catheter-related bacteremia (45%) and pneumonia (40%). We observed at 7 days and at the end of therapy a rate of microbiological failure of 20% and 10%, respectively, and of clinical failure of 47.5% and 32.5%, respectively; the 30-day mortality rate was 47.5%. At multivariate analysis clinical failure at 7 days of treatment was the only independent predictor of 30-day mortality. Comparing monotherapy (used in 72.5%) vs. combination therapy (used in 27.5%), no differences were observed in mortality (51.7 vs 45.5%) and clinical (41.4 vs 63.7%) or microbiological failure (24.1 vs 9.1%). CONCLUSIONS: The findings of this study reinforce the effectiveness of cefiderocol in CRAB infections, also as monotherapy. However, prospective multicenter studies with larger sample sizes and a control group treated with standard of care are needed to identify the best treatment for CRAB infections.

Role of nebulized colistin as a substitutive strategy against nosocomial pneumonia caused by CR-GNB in intensive care units: a retrospective cohort study.

BACKGROUND: Adverse reactions, especially nephrotoxicity, are great concerns of intravenous colistin treatment. The role of substitutive nebulized colistin in treating nosocomial pneumonia caused by carbapenem-resistant Gram-negative bacterial (CR-GNB) in critically ill patients remains unknown. METHODS: This retrospective study enrolled patients with nosocomial pneumonia caused by colistin-susceptible CRGNB in the intensive care unit (ICU) without intravenous colistin treatment. Patients were categorized based on whether substitutive nebulized colistin was used alongside other intravenous antibiotics. Clinical responses and mortality rates were compared between the two groups in the original and propensity score (PS)-matched cohorts. This study aimed to investigate the clinical effectiveness of substitutive nebulized colistin in treatment outcomes of nosocomial pneumonia caused by CR-GNB. The impact of dosing strategy of nebulized colistin was also explored. RESULTS: In total, 343 and 214 patients with and without substitutive nebulized colistin, respectively, were enrolled for analysis. In the PS-matched cohort, clinical failure rates on day 7 (22.6 vs. 42.6%, p = 0.001), day 14 (27.0 vs. 42.6%, p = 0.013), and day 28 (27.8 vs. 41.7%, p = 0.027) were significantly lower in patients with nebulized colistin. In multivariate analysis, nebulized colistin was an independent factor associated with lower day 14 clinical failure (Original cohort: adjusted odds ratio (aOR) 0.45, 95% confidence interval (CI) 0.30-0.67; PS-matched cohort: aOR 0.48, 95% CI 0.27-0.87). There were no differences in clinical failure rate and mortality rate between patients receiving high (> 6 MIU/day) and low (≤ 6 MIU/day) dose nebulized colistin in the PS-matched cohort. CONCLUSIONS: In ICU-admitted patients with nosocomial pneumonia caused by colistin-susceptible CRGNB, substitutive nebulized colistin was associated with better clinical outcomes.

Risk Factors for Carbapenem-Resistant Enterobacterales Clinical Treatment Failure.

The Centers for Disease Control and Prevention (CDC) categorized carbapenem-resistant Enterobacterales (CRE) infections as an "urgent" health care threat requiring public attention and research. Certain patients with CRE infections may be at higher risk for poor clinical outcomes than others. Evidence on risk or protective factors for CRE infections are warranted in order to determine the most at-risk populations, especially with newer beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotics available to treat CRE. We aimed to identify specific variables involved in CRE treatment that are associated with clinical failure (either 30-day mortality, 30-day microbiologic recurrence, or clinical worsening/failure to improve throughout antibiotic treatment). We conducted a retrospective, observational cohort study of hospitalized patients with CRE infection sampled from 2010 to 2020 at two medical systems in Detroit, Michigan. Patients were included if they were ≥18 years old and culture positive for an organism in the Enterobacterales order causing clinical infection with in vitro resistance by Clinical and Laboratory Standards Institute (CLSI) breakpoints to at least one carbapenem. Overall, there were 140 confirmed CRE infections of which 39% had clinical failure. The most common infection sources were respiratory (38%), urinary (20%), intra-abdominal (16%), and primary bacteremia (14%). A multivariable logistic regression model was developed to identify statistically significant associated predictors with clinical failure, and they included Sequential Organ Failure Assessment (SOFA) score (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.06 to 1.32), chronic dialysis (aOR, 5.86; 95% CI, 1.51-22.7), and Klebsiella pneumoniae in index culture (aOR, 3.09; 95% CI, 1.28 to 7.47). Further research on CRE infections is needed to identify best practices to promote treatment success. IMPORTANCE This work compares carbapenem-resistant Enterobacterales (CRE) infections using patient, clinical, and treatment variables to understand which characteristics are associated with the highest risk of clinical failure. Knowing which risk factors are associated with CRE infection failure can provide clinicians better prognostic and targeted interventions. Research can also further investigate why certain risk factors cause more clinical failure and can help develop treatment strategies to mitigate associated risk factors.

Clinical effectiveness of tigecycline in combination therapy against nosocomial pneumonia caused by CR-GNB in intensive care units: a retrospective multi-centre observational study.

BACKGROUND: Tigecycline has in vitro bacteriostatic activity against a broad spectrum of bacteria, including carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the role of tigecycline in treatment of nosocomial pneumonia caused by CR-GNB remains controversial and clinical evidences are limited. We aimed to investigate the clinical benefits of tigecycline as part of the combination treatment of nosocomial CR-GNB pneumonia in intensive care unit (ICU). METHODS: This multi-centre cohort study retrospectively enrolled ICU-admitted patients with nosocomial pneumonia caused by CR-GNB. Patients were categorized based on whether add-on tigecycline was used in combination with at least one anti-CR-GNB antibiotic. Clinical outcomes and all-cause mortality between patients with and without tigecycline were compared in the original and propensity score (PS)-matched cohorts. A subgroup analysis was also performed to explore the differences of clinical efficacies of add-on tigecycline treatment when combined with various anti-CR-GNB agents. RESULTS: We analysed 395 patients with CR-GNB nosocomial pneumonia, of whom 148 received tigecycline and 247 did not. More than 80% of the enrolled patients were infected by CR-Acinetobacter baumannii (CRAB). A trend of lower all-cause mortality on day 28 was noted in tigecycline group in the original cohort (27.7% vs. 36.0%, p = 0.088). In PS-matched cohort (102 patient pairs), patients with tigecycline had significantly lower clinical failure (46.1% vs. 62.7%, p = 0.017) and mortality rates (28.4% vs. 52.9%, p < 0.001) on day 28. In multivariate analysis, tigecycline treatment was a protective factor against clinical failure (PS-matched cohort: aOR 0.52, 95% CI 0.28-0.95) and all-cause mortality (original cohort: aHR 0.69, 95% CI 0.47-0.99; PS-matched cohort: aHR 0.47, 95% CI 0.30-0.74) at 28 days. Kaplan-Meier survival analysis in subgroups of patients suggested significant clinical benefits of tigecycline when added to a colistin-included (log rank p value 0.005) and carbapenem-included (log rank p value 0.007) combination regimen. CONCLUSIONS: In this retrospective observational study that included ICU-admitted patients with nosocomial pneumonia caused by tigecycline-susceptible CR-GNB, mostly CRAB, tigecycline as part of a combination treatment regimen was associated with lower clinical failure and all-cause mortality rates.

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study-The ARTHR-IS Study Group.

INTRODUCTION: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. METHODS: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. RESULTS: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. CONCLUSIONS: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov, registration no. NCT03826108.

Staphylococcus aureus is one of the most virulent bacteria and frequently causes prosthetic joint infections.Knowledge of the treatment of this type of infection has advanced in recent years, and treatment guidelines have led to improved management. Typically, the successful treatment of these infections has been determined by clinical cure, that is, the symptoms of infection have disappeared, but has not taken into account loss of function (such as significant difficulties walking), which is critical for the patient's quality of life. Our aim in this study was to evaluate the success of current management strategies for S. aureus prosthetic joint infection, including recovery of functionality, and the factors that predict why some of these infections are not cured, to identify areas for improvement.In a multinational cohort of 128 patients with S. aureus prosthetic joint infection, rates of treatment failure were found to be high, with significant rates of loss of function, especially when the prosthesis needed to be removed. Loss of function was less frequent when the infection was initially treated with surgical cleaning without removal of the prosthesis, even when this procedure failed at first. We found that anaemia and obesity were associated with lower treatment success, and that the probability of treatment success increased when surgical cleaning without prosthesis removal was performed early, and when the antibiotic rifampicin was used in combination with another antibiotic.

Fracture analysis of one/two-piece clinically failed zirconia dental implants.

OBJECTIVES: Analyzing factors that may have led to fracture of zirconia implants by macro/micro-fractography. METHODS: Six one-piece and ten two-piece full-ceramic zirconia implants from two manufacturers, Z-Systems and CeraRoot, were retrieved after clinical failure. The time-to-failure ranged from 3 to 49 months. Optical and scanning electron microscopy (SEM) were used to analyze the fracture planes at the macro- and microscopic level. Treatment planning, surgical protocol, fracture-origin location and characteristic fracture features were assessed. RESULTS: The fracture of all implants seemed to have been primarily due to overload in bending mode, while the fracture-initiation sites varied for the one- and two-piece implants. The fracture of all one-piece implants originated in the constriction region between two threads in the endosseous implant part. For two-piece implants, the abutment neck, internal abutment-implant connections and inner threads were found to be the main fracture-initiation sites. Surface defects at the root area for one-piece implants and damages at the abutment surface for two-piece implants were connected to the fracture origins. Importantly, the clinical failures of implants were often found to result from combined effects related to patient aspects, treatment planning/protocols, a high bending moment at the weakest link, implant-surface conditions and specific implant designs. SIGNIFICANCE: This study provided information to be considered for future optimization of treatment planning and the surgical protocol for zirconia implants. Optimization of the surface conditions and the zirconia-starting powder were also suggested.

Prognostic Factors of Mid- to Long-term Clinical Outcomes after Arthroscopic Partial Meniscectomy for Medial Meniscal Tears.

Backgroud: Arthroscopic partial meniscectomy (APM) continues to be the popular treatment for meniscal tears, but recent randomized controlled trials have questioned its efficacy. To provide more evidence-based criteria for patient selection, we undertook this study to identify prognostic factors associated with clinical failure after APM for medial meniscus tears. Methods: Medical records of 160 patients followed up for at least 5 years after APM for medial meniscal tears were retrospectively reviewed. Demographic data (age, sex, and body mass index), radiographic variables (Kellgren-Lawrence [K-L] grade and hip-knee-ankle [HKA] angle), and clinical scores (International Knee Documentation Committee score, Tegner activity scale score, Lysholm score, and Knee injury and Osteoarthritis Outcome Score) were recorded. Clinical failure was defined as the need for an additional surgical procedure (arthroscopy, osteotomy, or arthroplasty) or the presence of intolerable pain. Survivorship analysis with clinical failure as an end point was performed using Kaplan-Meier survival curves. Factors related to clinical failure were analyzed using a Cox proportional hazard model. Cutoff values were determined using areas under receiver operating characteristic (ROC) curves. Radiographic progression of osteoarthritis was analyzed using the chi-square test, and serial changes of clinical scores were analyzed using a linear mixed model. Results: Clinical success rates were 95.7% at 5 years, 75.6% at 10 years, and 46.3% at 15 years. Age, HKA angle, and K-L grade (p = 0.01, p = 0.02, and p = 0.04, respectively) were found to be significant risk factors of clinical failure. Cutoff values at 10 years postoperatively as determined by ROC analysis were 50 years for age (sensitivity = 0.778, 1-specificity = 0.589), grade 2 for K-L grade (sensitivity = 0.778, 1-specificity = 0.109), and 5.5° for HKA angle (sensitivity = 0.667, 1-specificity = 0.258). In patients who had clinical success until 10 years after APM, radiological osteoarthritis progressed gradually. However, the clinical scores of patients who achieved clinical success did not decrease significantly over the 10-year follow-up. Conclusions: The poor prognostic factors found to be related to clinical failure after APM for a medial meniscal tear were patient age (≥ 50 years), preoperative K-L grade (≥ grade 2), and preoperative HKA angle (≥ varus 5.5°).

HIV-1 Evolutionary Dynamics under Nonsuppressive Antiretroviral Therapy.

Prolonged virologic failure on 2nd-line protease inhibitor (PI)-based antiretroviral therapy (ART) without emergence of major protease mutations is well recognized and provides an opportunity to study within-host evolution in long-term viremic individuals. Using next-generation sequencing and in silico haplotype reconstruction, we analyzed whole-genome sequences from longitudinal plasma samples of eight chronically infected HIV-1-positive individuals failing 2nd-line regimens from the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) trial. On nonsuppressive ART, there were large fluctuations in synonymous and nonsynonymous variant frequencies despite stable viremia. Reconstructed haplotypes provided evidence for selective sweeps during periods of partial adherence, and viral haplotype competition, during periods of low drug exposure. Drug resistance mutations in reverse transcriptase (RT) were used as markers of viral haplotypes in the reservoir, and their distribution over time indicated recombination. We independently observed linkage disequilibrium decay, indicative of recombination. These data highlight dramatic changes in virus population structure that occur during stable viremia under nonsuppressive ART. IMPORTANCE HIV-1 infections are most commonly initiated with a single founder virus and are characterized by extensive inter- and intraparticipant genetic diversity. However, existing literature on HIV-1 intrahost population dynamics is largely limited to untreated infections, predominantly in subtype B-infected individuals. The manuscript characterizes viral population dynamics in long-term viremic treatment-experienced individuals, which has not been previously characterized. These data are particularly relevant for understanding HIV dynamics but can also be applied to other RNA viruses. With this unique data set we propose that the virus is highly unstable, and we have found compelling evidence of HIV-1 within-host viral diversification, recombination, and haplotype competition during nonsuppressive ART.

Evaluation of early clinical failure criteria in Enterococcus species bloodstream infection.

PURPOSE: Early clinical failure criteria (ECFC) were recently introduced to predict unfavorable outcomes in patients with Gram-negative bloodstream infections (BSI). ECFC include hypotension, tachycardia, tachypnea or mechanical ventilation, altered mental status, and leukocytosis evaluated at 72-96 h after BSI. The aim of this retrospective cohort study was to assess performance of ECFC in predicting 28-day mortality in Enterococcus species BSI. METHODS: Hospitalized adults with Enterococcus species BSI at Prisma Health hospitals from 1 January 2015 to 31 July 2018 were identified. Multivariate logistic regression was used to determine the association between ECFC and 28-day mortality. Area under the receiver operating characteristic (AUROC) curve was used to measure model discrimination. RESULTS: Among 157 patients, 28 (18%) died within 28 days of BSI. After adjustments in multivariate model, the risk of 28-day mortality increased in the presence of each additional ECFC (OR 1.6, 95% CI 1.2-2.3, p = 0.005). Infective endocarditis (OR 3.9, 95% CI 1.4-10.7, p = 0.01) was independently associated with 28-day mortality. AUROC curve of ECFC model in predicting 28-day mortality was 0.74 with ECFC of 2 identified as the best breakpoint. Mortality was 8% in patients with ECFC < 2 compared to 33% in those with ECFC ≥ 2 (p < 0.001). CONCLUSION: ECFC had good discrimination in predicting 28-day mortality in patients with Enterococcus species BSI. These criteria may have utility in future clinical investigations.

Clinical failure of dalbavancin for MRSA bacteremia in patient with severe obesity and history of IVDU.

Dalbavancin is a lipoglycopeptide antibiotic used off-label to treat serious gram-positive infections, including infections secondary to methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin has unique pharmacokinetic parameters and has a role in therapy for treating vulnerable patients, including intravenous drug users, who have challenges complying with typical care plans for serious infections. While there is data indicating successful clinical use of dalbavancin in patients with history of intravenous drug use as well as pharmacokinetic-pharmacodynamic data assessing dalbavancin in obesity, there is a lack of information regarding clinical effects of dalbavancin in patients with extreme obesity, especially in patients with concomitant drug use. This case report describes a 40-year-old morbidly obese female actively using intravenous drugs who developed prolonged MRSA bacteremia without a recognizable focus. Despite partial treatment with dalbavancin, the patient developed osteomyelitis and discitis of the spine with associated epidural phlegmon, likely complications of the MRSA bacteremia.

Meniscal allograft transplantation shows a mismatch between anatomic and clinical failures.

PURPOSE: Clinical results of meniscal allograft transplantation (MAT) are not always consistent with graft status. This study aimed to investigate (1) the degree and pattern of mismatch between anatomic and clinical failures in MAT and (2) preoperative factors associated with the mismatch. METHODS: Two hundred and ninety-eight consecutive patients who underwent primary medial or lateral MAT during 2004-2015 were reviewed. Anatomic failure was defined as an allograft showing meniscal tear involving > 50% of the graft or unstable peripheral rim. Clinical failure included poor Lysholm score of < 65 and any requirement for re-operations such as arthroplasty, realignment osteotomy, revision MAT, and meniscectomy (more than 50% of the graft or to the zone of meniscocapsular junction). Failure cases were categorised according to the type of failure as follows: (1) type 1, anatomic failure followed by clinical failure; (2) type 2, anatomic failure did not lead to clinical failure; and (3) type 3, clinical failure without anatomic failure. Preoperative factors including age, sex, body mass index, MAT compartment, time from previous meniscectomy, alignment, cartilage status, and accompanying procedures were analysed according to the failure type. RESULTS: Forty (13.4%) patients showed anatomical or clinical failure during the median (25th-75th percentile) follow-up duration of 47 (30-72) months (range 24-178 months). Eleven (3.7%) patients showed both anatomical and clinical failure (type 1 failure). Seventeen (5.7%) patients showed anatomic failure that did not lead to clinical failure (type 2 failure). Twelve (4.0%) patients failed clinically without meniscal tear (> 50% of graft) or unstable peripheral rim (type 3 failure). Comparative analyses among failure types found a significant difference in MAT compartment (p = 0.01). In particular, the incidence of type 3 failure was higher in medial than in lateral MAT (p = 0.003). CONCLUSION: A notable number of failure cases of MAT showed a mismatch between anatomic and clinical failures. Even with anatomic failure, MAT did not always lead to poor clinical scores or re-operations, whereas MAT could have poor results without substantial allograft problems. Therefore, both anatomic and clinical aspects should be considered when evaluating MAT. In particular, type 3 failure occurred more frequently in medial than in lateral MAT. LEVEL OF EVIDENCE: III.

Right Ventricular Function Predicts Adverse Clinical Outcomes in Patients With Chronic Thromboembolic Pulmonary Hypertension: A Three-Dimensional Echocardiographic Study.

Background: Right ventricular (RV) function plays a vital role in the prognosis of patients with chronic thromboembolic pulmonary hypertension (CTEPH). We used new machine learning (ML)-based fully automated software to quantify RV function using three-dimensional echocardiography (3DE) to predict adverse clinical outcomes in CTEPH patients. Methods: A total of 151 consecutive CTEPH patients were registered in this prospective study between April 2015 and July 2019. New ML-based methods were used for data management, and quantitative analysis of RV volume and ejection fraction (RVEF) was performed offline. RV structural and functional parameters were recorded using 3DE. CTEPH was diagnosed using right heart catheterization, and 62 patients underwent cardiac magnetic resonance to assess right heart function. Adverse clinical outcomes were defined as PH-related hospitalization with hemoptysis or increased RV failure, including conditions requiring balloon pulmonary angioplasty or pulmonary endarterectomy, as well as death. Results: The median follow-up time was 19.7 months (interquartile range, 0.5-54 months). Among the 151 CTEPH patients, 72 experienced adverse clinical outcomes. Multivariate Cox proportional-hazard analysis showed that ML-based 3DE analysis of RVEF was a predictor of adverse clinical outcomes (hazard ratio, 1.576; 95% confidence interval (CI), 1.046~2.372; P = 0.030). Conclusions: The new ML-based 3DE algorithm is a promising technique for rapid 3D quantification of RV function in CTEPH patients.

Effect of Obesity on Clinical Failure of Patients Treated With ß-Lactams.

BACKGROUND: Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a ß-lactam have worse clinical outcomes compared to nonobese patients and to identify if therapeutic drug monitoring may be beneficial. METHODS: This multicenter, retrospective cohort included hospitalized adults admitted from July 2015 to July 2017 treated with a ß-lactam as definitive monotherapy against a gram-negative bacilli for ≥72 hours. Patients were excluded if there was lack of source control or if polymicrobial infections required >1 antibiotic for definitive therapy. Patients were classified based on body mass index (BMI): nonobese (BMI ≤29.9 kg/m2) and obese (BMI ≥30.0 kg/m2). The primary outcome was clinical treatment failure, and secondary outcomes were hospital length of stay, inpatient all-cause mortality, and 30-day all-cause readmission. RESULTS: There were 257 (43.6%) obese patients and 332 (56.4%) nonobese patients included. The most common infections were urinary (50.9%) and respiratory (31.4%). Definitive treatment was driven by third-generation cephalosporins (46.9%) and cefepime (44.7%). Treatment failure occurred in 131 (51%) obese patients and 109 (32.8%) nonobese patients (P < .001). Obesity and respiratory source were independently associated with increased likelihood of treatment failure. Obese patients were hospitalized longer than nonobese patients (P = .002), but no differences were found for all-cause mortality (P = .117) or infection-related readmission (0 = 0.112). CONCLUSIONS: Obese patients treated with ß-lactams have higher rates of treatment failure and longer hospitalization periods than nonobese patients. Future studies are needed to assess the impact of therapeutic drug monitoring and specific dosing recommendations for targeted infection types.

Revision Hip Arthroscopy in the Native Hip: A Review of Contemporary Evaluation and Treatment Options.

Hip arthroscopy is a reproducible and efficacious procedure for the treatment of femoroacetabular impingement syndrome (FAIS). Despite this efficacy, clinical failures are observed, clinical entities are challenging to treat, and revision hip arthroscopy may be required. The most common cause of symptom recurrence after a hip arthroscopy that leads to a revision arthroscopy is residual cam morphology as a result of inadequate femoral osteochondroplasty and restoration of head-neck offset, though several other revision etiologies including progressive chondral and labral pathologies also exist. In these cases, it is imperative to perform a comprehensive examination to identify the cause of a failed primary arthroscopy as to assess whether or not a revision hip arthroscopy procedure is indicated. When a secondary procedure is indicated, approaches may consist of revision labral repair, complete labral reconstruction, or labral augmentation depending on labral integrity. Gross instability or imaging-based evidence of microinstability may necessitate capsular augmentation or plication. If residual cam or pincer morphology is present, additional resection of the osseous abnormalities may be warranted. This review article discusses indications, the evaluation of patients with residual symptoms after primary hip arthroscopy, and the evaluation of outcomes following revision hip arthroscopy through an evidence-based discussion. We also present a case example of a revision hip arthroscopy procedure to highlight necessary intraoperative techniques during a revision hip arthroscopy.

Efficacy of adjunctive nebulized colistin in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial pneumonia: a multi-centre observational study.

OBJECTIVES: To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia. METHODS: This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed. RESULTS: In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37-0.92; model 2: aOR 0.37, 95% CI 0.21-0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2. CONCLUSIONS: Adjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB.

Discerning the role of polymicrobial biofilms in the ascent, prevalence, and extent of heteroresistance in clinical practice.

Antimicrobial therapy is facing a worrisome and underappreciated challenge, the phenomenon of heteroresistance (HR). HR has been gradually documented in clinically relevant pathogens (e.g. Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia spp., Acinetobacter baumannii, Klebsiella pneumoniae, Candida spp.) towards several drugs and is believed to complicate the clinical picture of chronic infections. This type of infections are typically mediated by polymicrobial biofilms, wherein microorganisms inherently display a wide range of physiological states, distinct metabolic pathways, diverging refractory levels of stress responses, and a complex network of chemical signals exchange. This review aims to provide an overview on the relevance, prevalence, and implications of HR in clinical settings. Firstly, related terminologies (e.g. resistance, tolerance, persistence), sometimes misunderstood and overlapped, were clarified. Factors generating misleading HR definitions were also uncovered. Secondly, the recent HR incidences reported in clinically relevant pathogens towards different antimicrobials were annotated. The potential mechanisms underlying such occurrences were further elucidated. Finally, the link between HR and biofilms was discussed. The focus was to recognize the presence of heterogeneous levels of resistance within most biofilms, as well as the relevance of polymicrobial biofilms in chronic infectious diseases and their role in resistance spreading. These topics were subject of a critical appraisal, gaining insights into the ascending clinical implications of HR in antimicrobial resistance spreading, which could ultimately help designing effective therapeutic options.

Evaluation of sandblasting with acid etching versus acid etching alone in the preparation of enamel for rebonding orthodontic brackets: An in vitro study and a randomized controlled trial.

BACKGROUND: No clinical studies have evaluated shear bond strength and the clinical failure rates of the rebonded metallic brackets following different enamel-reconditioning methods. The objective of the study was to compare the in vivo clinical failure rate and the in vitro rebond strength of bonded brackets following two enamel surface preparation methods. METHODS: For the in vitro study, 45 extracted human premolars were etched; brackets were bonded using light-cured composite resin. Forty-five premolars were divided into three groups (15 in each group): the initial bonding group (IB group), the rebonding group in which enamel was reconditioned using sandblasting before acid etching (SBE group), and the rebonding group in which enamel was reconditioned using acid etching only (E group). For the in vivo study, 80 premolars in 20 patients (13-18 years old) were rebonded using the same procedures in the SBE group and E group. The two methods were used in all patients using a split-mouth design. The number of failing brackets was quantified over 6 months. Differences were statistically analyzed by one-way analysis of variance, followed by post hoc tests. RESULTS: The mean shear bond strength for the IB, SBE, and E groups was 19.38, 22.37, and 17.31 MPa, respectively. A significant difference was observed in the bond strength of the three evaluated groups (P < 0.001). The differences in the bond strength were significant between the IB group and the SBE group, as well as between the SBE group and the E group. The clinical failure rate for bonded brackets was 10% in the SBE group, and 25% in the E group and this difference was statistically significant (P < 0.001). CONCLUSIONS: Reconditioning of enamel surfaces using both intraoral air abrasion and etching in the rebonding process led to higher rebond strength than using acid etching alone and even higher than the initial brackets bonding. This trial was retrospectively registered at ClinicalTrials.gov (ID: NCT04606043).