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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. [ABSTRACT FROM AUTHOR]

Purpose: Innovations in materials and implant design, as well as refinement of procedures and countermeasures for various complications, have led to improved outcomes for patients undergoing total hip arthroplasty (THA). However, various issues remain. Here we performed a comprehensive review of literatures regarding clinical failure of THA and discuss the current situation regarding specific issues. Methods: A narrative review was conducted focusing on the various causes of clinical failure or complications after THA. Each cause or complication is listed according to time of occurrence, from the intraoperative period to the late stage post-surgery. For each specific condition requiring revision or further surgery, we summarize the important clinical information, including prevalence, diagnosis, risk factors, and treatment options. Results: We focused on specific conditions that cause failure of THA, including periprosthetic joint infection, dislocation, malalignment/malposition, iliopsoas impingement, and other causes of pain after THA. We also discuss the prevalence, risk factors, diagnostic algorithm, and treatment options. Conclusion: Identifying possible causes of THA failure at each stage after surgery is important. In addition, clinicians need to understand that patients may have an unsatisfactory outcome despite perfect surgical technique and/or postoperative radiographs.

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.

No clear evidence supports the use of cefiderocol as first line treatment in A. baumannii infections. 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. 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%). 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. [ABSTRACT FROM AUTHOR]

Abstract 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

Abstract 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.

ABSTRACT 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Plain Language Summary: 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. [ABSTRACT FROM AUTHOR]

Nursing student failure affects the number of nurses prepared to enter practice. Currently, there is a dearth of literature examining program factors that influence clinical failure. This survey of nursing directors used multiple linear regression to determine if the percentage of adjunct faculty, the number of simulation hours, and the number of clinical hours affect clinical failure rates. The results of the study showed a positive correlation between each of the independent variables and the percentage of student clinical failures. [ABSTRACT FROM AUTHOR]

Analyzing factors that may have led to fracture of zirconia implants by macro/micro-fractography. 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. 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. 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. • Fracture-initiation sites varied for the one- and two-piece implants. • Clinical implant failures resulted from combined effects related to patient-related aspects, treatment planning, surface quality and specific implant designs. • Implant surface conditions and zirconia starting powder can be optimized. [ABSTRACT FROM AUTHOR]

Study Design: Literature review.Objective: The aim of this review is to summarize recent literature on adult spinal deformity (ASD) treatment failure as well as prevention strategies for these failure modes.Summary Of Background Data: There is substantial evidence that ASD surgery can provide significant clinical benefits to patients. The volume of ASD surgery is increasing, and significantly more complex procedures are being performed, especially in the aging population with multiple comorbidities. Although there is potential for significant improvements in pain and disability with ASD surgery, these procedures continue to be associated with major complications and even outright failure.Methods: A systematic search of the PubMed database was performed for articles relevant to failure after ASD surgery. Institutional review board approval was not needed.Results: Failure and the potential need for revision surgery generally fall into 1 of 4 well-defined phenotypes: clinical failure, radiographic failure, the need for reoperation, and lack of cost-effectiveness. Revision surgery rates remain relatively high, challenging the overall cost-effectiveness of these procedures.Conclusion: By consolidating the key evidence regarding failure, further research and innovation may be stimulated with the goal of significantly improving the safety and cost-effectiveness of ASD surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT 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.

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. [ABSTRACT FROM AUTHOR]

Abstract Background Despite the increase in the number of people accessing antiretroviral therapy (ART), there is limited data regarding treatment failure and its related factors among HIV-positive individuals enrolled in HIV care in resource-poor settings. This review aimed to identify factors associated with antiretroviral treatment failure among individuals living with HIV on ART in resource-poor settings. Methods We conducted a comprehensive search on MEDLINE (PubMed), Excerpta Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization’s (WHO’s) library database, and Latin American and Caribbean Health Sciences Literature (LILACS). We included observational studies (cohort, case-control, and cross-sectional studies) where adolescents and adults living with HIV were on antiretroviral treatment regardless of the ART regimen. The primary outcomes of interest were immunological, virological, and clinical failure. Some of the secondary outcomes were mm3 opportunistic infections, WHO clinical stage, and socio-demographic factors. We screened titles, abstracts, and the full texts of relevant articles in duplicate. Disagreements were resolved by consensus. We analyzed the data by doing a meta-analysis to pool the results for each outcome of interest. Results Antiretroviral failure was nearly 6 times higher among patients who had poor adherence to treatment as compared to patients with a good treatment adherence (OR = 5.90, 95% CI 3.50, 9.94, moderate strength of evidence). The likelihood of the treatment failure was almost 5 times higher among patients with CD4 < 200 cells/mm3 compared to those with CD4 ≥ 200 CD4 cells/mm3 (OR = 4.82, 95% CI 2.44, 9.52, low strength of evidence). This result shows that poor adherence and CD4 count below < 200 cells/mm3 are significantly associated with treatment failure among HIV-positive patients on ART in a resource-limited setting. Conclusion This review highlights that low CD4 counts and poor adherence to ART were associated to ART treatment failure. There is a need for healthcare workers and HIV program implementers to focus on patients who have these characteristics in order to prevent ART treatment failure. Systematic review registration The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number: 2019 CRD42019136538.

Background: As the popularity of Osteochondral allograft (OCA) transplantation increases, studies have commonly investigated potential risk factors that may influence OCA transplantation survivorship. Objectives: To investigate which risk factors of OCA transplantation failure have been evaluated, which have been found to be significant, and the frequency of inclusion of identified risk factors. Data sources: EMBASE, OVID, and Medline Study eligibility criteria: Studies investigating failure after OCA transplantation comparing or investigating one or more risk factors for failure through any statistical approach. Study appraisal and synthesis: All investigated failure risk factors and associated statistical significance were extracted and tabulated by study. The frequency of significance of each factor and inclusiveness of risk factor analysis by each study were assessed. Results: A total of 15 studies were included for qualitative analysis. Age, sex, body mass index (BMI), previous surgeries, and lesion location were among the most frequently investigated variables. Only BMI and previous surgeries were significant in more than one study. Limitations: There was heterogeneity in surgical techniques and varying definitions of failure utilized by each study, making a direct comparison difficult. Conclusions and implications of key findings: OCA failure risk factor analyses are limited primarily to basic demographic factors (eg, age, sex). Furthermore, only 2 identified risk factors were significant in more than one study, limiting the ability to make evidence-based decisions with the current data available. This information could impact operative planning, the decision to perform an OCA over other cartilage restoration procedures, and patient expectations. Systematic review registration number: CRD42021282852

Abstract Background The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP). Methods 3011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis. Results The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH 10,000/mm3, pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors. Conclusions Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP. Trial registration A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb

BACKGROUND: In recent years, fractographic analysis has been applied to the study of fracture mechanics of ceramics. At present, most studies focus on the analysis of crack origin and propagation path of clinical fracture of all-ceramic crowns by using the typical crack characteristics of fractographic analysis, as well as the analysis of cyclic fatigue damage mode of all-ceramic crowns in vitro simulation state. OBJECTIVE: The fractographic analysis was used to analyze the crack origin and related defects of all-ceramic crowns. METHODS: From October 2018 to September 2019, a total of 12 patients with all-ceramic crowns fracture after failure in clinical use were selected from the Department of Stomatology, Eye&ENT Hospital of Fudan University. The stereomicroscope was used to observe the overall morphology of all-ceramic fracture section. The scanning electron microscope was used to observe the crack, surface damage and structural defects. The origin and propagation path of crack were deduced by the fractographic analysis. This trial was approved by the Ethics Committee of Eye & ENT Hospital of Fudan University. RESULTS AND CONCLUSION: (1) Cyclic fatigue was an important reason for the fracture of all-ceramic restorations. Different types of cyclic fatigue damage modes could be observed in 12 fractured pieces of all-ceramic crowns, such as cone crack, veneer chipping, veneer delamination, radial crack, and surface defects. Different all-ceramic crowns had different dominant fatigue damage modes. (2) Cyclic fatigue damage was an important reason for the failure of allceramic crowns, among which radial crack was the main mode. The thickness of porcelain layer and core/veneer thickness ratio have a close influence on its occurrence. The interface between veneer and core is the weak link of double-layer all-ceramic restorations. Structural defects and stress concentration caused by abnormal occlusion are potential risk factors for failure of all-ceramic crowns. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a β-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 β-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 β-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. [ABSTRACT FROM AUTHOR]

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.

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.

• The use of cefiderocol for CRAB infections is a matter of debate. • A systematic review assessing cefiderocol efficacy in CRAB infections is provided. • Six studies (one RCT and five observational) comprising a total of 561 patients were included. • Lower mortality rate was found in patients with CRAB infections treated with cefiderocol regimens. • Lower mortality rate with cefiderocol was confirmed in all subgroup analyses. 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. 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. 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; I 2=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; I 2=0.0%). 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. [ABSTRACT FROM AUTHOR]

Abstract Background Access to antiretroviral therapy (ART) in Ethiopia has been scaled up since the introduction of the service in 2003. Free ART was launched in 2005, resulting in fewer new human immunodeficiency virus (HIV) infections and deaths from acquired immunodeficiency syndrome (AIDS). However, immunological and clinical failures for first-line ART due to poor adherence and other factors have received less attention. Thus, this study aims to determine the magnitude and associated factors of clinical and immunological failure among HIV-positive adults after six months of first-line ART in Dire Dawa, Eastern Ethiopia. Methods A facility-based cross-sectional study was conducted using secondary data of patients on ART in all health facilities providing ART services in Dire Dawa. A total of 949 samples were collected. The data were entered into Epidata version 3.02, and the analysis was performed using SPSS version 16.0. Univariate and multivariate analyses were performed to determine the magnitude of clinical and immunological failure and identify factors significantly associated with the outcome variable. Results The magnitude of clinical and immunological failure was 22.7% (n = 215). Of these, 33 (15%) patients were switched to second-line ART. CD4 count ≤100 cells/mm3 (AOR: 1.78, 95% CI: 1.18–2.69), poor adherence (AOR: 2.5, 95% CI: 1.19–5.25), restarting after interruption of ART (AOR: 1.93, 95% CI: 1.23–3.07), regimen change (AOR: 1.50, 95% CI: 1.05–2.15), ambulatory/bedridden functional status at the last visit on ART (AOR: 2.41, 95% CI: 1.22–4.75) and patients who died (AOR: 3.94, 95% CI: 1.64–9.45) had higher odds of failure. Conclusion The magnitude of clinical and immunological failure was high. To curb this problem, initiation of ART before the occurrence of severe immune suppression, early detection and management of failure and improved adherence support mechanisms are recommended. Restarting treatment after interruption and regimen changes-should-be-made-cautiously.

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. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Despite the increase in the number of people accessing antiretroviral therapy (ART), there is limited data regarding treatment failure and its related factors among HIV-positive individuals enrolled in HIV care in resource-poor settings. This review aimed to identify factors associated with antiretroviral treatment failure among individuals living with HIV on ART in resource-poor settings. Methods: We conducted a comprehensive search on MEDLINE (PubMed), Excerpta Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization's (WHO's) library database, and Latin American and Caribbean Health Sciences Literature (LILACS). We included observational studies (cohort, case-control, and cross-sectional studies) where adolescents and adults living with HIV were on antiretroviral treatment regardless of the ART regimen. The primary outcomes of interest were immunological, virological, and clinical failure. Some of the secondary outcomes were mm3 opportunistic infections, WHO clinical stage, and socio-demographic factors. We screened titles, abstracts, and the full texts of relevant articles in duplicate. Disagreements were resolved by consensus. We analyzed the data by doing a meta-analysis to pool the results for each outcome of interest. Results: Antiretroviral failure was nearly 6 times higher among patients who had poor adherence to treatment as compared to patients with a good treatment adherence (OR = 5.90, 95% CI 3.50, 9.94, moderate strength of evidence). The likelihood of the treatment failure was almost 5 times higher among patients with CD4 < 200 cells/mm3 compared to those with CD4 ≥ 200 CD4 cells/mm3 (OR = 4.82, 95% CI 2.44, 9.52, low strength of evidence). This result shows that poor adherence and CD4 count below < 200 cells/mm3 are significantly associated with treatment failure among HIV-positive patients on ART in a resource-limited setting. Conclusion: This review highlights that low CD4 counts and poor adherence to ART were associated to ART treatment failure. There is a need for healthcare workers and HIV program implementers to focus on patients who have these characteristics in order to prevent ART treatment failure. Systematic review registration: The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number: 2019 CRD42019136538. [ABSTRACT FROM AUTHOR]

The U.S. Agency for Healthcare Research and Quality estimates that there are over 1 million total hip and total knee replacements each year in the U.S. alone. Twenty five percent of those implants will experience aseptic loosening, and bone cement failure is an important part of this. Bone cements are based on poly(methyl methacrylate) (PMMA) systems that are strong but brittle polymers. PMMA‐based materials are also essential to modern dental fillings, and likewise, the failure rates are high with lifetimes of 3–10 years. These brittle polymers are an obvious target for self‐healing systems which could reduce revision surgeries and visits to dentist. Self‐healing polymers have been described in the literature since 1996 and examples from Roman times are known, but their application in medicine has been challenging. This review looks at the development of self‐healing biomaterials for these applications and the challenges that lie between development and the clinic. Many of the most promising formulations involve introducing nanoscale components which offer substantial potential benefits over their microscale counterparts especially in composite systems. There is substantial promise for translation, but issues with toxicity, robustness, and reproducibility of these materials in the complex environment of the body must be addressed. This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging TechnologiesNanotechnology Approaches to Biology > Nanoscale Systems in BiologyImplantable Materials and Surgical Technologies > Nanomaterials and Implants [ABSTRACT FROM AUTHOR]

Background: Several recent studies have recommended offering unicompartmental knee arthroplasty (UKA) to all patients regardless of body mass index (BMI). The aim of this investigation was to evaluate the proposition that UKA can indeed be offered to the morbidly-obese and super-obese (morbidly-obese, BMI ≥ 40 kg/m2) without compromising results or survivorship.Methods: We retrospectively reviewed mobile-bearing medial UKA procedures performed at our facility from January 2012 to May 2015 with a minimum of 2-year follow-up. The study cohort was divided into patients with morbid obesity (BMI ≥ 40 kg/m2) and those without morbid obesity (BMI < 40 kg/m2). A detailed medical record review was performed. Extracted outcome data included the frequency of (1) major revision procedures (components revised), (2) minor secondary procedures (components not revised), (3) infection procedures, and (4) recommendations for revision.Results: We found 152 patients (190 knees) who met criteria for inclusion. Mean follow-up duration was 3.4 years (range: 2.0-6.8 years). Major revision surgery occurred more frequently in the morbid-obesity UKA group (15.7% vs 3.0%, P < .01). Rates of minor secondary surgery and infection were comparable for both groups. Most failures in the morbid-obesity UKA group (85.7%) were due to disease progression involving other compartments or mobile-bearing instability.Conclusion: We found the rate of early major revision surgery in morbidly-obese patients undergoing UKA to be over 5-times greater than that of other patients. Failure was predominantly due to disease progression in other compartments or mobile-bearing instability. Further study is warranted and needed before expanding UKA indications to the morbidly-obese population. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the clinical and economic burden of community-acquired (CA) or community-onset healthcare-associated (COHCA) multidrug-resistant (MDR) infections requiring hospitalization.Methods: Case-control study. Adults admitted with CA or COHCA MDR infections were considered cases, while those admitted in the same period with non-MDR infections were controls. The matching criteria were source of infection and/or microorganism. Primary outcome was 30-day clinical failure. Secondary outcomes were 90-day and 1-year mortality, hospitalization costs and resource consumption.Results: 194 patients (97 cases and 97 controls) were included. Multivariate analysis identified age (odds ratio [OR], 1.07, 95% confidence interval [CI], 1.01-1.14) and SOFA score (OR, 1.45, CI95%, 1.15-1.84) as independent predictors of 30-day clinical failure. Age (hazard ratio [HR] 1.09, 95%CI, 1.03-1.16) was the only factor associated with 90-day mortality, whereas age (HR 1.06, 95%CI, 1.03-1.09) and Charlson Index (HR 1.2, 95%CI, 1.07-1.34) were associated with 1-year mortality. MDR group showed longer hospitalization (p<0.001) and MDR hospitalization costs almost doubled those in the non-MDR group. MDR infections were associated with higher antimicrobial costs.Conclusions: Worse economic outcomes were identified with community-onset MDR infections. MDR was associated with worse clinical outcomes but mainly due to higher comorbidity of patients in MDR group, rather than multidrug resistance. [ABSTRACT FROM AUTHOR]

The aim was the development of early clinical failure criteria (ECFC) to predict unfavourable outcomes in patients with Gram-negative bloodstream infections (GN-BSI). Adults with community-onset GN-BSI who survived hospitalization for ≥72 hr at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 1, 2010 to June 30, 2015 were identified. Multivariable logistic regression was used to examine the association between clinical variables between 72 and 96 hr after GN-BSI and unfavourable outcomes (28-day mortality or hospital length of stay >14 days from GN-BSI onset). Among 766 patients, 225 (29%) had unfavourable outcomes. After adjustments for Charlson Comorbidity Index and appropriateness of empirical antimicrobial therapy in multivariable model, predictors of unfavourable outcomes included systolic blood pressure <100 mmHg or vasopressor use (adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.2–2.9), heart rate >100 beats/minute (aOR 1.7, 95% CI 1.1–2.5), respiratory rate ≥22 breaths/minute or mechanical ventilation (aOR 2.1, 95% CI 1.4–3.3), altered mental status (aOR 4.5, 95% CI 2.8–7.1), and white blood cell count >12 000/mm3 (aOR 2.7, 95% CI 1.8–4.1) between 72 and 96 hr after index GN-BSI. Area under receiver operating characteristic curve of ECFC model in predicting unfavourable outcomes was 0.77 (0.84 and 0.71 in predicting 28-day mortality and prolonged hospitalization, respectively). Risk of 28-day mortality or prolonged hospitalization can be estimated between 72 and 96 hr after GN-BSI using ECFC. These criteria may have clinical utility in management of GN-BSI and may improve methodology of future investigations assessing response to antimicrobial therapy based on a standard evidence-based definition of early clinical failure. [ABSTRACT FROM AUTHOR]

Objective: Glass-fiber-reinforced resin composites for the fabrication of esthetic single crowns and fixed partial dentures have been developed recently. However, little data on the clinical outcome of such restorations have been published. The purpose of this retrospective study was to evaluate the clinical outcome of crowns and fixed partial dentures made from the glass-fiber-reinforced resin composite material Targis/Vectris. Method and materials: Between 1995 and 1997, 39 patients were Heated with 67 single crowns and 83 fixed partial dentures. Twenty-five crowns and 28 Used partial dentures were cemented with temporary cement, while 42 crowns and 55 fixed partial dentures were cemented with either zinc-phosphate cement or glass-ionomer cement Results: In September 2001, 57 restorations in 17 patients were still in function. The three-year survival rate calculated according to the Kaplan-Meier method was 58.8% for all restorations However, after this time, it was 37.5% for crowns and 59.9% for fixed partial dentures cemented with temporary cement, and 55.1% for crowns and 67 9% for fixed partial dentures cemented with zinc phosphate or glass ionomer. The differences between the restoration groups were not statistically significant Conclusion: Glass-fiber-reinforced crowns and fixed partial dentures made with The glass-fiber-reinforced resin composite material Targis/Vectris showed a lower survival rate than that published for metal-ceramic crowns and fixed partial dentures Therefore, the use of this material for the fabrication of single crowns or fixed partial dentures as permanent restorations cannot be recommended. (Quintessence Int 2003;34:493-496) [ABSTRACT FROM AUTHOR]

Carbapenem resistance is defined as in vitro non-susceptibility to any carbapenem and/or documented production of a carbapenemase. This feature has rapidly spread worldwide among clinical isolates of Enterobacteriaceae , mostly Klebsiella spp., and is associated with diverse molecular mechanisms. Carbapenem resistance is often associated with resistance to all traditional β-lactams and other classes of antibiotics, denoting a typical example of an extensively drug-resistant phenotype. To summarize and interpret in a balanced manner the most clinically relevant data in terms of carbapenem-resistant Enterobacteriaceae (CRE) infection management. Data were extracted by PubMed and clinicaltrials.gov search and manual scrutiny among references of analysed articles. Features of newer and older, rediscovered antimicrobial options for CRE are described. Observational studies and randomized clinical trials (RCT) of CRE treatment are summarized, with a specific focus on the effects of monotherapy compared with combination treatment. The available evidence on the current management of CRE mostly comes from observational, non-comparative, retrospective, small studies, with a high risk of selection bias. Very little evidence comes from RCT. Conflicting results of RCT and observational studies call for caution before combination therapies are deemed superior to monotherapy. Data on newer agents have spurred enthusiasm but remain limited as concerns severe CRE infections. A balanced approach should guide the clinician in the choice of old or new drugs, and of monotherapies or combination regimens. Efforts should be made to perform adequately sized clinical trials answering well-defined research questions. [ABSTRACT FROM AUTHOR]

Abstract Objectives To provide fractographic analysis of clinically fractured zirconia implants recovered with their cemented crown. To calculate bending moments, corresponding stress and crack onset location on the implant's fracture surface using a mathematical model integrating spatial coordinates of the crown-implant part and occlusal loading obtained from 2D and 3D images. Methods 15 fractured zirconia implants parts (11 posterior and 4 anterior) with their all- ceramic crowns still cemented on it were recovered. The implants were first generations from four manufacturers (AXIS Biodental, Z-Systems, Straumann, Swiss Dental Solutions). The time-to-failure varied between 2 weeks and 9 years. Fractography was performed identifying the failure origin and characteristic surface crack features. From 2D and 3D digital images of the crown-implant part, spatial coordinates anchoring the crown's occlusal contacts with the implant's central axis and reference plane were integrated in a mathematical model spreadsheet. Loads of 500 N in total were selectively distributed over identified occlusal contacts from wear patterns. The resultant bending and torsion moments, corresponding shear, tensile, maximum principal stress and von Mises stress were calculated. The fracture crack onset location on the implant's fracture surface was given by an angular position with respect to an occlusal reference and compared with the location of the fracture origin identified from fractographic analysis. Results Implants fractured from the periphery of the smaller inner diameter between two threads at the bone-entrance level except for one implant which failed half-way within the bone. The porous coating (AXIS Biodental) and the large grit alumina sandblasting (Z-System) created surface defects directly related to the fracture origin. The model spreadsheet showed how occlusal loading with respect to the implant's central axis affects bending moments and crack onset. Dominant loads distributed on contacts with important wear pattern provided a calculated crack onset location in good agreement with the fractographic findings of the fracture origin. Significance Recovered broken zirconia implant parts with their restorative crowns can provide not only information regarding the failure origin using fractography but also knowledge regarding occlusal crown loading with respect to the implant's axis. The mathematical model was helpful in showing how occlusal loading affects the location of the fracture initiation site on clinical zirconia implant fracture cases. [ABSTRACT FROM AUTHOR]

Vertebral osteomyelitis (VO) is a compelling clinical entity for clinicians, because of its insidious and indolent course that makes diagnosis difficult. A concern is reported about the choice of antibiotic regimens, duration of therapy, and criteria to switch to oral therapy. We conducted a prospective observational study. All consecutive hospitalized patients with a confirmed diagnosis of VO caused by staphylococcal or enterococcal strains were analyzed. The primary endpoint was the analysis of clinical cure at the end of therapy. A propensity score for receiving therapy with daptomycin was added to the model. During the study period, 60 episodes of confirmed VO were observed. The main etiology of infection was methicillin-resistant Staphylococcus aureus (29%). Overall, clinical failure at end of therapy was reported in 11 (18.3%) patients. Logistic regression analysis, after propensity score, showed that >2 vertebrae involved (OR 2.4, CI95% 1.12–5.24, p = 0.002) and inadequate drainage of infection (OR 4.8, CI95% 2.45–8.51, p < 0.001) were independently associated with failure of therapy, while the use of a daptomycin-containing-regimen (OR 0.15, CI 95% 0.04–0.46, p < 0.001) with clinical cure. VO caused by staphylococcal or enterococcal strains is associated with an important rate of clinical failure. Daptomycin-containing regimen was strongly associated with clinical cure. Considering that over 70% of VO etiology is caused by Gram-positive strains but the etiology of infection is obtained in about 75% of cases, these data may help physicians to choose the appropriate antibiotic regimen.

Background: Ceftriaxone has standard, set dosing regimens that may not achieve adequate serum concentrations in obese patients compared to non-obese patients. The purpose of this study was to evaluate the effect of obesity on ceftriaxone efficacy when used as definitive monotherapy to treat infections. Methods: This retrospective cohort included adult inpatients treated with ceftriaxone monotherapy for ≥72 h between July 01, 2015–July 31, 2017. Patients were excluded if their infection lacked source control within 72 h or if they had polymicrobial infections requiring more than one antibiotic for definitive therapy. The primary outcome was the rate of clinical failure between obese versus non-obese patients, defined as a composite of (1) change in definitive therapy > 72 h due to clinical worsening; (2) residual leukocytosis (white blood cell count (WBC) > 10 × 109/L) > 72 h after treatment initiation; (3) presence of a fever (single temperature > 100.9 °F) > 72 h after treatment initiation; or (4) readmission within 30 days due to re-infection with the same organism. Results: A total of 101 patients were included in the study: 39 obese and 62 non-obese. The most common indications for ceftriaxone were urinary tract (52.5%), respiratory tract (24.8%), and bloodstream (24.8%) infections. The most commonly isolated organisms were Escherichia coli (48.5%) and Klebsiella species (15.8%). Most patients received 1g every 24 h. Clinical failure was observed in 61.5% of obese patients versus 40.3% of non-obese patients (p = 0.038). Conclusion: Obese patients treated with ceftriaxone were more likely to experience clinical failure when compared to non-obese patients. Further analyses are warranted to determine if weight-based dosing is required in obese patients treated with ceftriaxone.

Objectives: Objectives of this study were To compare the clinical and bacteriological cure rates of azithromycin and ciprofloxacin in the treatment of uncomplicated typhoid fever and To determine any difference in the clinical and bacteriological cure rates within the two groups of study. Study Design: Quasi experimental study. Setting: Department of Medicine, DHQ/ Teaching Hospital Dera Ghazi Khan. Period: April 2016 to September 2016. Patients and Methods: A total of 60 patients including both males and females over 18 years of age were included in the study by Simple random probability sampling. Patients fulfilling the inclusion criteria were divided in two equal groups of 30 by using the random numbers table. First group was treated with azithromycin one gram on day one and then 500 mg daily for next six days. Second group was treated with ciprofloxacin 500mg twice daily for ten days. All the data was analyzed by the computer programme SPSS. Frequency, percentages, mean values and standard deviations were calculated for age, sex, symptoms, signs, culture reports, clinical cure rates and bacteriological cure rates. Results: Most common clinical feature was fever noted in 100% patients followed by headache (86.6%) and nausea / vomiting (76.6%). Out of 60, 52 (86.6%) patients were culture positive. In Azithromycin group clinical and bacteriological responses were achieved in 93.3% and 92.3% respectively while in ciprofloxacin group they were 96.6% and 96.15% respectively. There was no significant statistical difference between the clinical and bacteriological cure rates among two groups. Conclusion: Both ciprofloxacin and azithromycin are equally effective in the treatment of uncomplicated typhoid fever. [ABSTRACT FROM AUTHOR]

Introduction: Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. Methods: The study population consisted of HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring =0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements =400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed. Results: Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution. Conclusions: The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non-clinical trial settings in Asian countries. [ABSTRACT FROM AUTHOR]

Besides inherent differences in in vitro susceptibilities, clinically-relevant yeast species may acquire resistance upon exposure to most antifungal drugs used in the clinic. In recent years, major fundamental research studies have been conducted to improve our understanding of the molecular basis of antifungal resistance. This topic is of major interest as antifungal resistance in yeast is clearly evolving and is correlated with clinical failure. This minireview is an overview of the most recent findings about key molecular mechanisms evolving in human pathogenic yeasts, particularly Candida spp., in the context of antifungal drug resistance. Also included are the methods currently available for in vitro antifungal susceptibility testing and for molecular detection of mutations associated with resistance. Finally, the genetic drivers of antifungal resistance are discussed in light of the spectra of multidrug resistance as observed in Candida glabrata . [ABSTRACT FROM AUTHOR]