Unraveling the Challenges of Difficult-to-Treat Spondyloarthritis: SPARTAN 2024 Annual Meeting Proceedings.

PURPOSE OF REVIEW: This review aims to explore the emerging concept of difficult-to-treat axial spondyloarthritis (D2T-axSpA), including its definitions, clinical challenges, and management strategies. The objective, as presented at the SPARTAN 2024 Annual Meeting, is to delineate the evolving framework for identifying and addressing D2T-axSpA, with a focus on inflammatory and non-inflammatory mechanisms of treatment failure and the implications for clinical practice. RECENT FINDINGS: Studies have highlighted a prevalence of D2T-axSpA ranging from 19.5 to 28.3% in real-world cohorts, with associated risk factors including peripheral arthritis, comorbidities, and female gender. Recent advances include the Assessment of SpondyloArthritis International Society's (ASAS) preliminary definition of "difficult-to-manage axSpA" (D2M-axSpA), which encompasses treatment-refractory cases and broader management challenges and `treatment refractory axSpA´ where objective evidence of ongoing inflammation is mandatory.  D2T-axSpA presents significant challenges due to persistent disease activity and the interplay of inflammatory and non-inflammatory drivers. The emerging definitions and research into personalized treatment strategies promise to refine clinical management. Future directions emphasize biomarker-driven precision medicine, novel therapeutic combinations, and holistic care models to improve outcomes in this complex patient population.

Predicting extubation failure in neonates: The role of lung ultrasound and corrected gestational age in safe weaning in the NICU.

To evaluate the accuracy of the lung ultrasound score (LUS) in predicting ventilatory weaning failure during neonatal hospitalization in the NICU and to identify factors associated with weaning failure, including corrected gestational age (CGA). This prospective, longitudinal, pragmatic and observational cohort study included neonates on mechanical ventilation for at least 48 h. The primary outcome was the accuracy of lung ultrasound in predicting 3-day weaning failure, with the ROC curve used to determine the best LUS cutoff (sensitivity and specificity). Among 55 neonates, the pre-extubation LUS did not show statistical significance in predicting weaning failure (AUC 0.61; 95% CI: 0.46-0.76, p = 0,169). In the subgroup analysis, a score ≥ 4 suggests the need for ventilatory support after extubation (area under the curve [AUC] = 0.91, 95% CI: 0.80-1.0, p < 0.001) in neonates with GA ≥ 28 weeks. In extremely preterm infants, the pre-extubation LUS was not statistically significant in predicting weaning failure (AUC = 0.38, 95% CI: 0-0.77, p = 0.535). In contrast, CGA ≥ 28.7 weeks at extubation was predictor of successful weaning within 3 days (AUC = 0.95, 95% CI: 0.85-1.0, p < 0.001). CONCLUSION: LUS show promise in predicting weaning failure, though its accuracy may be limited in extremely preterm infants, highlighting the need for further well-powered studies. CGA at extubation also emerges as a key consideration in this population, warranting confirmation through robust future research. WHAT IS KNOWN: • Identifying the optimal timing for extubation is crucial, as both prolonged mechanical ventilation and failed extubation are linked to increased morbidity. • Lung ultrasound plays a well-established role in diagnosing various neonatal lung pathologies, allowing clinicians to make rapid, bedside decisions for the treatment of newborns. WHAT IS NEW: • LUS appears to be accurate in predicting weaning failure, though its accuracy may be lower in extremely preterm infants. • In extremely preterm infants, CGA may play an important role in extubation decision-making. • These findings are hypothesis-generating and warrant further investigation in future studies.

Real-world outcomes and predictors of failure of gonioscopy-assisted transluminal trabeculotomy in a large glaucoma cohort: a multicenter study.

This retrospective, comparative, multicenter study aimed to evaluate the real-world outcomes and predictors of failure of Gonioscopy-assisted transluminal trabeculotomy (GATT) at 12 months in glaucoma patients. Predictors of failure of absolute success in bilateral cases (422 eyes of 308 patients) included pre-operative intraocular pressure (IOP; IRR = 1.02; p = 0.01), and pre-operative mean deviation (IRR = 0.98; p = 0.007). The significant predictors of failure of relative success included binocularity (IRR = 4.05; p = 0.001) and pre-operative IOP (IRR = 1.04; p = 0.022). Only one eye per patient (308 eyes) was included in the second analysis. IOP reduced from 21.84 ± 7.96 mmHg to 11.97 ± 2.89 mmHg at 12 months; the number of hypotensive eye drop medications decreased from 3.07 ± 1.04 to 1.06 ± 1.08 (p < 0.001 for both). The pre-operative IOP was a predictive factor for failure of absolute (IRR = 1.02; p = 0.026) and relative successes (IRR = 1.05; p = 0.014). The preoperative number of hypotensive medications only affected absolute success (IRR = 1.25; p = 0.004). The Kaplan-Meier graph revealed relative and absolute success in 88.9% and 43.9% of cases, respectively. In conclusion, GATT is a safe and effective treatment option for diverse forms of open-angle glaucoma with varying severity. Pre-operative number of medications and IOP, race, and the outcomes of the contralateral eye (if applicable) were identified as predictors of failure of the procedure.

Risk of viral failure after simplification therapy without using integrase inhibitors compared with maintenance of triple antiretroviral therapy: A systematic review and meta-analysis.

BACKGROUND: Antiretroviral drug simplification is a strategy to reduce drug exposure and improve treatment adherence. Nowadays, dolutegravir plus lamivudine is the most preferred regimen, which might lead in the future with problems related to drug resistance or drug intolerance. This meta-analysis aimed to assess the safety of HAART simplification without integrase inhibitors. METHODS: We conducted a systematic review and meta-analysis using the Embase and Medline databases to include clinical trials and observational studies published between 2008 and March 2024. The studies focused on HIV-positive individuals with suppressed viral load who either simplified their treatment to dual therapy without integrase inhibitors or continued triple therapy. The primary outcome of interest was the likelihood of viral failure within 48 weeks. RESULTS: Ten studies were included, with a total of 1,977 patients. Boosted Protease Inhibitors (PI) were the core of antiretroviral simplification therapy. The simplification group did not show an increased risk of virological failure, with a pooled RR in 48 weeks of 1.29 (0.61‒2.73, I² = 51 %) when compared to control group. Boosted protease inhibitors were preferred combined with lamivudine, nevirapine, efavirenz, and maraviroc). Only maraviroc plus boosted PI combination was associated with a higher risk of virological failure with an RR of 4.49 (1.99‒10.11). CONCLUSION: Simplification therapy with boosted PI plus lamivudine or non-nucleoside transcriptase reverse inhibitors was a safe strategy and not associated with a higher risk of virological failure. This approach might be an alternative to dolutegravir-based simplification regimens if needed.

"Comparative analysis of predictors of failure for high-flow nasal cannula in bronchiolitis".

OBJECTIVE: To assess a comparative analysis of the ROX index, Wood-Downes-Ferrés score (WDF), p-ROXI, and the SpO2/FiO2 ratio as predictors of high-flow nasal cannula (HFNC) failure in children hospitalized for bronchiolitis. METHODS: Data were extracted from the clinical trial "Comparison between HFNC and NIV in children with acute respiratory failure caused by bronchiolitis" conducted at a tertiary Brazilian hospital (Emergency Department and PICU). The inclusion criteria were children under 2 years of age admitted for bronchiolitis who developed mild to moderate respiratory distress and were eligible for HFNC therapy. Performance was determined by ROC and AUC metrics to define the best sensitivity and specificity for each variable. Children were evaluated at 0 h, 2 h, 6 h, 12 h, 24 h, 48 h, 72 h and 96 h after HFNC therapy initiation. RESULTS: A total of 126 patients were recruited for this analysis. The median age was 3 months. Ninety-one percent of the patients had an identified viral agent, with RSV being the most common (65%). Twenty-three percent (29/126) of patients experienced failed HFNC therapy and required mechanical ventilation. The best cutoff points at 12 hours were 4.5 for WDF (AUC = 0.83, 0.74-0.92), 8.8 for ROX (AUC = 0.7, 0.54-0.84), 1.45 for p-ROXI (AUC = 0.56, 0.38-0-74), and 269 for SpO2/FiO2 (AUC = 0.64, 0.48-0.74). The scores and indices were also correlated with the PICU and hospital LOS. CONCLUSIONS: The ROX index and WDF were the most accurate scores for assessing HFNC failure considering 12-hour cutoff points. TRIAL REGISTRATION NUMBER: U1111-1262-1740; RBR-104z966s. Date of registration: 03/01/2023.

[Risk assessment for complications and stone free status in percutaneous nephrolithotomy]. / Evaluación de complicaciones y estado libre de litos en nefrolitotomía percutánea.

Background: Percutaneous nephrolithotomy (PNL) is the first line treatment for kidney stones with a diameter > 2 cm. The available scores for measuring success in this procedure only consider the free stone status, without considering the complications. Objective: To present a new prognostic stratification system to predict treatment failure in PNL. Material and methods: Historic cohort in which prognostic factors and failure as residual stone with or without complication were identified. A bivariate analysis was performed using the numeric variables and with the use of conjunctive consolidation a prognostic stratification system was developed. Results: A total of 595 cases were included, out of which 73% concluded with free stone status and 12% developed major complications. 66% fulfilled the proposed success definition. In the first conjunct consolidation, a positive urine culture and a complex stone were identified as risk factors; after making one more conjunction with another stratum, the severe Charlson Comorbidity Index (CCI) was also identified as a risk factor. Finally, an operating time ≥ 120 minutes was added as an intraoperative factor that increases risk. Conclusions: The variables positive urine culture, severe CCI, complex stone and prolonged operating time are associated with major complications and residual stone. The proposed score is a simple and predictive tool that can be used in daily practice, given that it includes 3 pre-operative variables. The treatment success or failure rate of the score can be applied in the selection of patients ongoing PNL.

Introducción: la nefrolitotomía percutánea (NLP) es el procedimiento de primera línea de tratamiento para litos > 2 cm. Las escalas para valorar el éxito en este procedimiento consideran solo el estatus libre de litos, sin tomar en cuenta las complicaciones. Objetivo: presentar un nuevo sistema de estratificación pronóstica para predecir el fracaso en NLP. Material y métodos: cohorte histórica en la cual se identificaron factores pronósticos y fracaso como lito residual con o sin complicación. Se hizo un análisis bivariado y mediante el uso de consolidación conjunta se desarrolló un sistema de estratificación pronóstica. Resultados: se incluyeron 595 casos, de los cuales el estado libre de litos resultó en un 73% y 12% presentaron complicaciones mayores. El 66% cumplieron con la propuesta de definición de éxito. La primera consolidación conjunta encontró un urocultivo positivo y un lito complejo como factores de riesgo; al conjuntarlos con un nuevo estrato, se encontró también como un factor el índice de comorbilidad de Charlson (ICC). Finalmente, se añadió un tiempo ≥ 120 minutos con un factor transoperatorio extra que aumentó el riesgo. Conclusiones: las variables urocultivo positivo, ICC severo, lito complejo y tiempo quirúrgico prolongado están relacionadas con complicaciones mayores y el lito residual. La escala propuesta es una herramienta simple y predictiva que puede ser utilizada en la práctica diaria, pues solo incluye 3 variables preoperatorias. Las tasas de éxito y fracaso de esta escala se pueden implementar en la selección de los pacientes sometidos a NLP.

Role of histopathological, serological and molecular findings for the early diagnosis of treatment failure in leprosy.

BACKGROUND: Treatment failure (TF) in leprosy following multidrug therapy (MDT) presents a significant challenge. The current World Health Organization (WHO) fixed-duration MDT regimen, based on lesion count, might not be adequate. Leprosy lacks clear-cut objective cure criteria, and the predictive value of post-MDT histopathological findings remains uncertain. This study aims to identify predictive factors for TF among leprosy patients who have completed the WHO-recommended MDT. METHODS: An analysis was conducted on 80 individuals from a national leprosy reference center, comprising 40 TF cases (with a mean relapse at 13.0 months) and 40 controls (with a mean of 113.1 months without disease signs). Various epidemiological and clinical-laboratory parameters were assessed post-MDT. RESULTS: In skin samples, the presence of foamy granuloma (OR = 7.36; 95%CI2.20-24.60; p = 0.0012) and histological bacillary index (hBI) ≥ 1+ (OR = 1.55; 95%CI1. 22-1.99; p = 0.0004) were significantly associated with TF, with odds ratios of 7.36 and 1.55, respectively. Individuals who experienced TF had a mean hBI of 3.02+ (SD ± 2.02), while the control group exhibited a mean hBI of 1.8+ (SD ± 1.88). An hBI ≥ 3 + showed a sensitivity of 73% and a specificity of 78% for TF detection (AUC: 0.75; p = 0.0001). Other histopathological features like epithelioid granulomas, and skin changes did not show significant associations (p > 0.05). Additionally, higher anti-phenolic glycolipid-I (anti-PGL-I) ELISA index (EI) levels were linked to a 1.4-fold increased likelihood for TF (OR = 1.4; 95%CI1.13-1.74; p = 0.0019). A mean EI of 4.48 (SD ± 2.80) was observed, with an EI ≥ 3.95 showing a sensitivity of 79% and a specificity of 59% for TF detection (AUC: 0.74; p = 0.0001). Moreover, the presence of Mycobacterium leprae (M. leprae) DNA in real-time polymerase chain reaction (qPCR) was associated with a 3.43-fold higher likelihood of TF. Multivariate regression analysis indicated that concurrent presentation of neural/perineural lymphocytic infiltrate, foamy granuloma, hBI ≥ 1+, and EI ≥ 1 markedly increased the likelihood of TF by up to 95.41%. CONCLUSION: Persistence of nerve-selective lymphocytic infiltrate, foamy granulomas, and bacilli in skin biopsies, and elevated EI post-MDT, may serve as predictive factors for identifying individuals at higher probability of TF.

Factors associated with unsuccessful tuberculosis treatment in Manaus, Amazonas, from 2011 to 2021.

OBJECTIVE: To identify vulnerability factors associated with unsuccessful tuberculosis treatment outcomes between 2011 and 2021 in Manaus, Amazonas. METHOD: Ecological study using tuberculosis case notification data from the Notifiable Diseases Information System, from 2011 to 2021, of residents in Manaus. The variables refer to treatment outcomes and patient vulnerability, according to the theoretical model: individual, programmatic and social. The analysis tested the association between vulnerability and tuberculosis treatment non-success, measured by the occurrence of death, loss to follow-up or treatment default. The Odds Ratio estimate with confidence interval was obtained by logistic regression, according to a hierarchical model. RESULTS: The following factors were more likely to lead to unsuccessful tuberculosis treatment: individual vulnerability (age group 20 to 29 years and over 60 years, indigenous race, HIV+, drug use); programmatic vulnerability (not having an HIV test), social vulnerability (special population). CONCLUSION: Individual vulnerability was more strongly associated with non-success. Intervention is needed to explore the points of greatest individual vulnerability, enabling effective action to prevent unsuccessful tuberculosis treatment.

Predictors of high-flow nasal cannula failure in COVID-19 patients in a northern Peruvian hospital.

OBJECTIVES: To determine predictors of high-flow nasal cannula (HFNC) failure in COVID-19 patients in a hospital in northern Peru. METHODOLOGY: A retrospective cohort study was conducted during the months of March and May 2021. Data collection was based on a follow-up of 156 hospitalized patients with a diagnosis of COVID-19 who were users of HFNC. Epidemiological factors and clinical outcomes of treatment were analyzed from medical records. Epidemiological, analytical, and HFNC use-related characteristics were described using measures of absolute and relative frequencies, measures of central tendency, and dispersion. A multivariate Poisson regression analysis with robust variance and a 95% confidence interval was performed. RESULTS: We found that age, SpO2/FiO2, work of breathing (WOB scale) at admission, degree of involvement, type of infiltrate on CT scan, lymphocytes, c-reactive protein, and D-dimer were significantly associated with failure of HFNC (p < 0.05). In addition, the WOB scale, PaO2/FiO2, SaO2/FiO2, and ROX index were variables that presented statistical significance (p < 0.0001). In the multivariate analysis model, a risk of failure of HFNC was determined with age > = 60 years [RRa 1.39 (1.05-1.85)] and PaO2/FiO2 score less than 100 [Rra 1.65 (0.99-2.76)]. CONCLUSIONS: Predictors to failure of HFNC are age older than 60 years and minimally significantly lower PaO2/FiO2 than 100.

Traditional first-line treatment failure rates in neuromyelitis optica spectrum disorder patients included in the Argentinean registry (RelevarEM).

BACKGROUND: Immunosuppressive therapies as azathioprine (AZA), mycophenolate mofetil (MMF) and rituximab (RTX) are widely prescribed as first-line treatment to prevent relapses in NMOSD. However, the rate of response to these traditional therapies is unknown in Argentina. We aimed to describe and compare treatment failure rates in NMOSD patients included in the Argentinean MS and NMOSD registry (RelevarEM, NCT03375177). METHODS: A retrospective cohort study was conducted in NMOSD patients included in RelevarEM (a nationwide, longitudinal, observational, non-mandatory registry of MS and NMOSD in Argentina). NMOSD patients were defined based on validate diagnostic criteria. Only NMOSD patients who received AZA or MMF for at least 6 months or RTX for at least 1 month were included. Patients who were receiving AZA, MMF, or RTX and then switched to another 1 of these 3 therapies were included if the above-mentioned criteria for each drug were fulfilled. Data on patient demographics, clinical, neuroradiological findings, and treatments administered were collected. Treatment failure was defined as any new attack/relapse that occurred despite immunosuppressive treatment. RESULTS: We included 139 NMOSD patients who were receiving AZA (n = 105), MMF (n = 5) or RTX (n = 29) with a mean follow-up time of 41.3 ± 11.4 months and median of EDSS at treatment initiation of 3. We observed a reduction in the annualized relapse rate from pre-treatment to post-treatment of 51.1 %, 48.4 %, and 79.1 % respectively with a Hazard Risk relative to RTX (95 % CI) of 1.67 (1.34-3.54, p = 0.01) for AZA and 2.01 (1.86-4.43, p = 0.008) for MMF. AZA, MMF and RTX failure was observed in 45/105 (42.8 %), 2/5 (40 %) and 3/29 (10.3 %) patients, respectively. CONCLUSIONS: Treatment failure rates were higher for AZA and MMF than RTX in Argentinean NMOSD patients in a real-world setting. High-efficacy treatment increases the opportunity to prevent attacks of NMOSD.

Food Insecurity at Tuberculosis Treatment Initiation Is Associated With Clinical Outcomes in Rural Haiti: A Prospective Cohort Study.

BACKGROUND: Tuberculosis is a leading cause of death worldwide, and food insecurity is known to negatively influence health outcomes through multiple pathways. Few studies have interrogated the relationship between food insecurity and tuberculosis outcomes, particularly independent of nutrition. METHODS: We conducted a prospective cohort study of adults initiating first-line treatment for clinically suspected or microbiologically confirmed drug-sensitive tuberculosis at a rural referral center in Haiti. We administered a baseline questionnaire, collected clinical data, and analyzed laboratory samples. We used logistic regression models to estimate the relationship between household food insecurity (Household Hunger Scale) and treatment failure or death. We accounted for exclusion of patients lost to follow-up using inverse probability of censoring weighting and adjusted for measured confounders and nutritional status using inverse probability of treatment weighting. RESULTS: We enrolled 257 participants (37% female) between May 2020 and March 2023 with a median age (interquartile range) of 35 (25-45) years. Of these, 105 (41%) had no hunger in the household, 104 (40%) had moderate hunger in the household, and 48 (19%) had severe hunger in the household. Eleven participants (4%) died, and 6 (3%) had treatment failure. After adjustment, food insecurity was significantly associated with subsequent treatment failure or death (odds ratio 5.78 [95% confidence interval, 1.20-27.8]; P = .03). CONCLUSIONS: Household food insecurity at tuberculosis treatment initiation was significantly associated with death or treatment failure after accounting for loss to follow-up, measured confounders, and nutritional status. In addition to the known importance of undernutrition, our findings indicate that food insecurity independently affects tuberculosis treatment outcomes in Haiti.

Farnesyl Diphosphate Synthase Gene Associated with Loss of Bone Mass Density and Alendronate Treatment Failure in Patients with Primary Osteoporosis.

Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity of farnesyl diphosphate synthase (FDPS) enzyme in osteoclasts. Despite its efficacy, inadequate response to the drug and side effects have been reported. The A allele of the rs2297480 (A > C) SNP, found in the regulatory region of the FDPS gene, is associated with reduced gene transcription. This study evaluates the FDPS variant rs2297480 (A > C) association with OP patients' response to alendronate sodium treatment. A total of 304 OP patients and 112 controls were enrolled; patients treated with alendronate sodium for two years were classified, according to BMD variations at specific regions (lumbar spine (L1-L4), femoral neck (FN) and total hip (TH), as responders (OP-R) (n = 20) and non-responders (OP-NR) (n = 40). We observed an association of CC genotype with treatment failure (p = 0.045), followed by a BMD decrease in the regions L1-L4 (CC = -2.21% ± 2.56; p = 0.026) and TH (CC = -2.06% ± 1.84; p = 0.015) after two years of alendronate sodium treatment. Relative expression of the FDPS gene was also evaluated in OP-R and OP-NR patients. Higher expression of the FDPS gene was also observed in OP-NR group (FC = 1.84 ± 0.77; p = 0.006) when compared to OP-R. In conclusion, the influence observed of FDPS expression and the rs2897480 variant on alendronate treatment highlights the importance of a genetic approach to improve the efficacy of treatment for primary osteoporosis.

Natural resistance to meglumine antimoniate is associated with treatment failure in cutaneous leishmaniasis caused by Leishmania (Viannia) panamensis.

The multifactorial basis of therapeutic response can obscure the relation between antimicrobial drug susceptibility and clinical outcome. To discern the relationship between parasite susceptibility to meglumine antimoniate (SbV) and therapeutic outcome of cutaneous leishmaniasis, risk factors for treatment failure were considered in evaluating this relationship in ninety-one cutaneous leishmaniasis patients and corresponding clinical strains of Leishmania (Viannia) panamensis. Parasite susceptibility to 32 µg SbV/mL (plasma Cmax) was evaluated in primary human macrophages, PBMCs, and U937 macrophages. Early parasitological response to treatment was determined in lesions of a subgroup of patients, and pathogenicity of Sb-resistant and sensitive clinical strains was compared in BALB/c mice. Parasite survival in cell models and patient lesions was determined by qRT-PCR of Leishmania 7SLRNA transcript. Parasite loads in BALB/c mice were quantified by limiting dilution analysis. The disparate Sb-susceptibility of parasite subpopulations distinguished by isoenzyme profiles (zymodemes) was manifest in all cell models. Notably, Sb-resistance defined by parasite survival, was most effectively discerned in U937 macrophages compared with primary human host cells, significantly higher among strains from patients who failed treatment than cured and, significantly associated with treatment failure. Each unit increase in transformed survival rate corresponded to a 10.6-fold rise in the odds of treatment failure. Furthermore, treatment failure was significantly associated with naturally Sb-resistant zymodeme 2.3 strains, which also produced larger lesions and parasite burdens in BALB/c mice than Sb-sensitive zymodeme 2.2 strains. The confounding effect of host risk factors for treatment failure in discerning this association was evidenced in comparing strains from patients with and without the defined risk factors for treatment failure. These results establish the association of natural resistance to meglumine antimoniate with treatment failure, the importance of host risk factors in evaluating drug susceptibility and treatment outcome, and the clinical and epidemiological relevance of natural Sb-resistance in L. (V.) panamensis subpopulations.

A Descriptive Study of Corneal Graft Failure in Retransplant Patients.

OBJECTIVE: To identify the main predictors for corneal graft failure in patients who underwent retransplantation. METHOD: This is a cross-sectional research with a quantitative and analytical approach, conducted based on data from secondary sources of a Human Eye Tissue Bank (HETB) in Northeast Brazil. Data were collected from the medical charts of all patients transplanted between January 2010 and December 2014. Descriptive statistics were used for the univariate analysis by means of absolute and relative frequencies and means. For the inferential analysis, the chi-square (X²) and the Fisher's Exact tests were used. RESULTS: A total of 241 records were reviewed, representing 258 keratoplasties, of which 27 (10.46%) were retransplantations due to corneal graft failure. Of the total, 55.56% of the individuals were female, with a mean age of 58.56 years, 55.56% of the population was brown, and the highest relative frequency of housing found was in the Central Mesoregion. Of the corneal graft failure cases, 88.89% were due to late failure, 30.77% of cases were classified as pseudophakic and 11.57% as aphakic. Through inferential analysis, a statistical association was obtained among the variable "corneal graft failure" and mesoregion of the state, presence of glaucoma, vascularization, and classification of the eye. CONCLUSION: The prognosis of keratoplasty is of multifactorial nature. Factors such as mesoregion of the State (place of residence), glaucoma, corneal vascularization, and aphakic eyes represent predictors for graft failure in the analyzed sample.

Predictors of unsuccessful tuberculosis treatment outcomes in Brazil: an analysis of 259,484 patient records.

INTRODUCTION: Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors associated with unsuccessful treatment outcomes among individuals treated for TB in Brazil. METHODS: We obtained data on individuals treated for TB between 2015 and 2018 from Brazil's National Disease Notification System (SINAN). We excluded patients with a history of prior TB disease or with diagnosed TB drug resistance. We extracted information on patient-level factors potentially associated with unsuccessful treatment, including demographic and social factors, comorbid health conditions, health-related behaviors, health system level at which care was provided, use of directly observed therapy (DOT), and clinical examination results. We categorized treatment outcomes as successful (cure, completed) or unsuccessful (death, regimen failure, loss to follow-up). We fit multivariate logistic regression models to identify factors associated with unsuccessful treatment. RESULTS: Among 259,484 individuals treated for drug susceptible TB, 19.7% experienced an unsuccessful treatment outcome (death during treatment 7.8%, regimen failure 0.1%, loss to follow-up 11.9%). The odds of unsuccessful treatment were higher with older age (adjusted odds ratio (aOR) 2.90 [95% confidence interval: 2.62-3.21] for 85-100-year-olds vs. 25-34-year-olds), male sex (aOR 1.28 [1.25-1.32], vs. female sex), Black race (aOR 1.23 [1.19-1.28], vs. White race), no education (aOR 2.03 [1.91-2.17], vs. complete high school education), HIV infection (aOR 2.72 [2.63-2.81], vs. no HIV infection), illicit drug use (aOR 1.95 [1.88-2.01], vs. no illicit drug use), alcohol consumption (aOR 1.46 [1.41-1.50], vs. no alcohol consumption), smoking (aOR 1.20 [1.16-1.23], vs. non-smoking), homelessness (aOR 3.12 [2.95-3.31], vs. no homelessness), and immigrant status (aOR 1.27 [1.11-1.45], vs. non-immigrants). Treatment was more likely to be unsuccessful for individuals treated in tertiary care (aOR 2.20 [2.14-2.27], vs. primary care), and for patients not receiving DOT (aOR 2.35 [2.29-2.41], vs. receiving DOT). CONCLUSION: The risk of unsuccessful TB treatment varied systematically according to individual and service-related factors. Concentrating clinical attention on individuals with a high risk of poor treatment outcomes could improve the overall effectiveness of TB treatment in Brazil.

[Prognostic factors associated with failure of modular knee arthroplasty in oncologic patients]. / Factores pronósticos asociados al fracaso de la artroplastía modular de rodilla en pacientes oncológicos.

INTRODUCTION: reconstruction of large bone defects using modular knee arthroplasty (MKA) presents a significant challenge in terms of functionality. The objective of the present work was to identify the different prognostic factors associated with failure of MKA in cancer patients. MATERIAL AND METHODS: a retrospective cohort study was conducted, including patients with a diagnosis of musculoskeletal tumor in the distal femur or proximal tibia, who underwent MKA between January 1, 2010, and December 31, 2021. RESULTS: 49 patients were included, of which 25 (51.02%) were women and 24 (48.98%) men, with a mean age of 29.57 years. Of these, 14 (28.57%) patients experienced some type of MKA failure. The most frequent complication that led to failure was periprosthetic infection, observed in seven (14.29%) patients. Variables associated with MKA failure included biopsies performed outside our hospital (HR 3.2, 95% CI 1.4-6.4, p = 0.02), the length of the long axis of the tumor (HR 2.1, 95% CI 1.2-4.6, p = 0.01) and a prolonged surgical time (HR 3.37, 95% CI 1.1-8.6, p = 0.04). CONCLUSION: the most significant prognostic factors associated with MKA failure in our cohort were tumor size, prolonged surgical time, and performance of the diagnostic biopsy in a center not specialized in the management of this type of patient. These findings highlight the importance of considering these variables to improve outcomes in patients undergoing MKA.

INTRODUCCIÓN: la reconstrucción de grandes defectos óseos mediante artroplastía modular de rodilla (AMR) representa un desafío significativo en términos de funcionalidad. El objetivo del presente trabajo fue identificar los diferentes factores pronósticos asociados al fracaso de la AMR en pacientes oncológicos. MATERIAL Y MÉTODOS: se realizó un estudio de cohorte retrospectiva, incluyendo pacientes con diagnóstico de tumor musculoesquelético en el fémur distal o la tibia proximal, que fueron sometidos a AMR entre el 1 de Enero de 2010 y el 31 de Diciembre de 2021. RESULTADOS: se incluyeron 49 pacientes, de los cuales 25 (51.02%) eran mujeres y 24 (48.98%) hombres, con una edad media de 29.57 años. De éstos, 14 (28.57%) pacientes experimentaron algún tipo de fracaso de la AMR. La complicación más frecuente que condicionó el fracaso fue la infección periprotésica, observada en siete (14.29%) pacientes. Las variables asociadas con el fracaso de las AMR incluyeron biopsias realizadas fuera de nuestro hospital (HR 3.2, IC95% 1.4-6.4, p = 0.02), longitud del eje mayor del tumor (HR 2.1, IC95% 1.2-4.6, p = 0.01) y tiempo quirúrgico prolongado (HR 3.37, IC95% 1.1-8.6, p = 0.04). CONCLUSIÓN: los factores pronósticos asociados al fracaso de las AMR en nuestra cohorte fueron el tamaño del tumor, un tiempo quirúrgico prolongado y la realización de la biopsia diagnóstica en un centro no especializado en el manejo de este tipo de pacientes. Estos hallazgos resaltan la importancia de considerar estas variables en pacientes sometidos a AMR.

Interaction between peripheral blood mononuclear cells and Trypanosoma cruzi-infected adipocytes: implications for treatment failure and induction of immunomodulatory mechanisms in adipose tissue.

Background/Introduction: Adipose tissue (AT) has been highlighted as a promising reservoir of infection for viruses, bacteria and parasites. Among them is Trypanosoma cruzi, which causes Chagas disease. The recommended treatment for the disease in Brazil is Benznidazole (BZ). However, its efficacy may vary according to the stage of the disease, geographical origin, age, immune background of the host and sensitivity of the strains to the drug. In this context, AT may act as an ally for the parasite survival and persistence in the host and a barrier for BZ action. Therefore, we investigated the immunomodulation of T. cruzi-infected human AT in the presence of peripheral blood mononuclear cells (PBMC) where BZ treatment was added. Methods: We performed indirect cultivation between T. cruzi-infected adipocytes, PBMC and the addition of BZ. After 72h of treatment, the supernatant was collected for cytokine, chemokine and adipokine assay. Infected adipocytes were removed to quantify T. cruzi DNA, and PBMC were removed for immunophenotyping. Results: Our findings showed elevated secretion of interleukin (IL)-6, IL-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in the AT+PBMC condition compared to the other controls. In contrast, there was a decrease in tumor necrosis factor (TNF) and IL-8/CXCL-8 in the groups with AT. We also found high adipsin secretion in PBMC+AT+T compared to the treated condition (PBMC+AT+T+BZ). Likewise, the expression of CD80+ and HLA-DR+ in CD14+ cells decreased in the presence of T. cruzi. Discussion: Thus, our findings indicate that AT promotes up-regulation of inflammatory products such as IL-6, IL-2, and MCP-1/CCL2. However, adipogenic inducers may have triggered the downregulation of TNF and IL-8/CXCL8 through the peroxisome proliferator agonist gamma (PPAR-g) or receptor expression. On the other hand, the administration of BZ only managed to reduce inflammation in the microenvironment by decreasing adipsin in the infected culture conditions. Therefore, given the findings, we can see that AT is an ally of the parasite in evading the host's immune response and the pharmacological action of BZ.

Can the ROX index predict high-flow nasal cannula failure in children under 2 with lower respiratory tract infection?

OBJECTIVE: This study evaluates the ROX index's accuracy in predicting the success or failure of high-flow nasal cannula (HFNC) therapy in children under 2 years with acute respiratory failure (ARF) from lower respiratory tract infections. METHODS: From January 2018 to 2021 we conducted this multicenter retrospective cohort study, which included patients aged 2-24 months. We aimed to assess HFNC therapy outcomes as either success or failure. The analysis covered patient demographics, diagnoses, vital signs, and ROX index values at intervals from 0 to 48 h after initiating HFNC. We used bivariate analysis, repeated measures ANOVA, multivariate logistic regression, and the area under the receiver operating characteristic (AUC-ROC) curve for statistical analysis. RESULTS: The study involved 529 patients from six centers, with 198 females (37%) and a median age of 9 months (IQR: 3-15 months). HFNC therapy failed in 38% of cases. We observed significant variability in failure rates across different centers and physicians (p < .001). The ROX index was significantly associated with HFNC outcomes at all time points, showing an increasing trend in success cases over time (p < .001), but not in HFNC failure cases. Its predictive ability is limited, with AUC-ROC values ranging from 0.56 at the start to 0.67 at 48 h. CONCLUSION: While the ROX index is associated with HFNC outcomes in children under 2 years, its predictive ability is modest, impacted by significant variability among patients, physicians, and centers. These findings emphasize the need for more reliable predictive tools for HFNC therapy in this patient population.

Branched Endovascular Aortic Repair After a Migrated EVAR Bypassing a Severely Kinked Previous Endograft.

PURPOSE: To describe a novel technique to repair a juxtarenal abdominal aortic aneurysm (JAAA) after failed endovascular aortic repair (EVAR) with severely kinked anatomy. TECHNIQUE: We present a patient who underwent an EVAR with a Medtronic Talent device 15 years ago and a proximal cuff extension 3 years earlier for an abdominal aortic aneurysm. Computed tomography (CT) done for a known gastritis showed a 12 cm JAAA, with a migrated endograft and a type Ia endoleak (EL). Endovascular repair was performed, accessing and navigating the aneurysmal sac outside the previous graft. The type I EL was reached and the suprarenal aorta catheterized. A 4-vessel inner-branched EVAR device was deployed in the distal thoracic aorta and their target vessels bridged through femoral access. A distal bifurcated component was deployed and both iliac limbs were extended to the native distal iliac arteries. Completion angiogram as well as early and 12-month CT showed a fully patent straight course branched EVAR with no ELs. CONCLUSION: Complex aortic reinterventions in the presence of previous EVAR can be performed by choosing a straighter course along and parallel to the previous endograft. Several technical aspects must be considered to successfully perform this type of reinterventions. CLINICAL IMPACT: We present a technique of a complex endovascular aortic repair in a failed EVAR with kinked anatomy, navigating through the thrombosed aneurysmal sac, outside the previously placed endograft and thus obtaining a straighter path for a new branched endograft. The novelty lies in a different approach to repair a failed EVAR with a branched graft through an uncommon access on the side of the previous endograft, avoiding repeated displacement or occlusion of the new endograft. We exemplify the feasibility of such a complex procedure and highlight important steps to perform it, whether in the abdominal or even thoracic Aorta.