High Treatment Failure Research Articles

High-flow nasal cannula oxygen therapy is equally effective to noninvasive ventilation for mild-moderate acute respiratory distress syndrome in patients with acute pancreatitis: A single-center, retrospective cohort study.

The use of high-flow nasal cannula (HFNC) oxygen therapy is gaining popularity for the treatment of acute hypoxic respiratory failure. However, limited evidence exists regarding the effectiveness of HFNC for acute respiratory distress syndrome (ARDS) in patients with acute pancreatitis (AP). This retrospective analysis focused on AP patients with mild-moderate ARDS, who were treated with either HFNC or noninvasive ventilation (NIV) in the emergency medicine department, from January 2020 to December 2022. The primary endpoint was treatment failure, defined as either invasive ventilation or a switch to any other study treatment (NIV for patients in the NFNC group and vice versa). A total of 146 patients with AP (68 in the HFNC group and 78 in the NIV group) were included in this study. The treatment failure rate in the HFNC group was 17.6% and 19.2% in the NIV group - a risk difference of -1.6% (95% CI, -11.3 to 14.0%; P = 0.806). The most common causes of failure in the HFNC group were aggravation of respiratory distress and hypoxemia. However, in the NIV group, the most common reasons for failure were treatment intolerance and exacerbation of respiratory distress. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (16.7% vs 60.0%, 95% CI -66.8 to -6.2; P = 0.023). Multivariate logistic regression analysis showed that body mass index (≥28), acute physiology and chronic health evaluation II score (≥15), partial arterial oxygen tension/fraction of inspired oxygen (≤200), and respiratory rate (≥32/min) at 1 hour were independent predictors of HFNC failure. In AP patients with mild-moderate ARDS, the usage of HFNC did not lead to a higher rate of treatment failure when compared to NIV. HFNC is an ideal choice of respiratory support for patients with NIV intolerance, but clinical application should pay attention to the influencing factors of its treatment failure.

MRI assessment of seminal vesicle involvement by prostate cancer using T2 signal intensity and volume.

Seminal vesicle involvement (SVI) in patients with newly diagnosed prostate cancer is associated with high rates of treatment failure and tumor recurrence; correct identification of SVI allows for effective management decisions and surgical planning. This single-center retrospective study analyzed MR images of the seminal vesicles from patients undergoing radical prostatectomy with confirmed T3b disease, comparing them to a control group without SVI matched for age and Gleason grade with a final stage of T2 or T3a. Seminal vesicles were segmented by an experienced uroradiologist, "raw" and bladder-normalized T2 signal intensity, as well as SV volume, were obtained. Among the 82 patients with SVI, 34 (41.6%) had unilateral invasion, and 48 (58.4%) had bilateral disease. There was no statistically significant difference in the degree of distension between normal and involved seminal vesicles (P = 0.08). Similarly, no statistically significant difference was identified in the raw SV T2 signal intensity (P = 0.09) between the groups. In the 159 patients analyzed, SVI was prospectively suspected in 10 of 82 patients (specificity, 100%; sensitivity, 12.2%). In all these cases, lesions macroscopically invaded the seminal vesicle, and the raw T2 signal intensity was significantly lower than that in the SVI and control groups (P = 0.02 and 0.01). While signal intensity measurements in T2-weighted images may provide insight into T3b disease, our findings suggest that this data alone is insufficient to reliably predict SVI, indicating the need for further investigation and complementary diagnostic approaches.

Characteristics and management of juvenile type 2 diabetes mellitus

Background: Over the past two decades, there have been numerous reports on the increasing incidence of type 2 diabetes mellitus (T2DM) in children and adolescents. This trend, which parallels the increase in the prevalence and degree of pediatric obesity, is causing significant concern. This review focuses on the characteristics andcurrent management strategies for juvenile patients with T2DM. Current Concepts: Juvenile T2DM differs from type 1 diabetes mellitus (T1DM) in children and T2DM in adults as it is an aggressive disease with rapidly progressive β-cell decline, high treatment failure rate, and accelerated development of complications. Current management approaches include lifestyle changes such as improved diet and increased physical activity, and pharmacological interventions such as metformin, insulin, and liraglutide.Discussion and Conclusion: Early diagnosis and prevention of T2DM in children and adolescents are essential. Furthermore, compared to adults, there is still a lack of available treatment drugs or research in children and adolescents. Therefore, long-term research on the efficacy and safety of various drug treatments for T2DM in children and adolescents is required. Additionally, as it is often asymptomatic in its early stages, significant efforts by physicians are required for the early diagnosis and prevention of T2DM.

High treatment failure in two-stage revision of infected total elbow arthroplasty: report of a monocentric study

High treatment failure in two-stage revision of infected total elbow arthroplasty: report of a monocentric study

CT findings as predictive factors for treatment failure in Mycobacterium abscessus complex lung disease: a retrospective cohort study

PurposeMycobacterium abscessus complex (MABC) commonly causes lung disease (LD) and has a high treatment failure rate of around 50%. In this study, our objective is to investigate specific CT patterns for predicting treatment prognosis and monitoring treatment response, thus providing valuable insights for clinical physicians in the management of MABC-LD treatment.MethodsWe retrospectively assessed 34 patients with MABC-LD treated between January 2015 and December 2020. CT scores for bronchiectasis, cellular bronchiolitis, consolidation, cavities, and nodules were measured at initiation and after treatment. The ability of the CT scores to predict treatment outcomes was analyzed in logistic regression analyses.ResultsThe CT scoring system had excellent inter-reader agreement (all intraclass correlation coefficients, > 0.82). The treatment failure (TF) group (17/34; 50%) had higher cavitation diameter (p = 0.049) and extension (p = 0.041) at initial CT and higher cavitation diameter (p = 0.049) and extension (p =0 .045), consolidation (p = 0.022), and total (p = 0.013) scores at follow-up CT than the treatment success (TS) group. The changes of total score and consolidation score (p = 0.049 and 0.024, respectively) increased in the TF group more than the TS group between the initial and follow-up CT. Multivariable logistic regression analysis showed initial cavitation extension, follow-up consolidation extension, and change in consolidation extension (adjusted odds ratio: 2.512, 2.495, and 9.094, respectively, per 1-point increase; all p < 0.05) were significant predictors of treatment failure.ConclusionsA high pre-treatment cavitation extension score and an increase in the consolidation extension score during treatment on CT could be alarm signs of treatment failure requiring tailor the treatment of MABC-LD carefully.

Acute Promyelocytic Leukemia With Torque Teno Mini Virus::RARA Fusion: An Approach to Screening and Diagnosis

Acute promyelocytic leukemia (APL) with variant RARA translocation is linked to over 15 partner genes. Recent publications encompassing 6 cases have expanded the spectrum of RARA partners to torque teno mini virus (TTMV). This entity is likely underrecognized due to the lack of clinician and pathologist familiarity, inability to detect the fusion using routine testing modalities, and informatic challenges in its recognition within next-generation sequencing (NGS) data. We describe a clinicopathologic approach and provide the necessary tools to screen and diagnose APL with TTMV::RARA using existing clinical DNA- or RNA-based NGS assays, which led to the identification of 4 cases, all without other known cytogenetic/molecular drivers. One was identified prospectively and 3 retrospectively, including 2 from custom automated screening of multiple data sets (50,257 cases of hematopoietic malignancy, including 4809 acute myeloid leukemia/myeloid sarcoma/APL cases). Two cases presented as myeloid sarcoma, including 1 with multiple relapses after acute myeloid leukemia-type chemotherapy and hematopoietic stem cell transplant. Two cases presented as leukemia, had a poor response to induction chemotherapy, but achieved remission upon reinduction (including all-trans retinoic acid in 1 case) and subsequent hematopoietic stem cell transplant. Neoplastic cells demonstrated features of APL including frequent azurophilic granules and dim/absent CD34 and HLA-DR expression. RARA rearrangement was not detected by karyotype or fluorescent in situ hybridization. Custom analysis of NGS fusion panel data identified TTMV::RARA rearrangements and, in the prospectively identified case, facilitated monitoring in sequential bone marrow samples. APL with TTMV::RARA is a rare leukemia with a high rate of treatment failure in described cases. The diagnosis should be considered in leukemias with features of APL that lack detectable RARA fusions and other drivers, and may be confirmed by appropriate NGS tests with custom informatics. Incorporation of all-trans retinoic acid may have a role in treatment but requires accurate recognition of the fusion for appropriate classification as APL.

Time to Treatment Failure and Its Predictors Among Second-Line ART Clients in Amhara Region, Ethiopia: A Retrospective Follow-Up Study.

Second-line antiretroviral treatment failure has become a major public health issue, and the time to treatment failure among second-line ART clients varies globally, and the Sub-Saharan African region having a high rate of second-line ART treatment failures. In addition, after the ART treatment guideline changed there is limited information on Ethiopia. Therefore, this study aimed to assess time to treatment failure and its determinants among second-line ART clients in Amhara Region, Ethiopia. A multi-centered retrospective follow-up study was conducted. A random sample of 860 people on second-line ART was selected by using a computer-generated simple random sampling technique from January 30, 2016, to January 30, 2021, at the University of Gondar Compressive Specialized Hospital, Felege Hiwot Compressive Specialized Referral Hospital, and Debre Tabor Compressive Specialized Referral Hospital, in Amhara region, Ethiopia. Data was captured using a checklist. A total of 81 (9.4%) ART clients developed second-line treatment failure, with a median follow-up time of 29 months with an interquartile range (IQR: 18, 41]. The risk of second-line treatment failure is higher among patients aged 15 to 30 years (adjusted hazard ratio (AHR) = 2.01, 95% confidence interval (CI): [1.16, 3.48]). Being unable to read and write (AHR = 1.312, 95% CI: [1.068, 1.613]), and poor ART drug adherence (AHR = 3.067, 95% CI: [1.845, 5.099]) were significant predictors of second-line ART treatment failures. In the current study, the time to second-line ART treatment failure was high compared with a previous similar study in Ethiopia. Factors like being younger age, ART clients who are not being able to read and write, and having poor ART drug adherence was significant predictors of second-line ART treatment failure.

"Getting the Dose Right"-Revisiting the Topic With Focus on Biologic Agents.

Nearly two decades after the Peck and Cross article '"Getting the dose right: facts, a blueprint, and encouragements" was published, a review of dose recommendations for biologics shows that the success in getting the dose right appears to have improved given the relatively low incidence of drug withdrawals and dosing/label changes. However, the clinical experience with monoclonal antibodies (MAbs) following approval has been less than perfect. In inflammatory diseases, the disease burden changes with time and high treatment failure rates have been reported. In addition, the use of concomitant steroids and immunosuppressant drugs with MAbs is common. These concomitant agents have their own safety issues and many immunosuppressant agents are not well-tolerated although they have been shown to reduce the incidence of anti-drug antibodies (ADA). This same complexity is seen in MAbs used in oncology as well, although with these agents the doses appear to be higher than needed, which results in high treatment costs and incidence of adverse events. Given the complexity of MAb pharmacokinetics, which makes providing a detailed description of dose options difficult, product labeling should include the options for alternative dose strategies and potentially include the use of therapeutic drug monitoring with dose individualization which have been shown to improve clinical response and reduce the incidence of ADA. So, while the recommended dosing for biologics seems improved over the issues noted 17 years ago, we still have some work to do.

Magnetic resonance-guided focused ultrasound thalamotomy for essential tremor patients with low skull density ratio: a case-matched analysis.

Skull density ratio (SDR) is the ratio between the mean Hounsfield units of marrow and cortical bone, impacting energy transmission through the skull. Low SDR has been used as an exclusion criterion in major trials of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor (ET). However, some studies have suggested that patients with low SDR can safely undergo MRgFUS with favorable outcomes. In this case-matched study, we aim to compare the characteristics, sonication parameters, lesion sizes, and clinical outcomes of patients with low SDR vs. patients with high SDR who underwent unilateral MRgFUS thalamotomy for medication-refractory ET. Between March 2016 and April 2023, all patients (n = 270) who underwent unilateral MRgFUS thalamotomy for medication-refractory ET at a single institution were classified as low SDR (<0.40) and high SDR (≥0.40). All clinical and radiological data was prospectively collected and retrospectively analyzed using non-case-matched and 1:1 case-matched methodology. Thirty-one patients had low SDR, and 239 patients had high SDR. Fifty-six patients (28 in each cohort) were included in 1:1 case-matched analysis. There were no significant differences in baseline characteristics between the two groups in both non-case-matched and 1:1 case-matched analyses. In both analyses, compared to patients with high SDR, patients with low SDR required a significantly higher maximum sonication power, energy, and duration, and reached a lower maximum temperature with smaller lesion volumes. In the non-case-matched and case-matched analyses, low SDR patients did not have significantly less tremor control at any postoperative timepoints. However, there was a higher chance of procedure failure in the low SDR group with three patients not obtaining an appropriately sized lesion. In both analyses, imbalance was observed more often in high SDR patients on postoperative day 1 and month 3. ET patients with SDR <0.40 can be safely and effectively treated with MRgFUS, though there may be higher rates of treatment failure and intraoperative discomfort.

Outcomes in orthopedic device infections due to Streptococcus agalactiae: a retrospective cohort study

BackgroundGroup B streptococci (Streptococcus agalactiae) (GBS) is a rare cause of prosthetic joint infection (PJI) occurring in patients with comorbidities and seems to be associated with a poor outcome. Depiction of GBS PJI is scarce in the literature.MethodsA retrospective survey in 2 referral centers for bone joint infections was done Patients with a history of PJI associated with GBS between 2014 and 2019 were included. A descriptive analysis of treatment failure was done. Risk factors of treatment failure were assessed.ResultsWe included 61 patients. Among them, 41 had monomicrobial (67%) infections. The median duration of follow-up was 2 years (interquartile range 2.35) Hypertension, obesity, and diabetes mellitus were the most reported comorbidities (49%, 50%, and 36% respectively). Death was observed in 6 individuals (10%) during the initial management. The rate of success was 63% (26/41). Removal of the material was not associated with remission (p = 0.5). We did not find a specific antibiotic regimen associated with a better outcome.ConclusionThe results show that S. agalactiae PJIs are associated with high rates of comorbidities and a high treatment failure rate with no optimal treatment so far.

Home nursing and self-administered outpatient parenteral antimicrobial treatment: a comparison of demographics and outcomes from a large regional hospital in Queensland, Australia.

Outpatient parenteral antimicrobial treatment (OPAT) is a safe and effective therapy used in several settings across Australia. As OPAT services expand their inclusion criteria to include complex patient populations, there is an increased need for selecting appropriate patients to receive either healthcare-administered OPAT (H-OPAT) or self-administered OPAT (S-OPAT). To describe patient demographics, diagnosis, microbiology and outcomes of patients treated by H-OPAT and S-OPAT within the Sunshine Coast Hospital and Health Service, Australia. Data on demographics, diagnoses, treatment and outcomes on all patients treated by H-OPAT and S-OPAT from March 2017 to December 2019 were collected retrospectively. One hundred and sixty-five patients (62.26%) were enrolled in H-OPAT and 100 patients (37.74%) in S-OPAT. S-OPAT patients were significantly younger. H-OPAT patients were more comorbid. Bone and joint infections were the most treated infections and were more likely to be treated by S-OPAT. There was no difference in treatment duration, cure and complication rates between S-OPAT and H-OPAT. Longer duration of therapy was associated with more complications. Treatment failure was associated with infections due to multiple organisms, number of comorbidities and treatment of surgical site, skin and soft tissue infections. There were significant differences in demographics between H-OPAT and S-OPAT without any difference in outcomes. Overall failure and complication rates were low. Higher rates of treatment failure were predicted by the diagnosis, number of comorbidities and number of organisms treated.

Real-World Patterns and Economic Burden Associated With Treatment Failure With Advanced Therapies in Patients With Moderate-to-Severe Ulcerative Colitis

Abstract Background Some patients lose response during treatment for moderate-to-severe ulcerative colitis (UC). We aimed to characterize real-world treatment failure patterns and associated economic burdens during use of first-line advanced therapies for UC. Methods IBM MarketScan Commercial and Medicare Supplemental Databases were used to identify adults initiating ≥ 1 advanced therapy for UC (January 1, 2010–September 30, 2019). Treatment failure was defined as augmentation with non-advanced therapy, discontinuation, dose escalation/interval shortening, failure to taper corticosteroids, UC-related surgery, or UC-related urgent care ≤ 12 months after treatment initiation. The index date was the date of treatment failure (treatment failure cohort) or 12 months after treatment initiation (persistent cohort). Treatment failure rates were assessed using Kaplan–Meier analyses. All-cause and UC-related healthcare resource utilization (HCRU) and costs 12 months post-index were also assessed. Results Analysis of treatment failure patterns included data from 6745 patients; HCRU and cost analyses included data from 5302 patients (treatment failure cohort, n = 4295; persistent cohort, n = 1007). In the overall population, 75% experienced treatment failure within the first 12 months (median: 5.1 months). Augmentation with non-advanced therapy (39%) was the most common first treatment failure event. The treatment failure cohort had significantly (P &amp;lt; .001) higher mean costs than the persistent cohort (all-cause, $74 995 vs $56 169; UC-related, $57 096 vs $47 347) mainly attributed to inpatient admissions and outpatient visits. Dose escalation/interval shortening accounted for the highest total costs ($101 668) across treatment failure events. Conclusions Advanced therapies for moderate-to-severe UC are associated with high rates of treatment failure and significant economic burden. More efficacious and durable treatments are needed.

Association of blood eosinophils with corticosteroid treatment failure stratified by smoking status among inpatients with AECOPD

BackgroundRecent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been...

Co-axial hydrogel spinning for facile biofabrication of prostate cancer-like 3D models

Glandular cancers are amongst the most prevalent types of cancer, which can develop in many different organs, presenting challenges in their detection as well as high treatment variability and failure rates. For that purpose, anticancer drugs are commonly tested in cancer cell lines grown in 2D tissue culture on plastic dishes in vitro, or in animal models in vivo. However, 2D culture models diverge significantly from the 3D characteristics of living tissues and animal models require extensive animal use and time. Glandular cancers, such as prostate cancer—the second leading cause of male cancer death—typically exist in co-centrical architectures where a cell layer surrounds an acellular lumen. Herein, this spatial cellular position and 3D architecture, containing dual compartments with different hydrogel materials, is engineered using a simple co-axial nozzle setup, in a single step utilizing prostate as a model of glandular cancer. The resulting hydrogel soft structures support viable prostate cancer cells of different cell lines and enable over-time maturation into cancer-mimicking aggregates surrounding the acellular core. The biofabricated cancer mimicking structures are then used as a model to predict the inhibitory efficacy of the poly ADP ribose polymerase inhibitor, Talazoparib, and the antiandrogen drug, Enzalutamide, in the growth of the cancer cell layer. Our results show that the obtained hydrogel constructs can be adapted to quickly obtain 3D cancer models which combine 3D physiological architectures with high-throughput screening to detect and optimize anti-cancer drugs in prostate and potentially other glandular cancer types.

Characterization of the dispirotripiperazine derivative PDSTP as antibiotic adjuvant and antivirulence compound against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a major human pathogen, able to establish difficult-to-treat infections in immunocompromised and people with cystic fibrosis (CF). The high rate of antibiotic treatment failure is due to its notorious drug resistance, often mediated by the formation of persistent biofilms. Alternative strategies, capable of overcoming P. aeruginosa resistance, include antivirulence compounds which impair bacterial pathogenesis without exerting a strong selective pressure, and the use of antimicrobial adjuvants that can resensitize drug-resistant bacteria to specific antibiotics. In this work, the dispirotripiperazine derivative PDSTP, already studied as antiviral, was characterized for its activity against P. aeruginosa adhesion to epithelial cells, its antibiotic adjuvant ability and its biofilm inhibitory potential. PDSTP was effective in impairing the adhesion of P. aeruginosa to various immortalized cell lines. Moreover, the combination of clinically relevant antibiotics with the compound led to a remarkable enhancement of the antibiotic efficacy towards multidrug-resistant CF clinical strains. PDSTP-ceftazidime combination maintained its efficacy in vivo in a Galleria mellonella infection model. Finally, the compound showed a promising biofilm inhibitory activity at low concentrations when tested both in vitro and using an ex vivo pig lung model. Altogether, these results validate PDSTP as a promising compound, combining the ability to decrease P. aeruginosa virulence by impairing its adhesion and biofilm formation, with the capability to increase antibiotic efficacy against antibiotic resistant strains.

Cefdinir vs cephalexin for the treatment of urinary tract infections: A retrospective evaluation.

Cefdinir and cephalexin are cephalosporin antibiotics commonly used in the treatment of urinary tract infections (UTIs). Their efficacy depends on achieving sufficient time with concentrations exceeding the minimum inhibitory concentration (MIC). Despite being frequently prescribed for UTIs, cefdinir has markedly lower urine penetration compared to cephalexin. It is possible that differences in pharmacokinetics could result in dissimilar efficacy between these agents; however, comparative studies of cephalosporins in UTIs are lacking. This was a retrospective comparative study of patients discharged from emergency departments within a community health system with a diagnosis of acute cystitis who were prescribed cefdinir or cephalexin. Treatment failure rates at 7 and 14 days were compared between the 2 agents using a χ2 or Fisher's exact test, as appropriate. There were no differences in overall treatment failure between the cefdinir and cephalexin groups. Treatment failure at 7 days occurred in 11.6% (n = 14) of patients in the cefdinir group and 8.3% (n = 10) of patients in the cephalexin group (P = 0.389). Treatment failure at 14 days was higher for cefdinir at 20.7% (n = 25) than for cephalexin at 11.8% (n = 14), but this difference was not statistically significant (P = 0.053). There were no differences in the rate of treatment failure in subgroup analyses of uncomplicated or complicated UTIs. The results of this study suggest that cefdinir and cephalexin have comparable efficacy for the treatment of lower UTIs. While there was a numerically higher rate of treatment failure with cefdinir, there were no significant differences in treatment failure between the agents.

Emergence, transmission dynamics and mechanisms of artemisinin partial resistance in malaria parasites in Africa.

Malaria, mostly due to Plasmodium falciparum infection in Africa, remains one of the most important infectious diseases in the world. Standard treatment for uncomplicated P. falciparum malaria is artemisinin-based combination therapy (ACT), which includes a rapid-acting artemisinin derivative plus a longer-acting partner drug, and standard therapy for severe P. falciparum malaria is intravenous artesunate. The efficacy of artemisinins and ACT has been threatened by the emergence of artemisinin partial resistance in Southeast Asia, mediated principally by mutations in the P. falciparum Kelch 13 (K13) protein. High ACT treatment failure rates have occurred when resistance to partner drugs is also seen. Recently, artemisinin partial resistance has emerged in Rwanda, Uganda and the Horn of Africa, with independent emergences of different K13 mutants in each region. In this Review, we summarize our current knowledge of artemisinin partial resistance and focus on the emergence of resistance in Africa, including its epidemiology, transmission dynamics and mechanisms. At present, the clinical impact of emerging resistance in Africa is unclear and most available evidence suggests that the efficacies of leading ACTs remain excellent, but there is an urgent need to better appreciate the extent of the problem and its consequences for the treatment and control of malaria.

P785 Obesity in the response to biological treatments in Inflammatory Bowel Disease patients

Abstract Background Obesity rates in patients with IBD reach up to 40%. Several authors suggest that obese patients have worse response rates to treatments. The aim of the study is to determine whether body mass index (BMI) influences the response to biological therapies in IBD. Secondly, other risk factors will be analyzed, and response rates to different biological treatments will be compared. Methods A retrospective cohort study of patients with IBD on biologic drugs under treatment between February 2013 and September 2022 is presented. Patients were recruited from IBD consultation of a tertiary center (Hospital Rey Juan Carlos, Madrid). Inclusion criteria included being under biologic treatment due to IBD and being näive to these therapies. The follow-up of these patients were carried out from February 2013 to September 2022. The main objective of the study is to determine if BMI influences the response to biological treatment in patients with IBD. As secondary objectives we will try to find the existence of other risk factors for loss of response and between different treatments. Treatment failure was defined as: need of dose increase, switch or swap to another biological treatment, clinical deterioration (measured by clinical indexes), use of systemic corticosteroid therapy, hospitalization, endoscopic inflammatory activity or surgical complications. The percentage loss of response was estimated using Kaplan-Meier curves, and factors influencing long-term response were studied using Cox regression. Results A total of 135 patients were included in the study, (mean age of 46.3 years), 59.3% male, 25.9% smokers, with a mean BMI of 26.1 kg/m2 (18.5% with BMI&amp;gt;30 kg/m2). In the study, 60% received infliximab and 45.9% received combined immunosuppressive therapy. Treatment failure was 59.1% in the non-obese and 80% in the obese (p=0.051). There were no differences in long-term response rates according to biologic treatments or disease subtypes. The only predictor factor for long-term response was combined treatment with immunosuppressants (p=0.037). Conclusion Obesity is not associated with a higher treatment failure rate in patients with IBD undergoing biological therapy. Combined treatment with immunosuppressants acts as a long-term response factor.

CORR Insights®: High Rates of Treatment Failure and Amputation in Modular Endoprosthesis Prosthetic Joint Infections Caused by Fungal Infections With Candida.

CORR Insights®: High Rates of Treatment Failure and Amputation in Modular Endoprosthesis Prosthetic Joint Infections Caused by Fungal Infections With Candida.

Response to experimental cold-induced pain discloses a resistant category among endurance athletes, with a distinct profile of pain-related behavior and GABAergic EEG markers: a case-control preliminary study.

Pain is a major public health problem worldwide, with a high rate of treatment failure. Among promising non-pharmacological therapies, physical exercise is an attractive, cheap, accessible and innocuous method; beyond other health benefits. However, its highly variable therapeutic effect and incompletely understood underlying mechanisms (plausibly involving the GABAergic neurotransmission) require further research. This case-control study aimed to investigate the impact of long-lasting intensive endurance sport practice (≥7 h/week for the last 6 months at the time of the experiment) on the response to experimental cold-induced pain (as a suitable chronic pain model), assuming that highly trained individual would better resist to pain, develop advantageous pain-copying strategies and enhance their GABAergic signaling. For this purpose, clinical pain-related data, response to a cold-pressor test and high-density EEG high (Hβ) and low beta (Lβ) oscillations were documented. Among 27 athletes and 27 age-adjusted non-trained controls (right-handed males), a category of highly pain-resistant participants (mostly athletes, 48.1%) was identified, displaying lower fear of pain, compared to non-resistant non-athletes. Furthermore, they tolerated longer cold-water immersion and perceived lower maximal sensory pain. However, while having similar Hβ and Lβ powers at baseline, they exhibited a reduction between cold and pain perceptions and between pain threshold and tolerance (respectively -60% and - 6.6%; -179.5% and - 5.9%; normalized differences), in contrast to the increase noticed in non-resistant non-athletes (+21% and + 14%; +23.3% and + 13.6% respectively). Our results suggest a beneficial effect of long-lasting physical exercise on resistance to pain and pain-related behaviors, and a modification in brain GABAergic signaling. In light of the current knowledge, we propose that the GABAergic neurotransmission could display multifaceted changes to be differently interpreted, depending on the training profile and on the homeostatic setting (e.g., in pain-free versus chronic pain conditions). Despite limitations related to the sample size and to absence of direct observations under acute physical exercise, this precursory study brings into light the unique profile of resistant individuals (probably favored by training) allowing highly informative observation on physical exercise-induced analgesia and paving the way for future clinical translation. Further characterizing pain-resistant individuals would open avenues for a targeted and physiologically informed pain management.