Treatment Failure Research Articles

Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial

The clinical significance of FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) plus anti-EGFR monoclonal antibody using cetuximab for metastatic colorectal cancer (mCRC) remains controversial. We report results from a randomized phase 2 DEEPER trial (UMIN000018217, jRCTs061180022) to test the superiority of modified (m)-FOLFOXIRI plus weekly cetuximab over bevacizumab in patients with RAS wild-type (wt) mCRC. Primary endpoint was depth of response (DpR). Secondary endpoints included objective response rate (ORR), early tumor shrinkage (ETS) at week 8, progression-free survival (PFS), overall survival (OS), time to tumor growth (TTG), time to treatment failure (TTF), association between tumor shrinkage and prognosis, association between TTG and prognosis, R0 resection rate, and safety. In 359 enrolled patients with RAS wt mCRC, median DpR was significantly better in cetuximab (57.3% vs 46.0%, p = 0.0029); however, ORR, ETS, R0 resection rate, TTG, TTF, PFS and OS were similar between 2 treatments. There was a weak association between DpR and survival time in both treatments. The correlation between TTG and OS was slightly stronger in cetuximab. The post-hoc exploratory analysis showed that cetuximab produced greater PFS (15.3 vs 11.7 months; HR 0.68) and OS (53.6 vs 40.2 months; HR 0.54) in patients with left-sided and RAS/BRAF wt tumors. m-FOLFOXIRI plus cetuximab has clinical benefit for tumor shrinkage in RAS wt mCRC. The survival benefit for RAS/BRAF wt and left-sided mCRC needs further investigation.

CCDC34 maintains stemness phenotype through β-catenin-mediated autophagy and promotes EGFR-TKI resistance in lung adenocarcinoma.

Despite recent advances in treatment strategy, lung cancer remains the leading cause of cancer-related mortality worldwide, and it is a serious threat to human health. Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer, and approximately 40-50% of patients with LUAD in Asian populations have epidermal growth factor receptor (EGFR) mutations. The use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has revolutionarily improved the prognosis of patients with EGFR-mutated LUAD. However, acquired drug resistance is the main cause of treatment failure. Therefore, new therapeutic strategies are necessary to address the resistance to EGFR-TKIs in patients with LUAD. Cancer stemness-related factors lead to multiple-drug resistance in cancer treatment, including EGFR-TKI resistance. Coiled-coil domain-containing 34 (CCDC34) serves as an oncogene in several types of cancer. However, the role and molecular mechanism of CCDC34 in the malignant progression of LUAD have not been reported to date. In the present study, we found that CCDC34 may be associated with LUAD stemness through weighted gene co-expression network analysis (WGCNA). Furthermore, we demonstrated that CCDC34 promoted LUAD stemness properties through β-catenin-mediated regulation of ATG5-induced autophagy, which was conducive to acquired EGFR-TKI resistance in LUAD in vitro and in vivo. Knockdown CCDC34 can synergistically inhibit tumor growth when combined with EGFR-TKIs. This study reveals a positive association between CCDC34 and the stemness phenotype of LUAD, providing new insights into overcoming EGFR-TKI resistance in LUAD by inhibiting CCDC34 expression.

Overview of lysosome-mediated chemoresistance mechanisms in breast cancer: A mini review

It is widely acknowledged that chemoresistance is one of the major consequences that leads to chemotherapeutic treatment failure and cancer-related death. In recent studies, lots of attempts have been made to clarify the mechanisms that cancer cells utilize and/or modify to become resistant to chemotherapeutic drugs. Among these, lysosomes, also called ‘‘drug-safe house’’, have emerged as one of the crucial drivers of chemoresistance through trapping passively the chemotherapeutics, thereby preventing them from reaching their intracellular targets. Notably, lysosomes take part in regulating cellular metabolism, tumor growth and metastasis. Besides, lysosomes are a platform for inter- and intracellular communication among cellular organelles and/or cell surfaces and/or between tumor cells and extracellular microenvironment. In breast cancer (BCa), the mechanisms underlying chemotherapeutic resistance are perplexing and have not been fully understood. Therefore, in this review, we briefly highlight some aspects that describe lysosome-mediated regulation of chemoresistance in BCa.

Use of intravenous immunoglobulin for the treatment of severe COVID‐19 in the Chris Hani Baragwanath Academic Hospital intensive care unit, Johannesburg, South Africa

Background. COVID‐19 infection has a variable clinical presentation, with a small subgroup of patients developing severe disease, requiring intensive care with mechanical ventilation, with an increased mortality rate. South Africa (SA) has experienced multiple waves of this pandemic, spanning the pre‐vaccine and vaccine periods. The method and initiation of treatment is a debated topic, changing according to evolving research and the literature. The present study investigated the use of high‐dose intravenous immunoglobulin (IVIg) as a salvage therapy after initial medical treatment failure. Objectives. To compare disease progression among critically ill COVID‐19 pneumonia patients receiving IVIg therapy with that in patients receiving standard of care (SoC), in respect of inflammation, organ dysfunction and oxygenation. Methods. This was a single‐centre, retrospective study of patients admitted to the intensive care unit (ICU) at Chris Hani Baragwanath Academic Hospital, Johannesburg, SA, during the pre‐vaccine COVID‐19 pandemic. Demographics, inflammatory markers (C‐reactive protein (CRP)), organ function (Sequential Organ Failure Assessment (SOFA) score), oxygenation (ratio of partial pressure of oxygen in arterial blood to fraction of inspiratory oxygen (P/F ratio)), overall mortality and complications (nosocomial infections and thromboembolism) were recorded and compared. Results. We included 113 eligible patients in the study. The IVIg cohort had a significantly lower initial P/F ratio than the SoC cohort (p=0.01), but the change in P/F ratio was similar (p=0.54). Initial CRP and changes in CRP were similar in the two groups (p=0.38 and p=0.75, respectively), as were initial SOFA score and changes in SOFA score (p=0.18 and p=0.08, respectively) and vasopressor dose on day 0 and day 5 (p=0.97 and p=0.93, respectively). Duration of mechanical ventilation did not differ significantly between the IVIg group and the SoC group (p=0.13). There were no significant differences in measured complications between the two groups. On univariate analysis, the relative risk of death was 1.6 times higher (95% confidence interval (CI) 1.1 ‐ 2.3) in the IVIg group; however, a logistical regression model demonstrated that only a higher P/F ratio (odds ratio (OR) 0.991; 95% CI 0.983 ‐ 0.997) and higher mean airway pressure (OR 1.283; 95% CI 1.026 ‐ 1.604) were significantly associated with ICU mortality. Conclusion. Use of IVIg in our study was directed at an older population, with significantly worse oxygenation. We found no evidence of adverse effects of immunoglobulin therapy; however, we found no benefit either. Only the P/F ratio and mean airway pressure independently predicted ICU mortality.

Challenges and Opportunities in the Adoption of p-TIPS for Acute Variceal Bleeding: Insights from a US Tertiary Center.

Since the overwhelmingly positive results of the 'early use of TIPS' published in 2010, studies in Europe and Asia have confirmed early/pre-emptive transjugular intrahepatic portosystemic shunt (p-TIPS) in high-risk patients with acute variceal bleed (AVB) reduces treatment failure and mortality compared to standard of care (SOC). There are no studies evaluating p-TIPS in a US cohort. A review of patients with cirrhosis from June 2010 to June 2020 with AVB was conducted from a single large US center. Of 745 cirrhotic patients with AVB, 18% met criteria for p-TIPS. Alcohol and HCV accounted for 75% of etiology; 13% MASLD. The mean MELD-Na score in our cohort was 24, which is ten points higher than reported in the literature for over 600 p-TIPS cases. Only 9 patients underwent p-TIPS. Patients undergoing p-TIPS were less likely to have MASLD, more likely to be female and less likely to have PSE at baseline. One-year mortality in the SOC group (including patients undergoing 'rescue TIPS') was 53% versus 0% for p-TIPS (p = 0.01). Our observation suggests hesitancy among providers to recommend p-TIPS, likely due to concerns regarding a 'sicker' patient population. The current SOC in high-risk patients remain suboptimal. Limited data, including our own, suggest that p-TIPS may confer a survival benefit even in patients with high MELD. However, the recommendation of p-TIPS in such patients necessitates validation of its safety and efficacy. Consequently, we advocate for a RCT in the US to conclusively assess the utility of p-TIPS in this context. Until such evidence is established, it is likely that underutilization of this life-saving intervention will persist.

Raddeanin A Inhibits Colorectal Cancer Growth and Ameliorates Oxaliplatin Resistance Through the WNT/β-Catenin Signaling Pathway.

Background: Chemotherapy based on oxaliplatin (OXA) is the first-line treatment for advanced colorectal cancer (CRC), and acquired resistance to OXA is the main reason for clinical treatment failure in CRC. Methods: To search for compounds that can reverse OXA resistance, we screened a small molecule inhibitor drug library and identified a drug, Raddeanin A (RA), that enhanced the anticancer effect of OXA. Using human CRC cell lines, CRC organoid models, and invivo subcutaneous tumorigenic studies, we determined that RA inhibits the proliferation of CRC cells by promoting apoptosis and inducing cell cycle arrest. Results: We constructed OXA-resistant CRC cell lines and demonstrated that RA enhances the sensitivity of these cells to OXA. Further experiments showed that the mechanism by which RA enhanced the anticancer effects of OXA in CRC was by inhibiting the activation of the WNT/β-catenin signaling pathway. Conclusions: Because RA has been shown to be biocompatible in animal models, there is a possibility that RA could be developed as a sensitizer for resistant cancer cells or as a novel lead compound to enhance the therapeutic efficacy of OXA in resistant CRCs.

Cellular and Humoral Response After Induction of Protection and After Finishing Hymenoptera Venom Immunotherapy

Hymenoptera venom allergy (HVA) is an IgE-mediated hypersensitivity reaction caused by Hymenoptera species stings (honeybee, vespid, or ant). The only effective treatment is Hymenoptera venom immunotherapy (VIT). Our study aimed to evaluate whether humoral and cellular biomarkers measured before, during, and after honeybee VIT are associated with the success of VIT, which was assessed by the response to a sting challenge one year after finishing VIT. In this prospective study, blood biomarkers of 25 patients undergoing honeybee VIT at the referral center in Slovenia were evaluated. A controlled honeybee sting challenge confirmed successful VIT in 20 of 25 (80%) patients. Honeybee venom (HBV) recombinant allergen profiles, evaluated before the treatment, were comparable between responders and non-responders. Longitudinal follow-up, up to 1 year after finishing VIT, showed that the immune responses do not differ significantly between patients with successful VIT and treatment failure. Those responses were characterized by decreased sIgE, tIgE, and BST, whereas sIgG4 levels increased. The basophil sensitivity also significantly decreases after VIT in both groups of patients. The analyzed biomarker which correlated considerably with treatment failure was higher basophil sensitivity to allergen stimulation before VIT. Similarly, systemic adverse events (SAEs) during the build-up phase of VIT correlated with treatment failure. Our study demonstrated similar sensitization profiles, and humoral and basophil immune responses to immunotherapy, in two different well-characterized groups of patients, one with successful VIT and the other with treatment failure. Notably, only high basophil sensitivity measured before VIT and SAEs during VIT were significantly associated with VIT failure, and both have the potential to be predictors of VIT failure.

Temperamental and Character Traits as Risk Factors for Binge Eating Disorder in Women with Polycystic Ovary Syndrome

Background/Objectives: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. It is associated with an increased risk of somatic and mental health problems. The prevalence of binge eating disorder (BED) in women with PCOS is higher than in the healthy population. The co-occurrence of PCOS and BED increases the risk of negative health outcomes and may worsen patient compliance. For both groups of disorders, specific personality traits have been described in the literature. The aim of this study was to assess temperament and character in PCOS women with and without BED, in search of specific personality traits that may distinguish PCOS patients with a higher predisposition to BED. Methods: 128 women diagnosed with PCOS according to the modified Rotterdam criteria were included in the study. All completed the Temperament and Character Inventory by R.C. Cloninger (TCI). The collected data were statistically analyzed. Results: The PCOS–BED subgroup was characterized by specific personality traits in comparison with PCOS subgroup: statistically significantly higher scores of harm-avoidance dimensions (in anticipatory worry, shyness, and fatigability subscales) and statistically significantly lower scores of persistence and self-directedness dimensions (in purposeful, resourcefulness, self-acceptance, and enlightened second nature subscales). Conclusions: PCOS–BED women have certain personality traits. Screening PCOS patients for the presence of certain personality traits could identify those at risk. PCOS–BED women may be at higher risk of health problems and treatment failure and may require a different therapeutic approach to treatment, including psychotherapeutic interventions.

Comparison of clinical characteristics, risk factors, and outcomes of patients infected with Bacteroides fragilis group at a tertiary care hospital in central China between 2017 and March 2024

ObjectivesThis study aimed to explore the epidemiology, clinical presentation, and risk factors for treatment failure in patients infected with various Bacteroides fragilis group (BFG) species. MethodsWe analyzed clinical and laboratory data from 178 patients infected with BFG who were admitted to our hospital between 2017 and 2024. We analyzed categorical data using Chi-square and Fisher exact tests, continuous variables using Student's t-tests or Mann–Whitney U-tests, and risk factors using multivariate logistic regression and Pearson's chi-squared tests. ResultsBacteroides fragilis (69.7 %) and Bacteroides thetaiotaomicron (16.9 %) were the most prevalent species among 178 BFG isolates. Most patients had polymicrobial infections, with the following pathogens isolated from concurrent samples: Escherichia coli, Klebsiella spp., and Enterococcus spp. Intra-abdominal sites were most frequently infected with BFG. Patients aged >50 years and those who had intravascular catheters were infected with more other Bacteroides species than B. fragilis. Admission to an ICU, respiratory, renal and cardiovascular diseases, and chest drainage were associated more often with B. thetaiotaomicron than with B. fragilis. Gastrointestinal diseases, tracheal intubation, and ICU admission were associated more frequently with treatment failure in patients infected with B. fragilis whereas solid cancers, renal disease, multiple organ dysfunction syndrome, and tracheal intubation were more likely to be associated with treatment failure in patients infected with other Bacteroides spp. ConclusionsThe most prevalent BFG species in the patients were B. fragilis and B. thetaiotaomicron. The demographic characteristics of the patients, underlying diseases, and risk factors for poor clinical outcomes clearly differed among species.

Fractionated radiotherapy with stereotactic radiosurgery boost controls gross disease in grade 2 meningioma

Opportunity exists for improved local control rates of grade 2 meningiomas that recur despite maximal surgical resection and adjuvant fractionated radiotherapy. We describe a dose escalation strategy of increasing the total tumor radiation dose by adding a stereotactic radiosurgery (SRS) boost targeting gross disease to fractionated radiotherapy. A single institution retrospective cohort of patients from 2009-2023 with grade 2 meningioma treated with surgical resection, fractionated radiotherapy, and SRS boost were evaluated for baseline characteristics, local disease control, and adverse events (AE). Fourteen meningioma patients were included. Ten patients (71.4%) underwent radiosurgery at initial diagnosis, while 4 patients (28.6%) were treated for recurrent disease. The median fractionated dose was 54 Gy, while the median dose for SRS was 7.5 Gy. Among the 13 patients with follow-up available, median follow-up was 34 months. Three patients (23%) had treatment failures, however, none occurred within the SRS volume and two thirds occurred in patients treated for recurrent disease. 18-month PFS was 92.3%, while 18-month overall survival was 100%. Most patients experienced no or mild AEs, however, 3 patients (23%) experienced a high-grade (CTCAE v5.0 grade ≥ 3) AE including radiation necrosis, seizures and cognitive decline. We found 100% in-field local control at three years from an SRS boost to fractionated radiotherapy targeting gross disease with an acceptable toxicity profile, suggesting this may be an effective and improved adjuvant treatment strategy in patients with grade 2 meningioma.

Quinic acid enhances kanamycin efficacy against methicillin-resistant Staphylococcus aureus biofilms.

Methicillin-resistant Staphylococcus aureus (MRSA) form biofilms that contribute to increased antimicrobial resistance, leading to treatment failure and/or relapse. It is, therefore, necessary to develop new antibiofilm strategies to eradicate MRSA biofilms. This study was aimed to evaluate the effect of the combination of quinic acid and kanamycin against the preformed biofilms of methicillin-resistant Staphylococcus aureus. Broth microdilution method was deployed to evaluate antibacterial activity. Antibiofilm activity was evaluated by crystal violet staining, 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium-bromide (MTT) assay, and scanning electron microscopy (SEM). The checkerboard method was adopted to assess the combination effects. Quantification of exopolysaccharides was determined by the phenol-sulfuric acid method. The eDNA was quantified by spectrophotometry. Cytotoxic activity was evaluated by the MTT assay on the human embryonic kidney (HEK 293) cell line. Quinic acid, combined with kanamycin, effectively eradicated the methicillin-resistant S. aureus biofilms by affecting biofilm biomass and cell viability. Scanning electron microscopy demonstrated a less adherence of S. aureus cells was observed after treatment with quinic acid combined with kanamycin, as compared to each drug alone. The combination of quinic acid and kanamycin thus demonstrated the ability to destroy the exopolysaccharides and eDNA of biofilm matrix without any toxic effect on HEK 293 cells. Our results clearly demonstrate the possibility of using quinic acid in combination therapy, with an antibiotic, for combating infections caused by MRSA strains.

Association between homologous recombination deficiency and time to treatment failure to platinum-based chemotherapy for pancreatic cancer by using the C-CAT database.

Since homologous recombination deficiency (HRD) is relatively uncommon in pancreatic cancer (PC), its impact on time-to-treatment failure (TTF) among patients undergoing systemic chemotherapy for unresectable and recurrent PC remains uncertain. Among patients with unresectable and recurrent PC enrolled in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database by July 2023, a total of 1394 patients who underwent first-line chemotherapy with either gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX (FFX) and received tissue-based CGP tests after disease progression were included in this study. HRD was defined as the presence of germline or somatic genetic mutations in homologous recombination repair (HRR)-related genes such as ATM, BARD1, BRIP1, BRCA1/2, CHEK2, CDK12, PALB, and RAD51C/D. We investigated the correlation between HRD and TTF among patients treated with GnP and FFX. First-line chemotherapy consisted of GnP in 69% of the cases and FFX in 31%. The CGP tests used were NCC OncoPanel and FoundationOne CDx in 26% and 74%, respectively. HRR-related genetic abnormalities were identified in 107 patients (7.6%): BRCA2 (n = 51), ATM (n = 34), BRCA1 (n = 9), PALB2 (n = 9), among others. In the GnP cohort, the median TTF was comparable between the HRD and non-HRD groups (5.3 vs 4.6months, P = 0.44). Conversely, in the FFX cohort, it was significantly longer in the HRD group compared to the non-HRD group (7.3 vs. 4.7months, p < 0.01). Our findings suggest that HRR-related genetic abnormalities might be predictive of TTF in platinum-based chemotherapy for PC.

Pigmented pathological type and depth of follicular extension as predictors of treatment failure in 5-aminolevulinic acid photodynamic therapy for actinic keratosis: A retrospective, matched nested case-control study

Background: While 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is widely used to treat actinic keratosis (AK), treatment resistance and recurrence after ALA-PDT remain significant clinical challenges. Methods: This single-site, retrospective, matched case-control study included 119 patients with histologically confirmed AK to identify clinical and pathological predictors for effectiveness of ALA-PDT. Patients received four consecutive ALA-PDT sessions at intervals of 1 or 2 weeks. Initial complete clearance (ICC) at 3 months and sustained complete clearance (SCC) at 12 months were assessed. Case patients were those with treatment-resistant or recurrent AK, matched with controls based on age, sex, and the treatment date. Baseline characteristics were collected and compared between the case and control groups. Results: ICC at 3 months was achieved in 106 out of 119 patients (89.07%), with 65 out of 82 patients (79.27%) maintaining SCC at 12 months. Pigmented AK emerged as an independent predictor of treatment resistance (OR=44.05, p=0.00). Furthermore, follicular extension to the isthmus or deeper was significantly associated with recurrence within 1 year (OR=17.26, p=0.00). Conclusion: Pigmented AK and AK with follicular extension to the isthmus or deeper may serve as independent predictors of treatment resistance and recurrence, respectively. These findings highlight the importance of these specific features when assessing prognosis and tailoring treatment strategies for individual AK patients.

Genotyping and Characterizing Plasmodium falciparum to Reveal Genetic Diversity and Multiplicity of Infection by Merozoite Surface Proteins 1 and 2 (msp-1 and msp-2) and Glutamate-Rich Protein (glurp) Genes.

Resistance to current antimalarial drugs is steadily increasing, and new drugs are required. Drug efficacy trials remain the gold standard to assess the effectiveness of a given drug. The World Health Organization (WHO)'s recommendation for the optimal duration of follow-up for assessing antimalarial efficacy is a minimum of 28 days. However, assessing antimalarial drug efficacy in highly endemic regions can be challenging due to the potential risks of acquiring a new infection in the follow-up period, and thus, it may underestimate the efficacy of the given drugs. A new treatment should be introduced if treatment failure rates exceed 10%. Overestimation occurs as a result of retaining a drug with a clinical efficacy of less than 90% with increases in morbidity and mortality, while underestimation may occur due to a misclassification of new infections as treatment failures with tremendous clinical and economic implications. Therefore, molecular genotyping is necessary to distinguish true new infections from treatment failures to ensure accuracy in determining antimalarial efficacy. There are three genetic markers that are commonly used in antimalarial efficiency trials to discriminate between treatment failures and new infections. These include merozoite surface protein 1 (msp-1), merozoite surface protein 2 (msp-2), and glutamate-rich protein (glurp). The genotyping of P. falciparum by nested polymerase chain reaction (n-PCR) targeting these markers is discussed with the inherent limitations and uncertainties associated with the PCR technique and limitations enforced by the parasite's biology itself.

The FORWARD Psoriasis Registry: Patient-Reported Outcomes in a Novel Psoriasis Registry and Comparison of Traditional, Dermatologist-Led Enrollment With Web-Based Patient Enrollment.

Real-world evidence describing the natural history of all manifestations and severities of psoriasis is needed, as existing studies often recruit from a restricted patient population, and treatment failure and dissatisfaction is common. The FORWARD Psoriasis Registry collects patient-reported data directly online from participants independent of clinician involvement. To test the feasibility of this new registry design and compare baseline characteristics, patient-reported disease outcomes, and treatment utilization between participants enrolling through their clinician (primary enrollment group) and participants self-enrolling online (secondary). We summarized cross-sectional enrollment data from adults with clinician-diagnosed psoriasis who enrolled in the registry from September 2023 through June 2024 and compared baseline characteristics between enrollment groups. The registry enrolled 1560 adults with clinician-diagnosed psoriasis from 42 states and territories in the United States. In the primary enrollment group, 68% were female, mean age was 51years, 34% of participants had moderate or severe psoriasis based on PREPI, and 27% reported clinician-diagnosed psoriatic arthritis. Forty six percent actively used systemic therapies while 65% used topical therapies for psoriasis, and 20% were dissatisfied or very dissatisfied with their treatment. Comparatively, the secondary enrollment group reported statistically significantly worse psoriasis burden for nearly all disease outcomes. The FORWARD Psoriasis Registry rapidly enrolled a large, national cohort of participants with psoriasis, demonstrating feasibility of participant-driven data collection. We found important differences between participants enrolling through their clinician and self-enrolled participants, highlighting the need to collect real-world evidence to understand psoriasis regardless of access to clinical care.

Practices and efficacy of nematode control in sheep, goats and cattle in communal grazing settings of central Ethiopia.

Communal grazing is the predominant farming system in Ethiopia and the livelihood of millions of people depend on it. Gastrointestinal nematodes represent a serious threat to the sustainability of these systems, and there is further concern due to the worldwide spread of anthelmintic resistance (AR). This study aimed to assess nematode control practices and anthelmintic efficacy in three districts of central Ethiopia, where sheep, goats and cattle are reared together by resource-poor farmers. A total of 153 farmers were interviewed and 36 faecal egg count reduction tests (FECRTs) were conducted for each ruminant species grazing in the communal pastures, comprising a control group and three treatment groups (albendazole ABZ, tetramisole TET and ivermectin IVM) for each district. The questionnaire survey indicated that nematode control relies on poor practices and is substantially based on pharmacological treatments. About 91.8% of animals are treated at least twice a year often in absence of clinical signs and by untrained farmers, with no monitoring nor drug rotation implemented. In the FECRT-based survey, susceptibility to TET was confirmed in all trials, while treatment failure was a consistent finding for ABZ. IVM showed inefficacy in cattle and, to a lesser extent, in goats, while it was always effective in sheep. Research on AR in African countries is focused on small ruminants but in this study cattle had the worst results in terms of the number and severity of ineffective treatments, suggesting their inclusion in future studies on AR in this type of settings.

“Rosary Sign” at Somatostatin Receptor PET in a Case of Recurrent Meningioma

“Rosary Sign” at Somatostatin Receptor PET in a Case of Recurrent Meningioma

Improving Treatment and Lowering Costs for Behavioral Health Patients Through a Value-Based Care Program

Patients with psychotic disorders or severe substance use disorders historically have not been well served by traditional fee-for-service care systems, leading to disproportionately high rates of treatment failure, ED visits, inpatient hospitalizations, and a high total cost of care. This case study presents the implementation of Cityblock’s Advanced Behavioral Health program, a model of care led by specialized community health workers, designed to boost access to interventions such as second-generation long-acting injectable antipsychotics, medications for opioid use disorder, medications for alcohol use disorder, contingency management, care coordination, and social care navigation. Members enrolled in the program for a period of 10 months had a statistically significant 19.7% decrease in inpatient utilization and an 11.5% decrease in total per-member, per-month cost of care compared with a quasi-control group. Further research is needed to determine the contribution of each program element to those effects. Since its original implementation, Cityblock has expanded the program to five additional markets and is conducting ongoing research.

Embolization of the Middle Meningeal Artery for Chronic Subdural Hematoma.

Patients receiving standard treatment for chronic subdural hematoma have a high risk of treatment failure. The effect of adjunctive middle meningeal artery embolization on the risk of treatment failure in this population remains unknown. We randomly assigned patients with symptomatic chronic subdural hematoma to undergo middle meningeal artery embolization as an adjunct to standard treatment (embolization group) or to receive standard treatment alone (control group). Either surgical or nonsurgical standard treatment had been chosen for each patient before randomization. The primary efficacy outcome was a composite of the following events: recurrent or residual chronic subdural hematoma (measuring >10 mm) at 180 days; reoperation or surgical rescue within 180 days; or major disabling stroke, myocardial infarction, or death from neurologic causes within 180 days. The primary safety outcome was a composite of major disabling stroke or death from any cause within 30 days. Among 310 enrolled patients, 149 were randomly assigned to the embolization group and 161 to the control group; 189 patients were to receive surgical standard treatment and 121 nonsurgical standard treatment. The mean age of the patients was 73 years, and 70% were men. In the primary efficacy analysis, a primary-outcome event occurred in 19 of 120 patients (16%) in the embolization group, as compared with 47 of 129 patients (36%) in the control group (odds ratio, 0.36; 95% confidence interval, 0.20 to 0.66; P = 0.001). In the primary safety analysis, 4 of 144 patients (3%) in the embolization group and 5 of 166 patients (3%) in the control group either had a major disabling stroke or died within 30 days. Through 180 days, 12 patients (8%) in the embolization group and 9 patients (5%) in the control group had died, with death from neurologic causes occurring in 1 patient (1%) in the embolization group and in 3 patients (2%) in the control group. Among patients with symptomatic chronic subdural hematoma, adjunctive middle meningeal artery embolization resulted in a lower risk of treatment failure than standard treatment alone, without resulting in an increased incidence of disabling stroke or death in the short term. Further study of longer-term safety outcomes is warranted. (Funded by Balt USA; STEM ClinicalTrials.gov number, NCT04410146.).

A Multicenter Phase II Trial of Ruxolitinib for Treatment of Corticosteroid Refractory Sclerotic Chronic Graft-Versus-Host Disease.

Sclerotic chronic graft-versus-host disease (cGVHD) represents a highly morbid and refractory form of cGVHD, and novel therapies for sclerotic cGVHD are critically needed. This study aimed to determine the efficacy of ruxolitinib in patients with corticosteroid refractory sclerotic cGVHD. In a single-arm multicenter phase II trial (N = 47), adults with sclerotic cGVHD refractory to corticosteroids and ≥one additional line of systemic therapy for cGVHD received ruxolitinib for ≥six months (ClinicalTrials.gov identifier: NCT03616184). The primary end point was complete or partial response (PR) in skin and/or joint defined according to the 2014 National Institute of Health cGVHD Consensus Criteria. Following the use of ruxolitinib for a median of 11 months, PR in skin and/or joints was noted in 49% (95% CI, 34 to 64) at 6 months, with 45% having joint and fascia response and 19% having skin response. The duration of skin/joint response was 77% (95% CI, 48 to 91) at 12 months. Overall cGVHD PR was noted in 47% (95% CI, 32 to 61). Improvement in Lee Symptom Scale summary and skin subscale scores was noted in 38% of patients. With a cumulative incidence of treatment failure of 20.8% (95% CI, 10.0 to 34.1), nonrelapse mortality (NRM) of 2.2% (95% CI, 0.17 to 10.3), and no recurrent malignancy, failure-free survival (FFS) was 77.1% (95% CI, 61.3 to 87.0) at 12 months. Ruxolitinib was overall well tolerated with no new safety signals. The use of ruxolitinib was associated with relatively high rates of skin/joint responses and overall cGVHD responses, improvement in patient-reported outcomes, low NRM, and high FFS in patients with refractory sclerotic cGVHD. Ruxolitinib offers an effective treatment option for refractory sclerotic cGVHD.