Regorafenib in Patients With Solid Tumors With BRAF Alterations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

PURPOSE: Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with BRAF alterations treated with regorafenib are reported. METHODS: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-1, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as investigator assessment of patients with complete or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low accruing histology-specific cohorts with BRAF alterations treated with regorafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, 0.84; α, .10). Secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS: Twenty-eight patients with 12 tumor types with BRAF alterations were enrolled from June 2016 to June 2021. All patients were evaluable for efficacy. Two patients with PR and four with SD16+ were observed for DC and OR rates of 21% (90% CI, 12 to 100) and 7% (95% CI, 1 to 24), respectively. The null hypothesis of 15% DC rate was not rejected (P = .24). Eight patients had at least one grade 3 adverse event or serious adverse event at least possibly related to regorafenib. CONCLUSION: Regorafenib did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with BRAF alterations.

Sustained Disease Control in Immune Checkpoint Blockade Responders with Microsatellite Instability-high Colorectal Cancer after Treatment Termination.

Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas - MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed. Median progression-free and overall survival were estimated. Associations between the event of recurrence and coexisting mutations (KRAS/NRAS, BRAFV600E), metastatic organ involvement (lung, liver, lymph node, or peritoneum), metastatic timing (synchronous vs. metachronous), prior immunotherapy [anti-PD-(L)1 alone or in combination with anti-CTLA antibodies], etiology of MSI status (sporadic vs. hereditary non-polyposis colorectal cancer), and duration of immunotherapy were assessed. Sixty-four patients with MSI-H colorectal cancer without progression on immunotherapy were reviewed. Of these 48 and 16 received anti-PD(L)1 antibody alone or in combination with anti-CTLA-4 antibody, respectively. Median exposure to immunotherapy was 17.6 months (range, 1.3-51.9). After a median follow-up of 22.6 months (range, 0.3-71.7) after stopping immunotherapy, 56 of 64 patients (88%) remained without disease progression. Lung metastases were associated with recurrence/progression (OR, 6.1; P = 0.04), but coexisting mutation, primary tumor sidedness, and immunotherapy were not. These data provide a retrospective, single-institution analysis that showed that most patients with advanced MSI-H colorectal cancer do not recur after treatment cessation, regardless of the reason for stopping treatment or a variety of patient and disease features, supporting an optimistic prognosis of sustained disease control. SIGNIFICANCE: Outcomes for patients with MSI-H colorectal cancer stopping immunotherapy after disease control remain unknown. Sixty-four patients with MSI-H colorectal cancer from our institution stopping treatment for sustained benefit or toxicity were retrospectively assessed. After median follow up of 22 months and median immunotherapy exposure of 18 months, 88% patients remained without progression. All patients who recurred or progressed and were rechallenged with immunotherapy have continued to experience disease control.

Pathogenesis, Clinical Considerations, and Treatments: A Narrative Review on Leprosy.

Hansen disease, known as Leprosy, is an infectious disease caused by Mycobacterium leprae. The disease was once thought to be highly contiguous, and patients with leprosy were treated poorly and had to face discrimination due to the gruesome disease's complications. Mycobacterium leprae, the bacterium causative of leprosy, can generally be found in the nine-banded armadillo. The bacterium is transmitted via aerosol droplets and broken skin-to-skin contact. Once M. leprae enters the body, it will target peripheral nerves and the lining mucosa of the skin and eyes, thus causing inflammation and tenderness of the affected area. Over time, this will lead to peripheral neuropathy and weakness of the affected body parts. Treatment of leprosy involves multi-drug combinations such as dapsone, rifampin, and clofazimine. Even though leprosy is curable, early detection and treatment are crucial to preventing irreversible damage and disabilities. Prevention measures include early detection, treatment regimen adherence, close contact prophylaxis, contact tracing, and community awareness. This review aims to provide the latest diagnostic and therapeutic recommendations for leprosy. It outlines the epidemiology, microbiology, clinical treatment, and immunological methods used to detect leprosy.

Hydrophobizing cellulose surfaces via catalyzed transesterification reaction using soybean oil and starch.

Biodegradable modified natural polymers have great potential in curbing the threat of plastic pollution, but are still uncompetitive to petrochemical-based plastic. In this study, starch was hydrophobized by treating starch-dimethyl sulfoxide solutions with soybean oil at high temperature in the presence of sodium carbonate, then spray-coated on paper. The modified starch was evaluated by Fourier-transform infrared spectroscopy analysis and contact angle value measurement of coated paper. FTIR analysis confirmed the substitution of hydroxyl groups with fatty acid ester and provided an estimate of the degree of substitution. The contact angle value of starch-coated paper surfaces was 121°, and was 111° after 10 min, demonstrating the high hydrophobicity and potential of the modified starch coating as a water-resistant treatment. The high hydrophobicity of the coated paper was due to formation of a textured surface with two levels of roughness, caused by the deposition of rough hydrophobic starch particles on paper fibers.

Identification of critical isthmus using coherent mapping in patients with scar-related atrial tachycardia.

INTRODUCTION: Accurate identification of slow conducting regions in patients with scar-related atrial tachycardia (AT) is difficult using conventional electrogram annotation for cardiac electroanatomic mapping (EAM). Estimating delays between neighboring mapping sites is a potential option for activation map computation. We describe our initial experience with CARTO 3 Coherent Mapping (Biosense Webster Inc,) in the ablation of complex ATs. METHODS: Twenty patients (58 ± 10 y/o, 15 males) with complex ATs were included. We created three-dimensional EAMs using CARTO 3 system with CONFIDENSE and a high-resolution mapping catheter (Biosense Webster Inc). Local activation time and coherent maps were used to aid in the identification of conduction isthmus (CI) and focal origin sites. System-defined slow or nonconducting zones and CI, defined by concealed entrainment (postpacing interval < 20 ms), CV < 0.3 m/s and local fractionated electrograms were evaluated. RESULTS: Twenty-six complex ATs were mapped (mean: 1.3 ± 0.7 maps/pt; 4 focal, 22 isthmus-dependent). Coherent mapping was better in identifying CI/breakout sites where ablation terminated the tachycardia (96.2% vs 69.2%; P = .010) and identified significantly more CI (mean/chamber 2.0 ± 1.1 vs 1.0 ± 0.7; P < .001) with narrower width (19.8 ± 10.5 vs 43.0 ± 23.9 mm; P < .001) than conventional mapping. Ablation at origin and CI sites was successful in 25 (96.2%) with long-term recurrence in 25%. CONCLUSIONS: Coherent mapping with conduction velocity vectors derived from adjacent mapping sites significantly improved the identification of CI sites in scar-related ATs with isthmus-dependent re-entry better than conventional mapping. It may be used in conjunction with conventional mapping strategies to facilitate recognition of slow conduction areas and critical sites that are important targets of ablation.

Effect of the Optimize Heart Failure Care Program on clinical and patient outcomes - The pilot implementation in Vietnam.

BACKGROUND: The Ho-Chi-Minh-city Heart Institute in Vietnam took part in the Optimize Heart Failure (OHF) Care Program, designed to improve outcomes following heart failure (HF) hospitalization by increasing patient awareness and optimizing HF treatment. METHODS: HF patients hospitalized with left ventricular ejection-fraction (LVEF) <50% were included. Patients received guideline-recommended HF treatment and education. Clinical signs, treatments and outcomes were assessed at admission, discharge, 2 and 6 months (M2, M6). Patients' knowledge and practice were assessed at M6 by telephone survey. RESULTS: 257 patients were included. Between admission and M2 and M6, heart rate decreased significantly, and clinical symptoms improved significantly. LVEF increased significantly from admission to M6. 85% to 99% of patients received education. At M6, 45% to 78% of patients acquired knowledge and adhered to practice regarding diet, exercise, weight control, and detection of worsening symptoms. High use of renin-angiotensin-aldosterone-system inhibitors (91%), mineralocorticoid-receptor-antagonists (77%) and diuretics (85%) was noted at discharge. Beta-blocker and ivabradine use was less frequent at discharge but increased significantly at M6 (from 33% to 51% and from 9% to 20%, respectively, p < 0.001). There were no in-hospital deaths. Readmission rates at 30 and 60 days after discharge were 8.3% and 12.5%, respectively. Mortality rates at 30 days, 60 days and 6 months were 1.2%, 2.5% and 6.4%, respectively. CONCLUSIONS: The OHF Care Program could be implemented in Vietnam without difficulty and was associated with high usage of guideline-recommended drug therapy. Although education was delivered, patient knowledge and practice could be further improved at M6 after discharge.

Bleeding and New-Onset Cancers in Patients With Atrial Fibrillation Receiving Nonvitamin K Antagonist Oral Anticoagulants.

Whether bleeding should be considered a sufficient sign to justify thorough cancer surveillance in atrial fibrillation (AF) patients receiving nonvitamin K antagonist oral anticoagulants (NOACs) remains unclear. We investigated the relationships between bleeding events and new-onset cancers in AF patients receiving NOACs in a prospective cohort (n = 395, mean follow-up duration of 2.8 years). There were 18 patients who were diagnosed with new-onset cancers 584 ± 372 days after the initiation of NOACs. The patients with new-onset cancers had higher HAS-BLED scores (no, preexisting and new-onset cancer: 1.51 ± 0.81, 1.69 ± 0.87, and 2.11 ± 0.96, respectively; p = 0.006) and a higher incidence of bleeding events (22%, 33%, 67%, respectively; p<0.001) than did patients without new-onset cancers. Bleeding events that preceded the diagnosis of new-onset cancers were independently correlated with new-onset cancers (odds ratio: 7.89, p = 0.001) in the multivariate logistic regression. More than half of the patients (61%) with new-onset cancers had either a significant period of drug interruption for at least 2 months or discontinued NOACs. In conclusions, bleeding in AF patients receiving NOACs could be an alerting sign of new-onset cancers and should prompt the initiation of thorough surveillance to detect early cancers.

Study of ranking of bio-indices using benthic macroinvertebrates for Lower Dongnai River System, Vietnam.

It has been demonstrated by research that the most successful assessment methods have been based on the benthic macroinvertebrate communities. A lot of bio-indices have been applied to evaluate the water quality widely. However, most of them have got the rankings for the water quality assessment. In this study, based on the monitoring results of the benthic macroinvertebrate and the environmental parameters in the Lower Dongnai River System during three-year periods (2007 - 2009), the linear correlations among the most popular bio-indices and each environmental parameter were considered. These environmental variables having the most closed correlation with the biological indices were DO (dissolved oxygen), WQI (water quality index) and total nitrogen. From the analysis, the ranking of bio-indices using benthic macroinvertebrate for the Lower Dongnai River System were established. The findings proved that the ranking of bio-indices for water quality assessment can be used to evaluate the water quality for the Lower Dongnai River System.

Predictors and impact of second-line chemotherapy for advanced non-small cell lung cancer in the United States: real-world considerations for maintenance therapy.

INTRODUCTION: : Recent clinical trials incorporating maintenance chemotherapy into the initial treatment of advanced non-small cell lung cancer (NSCLC) have highlighted the benefits of exposing patients to second-line therapies. We, therefore, determined the predictors and impact of second-line chemotherapy administration in a contemporary, diverse NSCLC population. METHODS: : We performed a retrospective analysis of consecutive patients diagnosed with stage IV NSCLC from 2000 to 2007 at clinical facilities associated with the University of Texas Southwestern Medical Center. Demographic, disease, treatment, and outcome data were obtained from hospital tumor registries. The association between these variables was assessed using univariate analysis and multivariate logistic regression. RESULTS: : A total of 406 patients in this cohort received first-line chemotherapy and were included in the analysis. Mean age was 59 years, 28% were women, and 59% were white. Among these patients, 197 (49%) received second-line chemotherapy. Among those patients who had not progressed after four to six cycles of first-line chemotherapy, 67% received second-line chemotherapy. Receipt of second-line chemotherapy was significantly associated with patient insurance type (p = 0.007), number of cycles of first-line chemotherapy (p < 0.001), and receipt of prechemotherapy palliative radiation therapy (p = 0.005) but was not associated with patient age, gender, race, histology, or year of diagnosis. In a multivariate model, second-line chemotherapy administration remained associated with insurance type (p = 0.003), number of cycles of first-line chemotherapy (p < 0.001), and receipt of prechemotherapy palliative radiation therapy (p = 0.008). The number of cycles of first-line chemotherapy and administration of second-line chemotherapy were associated with overall survival in both univariate and multivariate analyses. CONCLUSIONS: : In this unselected, contemporary, and diverse cohort of patients with advanced NSCLC, 67% of individuals whose disease had not progressed after four to six cycles of first-line chemotherapy eventually received second-line chemotherapy. Markers of socioeconomic status, symptom burden, and response to and tolerance of first-line chemotherapy were associated with receipt of second-line chemotherapy. These factors may assist in the selection of patients most likely to benefit from maintenance chemotherapy.

In vitro performance assessment of tubular membrane oxygenators.

The definite advantage in oxygen transfer performance of staged (single, double and triple) tubular membrane oxygenators (TMO) is compared with reference to flat membrane oxygenators (Travenol or Landé Edwards). The overall construction of staged TMO with a blood mixing chamber is a very good way to destroy the blood boundary layer and modify the blood stagnant zone in the device. Four sizes of staged TMO were studied using the principle that gases dissolve in water in concentrations linearly proportional to the partial pressures of the gases when in equilibrium with the liquid. The experimental results show that the oxygen transfer rate and the corresponding overall oxygen mass transfer coefficient of staged TMO are increased by the same order as those of the reference membrane oxygenators. Furthermore the essential parameter analysis prove that oxygen transfer increases with the number of stages and decreases with the length of the blood tubular modules. The multistage design of TMO revealed an increase in the hydrodynamic resistance occurring in the apparatus. However the highest relative oxygen transfer efficiency suggests that better fluid distribution as well as better uniformity of oxygenation prevail in the staged devices.