Quality of life with encorafenib plus cetuximab with or without binimetinib treatment in patients with BRAF V600E-mutant metastatic colorectal cancer: patient-reported outcomes from BEACON CRC.

BACKGROUND: In the BEACON CRC study (NCT02928224), encorafenib plus cetuximab with binimetinib {9.3 versus 5.9 months; hazard ratio (HR) [95% confidence interval (CI)]: 0.60 [0.47-0.75]} or without binimetinib [9.3 versus 5.9 months; HR (95% CI): 0.61 (0.48-0.77)] significantly improved overall survival (OS) compared with the previous standard of care (control) in patients with BRAF V600E metastatic colorectal cancer (mCRC). Quality of life (QoL) was a secondary endpoint, assessed using validated instruments. PATIENTS AND METHODS: BEACON CRC was a randomized, open-label, phase III study comparing encorafenib plus cetuximab with or without binimetinib and the investigator's choice of irinotecan plus cetuximab or FOLFIRI plus cetuximab (chemotherapy control) in patients with previously treated BRAF V600E mCRC. Patient-reported QoL assessments included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC) and Functional Assessment of Cancer Therapy-Colorectal (FACT-C). The primary outcome for these tools was time to definitive 10% deterioration. RESULTS: Encorafenib plus cetuximab, both with and without binimetinib, was associated with longer median times to definitive 10% deterioration versus the control group in the EORTC Global Health Status scale [HR (95% CI): 0.65 (0.52-0.80) versus 0.61 (0.49-0.75), respectively] and the FACT-C functional well-being subscale [HR (95% CI): 0.62 (0.50-0.76) versus 0.58 (0.47-0.72), respectively]. Consistent results were observed across all subscales of the EORTC and FACT-C instruments. QoL was generally maintained during treatment for the global EORTC and FACT-C scales. CONCLUSIONS: In addition to improving OS, encorafenib plus cetuximab with or without binimetinib delays QoL decline in previously treated patients with BRAF V600E-mutant mCRC.

IL-10, but not IL-4, suppresses infection-stimulated bone resorption in vivo.

Periapical bone resorption occurs following infection of the dental pulp and is mediated mainly by IL-1alpha in the murine model. The production and activity of IL-1alpha is modulated by a network of regulatory cytokines, including those produced by Th1 (pro-inflammatory) and Th2 (anti-inflammatory) subset T cells. This study was designed to assess the functional role of the Th2-type cytokines IL-4 and IL-10 in infection-stimulated bone resorption in vivo. The dental pulps of the first molars were exposed and infected with a mixture of four common endodontic pathogens, and bone destruction was determined by micro-computed tomography at sacrifice on day 21. The results demonstrate that IL-10(-/-) mice had significantly greater infection-stimulated bone resorption in vivo compared with wild-type mice (p < 0.001), whereas IL-4(-/-) exhibited no increased resorption. IL-10(-/-) had markedly elevated IL-1alpha production within periapical inflammatory tissues (>10-fold) compared with wild type (p < 0.01), whereas IL-4(-/-) exhibited decreased IL-1alpha production (p < 0.05). IL-10 also suppressed IL-1alpha production by macrophages in a dose-dependent fashion in vitro, whereas IL-4 had weak and variable effects. We conclude that IL-10, but not IL-4, is an important endogenous suppressor of infection-stimulated bone resorption in vivo, likely acting via inhibition of IL-1alpha expression.

Three-year experience with sonicated vascular catheter cultures in a clinical microbiology laboratory.

Using a quantitative sonication method, we cultured 1,681 consecutive vascular catheters submitted to a clinical microbiology laboratory in a 36-month period. A total of 46% of the cultures were positive; the most common organisms isolated were coagulase-negative staphylococci (36.4%), Pseudomonas aeruginosa (13.9%), enterococci (10.0%), yeasts (9.2%), Staphylococcus aureus (5.8%), and Enterobacter species (4.4%). The frequencies of positive blood cultures within 48 h prior to a positive catheter culture result were as follows: Candida albicans (68.4%), S. aureus (60%), Enterobacter cloacae (42.9%), Staphylococcus epidermidis (32.1%), P. aeruginosa (27.7%), and enterococci (23.3%). The sonication method allowed quantification of the number of CFU removed from a catheter for between 10(2) and 10(7) CFU. For catheter cultures in which greater than or equal to 10(2) CFU grew, a linear regression equation could be calculated: (risk of positive blood culture for the same organism) = 14 [log10 (number of organisms removed from the catheter)] -21 (r = 0.93). For catheter cultures in which less than 10(2) CFU grew, positive blood cultures for the same organism were strongly associated with a proven infection at a site distant from the catheter (P = 0.001) or probable contamination (S. epidermidis). Our findings indicate that this technique has considerable potential for use in clinical microbiology laboratories to aid in the diagnosis of vascular catheter infections and for clinical investigations into the pathogenesis of these infections.

Impact of air filtration on nosocomial Aspergillus infections. Unique risk of bone marrow transplant recipients.

Bone marrow transplant recipients were found to have a 10-fold greater incidence of nosocomial Aspergillus infection than other immunocompromised patient populations (p less than 0.001) when housed outside of a high-efficiency particulate air (HEPA) filtered environment. Multivariate analysis demonstrated that number of infections, age, and graft-versus-host disease severe enough to require treatment were independent risk factors for development of nosocomial Aspergillus infection in this group. The use of whole-wall HEPA filtration units with horizontal laminar flow in patient rooms reduced the number of Aspergillus organisms in the air to 0.009 colony-forming units/m3, which was significantly lower than in all other areas of the hospital (p less than or equal to 0.03). No cases of nosocomial Aspergillus infection developed in 39 bone marrow transplant recipients who resided in this environment throughout their transplantation period compared with 14 cases of nosocomial Aspergillus infection in 74 bone marrow transplant recipients who were housed elsewhere (p less than 0.001). Thus, although bone marrow transplant recipients had an order-of-magnitude greater risk of nosocomial Aspergillus infection than other immunocompromised hosts, this risk could be eliminated by using HEPA filters with horizontal laminar airflow.

Strongyloides meningitis.

Acute pyogenic meningitis occurred in a 46-year-old woman receiving long-term steroid therapy. Cultures for bacteria and fungi were negative, and the meningitis failed to respond to broad spectrum antibiotics. Abundant Strongyloides stercoralis larvae were found in the patient's feces a sputum, and a filariform larva was found in a hanging drop preparation from centrifuged cerebrospinal fluid. Therapy with thiabendazole eradicated the Strongyloides from feces and sputum. The abnormal CSF values returned toward normal, and the patient has had no recurrence of illness.

Histoplasmosis presenting as a neck mass.

A unilateral neck mass is an unusual clinical presentation for histoplasmosis. A patient with a large, unilateral neck mass caused by Histoplasma capsulatum is presented to alert readers to such a possibility and to illustrate some of the difficulties in diagnosing and managing the disease.

Outbreak of staphylococcal infection in two hospital nurseries traced to a single nasal carrier.

In late January and early February 1983, an outbreak of skin infections (7 of 145 infants) caused by a penicillin/erythromycin resistant strain of Staphylococcus aureus (SA), phage type 3A/3C, occurred in our newborn nursery. A week following the first cluster of infections, another nursery outbreak due to SA with the same antibiogram occurred in a nearby community hospital (11 of 114 infants). Subsequently, a second cluster of infections with the same SA was identified at our nursery. The epidemic strain was carried in the anterior nares of a single nurse who worked at both hospital nurseries on alternate weeks. Investigation revealed that the nurse had an upper respiratory tract infection during each of these outbreaks--simulating "a cloud baby." No further infections have occurred since this nurse was treated and her SA nasal carrier state eliminated.

Vasculitis in a suspected AIDS patient.

A 29-year-old male Haitian refugee had generalized lymphadenopathy, weight loss, and bilateral lung infiltrates diagnosed by transbronchial lung biopsy as tuberculosis. He had previously been labeled as having "pre-AIDS," which led to multiple suicide attempts. Four months later, cyanosis and gangrene of both lower extremities necessitated amputation, which revealed vasculitis.