A multicenter,open‐label,phase II study of tirabrutinib (ONO/GS‐4059) in patients with Waldenström’s macroglobulinemia

Tirabrutinib is a second‐generation Bruton’s tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment‐naïve (Cohort A) or with relapsed/refractory (Cohort B) Waldenström’s macroglobulinemia (WM). Patients were treated with tirabrutinib 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall response rate (ORR; ≥ minor response), time to major response (TTMR), progression‐free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71 y, and the median serum immunoglobulin M level was 3600 mg/dL. Among the patients, 96.2% had the MYD88^L265P mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87 mo. PFS and OS were not reached with a median follow‐up of 6.5 and 8.3 mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug‐related atrial fibrillation or hypertension. Although the follow‐up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed/refractory WM with a manageable safety profile. (JapicCTI‐173646).     

Effects of dominant and nondominant eyes in binocular rivalry.

PURPOSE: To investigate the relation between sighting and sensory eye dominance and attempt to quantitatively examine eye dominance using a balance technique based on binocular rivalry. METHODS: The durations of exclusive visibility of the dominant and nondominant eye target in binocular rivalry were measured in 14 subjects. The dominant eye was determined by using the hole-in-card test (sighting dominance). In study 1, contrast of the target in one eye was fixed at 100% and contrast of the target in the other eye was varied from 100% to 80% to 60% to 40% to 20%, when using rectangular gratings of 1, 2, and 4 cycles per degree (cpd) at 2 degrees, 4 degrees , and 8 degrees in size. In study 2, contrast of the target in the nondominant eye was fixed at 100% and contrast of the target in the dominant eye was varied from 100% to 80% to 60% to 40% to 20%, when using a rectangular grating of 2 cpd at 4 degrees in size. RESULTS: In study 1, the total duration of exclusive visibilities of the dominant eye target; that is, the target seen by the eye that had sighting dominance was longer compared with that of the nondominant eye target. When using rectangular gratings of 4 cpd, mean total duration of exclusive visibility of the dominant eye target was statistically longer than that of the nondominant eye target (p < 0.05). In study 2, reversals (in which duration of exclusive visibility of the nondominant eye becomes longer than the dominant eye when the contrast of the dominant eye target is decreased) were observed for all contrasts except for 100%. CONCLUSIONS: The dominant sighting eye identified by the hole-in-card test coincided with the dominant eye as determined by binocular rivalry. The contrast at which reversal occurs indicates the balance point of dominance and seems to be a useful quantitative indicator of eye dominance to clinical applications.     

Functional electrical stimulation for the control of the upper extremities

A multi-channel functional electrical stimulation (FES) system for the restoration of hand function of the quadriplegic is described. The system is composed of a personal computer NEC PC-880lmkII, peripheral electronic circuits and two kinds of sensors, i.e. an analog displacement sensor for volitional control (channel 1) and a logical sensor (high pitch sound or head switch, channel 2). Combination of the two channel signals allow three major function: 1) designation of the desired prehension pattern among cylindrical grasp, key grip and parallel extension grip; 2) selection of the operation status--'start', 'proportional control', 'hold', 'stop'--and, 3) volitional control which can be controlled by the shoulder movement. In the clinical application, Caldwell-Reswick type multistrand stainless steel percutaneous electrodes were used. In this FES system, standard multi-channel stimulation patterns were obtained from electromyographical analysis of joint movement of the upper extremities in normal subjects which gave us precise information about a role of each muscle during various kinds of motion. Such stimulation patterns have enabled us to restore motor function of the paralyzed upper extremities for activities of daily living (ADL).     

Comparative efficacy of Hanifin and Rajka''s criteria and the UK working party''s diagnostic criteria in diagnosis of atopic dermatitis in a hospital setting in North India

BACKGROUND: Diagnosis of atopic dermatitis (AD) depends on clinical features because no definitive diagnostic test exists. Criteria proposed by Hanifin and Rajka (Acta Derm Venereol (Stockh) 1980; Suppl 92: 44-47) were acceptable for hospital-based studies but were found not to be suitable for field studies. A UK working party formulated clinical diagnostic criteria that could be used in both hospital and epidemiological settings. Validation studies of the criteria showed widely variable results, probably due to different clinical settings and ethnicity. AIM AND OBJECTIVE: This study was undertaken to validate Hanifin and Rajka's criteria and to assess the comparative efficacy of their criteria and the UK working party's diagnostic criteria in the diagnosis of AD in a hospital setting in North India. SUBJECTS AND METHODS: This study serially included 101 patients with AD and 48 controls of paediatric age group. The study period was from July 2003 to December 2004. RESULTS: Hanifin and Rajka's criteria (sensitivity 96%, specificity 93.75%, positive predictive value 97% (PPV) and negative predictive value (NPV) 91.84%) had a statistical advantage over the UK working party's diagnostic criteria (sensitivity 86%, specificity 95.83%, PPV 97.75% and NPV 76.67%), with a P-value < 0.005.     

Interface between the meningioma and the brain on magnetic resonance imaging

Magnetic resonance imaging of 31 meningiomas in 29 patients was retrospectively reviewed and compared with pathologic specimens in 25 tumors to investigate how magnetic resonance imaging could delineate a tumor-brain interface. The thick, collagenous connective tissue, which was seen around four tumors, was shown as a low signal intensity rim on both a T1-weighted image and a T2-weighted image. A rim of low signal intensity on a T1-weighted image and high signal intensity on a T2-weighted image most likely represented cerebrospinal fluid space: this finding was seen around eight tumors. No distinct rim could be identified in five tumors. Of these five, two tumors grew invasively into the brain. Although mixed features predominated in meningiomas, magnetic resonance imaging could well delineate a tumor-brain relationship in most of the cases.     

Clinical and epidemiological aspects of enteritis due to Salmonella hadar. II. Environmental contamination by Salmonella hadar in Shizuoka Prefecture--studies on the feasibility of reducing S. hadar infection]

A systematic examination was performed for environmental food contamination by Salmonella in poultry farms, broiler chickens, broiler processing plants and meat on the market. Salmonella was isolated from 219 of 1197 samples and the serotypes showed a wide distribution. (Table 1-1). S. hadar accounted for 37.1% (96) of all isolations (259). The contamination rate of broiler chickens on arrival at broiler processing plants is relatively low. However, in the broiler processing plants, containers, processing machinery, cooling water and slaughters were highly contaminated by Salmonella, S. hadar being the most prominent serotype in the plants. 64% of chicken meat on the market was contaminated by Salmonella, S. hadar being the second most prominent serotype. 11% of the pork and none of the beef or horseflesh was contaminated by Salmonella. These results indicate that poultry is the main source of S. hadar infection in humans. However, no S. hadar was isolated from cultures of 119 samples of feed for chickens from each delivery (Table 1-1). Thus, as the main source of infection by S. hadar of broiler chickens, an association with the feed seems to be ruled out. S. hadar was isolated at three of 18 poultry farms within Shizuoka Prefecture. Follow-up studies were performed at the three poultry farms which revealed that in two of them, Salmonella was completely eradicated on completion of disinfection. In the other one farm, which is still being disinfected, various strains of Salmonella including S. hadar still survived. We conclude that the main cause of the problem is the magnification of contamination of Salmonella-free material during the process at the broiler processing plants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Large Ulcerated Perianal Hidradenoma Papilliferum in a Young Female

BACKGROUND: Hidradenoma papilliferum is an uncommon benign tumor that is located almost exclusively in the vulvar and anal areas. It is usually very small and asymptomatic, and to make a correct diagnosis is clinically very difficult. Occasionally the tumor becomes elevated to form a reddish brown papillary mass, and the surface ulcerates, which may erroneously suggest malignancy. OBJECTIVE: We report a case of a large, perianal hidradenoma papilliferum with suspected malignancy in a young Japanese female. RESULTS: A 22-year-old female had been aware of a perianal nodule for approximately 1 year. Examination of the perianal area revealed a wide pedunculated, reddish nodule with several white maculae. It was ulcerated and bleeding, 2.0 x 1.2 x 0.8 cm in size, and located in the 3 o'clock position. The nodule was totally excised with a narrow margin. The histopathologic diagnosis was hidradenoma papilliferum. No recurrence was observed for 23 months. CONCLUSION: When dermatologists encounter tumors of the anogenital area of adult females, it is important to keep hidradenoma papilliferum in mind as the differential diagnosis. Dermatologists should recognize that the tumor is benign, eliminating the need for wide resection.