Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab

International Journal of Clinical Oncology - Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant...     

Carfilzomib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma: A Phase I Trial

IntroductionWe designed a multicenter, phase Ib dose-escalation trial of carfilzomib with bendamustine and rituximab in patients with relapsed/refractory non-Hodgkin lymphoma (NCT02187133) in order to improve the response rates of this difficult-to-treat population. Chemoimmunotherapy with bendamustine and rituximab has shown activity in a variety of lymphomas, and proteasome inhibitors have demonstrated pre-clinical synergy and early clinical activity in this population. The objectives were to determine the maximum tolerated dose of carfilzomib and the preliminary efficacy of this combination.Patients and MethodsThe protocol followed a 3+3 design of carfilzomib dose escalation combined with standard doses of bendamustine and rituximab. Patients were treated for up to 6 cycles with an interim positron emission tomography/computed tomography after cycle 3.ResultsTen patients were treated on the dose-escalation phase. The study was terminated at a carfilzomib dose of 56 mg/m², and the maximum tolerated dose was not reached. The most common grade 3/4 adverse event was thrombocytopenia. There was 1 dose-limiting toxicity observed, grade 3 febrile neutropenia, and there were no treatment-related deaths. The overall response rate was 40% (complete response rate, 30%), with a median duration of response of 12 months and a median progression-free survival of 2.1 months.ConclusionCarfilzomib in combination with bendamustine and rituximab is a safe and well-tolerated treatment for patients with relapsed/refractory non-Hodgkin lymphoma. Preliminary data indicate that this combination may have efficacy with an acceptable side effect profile in this heavily pre-treated patient population with limited treatment options.     

Demographic and clinical characteristics of persons with spinal cord injury in Turkey: One-year experience of a primary referral rehabilitation center

Objective: To define the demographic and clinical characteristics of persons with spinal cord injury, rehabilitated in a primary referral rehabilitation center in Turkey.

Design: Retrospective study.

Setting: Ankara Physical Medicine and Rehabilitation Training and Research Hospital, Ankara, Turkey.

Methods: Medical records of all patients with spinal cord injury (acute-subacute-chronic) at a single academic referral center over the course of one year were reviewed. Variables of each patient were recorded, including: age, sex, etiology, length of rehabilitation stay, neurological level of injury, level of neurological impairment and severity of injury.

Results: Among 262 persons with spinal cord injury, 69.8% were male (male:female ratio is 2.31?:?1). Mean age was 38.3?±?17.6 years. Falls were the most common cause of injury. The majority of falls were falls from a height (93.3%). More than 20% of falls from a height were related to occupational injury. The most common neurological level of injury was L1. Of all persons 46.2% had thoracic, 27.5% had lumbar and 26.3% had cervical lesions. The mean length of rehabilitation stay was 52.1?±?25.5 days. Persons with motor complete injury and with a shorter (<12 months) time since injury had longer length of rehabilitation stay.

Conclusion: The mean age of SCI population is increasing. Falls constitute the majority of etiologic factors and are more common in persons >60 years old. More than 20% of falls from a height are related to occupational injury. Male-female ratio is decreasing. Thoraco-lumbar injures are more common than cervical injuries.     

Urinary biomarkers in the early detection and follow-up of tubular injury in childhood urolithiasis

Background

To investigate relationships among urinary biomarkers [kidney injury molecule-1 (KIM-1), N-acetyl-β-glucosaminidase (NAG)], neutrophil gelatinase-associated lipocalin (NGAL) levels and renal tubular injury in childhood urolithiasis.

Methods

Seventy children [36 girls, mean age: 7.3 ± 5.0 years (0.5–18.2)] with urolithiasis/microlithiasis and 42 controls [18 girls, mean age: 8.5 ± 3.8 years (0.9–16.2)] were included in this multicenter, controlled, prospective cohort study. Patients were evaluated three times in 6-month intervals (0, 6 and 12th months). Anthropometric data, urinary symptoms, family history and diagnostic studies were recorded. Urine samples were analyzed for metabolic risk factors (urinary calcium, uric acid, oxalate, citrate, cystine, magnesium, and creatinine excretion), and the urinary KIM-1, NAG, and NGAL levels were measured.

Results

Stones were mostly located in the upper urinary system (82.9%), and six patients (8.6%) had hydronephrosis. Thirty patients (42.9%) had several metabolic risk factors, and the most common metabolic risk factor was hypocitraturia (22.9%). Urinary KIM-1/Cr, NAG/Cr and NGAL/Cr ratios were not significantly different between patients and controls. Furthermore, no significant changes in their excretion were shown during follow-up. Notably, the urinary KIM-1/Cr, NAG/Cr, and NGAL/Cr levels were significantly higher in children under 2 years of age (p = 0.011, p = 0.006, and 0.015, respectively). NAG/Cr and NGAL/Cr ratios were significantly increased in patients with hydronephrosis (n = 6, p = 0.031 and 0.023, respectively).

Conclusions

The results of this study suggest that none of the aforementioned urinary biomarkers (KIM-1, NAG and NGAL levels) may be useful for the early detection and/or follow-up of renal tubular injury and/or dysfunction in childhood urolithiasis.

     

Sonographic diagnosis of a glomus tumor of the thigh

Extradigital glomus tumors are a very rare entity. Here, we report a rare case of a glomus tumor in an atypical anatomic site: the thigh. The clinical features together with the results of MRI, and sonography and Doppler sonographic imaging helped to distinguish glomus tumor of the thigh from other soft tissue neoplasms. The tumor arising from the thigh was excised, and following surgery, the patient was symptom free without evidence of complications or recurrence. There have only been a few previously reported cases describing the use of Doppler sonography in the evaluation of extradigital glomus tumors. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45 :50–52, 2017     

Treatment of painful temporomandibular joints with a cyclooxygenase-2 inhibitor: a randomized placebo-controlled comparison of celecoxib to naproxen

To compare the efficacy and adverse effects of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, with naproxen, a non-steroidal anti-inflammatory drug, and placebo in the treatment of painful temporomandibular joints (TMJs). In this randomized, double-blind, placebo-controlled trial, 68 subjects with painful TMJs secondary to disc-displacement with reduction, received celecoxib 100 mg twice a day; naproxen, 500 mg twice a day; or placebo for 6 weeks. Subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analogue scale, maximal comfortable mandibular opening, and quality of life (SF-36), at baseline (1 week after discontinuing previous analgesic therapy) and again after 6 weeks of drug treatment. Naproxen significantly reduced the symptoms of painful temporomandibular joint disc-displacement (TMJ DD) with reduction as determined by most efficacy measures. Significant improvement in pain intensity occurred within 3 weeks of treatment, and was sustained throughout the 6-week study. Clinically significant improvement in mandibular range of motion was observed for naproxen compared to celecoxib and placebo. Celecoxib showed slightly better pain reduction than placebo, but was not significantly effective for temporomandibular disorder pain. Celecoxib and naproxen were well tolerated, with similar number of reported adverse effects. Dual COX-1 and COX-2 inhibition with naproxen was demonstrated to be effective for the treatment of painful TMJs, as seen by significant improvement in clinical signs and symptoms of TMJ DD with reduction compared to celecoxib and placebo. Inhibition of both COX isozymes is needed to achieve effective analgesia for this type of musculoskeletal pain.     

Automated fructosamine assay with improved accuracy used to quantify nonenzymatic glycation of serum proteins in diabetes mellitus and chronic renal failure

We optimally solubilized the diformazan that forms during the fructosamine reaction with a nonionic detergent; we then automated the assay. After optimal solubilization of diformazan, we found that serum urate contributed significantly to the color formation in fructosamine reaction. When the error introduced by urate was corrected mathematically by use of an experimental determined factor, the serum fructosamine concentrations obtained were comparable with those of a more specific test of the nonenzymatic glycation (HPLC of hydrolyzed proteins). We found that concentrations of fructosamine in serum increased with increasing age of subjects. In diabetic patients the average concentration of fructosamine in serum exceeded that in nondiabetic subjects and correlated with the preprandial serum glucose and with other measures of deteriorating glycemic control (e.g., increased need for insulin therapy). Serum fructosamine normalized for albumin content was also increased in patients with chronic renal failure. Multiple mechanisms (including exposure of patients to hypertonic glucose during dialysis) appear to be involved in the increase of serum fructosamine in patients with chronic renal failure.     

Spectral ratio method to estimate broadband ultrasound attenuation of cortical bones in vitro using multiple reflections

Broadband ultrasound attenuation (BUA) is commonly measured by the spectral ratio method. Conventionally BUA is measured in transverse transmission mode where ultrasound signal is recorded with and without the sample. The spectral ratio method was extended to estimate nBUA (BUA normalized by thickness) in axial transmission mode using spectral amplitudes of the primary reflection and multiple reflection, which echoes more than once between the material interfaces within a layer. We performed three experiments. First, reflections were numerically simulated to verify the accuracy of the method. We then applied the method to estimate attenuation of silicon rubber and the cortex of a bovine femur. The center frequency of the transducers is 2.25 MHz. We obtained 93% accuracy for a simulated data set with 10% random noise after bandpass filtering. For the silicon rubber, 15 measurements were collected and the mean attenuation was 6.33 +/- 0.19 dB MHz(-1) cm(-1). For the bovine bone, eight measurements were performed in the middle portion of the femur. The mean attenuation was 4.91 +/- 0.65 dB MHz(-1) cm(-1) and compared well with those reported in the literature. The results demonstrate that the proposed method has the potential to provide a quick, reliable and robust cortical attenuation assessment in vivo.