Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy.

In this open-label, intra-patient phase I/II trial, bortezomib was replaced with carfilzomib (escalated from 20 to 45 mg/m(2) on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle) for multiple myeloma (MM) patients who progressed while on or within 12 weeks of receiving a bortezomib-containing combination regimen. Study objectives included determination of the maximum tolerated dose (MTD), overall response rate (ORR), clinical benefit rate (CBR), time to progression, time to response, duration of response, progression-free survival and overall survival (OS). Of 38 registered patients, 37 were treated and evaluable for efficacy and safety. Thirty-one carfilzomib-based regimens using 14 different drug combinations were tested. One regimen (carfilzomib (45 mg/m(2)), ascorbic acid (1000 mg) and cyclophosphamide (2.2 mg/kg)) reached MTD. ORR and CBR were 43.2 and 62.2%, respectively. Median progression-free survival, time to progression and OS were 8.3, 9.9 and 15.8 months, respectively. Hematologic adverse events (AEs; ⩾grade 3) included lymphopenia (35.1%), thrombocytopenia (24.3%), anemia (10.8%) and neutropenia (10.8%). Nonhematologic AEs (⩾grade 3) included fever (5.4%) and hypokalemia (5.4%). These results demonstrate that replacing bortezomib with carfilzomib is safe and can be effective for MM patients failing bortezomib-containing combination regimens. This trial was registered at http://www.clinicaltrials.gov (#NCT01365559).

A global representation of vitamin D status in healthy populations.

PURPOSE: This paper visualizes the available data on vitamin D status on a global map, examines the existing heterogeneities in vitamin D status and identifies research gaps. METHODS: A graphical illustration of global vitamin D status was developed based on a systematic review of the worldwide literature published between 1990 and 2011. Studies were eligible if they included samples of randomly selected males and females from the general population and assessed circulating 25-hydroxyvitamin D [25(OH)D] levels. Two different age categories were selected: children and adolescents (1-18 years) and adults (>18 years). Studies were chosen to represent a country based on a hierarchical set of criteria. RESULTS: In total, 200 studies from 46 countries met the inclusion criteria, most coming from Europe. Forty-two of these studies (21 %) were classified as representative. In children, gaps in data were identified in large parts of Africa, Central and South America, Europe, and most of the Asia/Pacific region. In adults, there was lack of information in Central America, much of South America and Africa. Large regions were identified for which the mean 25(OH)D levels were below 50 nmol/L. CONCLUSIONS: This study provides an overview of 25(OH)D levels around the globe. It reveals large gaps in information in children and adolescents and smaller but important gaps in adults. In view of the importance of vitamin D to musculoskeletal growth, development, and preservation, and of its potential importance in other tissues, we strongly encourage new research to clearly define 25(OH)D status around the world.

A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed/refractory multiple myeloma.

Our previous studies have shown that lowering the dose of pegylated liposomal doxorubicin (PLD) and bortezomib in combination with intravenous dexamethasone on a longer 4-week cycle maintained efficacy and improved tolerability in both previously untreated and relapsed/refractory (R/R) multiple myeloma (MM) patients. Lenalidomide has shown efficacy in combination with bortezomib and dexamethasone but this combination has been poorly tolerated. We conducted this phase 2 study (clinicaltrials.gov identifier: NCT01160484) to evaluate whether a longer 4-week schedule using modified doses and schedules of IV dexamethasone (40 mg), bortezomib (1.0 mg/m(2)) and PLD (4.0 mg/m(2)) administered on days 1, 4, 8, and 11 with lenalidomide 10 mg daily on days 1-14 (DVD-R) would be effective and tolerated for patients with R/R MM. A total of 40 heavily pretreated patients were enrolled and 84.6% showed clinical benefit (complete response, 20.5%; very good partial response, 10.3%; partial response, 17.9%; minimal response, 35.9%) to the combination regimen. An additional 10.3% showed stable disease and 5.1% progressed while on study. The regimen was well tolerated, with a low incidence of adverse events such as fatigue (40%), thrombocytopenia (35%), neutropenia (35%), anemia (30%), peripheral neuropathy (25%) and pneumonia (15%). Thus, the DVD-R regimen is well tolerated and produces high response rates for patients with R/R MM.

Seroprevalence of Bartonella henselae in cats in Germany.

Bartonella henselae and B. quintana infections in man are associated with various clinical manifestations including cat-scratch disease, bacillary angiomatosis and bacteraemia. While cats are the natural reservoir for B. henselae, the source of B. quintana is unclear. In this study, the sera of 713 cats from Germany were examined for the presence of antibodies against B. henselae, B. quintana or Afipia felis by an indirect immunofluorescence assay (IFA). Bartonella-specific antibody titres of > or =50 were found in 15.0% of the cats. There was substantial cross-reactivity among the various Bartonella antigens, although single sera showed high titres against B. henselae but not against B. quintana and vice versa. Antibodies against A. felis were not detected in any of these cats. Statistical analysis indicated that there is no correlation between Bartonella infections and the sex, age or breed of the cat or its hunting behavior. There was also no correlation between bartonella and toxoplasma infections in cats. However, whereas 16.8% of cats from northern Germany had B. quintana-specific antibodies, only 8.0% of cats from southern Germany were seropositive for B. quintana. No statistically significant difference was found for B. henselae. IFA-positive and IFA-negative sera were used for immunoblot analysis including B. henselae and B. quintana. Marked reactivity was observed with protein bands at 80, 76, 73, 65, 37, 33 and 15 kDa. The results of this study suggest that B. henselae, and possibly a B. quintana-related pathogen, but not A. felis, are common in cats in Germany, and that there are differences in the geographic distribution of bartonella infections in cats.

Computed tomography in the diagnosis of cochlear otosclerosis.

Twelve patients with surgically proven otosclerosis and sensorineural hearing loss were studied with high-resolution computed tomography (CT). The purpose was to identify abnormal bony changes that could be diagnostic of cochlear otosclerosis. Of the 24 temporal bones thus studied, 10 showed positive findings. The findings in our study--as well as those of others--show a pericochlear zone of radiolucency. The precise origin of this is undetermined.

A computerized nasal analysis system.

Critical analysis of an aesthetic surgeon's presurgical and postsurgical photographs may provide an excellent tool for self-assessment, research, and teaching. Techniques are presented that allowed precise definition by personnel other than the surgeon of each patient's deformities and the effects of surgery on them. Trigonometric formulas were developed and a computer was programmed to use the X and Y coordinates for facial landmarks to perform many calculations providing distances, angles, projections, and rotations relating to the rhinoplastic surgery. Cases are reported showing typical changes and some results not readily apparent in the photographs. Such data provide not only current analysis of individual cases, but they eventually will become a large data base that may be used to select groups of rhinoplastic cases having common degrees of deformity or of postoperative changes.

Conchal bowl and postauricular flaps for reconstruction of the external auditory canal.

Two techniques for reconstructing the external auditory canal are presented; to our knowledge they have not been described previously. The first technique can be used for disease that does not affect the conchal bowl. The canal is reconstructed with an inferiorly based conchal bowl flap. A second inferiorly based postauricular flap, tunneled through the conchal cartilage, resurfaces the conchal bowl. The postauricular defect is closed primarily. The second technique can be used for disease affecting the conchal bowl. A posteriorly based flap that includes skin overlying the mastoid and posterior surfaces of the pinna is tunneled through the conchal cartilage and resurfaces the conchal bowl and external auditory canal. The defect on the posterior surface of the pinna is closed with tissue advanced from the anterior surface of the pinna at the conchal bowl-antihelical fold junction. The remainder of the retroauricular defect is closed primarily. The advantages of these techniques over current methods are described and illustrative cases presented.

Sequential changes in placental blood gases and pH during the hour following delivery.

We studied the effect of a delay in blood sampling on the measurement of placental blood gases, pH and calculated bicarbonate. Blood was sampled serially at 15-minute intervals during the hour following delivery from placentas and attached umbilical cords of unasphyxiated term neonates. Placentas and attached cords were stored at room temperature. When blood was sampled exclusively from the segment of the umbilical vein lying within the umbilical cord, there were no statistically significant changes during the time of study in pH, PCO2 or PoO2. When some or all of the serial samples were taken from vessels on the surface of the placenta, there was a statistically and biologically significant decrease in the pH and increase in the PCO2 values of the blood. Our results indicate that the validity of the measurements of umbilical venous blood gases and pH is not affected by up to an hour's delay in blood sampling.

Computerized axial-tomography in the preoperative evaluation of an angiofibroma.

Computerized axial tomography (CAT) of the head provides the otolaryngologist with an effective diagnostic tool. This technique is particularly useful when used in the preoperative evaluation of head and neck pathology and may be used to define the extent of disease and to direct the surgical approach. The case of a 16-year-old male with an extensive angiofibroma involving the paranasal sinuses and nasopharynx is presented as an example of CAT in preoperative planning of the surgical procedure. Computerized tomography was used initially to define the tumor margins. Serial CAT scans were also obtained at intervals during the patient's preoperative estrogen therapy. Evidence was obtained which suggests CAT may be used to monitor the effects of preoperative hormone management of angiofibromas and in the definition of the optimal time for surgery. In the case presented the final CAT scan provided a detailed and accurate description of the tumor margins which were confirmed at surgery. Our experience with a case of an extensive nasopharyngeal angiofibroma demonstrates the CAT scan to be a useful objective diagnostic method for preoperative planning.