Effectiveness of Hypofractionated Radiotherapy in Painful Bone Metastases Two Prospective Studies with 1 × 4 Gy and 4 × 4 Gy

BACKGROUND: Although effectiveness of fractionated radiotherapy for painful bone metastases is well documented, there are unanswered questions regarding the adequacy of low-dose short radiation schedules for long-term pain control which give maximum benefit in patients with a short life expectancy. PATIENTS AND METHODS: Two consecutive non-randomized prospective follow-up studies were performed at a single institution to analyze pain response and duration of response in patients with a variety of primary tumors. Included were only patients with symptomatic nonvertebral bone metastases and without impending pathologic fracture. Forty-five patients received 1 x 4 Gy to 50 different sites (group I) while 86 patients received 4 x 4 Gy to 96 sites (group II). Pain relief to irradiation was evaluated according to patient interviews using a 4-point categorical scale. Follow-up was performed 7 and 90 days after radiotherapy. RESULTS: Pain relief after 4 x 4 Gy was significantly superior to 1 x 4 Gy with pain control rates being 86.5% vs 48% at day 7 (after end of treatment) and 80% vs 55% at day 90, respectively. A subgroup analysis of patients treated with 4 x 4 Gy demonstrated a more favorable outcome for breast cancer patients in comparison to patients with other primaries concerning pain relief (96% vs 81%), pain control after 90 days (93% vs 72%), median time to pain progression (9 vs 3 months), and median overall survival (14 vs 5.5 months). CONCLUSIONS: In this study 4 x 4 Gy proved to be clearly superior to 1 x 4 Gy in relieving pain from symptomatic nonvertebral bone metastases without impending pathologic fracture. Even if radiotherapy with 1 single fraction seems to be applicable in specific cases doses higher than 4 Gy should be chosen. In breast cancer patients pain control seems to be better compared to other primaries.     

Quantification of immobilization-induced changes in human calf muscle using speed-of-sound ultrasound: An observational pilot study

Short-term immobilization leads to fatty muscular degeneration, which is associated with various negative health effects. Based on literature showing very high correlations between MRI Dixon fat fraction and Speed-of-Sound (SoS), we hypothesized that we can detect short-term-immobilization-induced differences in SoS.Both calves of 10 patients with a calf cast on one side for a mean duration of 41 ± 26 days were examined in relaxed position using a standard ultrasound machine. Calf perimeters were measured for both sides. A flat Plexiglas-reflector, placed vertically on the opposite side of the probe with the calf in-between, was used as a timing reference for SoS. SoS was both manually annotated by two readers and assessed by an automatic annotation algorithm. The thickness values of the subcutaneous fat and muscle layers were manually read from the B-mode images. Differences between the cast and non-cast calves were calculated with a paired t test. Correlation analysis of SoS and calf perimeter was performed using Pearson''s correlation coefficient.Paired t test showed significant differences between the cast and non-cast side for both SoS (P < .01) and leg perimeter (P < .001). SoS was reduced with the number of days after cast installment (r = −0.553, P = .097). No significant differences were found for muscle layer thickness, subcutaneous fat layer thickness, mean fat echo intensity, or mean muscle echo intensity.Short-term-immobilization led to a significant reduction in SoS in the cast calf compared to the healthy calf, indicating a potential role of SoS as a biomarker in detecting immobilization-induced fatty muscular degeneration not visible on B-mode ultrasound.     

Quantification of glycoproteins by nuclear magnetic resonance associated with preclinical carotid atherosclerosis in patients with type 1 diabetes

Background and aimsGlycoproteins play a key role in inflammatory and cardiometabolic processes. Their implication in atherosclerosis in type 1 diabetes (T1D) is unknown. We assessed the relationships between classic inflammatory markers, glycoproteins measured by nuclear magnetic resonance (¹H-NMR), and preclinical atherosclerosis in these patients.Methods and resultsWe selected patients with T1D, without cardiovascular disease (CVD), with: age ≥40 years, nephropathy (micro/macroalbuminuria), or ≥10 years of evolution with another risk factor. The presence of plaque (intima-media thickness >1.5 mm) was determined by ultrasonography. Concentrations of high-sensitive C-reactive protein (hsCRP), circulating leukocytes (classical inflammation markers) and ¹H-NMR-glycoproteins (GlycA, GlycB, GlycF, and the height/width [H/W] ratios of GlycA and GlycB) were determined. We included 189 patients (58% male, age 47.0 [40.7–55.2] years). Thirty-five percent presented plaques (22%, ≥2 plaques). There was no association between hsCRP or leukocytes and atherosclerosis. However, in age- and sex-adjusted models, GlycA, GlycF, and the H/W ratios of GlycA and GlycB gradually increased with the number of plaques (0, 1, ≥2 plaques) only in patients without statins (p < 0.05), with no association in patients receiving this drug (p for interaction <0.05; in ≥2 plaques). Finally, in models adjusted for other classical and T1D-specific risk factors, GlycA and GlycB H/W ratios remained associated with carotid plaque (OR 1.39 [1.12–1.90] and OR 6.89 [1.85–25.62], respectively).ConclusionIn T1D individuals without lipid-lowering treatment, ¹H-NMR-glycoproteins were independently associated with the presence and amount of carotid atherosclerosis, unlike other classical inflammatory markers. Further studies are needed to ascertain their utility as CVD biomarkers.     

Glycaemic profile characteristics and frequency of impaired awareness of hypoglycaemia in subjects with T1D and repeated hypoglycaemic events

The aim of our study was to evaluate the frequency of hypoglycaemia unawareness and the continuous glucose profile in a group of subjects with Type 1 diabetes (T1D) with repeated non-severe/severe hypoglycaemia. Twenty patients (aged 35.2 ± 7.6 years, duration of disease 16.4 ± 6.4 years) were included. Hypoglycaemia awareness was evaluated using questionnaires and after an acute-induced hypoglycaemia. Glucose profile was studied using 72-h continuous glucose monitoring (CGM). All subjects were classified as having hypoglycaemia unawareness by questionnaires. Four patients displayed a “normal” signs/symptoms response to hypoglycaemia. The CGM revealed 18% of the measurements <70 mg/dl and this percentage was correlated with questionnaire score (r = 0.55, P < 0.035) and with the increase in the percentage of signs/symptoms during the induced hypoglycaemia (r = −0.57, P < 0.015). In patients exhibiting an “abnormal” response during hypoglycaemia, CGM values <70 mg/dl was higher (22.6 ± 8.4%) than in those with a “normal” response (10.2 ± 9.0%; P < 0.028). Summarising, in subjects with T1D and repeated hypoglycaemia the frequency of impaired awareness is substantially common. Its presence is related to a high proportion of ambulatory glycaemic profile below the desirable range.     

Comparison of ultrasound speed-of-sound of the lower extremity and lumbar muscle assessed with computed tomography for muscle loss assessment

To compare the speed of propagation of ultrasound (US) waves (SoS) of the lower leg with the clinical reference standard computed tomography (CT) at the level of lumbar vertebra 3 (L3) for muscle loss assessment. Both calf muscles of 50 patients scheduled for an abdominal CT were prospectively examined with ultrasound. A plexiglas-reflector located on the opposite side of the probe with the calf in between was used as a timing reference for SoS (m/s). CT measurements were performed at the level of L3 and included area (cm²) and attenuation (HU) of the psoas muscle, abdominal muscles, subcutaneous fat, visceral fat and abdominal area. Correlations between SoS, body mass index (BMI) and CT were determined using Pearson''s correlation coefficient. Based on reported CT sarcopenia threshold values, receiver operating characteristic (ROC) analysis was performed for SoS. Inter-examiner agreement was assessed with the median difference, inter-quartile range (IQR) and intraclass correlation coefficients. SoS of the calf correlated moderately with abdominal muscle attenuation (r = 0.48; P < .001), psoas muscle attenuation (r = 0.40; P < .01), abdominal area (r = −0.44; P < .01) and weakly with subcutaneous fat area (r = −0.37; P < .01). BMI correlated weakly with psoas attenuation (r = −0.28; P < .05) and non-significantly with abdominal muscle attenuation. Normalization with abdominal area resulted in moderate correlations with abdominal muscle area for SoS (r = 0.43; P < .01) and BMI (r = −0.46; P < .001). Based on sarcopenia threshold values for skeletal muscle attenuation (SMRA), area under curve (AUC) for SoS was 0.724. Median difference between both examiners was −3.4 m/s with IQR = 15.1 m/s and intraclass correlation coefficient = 0.794. SoS measurements of the calf are moderately accurate based on CT sarcopenia threshold values, thus showing potential for muscle loss quantification.     

Identifying Radiological Needs of Referring Clinicians

To provide prospective information about quality- and satisfaction-related product features in radiology, a customer-centered approach for acquiring clinicians' requirements and their prioritizations is essential. We introduced the Kano model for the first time in radiology to obtain such information. A Kano questionnaire, consisting of pairs of questions regarding 13 clinician requirements related to computed tomography (CT), magnetic resonance imaging (MRI) access and report turnaround time (RTT), was developed and administered. Each requirement was assigned a Kano category, and its satisfaction and dissatisfaction coefficients were calculated and presented in a Kano diagram. The data were stratified based on different clinics and on staff and resident clinicians. The time interval was evaluated between the completion of an examination and the first attempt to access the report by a clinician. Consultation for modality selection and scheduling and access to CT within 24 h and RTT within 8 to 24 h were considered as must-be requirements. Access to CT within 4 h and within 8 h, access to MRI within 8 h and within 24 h, and access to RTT within 4 h were one-dimensional requirements. The extension of operation time for CT or MRI, as well as MRI access within 4 h, was considered attractive. Eight out of nine clinics considered RTT within 8 h as a must-be requirement. There were differences in responses both among different clinics and between staff and resident clinicians. Access attempts to reports by clinicians in the first 4 h after the examination completion accounted for 65 % of CTs and 49 % of MRIs.     

Characterization of the non-functional Fas ligand of gld mice

Mice homozygous for either the gld or Ipr mutation develop autoimmunediseases and progressive lymphadenopathy. The Ipr mutation Ischaracterized by the absence of unctional Fas, whereas gld miceexhibit an inactive FasL due to a point mutation proximal tothe extracellular C-terminus. The structural repercussions ofthis amino acid substitution remain unknown. Here we reportthat FasL Is expressed at similar levels on the surface of activatedT lymphocytes from gld and wild-type mice. Using a polyclonalanti-FasL antibody, Indistinguishable amounts of a 40 kDa proteinare detected In both gld and wild-type splenocytes. The molecularmodel of FasL, based on the known structure of TNF-, predictsthat the PheLeu gld mutation is located at the protomer interfacewhich Is close to the FasR Interaction site. We conclude thatthe gld mutation allows normal FasL biosynthesis, surface expressionand ollgomerlzatlon, but induces structural alterations to theFas binding region leading to the phenotypic changes observed.     

The TRPV1 receptor: target of toxicants and therapeutics.

Understanding the structural and functional complexities of the transient receptor potential vanilloid receptor (TRPV1) is essential to the therapeutic modulation of inflammation and pain. Because of its central role in initiating inflammatory processes and integrating painful stimuli, there is an understandable interest in its pharmacological manipulation (sensitization/desensitization). The present Highlight entitled "TRPV1 antagonists elevate cell surface populations of receptor protein and exacerbate TRPV1 mediated toxicities in human lung epithelial cells" describes how exposure to various antagonists produces TRPV1 sensitization and proposes a possible mechanistic explanation to that sensitization.     

Changes in infant sleep problems after a family-centered intervention

PURPOSE: To describe a family-centered intervention for sleep disturbed infants and its effect on the infants' sleep pattern. METHODS: The sample consisted of 33 infants (6-23 month of age) hospitalized because of sleep problems in The City Hospital in Reykjavik, Iceland, and 33 mothers and 30 fathers. Infants' sleep patterns were assessed by a 1-week diary and by interviews with parents before hospital admission, 1 week and 2 months after discharge. The intervention was based on correction of day-sleep rhythm, support of self-comforting capabilities of the infant, and education of parents in regard to the infants' characteristics and developmental status. Changes in day naps and infant irritability over daytime also improved significantly. FINDINGS: Night sleep improved significantly 1 week after discharge and even more so 2 months later. CONCLUSIONS: Offering a family-centered intervention improves infants' sleep patterns up to 2 months after discharge.