PULMONARY FUNCTION IN RHEUMATOID ARTHRITIS TREATED WITH LOW-DOSE METHOTREXATE: A LONGITUDINAL STUDY

Lung volumes and gas exchange were investigated prospectively in 96 patients with rheumatoid arthritis selected without regard to pulmonary disorders and treated with i.m. methotrexate (MTX) injections [mean weekly dose 13.0 mg (5th-95th percentile (5-95 PC) 7.6-20.8)]. Individual changes over time during MTX treatment [mean duration 2.9 yr (5-95 PC 0.4-5.3)] were assessed by regression analyses in each individual. Forced vital capacity (FVQ remained stable in the majority of patients [mean annual change +0.8% (5-95 PC −8.1 to +14.0) of calculated normal value]. In addition, transfer factor using the indicator gas CO (TLCO) was unaltered in most patients [mean annual change − 2.1% (5-95 PC −16.2 to +11.8) of predicted value]. However, there were significant decreases in the forced expiratory volume in 1 s (FEV1) before and after inhalation of 0.2 mg salbutamol [mean annual change - 0.8% (5-;95 PC −8.4 to +3.2) and −1.3% (5-95 PC −7.8 to +3.9) of the FVC measured, respectively]. In addition, there were significant increases in alveolar-arterial Po2, gradients (P(A-a), O2) at rest and after exercise [mean annual change +1.7 mmHg (5-;95 PC −5.2 to +12.2) and +1.8 mmHg (5-95 PC −3.5 to 9.0), respectively]. Nevertheless, the amounts were small in view of the reliability of the methods applied and reflect, at least in part, the normal process of ageing. The annual change in FEV1 /FVC was negatively correlated with FEV1 /FVC at baseline (Rs = − 0.46, P < 0.001). The annual change in TL, co was also negatively correlated with TL, co at baseline (Rs = − 0.31, P = 0.028). No other risk factors for deterioration of lung volumes or gas exchange were found, including mean weekly MTX dose, age, gender, smoking, presence of rheumatoid factor and pulmonary function at baseline. We conclude that MTX has no major effect on pulmonary function in the majority of patients and that there is no evidence that patients with pre-existing pulmonary disease are at increased risk for further deterioration of lung functio

Quality of analgesic treatment in patients with advanced prostate cancer: do we do a better job now? The Swiss Group for Clinical Cancer Research (SAKK) experience

Goals of work: The aim of this study was to evaluate pain intensity and the application of the WHO guidelines for cancer pain treatment in patients with prostate cancer treated at Swiss cancer centers. Materials and methods: We analyzed a series of five multicenter phase II clinical trials which examined the palliative effect of different chemotherapies in patients with advanced hormone-refractory prostate carcinoma. Of 170 patients, 1,018 visits were evaluable for our purpose, including ratings of pain intensity by patients and prescribed analgesics. Main results: No or mild pain was indicated by patients in 36 to 55% of the visits, more than mild pain in 30 to 46%. In 21% of the visits, the WHO pain treatment criteria (treatment according to one of the three steps; oral, rectal or transdermal application of the main dose; administration on a regular schedule) were fulfilled, and the Cleeland index was positive according to all recommendations. In 6% of the visits, neither the WHO criteria were fulfilled nor was the Cleeland index positive. This indicates insufficient pain treatment not following the WHO guidelines and that the prescribed analgesics were not sufficiently potent for the rated pain intensity. Conclusions: In this selective Swiss sample, the standard of analgesic treatment is high. However, there is still scope for improvement. This cannot solely be solved by improving the knowledge of the physicians. Programs to change the patients' attitude towards cancer pain, training to improve the physicians' communication skills, and institutional changes may be promising strategie

Evidence for Magnetic Field Induced Changes of the Phase of Tunneling States: Spontaneous Echoes in (KBr)1−x_{1-x}(KCN)x_x in Magnetic Fields

Recently, it has been discovered that in contrast to expectations the low-temperature dielectric properties of some multi-component glasses depend strongly on magnetic fields. In particular, the low-frequency dielectric susceptibility and the amplitude of coherent polarization echoes show striking non-monotonic magnetic field dependencies. The low-temperature dielectric response of these materials is governed by atomic tunneling systems. We now have investigated the coherent properties of tunneling states in a crystalline host in magnetic fields up to 230$$mT. Two-pulse echo experiments have been performed on a KBr crystal containing about 7.5% CN$^-$. Like in glasses, but perhaps even more surprising in the case of a crystalline system, we observe a very strong magnetic field dependence of the echo amplitude. Moreover, for the first time we have direct evidence that magnetic fields change the phase of coherent tunneling systems in a well-defined way. We present the data and discuss the possible origin of this intriguing effect.Comment: 4 pages, 3 figures, submitted to PR

SEVERE OSTEOPOROSIS DUE TO SYSTEMIC MAST CELL DISEASE: SUCCESSFUL TREATMENT WITH INTERFERON ALPHA-2B

We describe a 33-yr-old man suffering from severe vertebral osteoporosis and urticaria pigmentosa due to systemic mast cell disease (SMCD). Because i.v. clodronate therapy could not prevent further vertebral fractures, an additional treatment with interferon alpha-2b was initiated. During 24 months of treatment, our patient had no further pain episodes, no new vertebral fractures were discovered, trabecular bone mineral density (BMD) increased significantly and urticarial symptoms improved. Nevertheless, the extent of skin lesions remained unchanged. On histological examination, a remarkable decrease of mast cells was observed in the bone marrow, but not in the skin. Five months after discontinuation of interferon alpha-2b, trabecular BMD decreased and urticarial symptoms deteriorated. These findings illustrate a beneficial effect of interferon alpha-2b on SMCD-induced osteoporosis as well as urticarial symptoms, and raise the question whether this treatment may have a diverse impact on mast cell populations in different tissue

SARS-CoV-2 / COVID-19 in patients on the Swiss national transplant waiting list.

The impact of coronavirus disease 2019 (COVID-19) on patients listed for solid organ transplantation has not been systematically investigated to date. Thus, we assessed occurrence and effects of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on patients on the Swiss national waiting list for solid organ transplantation. Patient data were retrospectively extracted from the Swiss Organ Allocation System (SOAS). From 16 March to 31 May 2020, we included all patients listed for solid organ transplantation on the Swiss national waiting list who were tested positive for SARS-CoV-2. Severity of COVID-19 was categorised as follows: stage I, mild symptoms; stage II, moderate to severe symptoms; stage III, critical symptoms; stage IV, death. We compared the incidence rate (laboratory-confirmed cases of SARS-CoV-2), the hospital admission rate (number of admissions of SARS-CoV-2-positive individuals), and the case fatality rate (number of deaths of SARS-CoV-2-positive individuals) in our study population with the general Swiss population during the study period, calculating age-adjusted standardised incidence ratios and standardised mortality ratios, with 95% confidence intervals (CIs). A total of 1439 patients were registered on the Swiss national solid organ transplantation waiting list on 31 May 31 2020. Twenty-four (1.7%) waiting list patients were reported to test positive for SARS-CoV-2 in the study period. The median age was 56 years (interquartile range 45.3&amp;ndash;65.8), and 14 (58%) were male. Of all patients tested positive for SARS-CoV-2, two patients were asymptomatic, 14 (58%) presented in COVID-19 stage I, 3 (13%) in stage II, and 5 (21%) in stage III. Eight patients (33%) were admitted to hospital, four (17%) required intensive care, and three (13%) mechanical ventilation. Twenty-two patients (92%) of all those infected recovered, but two male patients aged &amp;gt;65 years with multiple comorbidities died in hospital from respiratory failure. Comparing our study population with the general Swiss population, the age-adjusted standardised incidence ratio was 4.1 (95% CI 2.7&amp;ndash;6.0). The overall rate of SARS-CoV-2 infections in candidates awaiting solid organ transplantation was four times higher than in the Swiss general population; however, the frequency of testing likely played a role. Given the small sample size of affected patients, conclusions have to be drawn cautiously and results need verification in larger cohorts

Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG)

Background: Combination of temozolomide (TMZ) with nonpegylated interferon alfa is associated with increased efficacy in terms of response rates compared with monotherapy. A multicenter phase II study was carried out to assess the activity and toxicity of TMZ plus pegylated interferon alfa-2b (peg-IFNα-2b), hypothesizing improved efficacy due to modified pharmacokinetic properties of the novel interferon (IFN) formulation. Patients and methods: In all, 124 patients with stage IV melanoma without prior chemotherapy and no cerebral metastases were treated with 100 μg peg-IFNα-2b s.c. per week and oral TMZ 200 mg/m2 (days 1-5, every 28 days). Primary study end point was objective response, and secondary end points were overall and progression-free survival (PFS) and safety. Results: In all, 116 patients were assessable for response: 2 (1.7%) had a complete response and 19 (16.4%) a partial response (overall response rate 18.1%). Of total, 25.0% achieved disease stabilization and 56.9% progressed. Overall survival was 9.4 months; PFS was 2.8 months. Grade 3/4 thrombocytopenia occurred in 20.7% and grade 3/4 leukopenia in 23.3%. Conclusions: The efficacy of TMZ plus peg-IFNα-2b in this large phase II study is moderate and comparable to published results of the combination of TMZ with non-peg-IFN. Likewise, the safety profile of peg-IFNα-2b seems to be similar to non-peg-IFN when combined with TM

The Accuracy of Automatic Photogrammetric Techniques on Ultra-light UAV Imagery

This paper presents an affordable, fully automated and accurate mapping solutions based on ultra-light UAV imagery. Several datasets are analysed and their accuracy is estimated. We show that the accuracy highly depends on the ground resolution (flying height) of the input imagery. When chosen appropriately this mapping solution can compete with traditional mapping solutions that capture fewer high-resolution images from airplanes and that rely on highly accurate orientation and positioning sensors on board. Due to the careful integration with recent computer vision techniques, the post processing is robust and fully automatic and can deal with inaccurate position and orientation information which are typically problematic with traditional techniques

Fractal Spin Glass Properties of Low Energy Configurations in the Frenkel-Kontorova chain

We study numerically and analytically the classical one-dimensional Frenkel-Kontorova chain in the regime of pinned phase characterized by phonon gap. Our results show the existence of exponentially many static equilibrium configurations which are exponentially close to the energy of the ground state. The energies of these configurations form a fractal quasi-degenerate band structure which is described on the basis of elementary excitations. Contrary to the ground state, the configurations inside these bands are disordered.Comment: revtex, 9 pages, 9 figure

Heterogeneity of the Relative Benefits of TICI 2c/3 over TICI 2b50/2b67 : Are there Patients who are less Likely to Benefit?

PURPOSE Incomplete reperfusion after mechanical thrombectomy (MT) is associated with a poor outcome. Rescue therapy would potentially benefit some patients with an expanded treatment in cerebral ischemia score (eTICI) 2b50/2b67 reperfusion but also harbors increased risks. The relative benefits of eTICI 2c/3 over eTICI 2b50/67 in clinically important subpopulations were analyzed. METHODS Retrospective analysis of our institutional database for all patients with occlusion of the intracranial internal carotid artery (ICA) or the M1/M2 segment undergoing MT and final reperfusion of ≥eTICI 2b50 (903 patients). The heterogeneity in subgroups of different time metrics, age, National Institutes of Health Stroke Scale (NIHSS), number of retrieval attempts, Alberta Stroke Programme Early CT Score (ASPECTS) and site of occlusion using interaction terms (pi) was analyzed. RESULTS The presence of eTICI 2c/3 was associated with better outcomes in most subgroups. Time metrics showed no interaction of eTICI 2c/3 over eTICI 2b50/2b67 and clinical outcomes (onset to reperfusion pi = 0.77, puncture to reperfusion pi = 0.65, onset to puncture pi = 0.63). An eTICI 2c/3 had less consistent association with mRS ≤2 in older patients (>82 years, pi = 0.038) and patients with either lower NIHSS (≤9) or very high NIHSS (>19, pi = 0.01). Regarding occlusion sites, the beneficial effect of eTICI 2c/3 was absent for occlusions in the M2 segments (aOR 0.73, 95% confidence interval [CI] 0.33-1.59, pi = 0.018). CONCLUSION Beneficial effect of eTICI 2c/3 over eTICI 2b50/2b67 only decreased in older patients, M2-occlusions and patients with either low or very high NIHSS. Improving eTICI 2b50/2b67 to eTICI 2c/3 in those subgroups may be more often futile

Quantum phase transition in the Frenkel-Kontorova chain: from pinned instanton glass to sliding phonon gas

We study analytically and numerically the one-dimensional quantum Frenkel-Kontorova chain in the regime when the classical model is located in the pinned phase characterized by the gaped phonon excitations and devil's staircase. By extensive quantum Monte Carlo simulations we show that for the effective Planck constant $\hbar$ smaller than the critical value $\hbar_c$ the quantum chain is in the pinned instanton glass phase. In this phase the elementary excitations have two branches: phonons, separated from zero energy by a finite gap, and instantons which have an exponentially small excitation energy. At $\hbar=\hbar_c$ the quantum phase transition takes place and for $\hbar>\hbar_c$ the pinned instanton glass is transformed into the sliding phonon gas with gapless phonon excitations. This transition is accompanied by the divergence of the spatial correlation length and appearence of sliding modes at $\hbar>\hbar_c$.Comment: revtex 16 pages, 18 figure