Vector autoregression: useful in rare diseases? — Predicting organ response patterns in a rare case of secondary AA amyloidosis

Background Statistical analyses of clinical data are a cornerstone in understanding pathomechanisms of disorders. In rare disorders, cross-sectional datasets of sufficient size are usually not available. Taking AA amyloidosis as an example of a life-threatening rare disorder resulting from of uncontrolled chronic inflammation, we propose techniques from time series analysis to predict organ response to treatment. The advantage of time-series analysis is that it solely relies on temporal variation and therefore allows analyzing organ response to treatment even when the cross-sectional dimension is small. Methods The joint temporal interdependence of inflammatory activity and organ response was modelled multivariately using vector autoregression (VAR) based on a unique 4.5 year spanning data set of routine laboratory, imaging data (e.g., 18F-Florbetaben-PET/CT) and functional investigations of a 68-year-old patient with multi-organ involvement of AA amyloidosis due to ongoing inflammatory activity of a malignant paraganglioma in stable disease for >20 years and excellent response to tocilizumab). Results VAR analysis showed that alterations in inflammatory activity forecasted alkaline phosphatase (AP). AP levels, but not inflammatory activity at the previous measurement time point predicted proteinuria. Conclusion We demonstrate the feasibility and value of time series analysis for obtaining clinically reliable information when the rarity of a disease prevents conventional prognostic modelling approaches. We illustrate the comparative utility of blood, functional and imaging markers to monitor the development and regression of AA amyloidosis

Investigation of emitter homogeneity on laser doped emitters

The selective emitter formation by laser doping is a well known process to increase the efficiency of silicon solar cells [1], [2]. For the characterization of laser doped emitters, SIMS (Secondary Ion Mass Spectroscopy) and ECV (Electrochemical Capacitance Voltage Measurement) techniques are used to analyze the emitter profile [3]. It is very difficult to get acceptable result by SIMS on a textured surface, so only ECV can be used. It has been shown, that a charge carrier depth profile can be measured on a homogeneous emitter only by ECV. The use of laser doping results in a non-homogeneous emitter. We have shown that the emitter depth is not just a function of the pulse power, but in addition of the surface structure of the wafer. The texture seems responsible for a strong variability in the doping profile. It has been shown, that the ECV measurement is not applicable to characterize the emitter depth on laser doped areas, because of the microscopic inhomogeneities in the emitter on the macroscopic measurement area. The real emitter profiles are to complex to be characterized by SIMS or ECV. We have shown that the variation in the emitter profile is resulting from the texture in the laser-doped regions

Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy

Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21 mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRASwt genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations

Investigation of emitter homogeneity on laser doped emitters

The selective emitter formation by laser doping is a well known process to increase the efficiency of silicon solar cells [1], [2]. For the characterization of laser doped emitters, SIMS (Secondary Ion Mass Spectroscopy) and ECV (Electrochemical Capacitance Voltage Measurement) techniques are used to analyze the emitter profile [3]. It is very difficult to get acceptable result by SIMS on a textured surface, so only ECV can be used. It has been shown, that a charge carrier depth profile can be measured on a homogeneous emitter only by ECV. The use of laser doping results in a non-homogeneous emitter. We have shown that the emitter depth is not just a function of the pulse power, but in addition of the surface structure of the wafer. The texture seems responsible for a strong variability in the doping profile. It has been shown, that the ECV measurement is not applicable to characterize the emitter depth on laser doped areas, because of the microscopic inhomogeneities in the emitter on the macroscopic measurement area. The real emitter profiles are to complex to be characterized by SIMS or ECV. We have shown that the variation in the emitter profile is resulting from the texture in the laser-doped regions

Effect of conditioning regimen intensity on CMV infection in allogeneic hematopoietic cell transplantation.

Nonmyeloablative conditioning is less toxic and results in initial establishment of mixed hematopoietic T cell chimerism for up to half a year with prolonged presence of host T cell immunity. In this study, we examined whether this translates into differences in the risks and/or severity of cytomegalovirus (CMV) infection and disease. We analyzed data from 537 nonmyeloablative (NM-HCT) and contemporaneous 2489 myeloablative hematopoietic cell transplant (M-HCT) recipients. In CMV seropositive recipients, no difference in the overall hazards of CMV infection at any level (adjusted hazard ratio [adj. HR] 0.9, 95% confidence interval [95% CI]: 0.7-1.0, P = .14) was noted; however, NM-HCT was associated with a lower risk of high-grade CMV infection (adj. HR 0.7, 95% CI: 0.5-0.9, P = .02). CMV disease rates were similar between the groups during the first 100 days after HCT, but NM-HCT recipients had an increased risk of late CMV disease (adj. HR 2.0, 95% CI 1.2-3.4). The increased risk of late CMV disease after NM-HCT was pronounced during the earlier years of the study period, but not detectable in more recent years. Contrary to earlier reports, survival following CMV disease was not reduced after NM-HCT when compared to M-HCT recipients. These results suggest that residual host cells after NM-HCT reduce progression to higher CMV viral load in NM-HCT recipients; however, this effect does not appear to protect against serious complications of CMV. Therefore, CMV prevention strategies in NM-HCT recipients should be similar to those used in M-HCT recipients

Cardiovascular adverse events in modern myeloma therapy - incidence and risks. A review from European Myeloma Network (EMN) and Italian Society of Arterial Hypertension (SIIA)

Cardiovascular disease in myeloma patients may derive from factors unrelated to the disease (age, diabetes, dyslipidemia, obesity, prior cardiovascular diseases), related to the disease (cardiac AL-amyloidosis, hyperviscosity, high-output failure, arteriovenous shunting, anemia, renal dysfunction) and linked to antimyeloma treatment (anthracyclines, corticosteroids, alkylating agents, immunomodulatory drugs, proteasome inhibitors). An accurate knowledge of cardiovascular events, effective dose reductions, prevention and management of early and late cardiovascular side effects of chemotherapeutic agents are essential in current clinical practice. Myeloma experts are obliged to carefully balance drugs' efficacy and toxicity for each individual patient. This review summarizes current data and novel insights on cardiovascular adverse events of today's antimyeloma treatment, focusing on carfilzomib, which is the starting point to develop consensus recommendations on preventing and managing cardiovascular side effects in myeloma patients