Secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation in multiple myeloma

In the course of multiple myeloma, patients may develop a M-protein band different from the original: secondary monoclonal gammopathy of undetermined significance. In this retrospective single center analysis, we describe the occurrence and clinical relevance of secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation (post-transplant monoclonal gammopathy of undetermined significance). A total of 138 patients who had undergone 139 allogeneic stem cell transplantations (39.6% in the upfront setting and 60.4% for relapsed multiple myeloma) were included in the study. Sixty-seven (48.2%) patients developed secondary monoclonal gammopathy of undetermined significance, after a median latency of 6.9 months. Secondary monoclonal gammopathy of undetermined significance occurred more often in patients who achieved at least very good partial response after allogeneic stem cell transplantation, compared to partial response or less (54.8% vs. 26.5%; P=0.005). The incidence was also higher in the upfront setting as compared to relapsed disease, or with a sibling donor compared to matched unrelated donor, but less often after T-cell depletion. Importantly, development of post-transplant monoclonal gammopathy of undetermined significance as a time-dependent variable independently predicted for superior progression-free and overall survival (median progression-free survival 37.5 vs. 6.3 months, P<0.001; median overall survival 115.3 vs. 31.0 months, P=0.004). Clinicians should be aware of the benign nature of this phenomenon, and secondary monoclonal gammopathy of undetermined significance should not be confused with relapse or progression of disease. (Trial registered with trialregister.nl; HOVON 108: NTR 2958.)     

Comparing algorithms for deriving psychosis diagnoses from longitudinal administrative clinical records

Purpose

Registers derived from administrative datasets are valuable tools in psychosis research, but diagnostic accuracy can be problematic. We sought to compare the relative performance of four methods for assigning a single diagnosis from longitudinal administrative clinical records when compared with reference diagnoses.

Methods

Diagnoses recorded in inpatient and community mental health records were compared to research diagnoses of psychotic disorders obtained from semi-structured clinical interviews for 289 persons. Diagnoses were derived from administrative datasets using four algorithms; ‘At least one’ diagnosis, ‘Last’ or most recent diagnosis, ‘Modal’ or most frequently occurring diagnosis, and ‘Hierarchy’ in which a diagnostic hierarchy was applied. Agreements between algorithm-based and reference diagnoses for overall presence/absence of psychosis and for specific diagnoses of schizophrenia, schizoaffective disorder, and affective psychosis were examined using estimated prevalence rates, overall agreement, ROC analysis, and kappa statistics.

Results

For the presence/absence of psychosis, the most sensitive and least specific algorithm (‘At least one’ diagnosis) performed best. For schizophrenia, ‘Modal’ and ‘Last’ diagnoses had greatest agreement with reference diagnosis. For affective psychosis, ‘Hierarchy’ diagnosis performed best. Agreement between clinical and reference diagnoses was no better than chance for diagnoses of schizoaffective disorder. Overall agreement between administrative and reference diagnoses was modest, but may have been limited by the use of participants who had been screened for likely psychosis prior to assessment.

Conclusion

The choice of algorithm for extracting a psychosis diagnosis from administrative datasets may have a substantial impact on the accuracy of the diagnoses derived. An ‘Any diagnosis’ algorithm provides a sensitive measure for the presence of any psychosis, while ‘Last diagnosis’ is more accurate for specific diagnosis of schizophrenia and a hierarchical diagnosis is more accurate for affective psychosis.     

Radical Scavenging Evaluation of Green Tea Extracts

The free radical scavenging activity of Thea sinensis leaf extract was evaluated with a chemical test involving diphenylpicrylhydrazyl radical (DPPH). The hot aqueous green tea extract demonstrated antiradical activity comparable with rutin and vitamin E used as a standard. Liquid–liquid fractionation monitored by scavenging radical bioassay followed by preparative high pressure liquid chromatography led to catechin derivatives. The antiradical activity of the main component of tea leaves was identified as epigallocatechin gallate the major component demonstrating activity.     

Wound healing with “spray‐on” autologous skin grafting (ReCell) compared with standard care in patients with large diabetes‐related foot wounds: an open‐label randomised controlled trial

There is an urgent need for interventions that improve healing time, prevent amputations and recurrent ulceration in patients with diabetes‐related foot wounds. In this randomised, open‐label trial, participants were randomised to receive an application of non‐cultured autologous skin cells (“spray‐on” skin; ReCell) or standard care interventions for large (>6 cm²), adequately vascularised wounds. The primary outcome was complete healing at 6 months, determined by assessors blinded to the intervention. Forty‐nine eligible foot wounds in 45 participants were randomised. An evaluable primary outcome was available for all wounds. The median (interquartile range) wound area at baseline was 11.4 (8.8‐17.6) cm². A total of 32 (65.3%) index wounds were completely healed at 6 months, including 16 of 24 (66.7%) in the spray‐on skin group and 16 of 25 (64.0%) in the standard care group (unadjusted OR [95% CI]: 1.13 (0.35‐3.65), P = .845). Lower body mass index (P = .002) and non‐plantar wounds (P = .009) were the only patient‐ or wound‐related factors associated with complete healing at 6 months. Spray‐on skin resulted in high rates of complete healing at 6 months in patients with large diabetes‐related foot wounds, but was not significantly better than standard care (Australian New Zealand Clinical Trials Registry: ACTRN12618000511235).     

RSV-induced bronchiolitis but not upper respiratory tract infection is accompanied by an increased nasal IL-18 response

The aim of this study was to investigate potential differences in the local nasal immune response between bronchiolitis and upper respiratory tract infection induced by respiratory syncytial virus (RSV). Nasal brush samples were obtained from 14 infants with RSV bronchiolitis and from 8 infants with RSV upper respiratory tract infection. The samples were taken during infection (acute phase) and 2-4 weeks later (convalescent phase). Cytospin preparations were stained immunohistochemically for T cells, macrophages, and eosinophils. Staining also took place for intercellular adhesion molecule-1 (ICAM-1), T-helper 1 (Th1)-like (interleukin-12 [IL-12], interferon-gamma [IFN-gamma]), Th2-like (IL-4, IL-10), and proinflammatory cytokines (IL-6, IL-8, IL-18). During both RSV-induced bronchiolitis and upper respiratory tract infection, cellular inflammation was observed. This was characterised by an increase in the numbers of nasal macrophages, which tended to be higher in bronchiolitis than in upper respiratory tract infection. Numbers of T lymphocytes and ICAM-1 positive cells increased during both bronchiolitis and upper respiratory tract infection. There were no differences between numbers in the groups. Interestingly, a distinct nasal proinflammatory cytokine response was observed in RSV-induced bronchiolitis. This is characterised by an increase in the number of IL-18 positive cells. This increase is specific for bronchiolitis, as a similar increase could not be detected in RSV-induced upper respiratory tract infection. Numbers of IL-6 and IL-12 positive cells were higher in both bronchiolitis and upper respiratory tract infection, and there were no differences between the groups. By contrast, the number of IL-8, IFN-gamma, IL-4, and IL-10-positive cells remained constant. In conclusion, clear differences were found in nasal immune responses of children with RSV-induced upper respiratory tract infection or bronchiolitis. The induction of a strong IL-18 response was typical for bronchiolitis, as this could not be observed in RSV-induced upper respiratory tract infection, and could explain the eosinophilia that is observed frequently during bronchiolitis.     

The hemodynamics of oddball processing during single-tone and two-tone target detection tasks

Event-related potential (ERP) studies have shown that the neural systems engaged during performance of oddball tasks are sensitive to contextual manipulations, such as the number of stimulus classes. Some ERP components (i.e., N1) are modulated by the number of stimulus types, while others (i.e., P3) are not greatly affected. However, little is known about how these contextual manipulations affect the hemodynamics underlying oddball processing. The purpose of this study was to examine the hemodynamic correlates of target stimulus processing in single-tone (targets alone) and two-tone (targets and standard tones) auditory oddball tasks. The primary hypothesis was that processing of salient stimuli in both contextual conditions would engage the same spatially distributed cortical and subcortical networks observed in previous oddball fMRI studies. Results were consistent with this hypothesis and suggest that the brain engages many potentially useful brain regions during salient stimulus processing despite the low probability that said regions are necessary for task performance, which likely reflects a form of “adaptive reflexive processing”. Results were also consistent with ERP data that shows that the N1 is larger for single-tone tasks by showing greater amplitude of hemodynamic response for single-tone targets, relative to two-tone targets, in bilateral temporal cortex and bilateral inferior lateral frontal cortex. The results are discussed as they relate to the understanding of neurocognitive function pertaining to contextual manipulations in general, and orienting processes in particular.     

Using distraction forces to drive an autodistractor during limb lengthening

Distraction osteogenesis can result in high forces developing in the limb. To determine and control the distraction forces (DF), a motorized distractor driven by feedback from DF was developed and used to lengthen the tibiae of 6 sheep undergoing distraction osteogenesis. The forces were measured continually, and, in 4 of the sheep, a force threshold was set, above which an increase in rate was initiated. The rate kept increasing to a set limit if forces remained above the threshold; otherwise, the rate was decreased. Radiographs were acquired biweekly, and muscle samples were analyzed from both the operated and contralateral limbs upon termination of the experiment. Results demonstrated a drop in DF associated with increased lengthening rate, attributed to separation of the callus as indicated by radiography. Histological evidence of muscle damage generally correlated with higher DF levels. There was a significant decrease in muscle fiber diameter in lengthened relative to contralateral limbs. Collectively, the results demonstrated the use of a force-driven distraction system and support the need for considering force data in regulating distraction rates to achieve optimal clinical outcomes.     

Mallory-Weiss tear following cardiac surgery: transoesophageal echoprobe or nasogastric tube?

A case of fatal upper gastrointestinal bleeding from a Mallory–Weisstear after transoesophageal echocardiography during cardiacsurgery is reported. After the echocardiographic examination,which is considered a safe procedure, a nasogastric tube wasinserted which immediately revealed bright red blood. Eventuallythe patient lost 9 litres of blood. The role of the echoprobeand the nasogastric tube in causing the Mallory–Weisstear is discussed. Although this case is not conclusive aboutthe mechanism of oesophageal damage, it is suggested that thesafety recommendations for transoesophageal echocardiographyalso apply for instrumentation of the oesophagus with a nasogastrictube after the transoesophageal echocardiographic examination.