Overuse of organ biopsies in immunoglobulin light chain amyloidosis (AL): the consequence of failure of early recognition

Introduction: The diagnosis of amyloidosis requires histological confirmation of Congo-red (CR) deposits. The tissue source is preferably fat aspiration and/or bone marrow (BM) biopsy, but at times organ biopsy is required.

Methods: We studied 612 patients with systemic immunoglobulin light chain amyloidosis to characterise the tissues used to establish the diagnosis.

Results: The median number of tissue samples was 3. About 95% of BM biopsies were stained for CR, while 79% of patients had fat aspiration CR-stained. CR stain sensitivity was 69% in BM, 75% in fat aspiration and 89% for both sources combined. In comparison, CR sensitivity was 97–100% for heart, renal and liver biopsies. About 42% of patients with renal involvement, 21% of patients with liver involvement and 13% of patients with heart involvement underwent organ biopsy, when a less invasive biopsy would have established the diagnosis. Predictors for the requirement for organ biopsy were male sex, limited organ involvement and lack of fat aspiration.

Discussion: Fat aspiration is underutilised for histologic confirmation of amyloidosis. A high rate of organ biopsies represents a failure to recognise the disease. Early awareness of amyloidosis in patients with organ dysfunction may lead to more judicious use of organ biopsies in this disease.

• Key messages

• Fat pad aspiration is underutilised to establish the diagnosis of amyloidosis.

• Bone marrow and fat pad aspiration obviates the need for invasive biopsies.

• The excessive use of organ biopsy in AL amyloidosis reflects failure to recognise the disease early in its course.

     

Prevalence of chronic obstructive pulmonary disease and chronic bronchitis in eight countries: a systematic review and meta-analysis

ObjectiveTo estimate the prevalence of chronic obstructive pulmonary disease (COPD) and chronic bronchitis in eight countries in South Asia through a systematic review and meta-analysis.MethodsWe searched MEDLINE® Complete, Web of Science, Embase®, Scopus, CINAHL and reference lists of screened studies for research on the prevalence of COPD and chronic bronchitis in South Asian countries published between January 1990 and February 2021. We used standardized diagnostic criteria for definitions of COPD and chronic bronchitis. Two reviewers undertook study screening, full-text review, quality appraisal and data extraction.FindingsOf 1529 studies retrieved, 43 met the inclusion criteria: 32 provided data from India; four from Bangladesh; three from Nepal; two from Pakistan; and two from both India and Sri Lanka. Twenty-six studies used standardized diagnostic definitions and 19 were included in the meta-analysis. The estimated pooled prevalence of COPD was 11.1% (95% confidence interval, CI: 7.4–14.8%), using the Global Initiative for Chronic Obstructive Lung Disease fixed criteria and 8.0% (95% CI: 5.6–10.4%) using the lower limit of normal criteria. The prevalence of COPD was highest in north India (19.4%) and Bangladesh (13.5%) and in men. The estimated pooled prevalence of chronic bronchitis was 5.0% (95% CI: 4.1–6.0%) in India and 3.6% (95% CI: 3.1–4.0%) in Pakistan.ConclusionIncluded countries have a high prevalence of COPD although it varied by geographical area and study characteristics. Future research in South Asia should use standardized diagnostic criteria to examine the contribution of setting-specific risk factors to inform prevention and control strategies.     

The Effect of Water Absorption on Acrylic Surface Properties

PURPOSE: The aim of the present study was to determine whether an increased water content during thermal cycling of hot water-treated acrylic was associated with a reduction in surface hardness and an increased opacity or whitening of the surface. MATERIALS AND METHODS: Ten acrylic samples were treated with 30 soak cycles (cycle duration, 24 hours), using warm water (40 degrees C) and an alkaline peroxide tablet (Efferdent control group); a further ten samples were treated with boiling water (100 degrees C) and one Efferdent tablet (experimental group). Indentation hardness of the acrylic specimens was measured prior to and immediately following the completion of the warm and hot water treatments, using an automated micro-indentation system. The hydrated acrylic specimens were then allowed to air dry at room temperature (20 degrees C) and were weighed weekly until they had obtained a constant dry weight. The loss in weight of the acrylic specimens represented the maximum water absorption. RESULTS: The hot water-treated specimens were much whiter than the warm water-treated specimens. The mean reduction in hardness (H(IT)) of the acrylic specimens following the treatment with hot water and alkaline peroxide tablet was 12.9%. Treatment with warm water and alkaline peroxide resulted in a slight increase in mean hardness (2.63%). There was a significant correlation between the water content of the acrylic specimens after treatment and the percentage of change in indentation hardness (r= 0.495, p= 0.026). CONCLUSIONS: The hot water treatment of the acrylic was associated with a significant reduction in hardness. We attribute the whitening and reduction in the hardness of the hot water-treated specimens to absorption of water and a disruption of the acrylic surface structure.     

Thermal contribution of compact bone to intervening tissue-like media exposed to planar ultrasound

The presence of bone in the ultrasound beam path raises concerns, both in diagnostic and therapeutic applications, because significant temperature elevations may be induced at nearby soft tissue-bone interfaces due the facts that ultrasound is (i) highly absorbed in bone and (ii) reflected at soft tissue-bone interfaces in various degrees depending on angle of incidence. Consequently, in ultrasonic thermal therapy, the presence of bone in the ultrasound beam path is considered a major disadvantage and it is usually avoided. However, based on clinical experience and previous theoretical studies, we hypothesized that the presence of bone in superficial unfocused ultrasound hyperthermia can actually be exploited to induce more uniform and enhanced (with respect to the no-bone situation) temperature distributions in superficial target volumes. In particular, we hypothesize that the presence of underlying bone in superficial target volume enhances temperature elevation not only by additional direct power deposition from acoustic reflection, but also from thermal diffusion from the underlying bone. Here we report laboratory results that corroborate previous computational studies and strengthen the above-stated hypothesis. Three different temperature measurement techniques, namely, thermometric (using fibre-optic temperature probes), thermographic (using an infrared camera) and magnetic resonance imaging (using proton resonance frequency shifts), were used in high-power short-exposure, and in low-power extended-exposure, experiments using a 19 mm diameter planar transducer operating at 1.0 and 3.3 MHz (frequencies of clinical relevance). The measurements were performed on three technique-specific phantoms (with and without bone inclusions) and experimental set-ups that resembled possible superficial ultrasound hyperthermia clinical situations. Results from all three techniques were in general agreement and clearly showed that significantly higher heating rates (greater than fourfold) were induced in soft tissue-like phantom materials adjacent (within approximately 5 mm) to a bovine bone as compared to similar experiments without bone inclusions. For low-power long-exposure experiments, where thermal conduction effects are significant, the thermal impact of bone reached at distances > 10 mm from the bone surface (upstream of the bone). Therefore, we hypothesize that underlying bone exposed to planar ultrasound hyperthermia creates a high-temperature thermal boundary at depth that compensates for beam attenuation, thus producing more uniform temperature distribution in the intervening tissue layers. With appropriate technology, this finding may lead to improved thermal doses in superficial treatment sites such as the chest wall and the head/neck.     

High epidermal growth factor receptor amplification rate but low mutation frequency in Middle East lung cancer population

Epidermal growth factor receptor (EGFR) exon 18-21 mutations were shown to be highly predictive of response to gefitinib (Iressa) therapy in lung cancer. Studies on Western and Japanese lung cancers have indicated substantial differences in the EGFR mutation frequency between these populations. To investigate the prevalence of EGFR in another distinct ethnic group, EGFR alterations were studied in 47 consecutive non small cell lung cancers from Saudi Arabia by immunohistochemistry, fluorescence in situ hybridization, and DNA sequencing. Detectable EGFR expression was seen in 69.8% of 43 interpretable cancers. Epidermal growth factor receptor amplification, present in 15.3% of 39 analyzable cancers, was strongly associated with high levels of EGFR expression (P = .0047). Only 1 exon 18-21 mutation was seen among 34 lung cancers that could be successfully sequenced. It is concluded that EGFR exon 18-21 mutations are rare in Middle East patients with lung cancer and occur in a similar range as in Western patients. The remarkable high rate of EGFR gene amplifications could potentially facilitate studies on the predictive role of gene copy number changes for response to anti-EGFR therapies in Middle East patient sets.     

High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia.

Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation. Reduced or absent FHIT expression was found in 75 of 114 diffuse large B-cell lymphoma (66%), but was unrelated to clinical tumor stage or patient prognosis. FHIT promotor hypermethylation was observed in 29 of 93 (23%) interpretable diffuse large B-cell lymphoma. Hypermethylation was not significantly correlated to protein expression loss, which could be explained by competing mechanisms for FHIT inactivation in a substantial fraction of non FHIT hypermethylated diffuse large B-cell lymphoma. Hypermethylation was significantly associated with poor prognosis of diffuse large B-cell lymphoma patients and predominantly seen in nongerminal center diffuse large B-cell lymphoma (27%), but less frequent (13%) in germinal center diffuse large B-cell lymphoma. In summary, these data suggest that promotor hypermethylation is responsible for reduced FHIT expression in a substantial subset of diffuse large B-cell lymphoma, which is primarily composed of nongerminal center subtype with poor patient prognosis.     

Management of adenovirus infection in patients after haematopoietic stem cell transplantation: State‐of‐the‐art and real‐life current approach

The important insights gained over the past years in diagnosis and treatment of invasive adenoviral infections provide new paradigms for the monitoring and clinical management of these life‐threatening complications. A meeting was held to discuss and subsequently disseminate the current advances in our understanding of the aetiology/pathogenesis and future treatment options facilitating effective control or prevention of adenovirus‐related diseases in the allogeneic haematopoietic stem cell transplant setting. Invited experts in the field discussed recent progress with leading members of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation at the “State‐of‐the‐art” Meeting in Poznan, Poland, in October 2017. In this review article, the panel of experts presents a concise summary of the current evidence based on published data from the last 15 years and on recent achievements resulting from real‐life practice. The present position statement reflects an expert opinion on current approaches to clinical management of adenovirus infections in patients undergoing allogeneic haematopoietic stem cell transplant and provides graded recommendations of the panel for diagnostic approaches and preemptive therapy reflecting the present state of knowledge.     

A Study of Diphenylfumaronitrile and Furan‐Substituted Diketopyrrolopyrrole Alternating Copolymer and Its Thin‐Film Transistors

A fused aromatic furan‐substituted diketopyrrolopyrrole and novel diphenylfumaronitrile conjugated building blocks are used for the synthesis of an alternating copolymer ( DPFN‐DPPF ) via Suzuki polycondensation. In this paper, the first attempt to use the diphenylfumaro­nitrile building block for the synthesis of conjugated polymer is described. The number‐average and weight‐average ­molecular weights calculated for DPFN‐DPPF are 20 661 and 66 346 g mol^?1, respectively. The optical bandgap calculated for DPFN‐DPPF is 1.53 eV whereas the highest occupied molecular orbital (HOMO) value calculated by photoelectron spectroscopy in air (PESA) is 5.50 eV. The calculated HOMO value is lower, which is suitable for stable organic electronic devices. DPFN‐DPPF polymer is used as an active layer in bottom‐contact bottom‐gate organic thin‐film transistor devices and the thin film exhibits a hole mobility of 0.20 cm² V^?1 s^?1 in air.

     

Prognostic significance of alterations in KRAS isoforms KRAS‐4A/4B and KRAS mutations in colorectal carcinoma

Somatic KRAS mutation is an early well‐known event in colorectal carcinogenesis but a complete understanding of RAS function and dysfunction in colorectal cancer is still to come. Our aim was to study the incidence of KRAS mutation; KRAS splice variants: KRAS4A and KRAS4B; and their relationships with various clinico‐pathological characteristics in colorectal cancer (CRC).In this study, 285 CRC cases were analysed for KRAS mutation by direct DNA sequencing followed by immunohistochemical analysis after validation with real‐time PCR assay, to study the protein expression of KRAS4A and ‐4B isoforms. KRAS gene mutations were seen in 80/285 CRCs (28.1%) and of the mutated cases, the majority of the mutations were seen in codon 12 (81.2%) as opposed to codon 13 (18.8%). CRCs with KRAS mutations were associated with a poor overall survival (p = 0 . 0009). Furthermore, KRAS mutations at codon 12 were associated with a poor overall survival of 64.4% at 5 years compared with a 5‐year overall survival of 75.8% and 78.2% with codon 13 mutation and absence of KRAS mutations, respectively (p = 0 . 0025). KRAS4A protein expression was predominantly seen in the cytoplasm, while KRAS4B protein was nuclear. KRAS4A overexpression was significantly associated with left colon, histology subtype of adenocarcinoma, p27kip1, and cleaved caspase3 expression. Interestingly, KRAS4A overexpression was associated with a better overall survival (p = 0 . 0053). On the other hand, KRAS4B overexpression (33.2%) was significantly associated with larger tumour size (p = 0 . 0234) and inversely correlated with p27kip1 protein (p = 0 . 0159). Both KRAS mutation and KRAS4A were independent prognostic markers in a multivariate analysis with age, gender, stage, differentiation, and MSI status. Our results highlight the differential role of KRAS isoforms in CRC, their utility as a prognostic biomarker, and underline the importance of KRAS alterations as a potential therapeutic target for CRC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.