Asthma caused by potassium aluminium tetrafluoride: a case series

The objective of this study is to describe a case-series of potassium aluminium tetrafluoride (KAlF₄)-induced occupational asthma (OA) and/or occupational rhinitis (OR). The study involves five patients from a heat-exchanger production line who were examined (including specific inhalation challenge tests) for suspected OA and/or OR caused by a flux containing almost 100% KAlF₄ − with fluorides’ workplace air concentrations ranging between 1.7 and 2.8 mg/m³. No subject had a previous history of asthma. All five patients had a positive specific challenge test (three patients were diagnosed with OA alone, one with OR and one with both OR and OA). At the follow-up visit, after three years on average, all patients needed permanent corticosteroid therapy (four topical, one oral). After elimination from the exposure, only one of the observed subjects gave an indication of an improvement, two subjects stabilized and two worsened. Our case series focuses on the correlation between patients’ exposure to fluorides in air-conditioner production and the subsequent occurrence of OR/OA. Currently, it is uncertain whether these OR/OA were caused by hypersensitivity or irritation.     

Increase in Skin Autofluorescence and Release of Heart‐Type Fatty Acid Binding Protein in Plasma Predicts Mortality of Hemodialysis Patients

Advanced glycation end‐products (AGEs) are uremic toxins that accumulate progressively in hemodialysis (HD) patients. The aim of this study was to assess the 1‐year increase in skin autofluorescence (ΔAF), a measure of AGEs accumulation and plasma markers, as predictors of mortality in HD patients. One hundred sixty‐nine HD patients were enrolled in this study. Skin autofluorescence was measured twice, 1 year apart using an AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands). Besides routine blood chemistry, additional plasma markers including superoxide dismutase, myeloperoxydase, intercellular adhesion molecule 1 (ICAM‐1), C‐reactive protein (hs‐CRP), heart‐type fatty acid binding protein (H‐FABP), and von Willebrand factor were measured at baseline. The mortality of HD patients was followed for 36 months. Skin autofluorescence values of the HD patients at the two time points were significantly higher (P < 0.001) than those of healthy subjects of the same age. Mean 1‐year ΔAF of HD patients was 0.16 ± 0.06, which was around seven‐ to ninefold higher than 1‐year ΔAF in healthy subjects. Multivariate Cox regression showed that age, hypertension, 1‐year ΔAF, hs‐CRP, ICAM‐1, and H‐FABP were independent predictors of overall mortality. Hypertension, 1‐year ΔAF, hs‐CRP, and H‐FABP were also independent predictors of cardiovascular mortality. One‐year ΔAF and plasma H‐FABP, used separately and in combination, are strong predictors of overall and cardiovascular mortality in HD patients.     

Decompression only versus fusion in octogenarians with spinal epidural abscesses: early complications,clinical and radiological outcome with 2-year follow-up

Despite increased life expectancy due to health care quality improvements globally, pyogenic vertebral osteomyelitis (PVO) treatment with a spinal epidural abscess (SEA) remains challenging in patients older than 80 years. We aimed to assess octogenarians for PVO prevalence with SEA and compare after-surgery clinical outcomes of decompression and decompression and instrumentation. A retrospective review of electronic medical records at a single institution was conducted between September 2005 and December 2020. Patient demographics, surgical characteristics, complications, hospital course, and 90-day mortality were collected. Comorbidities were assessed using the age-adjusted Charlson comorbidity index (CCI). Over 16 years, 35 patients aged ≥80 years with PVO and SEA were identified. Eighteen patients underwent surgical decompression (“decompression group”), and 17 underwent surgical decompression with instrumentation (“instrumentation group”). Both groups had a CCI >6 (mean±SD, 8.9±2.1 vs. 9.6±2.7, respectively; p=0.065). Instrumentation group patients had a significantly longer hospital stay but no ICU stay. In-hospital and 90-days mortality rates were similar in both groups. The mean follow-up was 26.6±12.4 months. No further surgeries were performed. Infection levels and neurological status were improved in both groups at discharge. At the second-stage analysis, significant improvements in the blood infection parameters and the neurological status were detected in the decompression group. Octogenarians with PVO and SEA have a high adverse events risk after surgical procedures. Surgical decompression might contribute to earlier clinical recovery in older patients. Thus, the surgical approach should be discussed with patients and their relatives and be carefully weighed.

     

Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum

During the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, which we term the "Big Gulp," appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment-the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (<0.004 fl) vesicles that are marked by the early endosomal regulatory protein Rab5a. A third process, also arising from cytostomes, creates long thin tubes previously termed cytostomal tubes in an actin-dependent manner. The fourth pathway, which we term phagotrophy, is similar to the Big Gulp in that it more closely resembles phagocytosis, except that phagotrophy does not require actin polymerization. Each of these four processes has aspects that are unique to Plasmodium, thus opening avenues to antimalarial therapy.     

Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: A systematic reappraisal of classic cytogenetic data

The significance of chromosomal translocations (CTRAs) and karyotype complexity (KC) in chronic lymphocytic leukemia (CLL) remains uncertain. To gain insight into these issues, we evaluated a series of 1001 CLL cases with reliable classic cytogenetic data obtained within 6 months from diagnosis before any treatment. Overall, 320 cases were found to carry ≥1 CTRAs. The most frequent chromosome breakpoints were 13q, followed by 14q, 18q, 17q, and 17p; notably, CTRAs involving chromosome 13q showed a wide spectrum of translocation partners. KC (≥3 aberrations) was detected in 157 cases and significantly (P < 0.005) associated with unmutated IGHV genes and aberrations of chromosome 17p. Furthermore, it was identified as an independent prognostic factor for shorter time‐to‐first‐treatment. CTRAs were assigned to two categories (i) CTRAs present in the context of KC, often with involvement of chromosome 17p aberrations, occurring mostly in CLL with unmutated IGHV genes; in such cases, we found that KC rather than the presence of CTRAs per se negatively impacts on survival; (ii) CTRAs in cases without KC, having limited if any impact on survival. On this evidence, we propose that all CTRAs in CLL are not equivalent but rather develop by different processes and are associated with distinct clonal behavior. Am. J. Hematol. 89:249–255, 2014. © 2013 Wiley Periodicals, Inc.     

Treatment with bortezomib‐based regimens improves overall response and predicts for survival in patients with primary or secondary plasma cell leukemia: Analysis of the Greek myeloma study group

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomib‐based regimens (BBR) are highly effective in myeloma, but there is limited information about their efficacy and safety in PCL. Thus, we retrospectively collected data from 42 consecutive PCL patients (25 with primary PCL‐pPCL and 17 with secondary PCL‐sPCL) to explore the role of BBR in this entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with pPCL underwent autologous transplantation. Objective response (≥partial response) was significantly higher in patients treated with BBR versus conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with BBR achieved at least very good partial response (vgPR). The highest ORR was observed in pPCL patients treated with BBR (88.9%; ≥vgPR: 33.3%). In BBR‐group, grade 3 of 4 hematological, neurological and renal toxicity and neutropenic infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median follow‐up of 51 months, median overall survival (OS) for patients treated with BBR versus conventional therapies was 13 versus 2 months (P < 0.007). Median OS of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively (P < 0.001). In the multivariate analysis normal PLTs, treatment with BBR and high quality response were the only powerful predictors for survival. Our study carrying the longest reported median follow‐up, demonstrated that treatment of PCL with BBR induces high response rates and prolongs survival over conventional therapies, regardless of additional autologous transplantation rescue or established high risk features, with manageable toxicity. Am. J. Hematol. 89:145–150, 2014. © 2013 Wiley Periodicals, Inc.     

Rapid Detection and Identification of Mucormycetes in Bronchoalveolar Lavage Samples from Immunocompromised Patients with Pulmonary Infiltrates by Use of High-Resolution Melt Analysis

Rapid differential diagnostics of pulmonary infiltrates suspected of invasive fungal disease in an immunocompromised host and early initiation of effective antifungal therapy are crucial for patient outcomes. There are no serological tests available to detect mucormycetes; therefore, PCR-based methods are highly suitable. We validated our previously published PCR followed by high-resolution melt analysis (PCR/HRMA) to detect Rhizopus spp., Rhizomucor pusillus, Lichtheimia corymbifera, and Mucor spp. in bronchoalveolar lavage (BAL) samples from immunocompromised patients who were at risk of invasive fungal disease. All PCR/HRMA-positive samples were retested using novel real-time quantitative PCR (RQ PCR) assays specific to the species identified. In total, between January 2009 and December 2012 we analyzed 99 BAL samples from 86 patients with pulmonary abnormalities using PCR/HRMA. Ninety (91%) BAL samples were negative, and 9 (9%) samples were positive. The sensitivity and specificity of PCR/HRMA were 100% and 93%, respectively. By combining the positive results of PCR/HRMA with positive RQ PCR results, the specificity was raised to 98%. PCR/HRMA, due to its high negative predictive value (99%), represents a fast and reliable tool for routine BAL sample screening for the differential diagnosis of pulmonary infiltrates in immunocompromised patients for the four most clinically important mucormycetes.     

Hearing impairment among workers occupationally exposed to excessive levels of noise

Pure tone audiometry screening and ear examinations were conducted among 138 males working as machine and equipment operators occupationally exposed to intermittent noise of 85 to 105 dBA. Hearing loss up to 30 dB (preserved socially adequate hearing) was found in 25 workers. The hearing impairment was confirmed by distortion products of otoacoustic emissions measurements. A sharp increase in the frequency of cases can be found among the workers with service length over 10 years. While the frequency of the cases among workers with service length below 10 years is 5.45%, it is 26.5% among the subjects with service length over 10 years, with a gradual increase as a result of the increase in exposure duration. A positive correlation (p < 0.05) was found between the frequency of hearing impairment among the workers and the years of exposure to excessive noise levels. Some measures for preventing occupational noise-induced hearing loss were suggested.