https://uhra.herts.ac.uk/bitstream/handle/2299/2030/901263.pdf;sequence=1

Platinum group elements in the environment and their health risk.

Palladium--a Review of Exposure and Effects to Human Health

Environmental risk of particulate and soluble platinum group elements released from gasoline and diesel engine catalytic converters.

Thrombotic microangiopathy (TMA) is a microvascular occlusive disorder characterized by predominantly platelet thrombi in the renal and/or systemic circulations Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are the clinical entities comprising TMA, with predominantly renal manifestations in the former, while the latter more often presents with systemic and neurological findings In some cases, TMA includes de novo hypertension and pulmonary or central nervous system symptoms TMA is a rare condition, which is severe and may be fatal Globally, two biological abnormalities explain TMA, namely: ADAMTS13 (A Disintegrin-like And Metalloprotease with ThromboSpondin type 1 repeats) deficiency and various complement component deficiencies Studies aimed at determining these deficiencies in cases of chemotherapy-induced TMA were not systematically available in the articles reviewed Gemcitabine was approved by the US Food and Drug Administration (FDA) in 1996 for the treatment of patients with metastatic pancreatic cancer and is currently used for the treatment of a wide range of malignancies, including lymphoma, lung, bladder and breast cancer Casper et al [1] first linked TMA to gemcitabine therapy in 1994, during a phase II trial of pancreatic cancer patients receiving this agent The reported incidence of gemcitabine-associated TMA in the literature is very low, with a manufacturer’s estimate of 0015% (range 0008–0078%) according to adverse event reports in 1997 [2], contrasting with the apparent frequency of patients with gemcitabineassociated TMA at local institutions [3,4] Since most gemcitabine-treated patients presenting with TMA have far advanced disease and some have received other agents known to be associated with TMA, the exact role of the underlying disease and chemotherapeutic agents is not easily delineated Although microangiopathy caused by disseminated cancer and chemotherapy-associated TMA may represent two distinct syndromes, and distinguishing clinical and histological features have been identified for these two conditions, there may be more similarities than differences Nevertheless, clinical improvement after gemcitabine withdrawal in some cases and the result from re-exposure to the drug strongly suggest gemcitabine to be causative for TMA We report three patients who developed gemcitabine-associated TMA from January 2001 to December 2005, and we undertook a retrospective review to investigate the clinical manifestations and outcomes associated with this condition in case reports and Phase II/III trials

Gemcitabine-induced thrombotic microangiopathy: a systematic review

The term thrombotic microangiopathy (TMA) describes syndromes characterised by microangiopathic haemolytic anaemia, thrombocytopenia and variable signs of organ damage due to platelet thrombi in the microcirculation. In children, infections with Shigella dysenteriae type 1 or particular strains of Escherichia coli are the most common cause of TMA; in adults, a variety of underlying causes have been identified, such as bacterial and viral infections, bone marrow and organ transplantation, pregnancy, immune disorders and certain drugs. Although drug-induced TMA is a rare condition, it causes significant morbidity and mortality. Antineoplastic therapy may induce TMA. Most of the cases reported are associated with mitomycin. TMA has also been associated with cyclosporin, tacrolimus, muromonab-CD3 (OKT3) and other drugs such as interferon, anti-aggregating agents (ticlopidine, clopidogrel) and quinine. The early diagnosis of drug-induced TMA may be vital. Strict monitoring of renal function, urine and blood abnormalities, and arterial pressure has to be performed in patients undergoing therapy with potentially toxic drugs. The drug must be discontinued immediately in the case of suspected TMA. Treatment modalities sometimes effective in other forms of TMA have been used empirically. Although plasma exchange therapy seems to be of value, the effectiveness of this approach has yet to be proved in multicentre, randomised clinical studies.

Drug-induced thrombotic microangiopathy: incidence, prevention and management.

Occupational exposure to complex platinum salts is a well-known cause of occupational asthma. Although there is evidence that platinum refinery workers may also be sensitized to other precious metals, such as palladium or rhodium, no instances of occupational asthma due to an isolated sensitization to palladium have been reported. A case is reported of occupational rhinoconjunctivitis and asthma in a previously healthy worker exposed to the fumes of an electroplating bath containing palladium. There was no exposure to platinum. Sensitization to palladium was documented by skin-prick tests. The skin-prick test was positive with Pd(NH3)4Cl2, but not with (NH4)2PdCl4. Corresponding salts of platinum were all negative. A bronchial provocation test with Pd(NH3)4Cl2 (0.0001% for a total of 315 s, followed by 0.001% for a total of 210 s) led to an early decrease in forced expiratory volume in one second (-35%). A similar exposure (0.001% for a total of 16 min) in an unrelated asthmatic gave no reaction. This case shows that an isolated sensitization to palladium can occur and that respiratory exposure to palladium is a novel cause of metal-induced occupational asthma.

https://erj.ersjournals.com/content/erj/13/1/213.full.pdf

Occupational asthma caused by palladium.

Hemolytic-uremic syndrome caused by gemcitabine.

Impact of acute exacerbations of COPD on patients' health status beyond pulmonary function: A scoping review.

Background: Preoperative physical function is a predictor of postoperative complications (PCs) in people undergoing lung resection for non-small cell lung cancer (NSCLC). We aim to evaluate whether the preoperative performance in the 1-minute sit-to-stand test (1-MSTST) – a simple test of physical function – is a prognostic marker of PCs. Methods: We included patients prior to lung resection for NSCLC from two hospitals (Genk, Belgium and Perth, Australia). Before surgery, the 1-MSTST was assessed twice with 15 minutes rest in between, and the best was used for analysis. PCs were prospectively recorded and graded with the Clavien-Dindo classification. Receiver Operating Characteristic (ROC) analysis was performed and the area under the curve (AUC), sensitivity and specificity were calculated. Data of both centres were combined following analysis that demonstrated similar characteristics and findings in both centres. Results: We recruited 32 participants (20 male; age 66±9yr) who underwent video-assisted thoracic surgery (78%) or thoracotomy (22%). The median [interquartile range] number of repetitions on the 1-MSTST was 27 [21 to 28]. PCs were reported in 13 participants. Cut-off values of 22 repetitions (AUC 0.65; sensitivity 62%; specificity 79%) and 59% predicted (AUC 0.60; sensitivity 38%; specificity 95%) were identified. Conclusion: The preoperative assessment of the 1-MSTST has an acceptable discriminative ability to predict the risk of postoperative complications in patients with NSCLC. A cut-off of 22 repetitions or 59% predicted on the 1-MSTST has prognostic value to assess risk of PCs in people undergoing surgery for NSCLC.

M Daenen

Papers

Occupational asthma caused by palladium.

Hemolytic-uremic syndrome caused by gemcitabine.

Impact of acute exacerbations of COPD on patients' health status beyond pulmonary function: A scoping review.

Prognostic value of the 1-minute sit-to-stand test on postoperative complications in people with lung cancer elected for lung surgery

Functional and Patient-reported Outcomes at Diagnosis of Non-small Cell Lung Cancer