Calcium Channel Blocker-Induced Thrombocytopenia in the Intensive Care Unit: A Rare Presentation and Review of the Literature.

Patients with thrombocytopenia may report easy bruising, abnormal bleeding, and fatigue. Drug-induced thrombocytopenia has been reported with a variety of medications, most commonly heparin products, sulphonamides, carbamazepine, nonsteroidal anti-inflammatory drugs, anti-epileptic drugs, and chemotherapy. We present the case of a 58-year-old female with severe thrombocytopenia attributed to a calcium channel blocker (CCB) overdose, a very rare cause of thrombocytopenia. We discuss the diagnostic work-up and management in the intensive care unit and perform a literature review.

South-West of England's Experience of the Safety and Tolerability Pirfenidone and Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis (IPF).

Purpose: Pirfenidone and nintedanib are two novel antifibrotic agents licensed for the treatment IPF. Prior to being approved for use in England for patients with FVC >50% and <80%, these were made available for all IPF patients under the Mild Patient Program (MPP) and Patient In Need Scheme (PIN). Prescribing of these medications is restricted to specialist centers. We sought to characterize the population of patients prescribed antifibrotics and determine the drug tolerability of these medications in the Northern hub of the Southwest of England regional ILD network. Methods: A retrospective analysis of all patients treated with antifibrotics between August 2012 and July 2017 was undertaken. Baseline characteristics including patient demographics and pulmonary physiology, in addition to drug tolerability and reasons for treatment cessation were collated. Data were compared using unpaired student's t-test, Chi-squared, Mann-Whitney rank sum or ANOVA as appropriate. Logistic regression analysis evaluated clinical characteristics associated with discontinuation of pirfenidone therapy. P < 0.05 was considered statistically significant. Findings: A total of 164 patients, all with consensus diagnoses of IPF, were identified. Of these, 70.1% (115/164) received pirfenidone as their initial therapy. Baseline age, gender and pulmonary physiology did not differ significantly between groups. Drug discontinuation occurred most commonly due to adverse drug reactions events (ADRs) for both pirfenidone [40.0% (46/115)] and nintedanib [16.3% (8/49)]. Anorexia, rash and gastrointestinal disturbance were reported most commonly as the reason for cessation of pirfenidone; anorexia, nausea and weight loss for nintedanib. Duration of therapy prior to discontinuation because of ADRs did not differ significantly between medication groups but patients with a baseline FVC < 65% predicted, had a significantly shorter duration of pirfenidone prior to discontinuation due to ADRs, compared to those with a FVC 65-80% predicted. Multivariate logistic regression did not identify any independent baseline characteristics that predicted discontinuation of pirfenidone therapy prior to 52 weeks. Implications: Idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib had comparable treatment emergent adverse event (TEAE) profiles in clinical practice to those reported in clinical trials. The TEAE profile of pirfenidone was higher than clinical trial data would suggest, although comparable to real-world datasets. Further work is required to explore the possible reasons underpinning this finding, including whether this is related to population co-morbidities or center threshold. No new safety concerns were identified.

Connective Tissue Disease-associated Interstitial Lung Disease: A review.

Interstitial lung disease (ILD) is commonly encountered in patients with connective tissue diseases (CTD). Besides the lung parenchyma, the airways, pulmonary vasculature and structures of the chest wall may all be involved, depending on the type of CTD. As a result of this so-called multi-compartment involvement, airflow limitation, pulmonary hypertension, vasculitis and extrapulmonary restriction can occur alongside fibro-inflammatory parenchymal abnormalities in CTD. Rheumatoid arthritis (RA), systemic sclerosis (SSc), poly-/dermatomyositis (PM/DM), Sjögren's syndrome (SjS), systemic lupus erythematosus (SLE), and undifferentiated (UCTD) as well as mixed connective tissue disease (MCTD) can all be associated with the development of ILD. Non-specific interstitial pneumonia (NSIP) is the most commonly observed histopathological pattern in CTD-ILD, but other patterns including usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP) may occur. Although the majority of patients with CTD-ILD experience stable or slowly advancing ILD, a small yet significant group exhibits a more severe and progressive course. Randomized placebo-controlled trials evaluating the efficacy of immunomodulatory treatments have been conducted only in SSc-associated ILD. However, clinical experience suggests that a handful of immunosuppressive medications are potentially effective in a sizeable portion of patients with ILD caused by other CTDs. In this manuscript, we review the clinical characteristics and management of the most common CTD-ILDs.

Hemoptysis due to breath-hold diving following chemotherapy and lung irradiation.

Breath-hold diving, also known as free-diving, describes the practice of intentional immersion under water without an external supply of oxygen. Pulmonary hemorrhage with hemoptysis has been reported as a complication of immersion and breath-hold diving in young healthy athletes. We report the case of a 60-year-old man with a history of radiation and chemotherapy for breast carcinoma, who developed the abrupt onset of hemoptysis in the setting of swimming and breath-hold diving. A computed tomography (CT) scan of the chest demonstrated an area of ground glass opacification, suggestive of pulmonary hemorrhage, superimposed on a background of reticular opacities within the prior radiation field. A follow-up CT scan of the chest, obtained 2 months after presentation, demonstrated resolution of the ground glass opacification, but persistence of fibrotic features attributable to prior radiation therapy. We postulate that prior irradiation of the chest resulted in lung injury and fibrosis which, in turn, rendered the affected region of the lung susceptible to "stress failure," due to an increase in the transcapillary pressure gradient arising from immersion and breath-hold diving. Patients with a history of lung injury resulting from chest irradiation should be cautioned about pulmonary hemorrhage and hemoptysis as a potential complication of swimming and breath-hold diving.