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Background The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis. Methods The INBUILD trial was a randomised, double-blind, placebo-controlled, parallel group trial done at 153 sites in 15 countries. Participants had an investigator-diagnosed fibrosing ILD other than IPF, with chest imaging features of fibrosis of more than 10% extent on high resolution CT (HRCT), forced vital capacity (FVC) of 45% or more predicted, and diffusing capacity of the lung for carbon monoxide (DLco) of at least 30% and less than 80% predicted. Participants fulfilled protocol-defined criteria for ILD progression in the 24 months before screening, despite management considered appropriate in clinical practice for the individual ILD. Participants were randomly assigned 1:1 by means of a pseudorandom number generator to receive nintedanib 150 mg twice daily or placebo for at least 52 weeks. Participants, investigators, and other personnel involved in the trial and analysis were masked to treatment assignment until after database lock. In this subgroup analysis, we assessed the rate of decline in FVC (mL/year) over 52 weeks in patients who received at least one dose of nintedanib or placebo in five prespecified subgroups based on the ILD diagnoses documented by the investigators: hypersensitivity pneumonitis, autoimmune ILDs, idiopathic non-specific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. The trial has been completed and is registered with ClinicalTrials.gov, number NCT02999178.

Aims To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). Methods and results TRANSITION was a randomised, multicentre, open‐label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre‐admission use of renin–angiotensin–aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12‐h pre‐discharge or between Days 1–14 post‐discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up‐ or down‐titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day –1 and Day +1 in the pre‐discharge group and the post‐discharge group, respectively. Comparable proportions of patients in the pre‐ and post‐discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79–1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83–0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92–1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90–2.46). Conclusions Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. Clinical Trial Registration: http://ClinicalTrials.gov ID: NCT02661217

The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701).

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Colon cancer is the second most common type of cancer in females and the third in males, worldwide. The most common sites of colon cancer metastasis are the regional lymph nodes, liver, lung, bone and brain. In this study, an extremely rare case of colon adenocarcinoma with extensive metastasis to the mediastinal lymph nodes without any other organ involvement is presented. A 44-year-old Caucasian male presented with abdominal pain, a change in bowel habits, melena and weight loss. Colonoscopy revealed a large friable, ulcerated, circumferential mass in the ascending colon. Biopsies were consistent with the diagnosis of invasive moderately differentiated adenocarcinoma. Subsequently, right colon resection was performed, and pathological analysis revealed moderately differentiated adenocarcinoma of the right colon with extensive regional lymph node involvement. Computed tomography (CT) scans of the chest, abdomen and pelvis were performed preoperatively as part of routine staging for colon cancer. No liver or lung pathology was identified; however, multiple pathologically enlarged mediastinal lymph nodes were observed. Endoscopic ultrasound with fine needle aspiration of the largest mediastinal lymph node, which measured 5.2×3.5 cm on CT scans, was performed. The pathology was again consistent with the diagnosis of metastatic colorectal primary adenocarcinoma. At present, no optimum treatment has been identified for metastatic colon cancer to the mediastinal lymph nodes. The patient in the current case received chemotherapy with folinic acid, fluorouracil and oxaliplatin (FOLFOX), as well as with bevacizumab. Initial follow-up CT scans of the chest revealed a positive response to treatment. Physicians, in particular, radiologists, must consider the mediastinum during the first evaluation and further follow-up of patients with colorectal carcinoma even in the absence of metastasis.

Patients with interstitial lung disease (ILD) have many unmet palliative care needs. The majority of patients with chronic ILD have poor access to a specialist in palliative medicine and that is due to several barriers. The mortality for the ILD patient is high and reaches up to 80% if admitted to the ICU with respiratory failure. Palliative care addresses symptoms in diseases where cure is unlikely or impossible. Palliative care consultation also ensures communication among patients, caregivers and providers regarding treatments, prognosis, and end of life planning. Methods: We performed a literature review on palliative care and ILD, accessing articles published since 2002. We found 71 articles related to the topic. We chose 37 that were most relevant and with no redundancy of information to include in this review. Objectives: Summarize the palliative care needs of patients with ILD, discuss the barriers to receiving palliative care, and summarize clinical practice for providing palliative care to this patient population.

Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving.