Predictive factors for dose reduction and discontinuation of nintedanib in fibrotic interstitial lung diseases: Real life data.

Nintedanib, an intracellular inhibitor targeting multiple tyrosine kinases, has emerged as a standard treatment for various fibrotic lung diseases. Despite its efficacy, side effects such as nausea, diarrhea, and hepatotoxicity often lead to dose reduction or discontinuation. In this retrospective analysis at an university hospital's interstitial lung disease clinic, we aimed to identify baseline characteristics associated with dose adjustment or treatment discontinuation. Of the 58 patients included, 41.4% maintained the full nintedanib dose, while 31.0% required dosage reduction, and 27.6% discontinued treatment due to adverse events, predominantly gastrointestinal and hepatotoxic effects. Multivariate analysis revealed body surface area (BSA) as an independent and significant baseline risk factor (adjusted Odds Ratio [aOR] 0.22), suggesting a 78% decreased chance of requiring dose modification for every decimal point increase in BSA. A BSA cutoff of ≤1.73 m [2] exhibited a sensitivity of 73% and specificity of 91.7%, with significant impact on one-year survival under full-dose treatment (p < 0.001). Lower BSA was associated with early onset adverse effects, particularly gastrointestinal, supporting the need for regular clinical monitoring. The study emphasizes the importance of recognizing baseline factors to ensure the safety and tolerability of nintedanib, thereby preventing the progression of pulmonary fibrosis. These findings contribute to the evolving understanding of nintedanib management in fibrotic interstitial lung diseases, guiding clinicians in personalized treatment approaches.

Sarcoidosis-like reaction secondary to adalimumab treatment in a patient with axial spondyloarthritis.

Anti-TNF agents, namely adalimumab, are safe drugs that represent an important arsenal in the treatment of immune-mediated inflammatory diseases. "Paradoxical effects" have been described with their use. A sarcoidosis "like" reaction induced by these agents is rare and is characterized by a systemic granulomatous reaction indistinguishable from sarcoidosis. We present a 55-year-old male patient, with axial spondyloarthritis, treated with with adalimumab. About 17 months under this therapy, he complained of dry cough and wheezing. Chest CT showed a peri-lymphatic and pericisural micronodular pattern and hilo-mediastinal lymph nodes, suggestive of sarcoidosis. Angiotensin converting enzyme was increased. Assuming the hypothesis of a sarcoidosis-like reaction secondary to adalimumab this therapy was discontinued with progressive improvement in the patient's complaints and in the radiological changes.

Interstitial nephritis secondary to treatment with pembrolizumab, a rare complication in two patients with lung adenocarcinoma.

Immune checkpoint inhibitors (ICPi) have become nowadays one of the most widely prescribed anticancer treatments. Pembrolizumab is a highly selective monoclonal immunoglobulin approved as a first-line monotherapy treatment in adult patients with untreated advanced non-small cell lung cancer (NSCLC) with programmed cell death 1 (PD-L1) expression greater than 50% and lack of mutations. ICPi can precipitate immune-related adverse events. Data on the incidence and characteristics of nephrotoxicity from ICPi are limited and caused largely from small case series and oncologic studies. Two patients with a diagnosis of pulmonary adenocarcinoma, undergoing treatment with pembrolizumab who manifested interstitial nephritis secondary to this treatment, are presented below. The growing use of immunotherapy in the treatment of cancer imposes the physician's attention to possible adverse effects.

Pentraxin 3 Inhibits Complement-driven Macrophage Activation to Restrain Granuloma Formation in Sarcoidosis.

Rationale: Sarcoidosis is a multisystemic inflammatory disease characterized by the formation of granulomas in response to persistent stimuli. The long pentraxin PTX3 (pentraxin 3) has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown. Objectives: To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis. Methods: Peripheral blood mononuclear cells obtained from patients with sarcoidosis harboring loss-of-function genetic variants and gene-deleted mice were used to assess the role of PTX3 in experimental models of granuloma formation in vitro and in vivo. The identified mechanisms of granulomatous inflammation were further evaluated in tissue and BAL samples and correlated with the disease course. Measurements and Main Results: We have identified a molecular link between PTX3 deficiency and the pathogenic amplification of complement activation to promote granuloma formation. Mechanistically, PTX3 deficiency licensed the complement component C5a-mediated activation of the metabolic checkpoint kinase mTORC1 (mammalian target of rapamycin complex 1) and the reprogramming of macrophages toward increased glycolysis to foster their proliferation and aggregation. This process sustained the further recruitment of granuloma-promoting immune cells and the associated proinflammatory microenvironment and influenced the clinical course of the disease. Conclusions: Our results identify PTX3 as a pivotal molecule that regulates complement-mediated signaling cues in macrophages to restrain granulomatous inflammation and highlight the therapeutic potential of this signaling axis in targeting granuloma formation in sarcoidosis.

Erlotinib as an alternative treatment for NSCLC. Case Report. / Erlotinib no tratamento de CPNPC em terceira linha linha. Caso clínico.

INTRODUCTION: Erlotinib is an approved treatment for NSCLC locally advanced or with metastases, after failure of initial chemotherapy. The authors present a NSCLC clinical case of great clinical and imaging improvement, with no drug-induced toxicity observed, after treatment with erlotinib. CASE PRESENTATION: A 76-year-old woman, never-smoker, had been diagnosed for lung adenocarcinoma, through thoracoscopy, after presenting a large-volume pleural effusion. At the time of diagnosis it was inoperable (stage IIIB - T4 N1 M0). She was submitted to two consecutive chemotherapy treatments with carboplatin+gemcitabin and pemetrexed, respectively. Due to its failure, with lack of response, erlotinib was set as the alternative choice, with great clinical and imaging improvement after 6 months of treatment. CONCLUSION: The authors recommend, even in the absence of EGFR result, the use of erlotinib when progression of the disease is seen, after initial chemotherapy, especially in lung adenocarcinoma and in never-smokers. Rev Port Pneumol 2008; XIV (Supl 3): S61-S63.