Adi Hollander’s research while affiliated with Hebrew University of Jerusalem and other places

Lung cancer is uncommon among people with cystic fibrosis (pwCF). We describe the case of a 35-year-old man with mild, stable CF disease who presented with severe respiratory distress, systemic symptoms, elevated liver enzymes and hypereosinophilia along with a lung mass and pleural effusion. The patient was subsequently diagnosed with non-small cell lung carcinoma (NSCLC), featuring anaplastic lymphoma kinase (ALK) translocation. Following treatment with a targeted tyrosine kinase inhibitor (TKI) there was a rapid tumor regression, however, his dyspnea and hypoxemia subsequently worsened. A trial of Elexacaftor/Tezacaftor/Ivacaftor (ETI) led to significant clinical improvement and enhanced pulmonary function. In vitro testing using patient-derived intestinal organoids was performed in parallel and also demonstrated a significant response to ETI. The deterioration observed following the initiation of ALK inhibitor treatment and subsequent improvement with CFTR modulators suggest that ALK inhibitor therapy may potentially impair CFTR activity. A better understanding of the relationship between these pathways could provide valuable insights and contribute to the development of more effective and tailored treatment strategies for patients with coexisting conditions. To our knowledge, this is the first reported case of ALK-translocated lung cancer in a CF patient, underscoring the necessity for a high degree of clinical suspicion in atypical presentations of pulmonary exacerbation and potentially linking ALK-EML4 activation pathways, TKI therapy and CFTR. Care for pwCF with lung cancer requires a unique multi-disciplinary approach to optimize their complex multifactorial treatment.

Highlights What are the main findings? The constrained disorder principle (CDP) defines systems by their inherent disorder bounded by variable boundaries. What is the implication of the main finding? The present paper describes the mechanisms of breathing and cellular respiration, focusing on their inherent variability and how the CDP accounts for the variability in breathing and respiration. The article describes using CDP-based artificial intelligence platforms to augment the respiratory process’s efficiency and treat respiratory diseases. Abstract Variability characterizes breathing, cellular respiration, and the underlying quantum effects. Variability serves as a mechanism for coping with changing environments; however, this hypothesis does not explain why many of the variable phenomena of respiration manifest randomness. According to the constrained disorder principle (CDP), living organisms are defined by their inherent disorder bounded by variable boundaries. The present paper describes the mechanisms of breathing and cellular respiration, focusing on their inherent variability. It defines how the CDP accounts for the variability and randomness in breathing and respiration. It also provides a scheme for the potential role of respiration variability in the energy balance in biological systems. The paper describes the option of using CDP-based artificial intelligence platforms to augment the respiratory process’s efficiency, correct malfunctions, and treat disorders associated with the respiratory system.