Riccardo Fantini

Ultrasound assessment of diaphragmatic function in patients with amyotrophic lateral sclerosis.

Evaluation of diaphragm function in Amyotrophic Lateral Sclerosis (ALS) is critical in determining when to commence non‐invasive mechanical ventilation (NIV).

Chronic critical illness: the price of survival

The evolution of the techniques used in the intensive care setting over the past decades has led on one side to better survival rates in patients with acute conditions and severely impaired vital functions. On the other side, it has resulted in a growing number of patients who survive an acute event, but who then become dependent on one or more life support techniques. Such patients are called chronically critically ill patients.

Fishing for ALK with immunohistochemistry may predict response to crizotinib.

BACKGROUND ALK (anaplastic lymphoma kinase) gene rearrangement is a novel oncogenic driver in non-small cell lung cancer (NSCLC) against which a selective inhibitor, namely crizotinib, is effective. Fluorescence in situ hybridization (FISH) is considered the reference method in selecting patients with ALK-positive tumors for treatment with crizotinib. CASE REPORT We report the case of a 42-year-old non-smoking woman with an advanced pulmonary ALK FISH-negative adenocarcinoma characterized by strong immunohistochemical expression of ALK fusion protein. The patient received targeted therapy with crizotinib in compassionate use and experienced a long-lasting clinical response. CONCLUSION FISH testing should not be considered the only method to select patients for therapy with ALK inhibitors and the use of multiple ALK-detecting techniques could be helpful in screening ALK-positive patients more appropriately.

The encaged lung: rapidly progressive idiopathic pleurisy

Abstract A 56-year-old, non-smoker male with no exposure, presented with right chest pain and a huge loss in forced vital capacity due to right lung volume reduction with consensual pleural thickening on high-resolution computed tomography. All serological and microbiological tests were negative. The surgical lung biopsy showed fibrinous pleurisy while the search for neoplastic cells resulted negative. Because of symptoms worsening he started low dose steroids without benefits until he died 3 months later for cardiac ischemic attack. We reviewed the literature to identify possible etiologies and a rapidly progressive idiopathic pleurisy revealed to be the most probable diagnosis.

COPD exacerbation and diaphragmatic dysfunction: Conditions with mutual influence influencing outcomes? – Reply

The word ‘central’ in central sleep apnoea refers to the influence of the central nervous system. Orr et al., in their review of the pathogenesis of central and complex sleep apnoea, make only scant mention of the central nervous system—merely saying that ‘increased Partial Pressure of Carbon Dioxide (PCO2) (in the form of H+) is also sensed at the medulla and pons, particularly at the retrotrapezoid nucleus in the ventrolateral medulla, making up the central chemoreceptors’. In fairness to the authors, there is little known about central nervous system causality and/or involvement in central sleep apnoea, including whether the retrotrapezoid nucleus is in any way involved in its pathophysiology. But some neuropathology case reports have described components of the mysterious pathogenesis in individuals, and they have especially provided context for some of the sleep apnoea’s most important complications— sudden cardiovascular events and sudden unexpected death—barely alluded to by the authors, who mention only that ‘in patients with heart failure, Central Sleep Apnea (CSA) can promote cardiac arrhythmia, reduced cardiac function and is strongly associated with mortality’. In my opinion, there is significant evidence that in cases of sudden death, the specific medullary site most often found to contain pathology is the solitary tract nucleus, which is believed to commonly develop very small ischemic lesions during the course of chronic cardiorespiratory illnesses such as heart failure and sleep apnoea. These ischaemic lesions are thought to form as a result of excitotoxic neural input carried by the vagus nerve from thoracic organs during illness and inducing increased metabolism in dendritic areas of solitary tract nucleus parenchymal tissue in the setting of a limited watershed vasculature. The resulting ischaemic lesions then seem capable of triggering life-threatening cardiac arrhythmias by an unknown mechanism. These neuropathology reports potentially have implications for prevention of adverse cardiovascular events. Some investigators see vagus nerve stimulation as a rudimentary model for preventive therapy, due to its success in epilepsy by modulating brain electrical discharges. Because vagal afferent fibres travel (upstream) from the point of stimulation directly into the solitary tract nucleus, some see a potential modulation of electrical discharges there; however, these benefits seem to be mitigated by vagal efferent fibres travelling (downstream) directly to the heart. Phrenic nerve stimulation was developed to elicit purposeful muscle contractions in specific muscles of respiration to enhance breathing, but its efficacy may ultimately be shown to be more related to other factors such as indirect (upstream) electrical stimulation of the medulla through its sensory and autonomic fibres, and the failure of mechanical ventilation to prevent sudden death in the treatment of ‘sleep apnoea with heart failure’ might tend to support this. It seems that we cannot ventilate our way around the influence of small sequestered ischaemic lesions in the brain medulla. Finally, the authors discuss central sleep apnoea in infancy, but do not mention sudden infant death syndrome in which a subset of cases has been shown pathologically to involve infants with an abnormal retrotrapezoid nucleus.

An uncommon cause of pneumonia: The golden diagnosis

A 28-year-old sub-Saharan African Italian non-smoker male presented with signs and symptoms of pneumonia and respiratory failure. Despite antibiotic treatment he experienced a significant worsening of respiratory conditions and admission to intensive care unit. He thus underwent chest computed tomography followed by fiberopict bronchoscopy with bronchoalveolar lavage whose macroscopic examination led to the diagnosis of acute chest syndrome. A brief literature review was conducted to discuss the first manifestation of this disease.

When Acute Respiratory Distress Syndrome is not ARDS

A 58-year-old male with Ehler–Danlos syndrome was referred to our hospital for admission to respiratory intensive care unit (RICU) as he presented with fever (38.0 C) followed by an extremely rapid onset of acute respiratory failure with a radiological pattern of acute respiratory distress syndrome (ARDS) on high-resolution computed tomography (HRCT) (Fig. 1). In the days prior to admission, he had developed progressive cognitive and motor deficits with associated mild dysphagia and swallowing impairment due to considerable enlargement of a partially thrombosed aneurysm in the basilar artery. No recent chest radiographic images were available. After RICU admission the patient was treated with invasive mechanical ventilation. Since acute respiratory infection was suspected, he underwent fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) whose sample presented with a milky appearance. A few minutes after the procedure, the different components of the sample started separating into fluid and corpuscolated parts (Fig. 2). BAL fluid resulted negative on microbiological analysis, while cytological examination showed multiple lipid-laden macrophages. Based on BAL fluid evidence, we reviewed the patient’s recent medical history and we learned that during the previous week he had been aspirating a minimum quantity of petroleum jelly used as a laxative to treat a form of transient constipation. The progressive neurological impairment due to vascular disease had probably favored the aspiration process. On this ground, the diagnosis of ARDS-like exogenous lipoid pneumonia was made. Despite a wide range of reported manifestations [1], acute respiratory failure requiring RICU admission and mechanical ventilation is a very rare presentation of the disease and it is usually due to a massive aspiration [2]. In our case, petroleum jelly served as a laxative for an intercurrent constipation and was used for only a week. We conclude that although a rare occurrence, even low amounts of oil-based laxatives may increase the risk of ARDS-like life-threatening lipoid pneumonia in patients with neurological impairment.

An uncommon cause of weaning failure from mechanical ventilation.

A 70-year-old man with a history of surgery for thoracic aortic aneurysm arrived at the emergency department with shortness of breath and wheezing. The chest radiograph showed no parenchymal lesions, while gas analysis was consistent with acute hypercapnic respiratory failure. As a result of the patient’s rapid clinical deterioration, endotracheal intubation was performed and mechanical ventilation was started in pressure controlled ventilation (PCV) mode. A subsequent CT scan of the chest showed a severe reduction in the diameter of distal trachea and of both main bronchi by the extrinsic compression of a recurrent aneurysm of the descending thoracic aorta (Fig. 1a, b). We therefore performed a bronchoscopy which confirmed the presence of severe stenosis of distal trachea and of both main bronchi without alteration of the bronchial mucosa (Fig. 2a). Owing to his clinical condition and previous surgery for aneurysm, the patient was judged to be inoperable by the vascular surgery team. After several failed attempts at weaning from mechanical ventilation, we performed tracheobronchial stent placement with rigid bronchoscopy restoring the lumen of the trachea and both main bronchi (Fig. 2). After the