Adapting the Fitness Criteria for Non-Intensive Treatments in Older Patients with Acute Myeloid Leukemia to the Use of Venetoclax-Hypomethylating Agents Combination-Practical Considerations from the Real-Life Experience of the Hematologists of the Rete Ematologica Lombarda.

A retrospective survey was conducted in hematologic centres of the Rete Ematologica Lombarda (REL) on 529 older AML patients seen between 2020-2022. Compared to 2008-2016, the use of intensive chemotherapy (ICT) decreased from 40% to 18.1% and of hypomethylating agents (HMAs) from 19.5% to 13%, whereas the combination of Venetoclax/HMA, initially not available, increased from 0% to 36.7%. Objective treatment-specific fitness criteria proposed by SIE/SIES/GITMO in 2013 allow an appropriate choice between ICT and HMAs by balancing their efficacy and toxicity. Venetoclax/HMA, registered for patients unfit to ICT, has a unique toxicity profile because of prolonged granulocytopenia and increased infectious risk. Aiming at defining specific fitness criteria for the safe use of Venetoclax/HMA, a preliminary investigation was conducted among expert REL hematologists, asking for modifications of SIE/SIES/GITMO criteria they used to select candidates for Venetoclax/HMA. While opinions among experts varied, a general consensus emerged on restricting SIE/SIES/GITMO criteria for ICT-unfit patients to an age limit of 80-85, cardiac function > 40%, and absence of recurrent lung infections, bronchiectasis, or exacerbating COPD. Also, the presence of an adequate caregiver was considered mandatory. Such expert opinions may be clinically useful and may be considered when treatment-specific fitness criteria are updated to include Venetoclax/HMA.

Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome.

RATIONALE: Lung injury caused by a ventilator results from nonphysiologic lung stress (transpulmonary pressure) and strain (inflated volume to functional residual capacity ratio). OBJECTIVES: To determine whether plateau pressure and tidal volume are adequate surrogates for stress and strain, and to quantify the stress to strain relationship in patients and control subjects. METHODS: Nineteen postsurgical healthy patients (group 1), 11 patients with medical diseases (group 2), 26 patients with acute lung injury (group 3), and 24 patients with acute respiratory distress syndrome (group 4) underwent a positive end-expiratory pressure (PEEP) trial (5 and 15 cm H2O) with 6, 8, 10, and 12 ml/kg tidal volume. MEASUREMENTS AND MAIN RESULTS: Plateau airway pressure, lung and chest wall elastances, and lung stress and strain significantly increased from groups 1 to 4 and with increasing PEEP and tidal volume. Within each group, a given applied airway pressure produced largely variable stress due to the variability of the lung elastance to respiratory system elastance ratio (range, 0.33-0.95). Analogously, for the same applied tidal volume, the strain variability within subgroups was remarkable, due to the functional residual capacity variability. Therefore, low or high tidal volume, such as 6 and 12 ml/kg, respectively, could produce similar stress and strain in a remarkable fraction of patients in each subgroup. In contrast, the stress to strain ratio-that is, specific lung elastance-was similar throughout the subgroups (13.4 +/- 3.4, 12.6 +/- 3.0, 14.4 +/- 3.6, and 13.5 +/- 4.1 cm H2O for groups 1 through 4, respectively; P = 0.58) and did not change with PEEP and tidal volume. CONCLUSIONS: Plateau pressure and tidal volume are inadequate surrogates for lung stress and strain. Clinical trial registered with www.clinicaltrials.gov (NCT 00143468).

Effect of a heated humidifier during continuous positive airway pressure delivered by a helmet.

INTRODUCTION: The helmet may be an effective interface for the delivery of noninvasive positive pressure ventilation. The high internal gas volume of the helmet can act as a 'mixing chamber', in which the humidity of the patient's expired alveolar gases increases the humidity of the dry medical gases, thus avoiding the need for active humidification. We evaluated the temperature and humidity of respiratory gases inside the helmet, with and without a heated humidifier, during continuous positive airway pressure (CPAP) delivered with a helmet. METHODS: Nine patients with acute respiratory failure (arterial oxygen tension/fractional inspired oxygen ratio 209 +/- 52 mmHg) and 10 healthy individuals were subjected to CPAP. The CPAP was delivered either through a mechanical ventilator or by continuous low (40 l/min) or high flow (80 l/min). Humidity was measured inside the helmet using a capacitive hygrometer. The level of patient comfort was evaluated using a continuous scale. RESULTS: In patients with acute respiratory failure, the heated humidifier significantly increased the absolute humidity from 18.4 +/- 5.5 mgH2O/l to 34.1 +/- 2.8 mgH2O/l during ventilator CPAP, from 11.4 +/- 4.8 mgH2O/l to 33.9 +/- 1.9 mgH2O/l during continuous low-flow CPAP, and from 6.4 +/- 1.8 mgH2O/l to 24.2 +/- 5.4 mgH2O/l during continuous high-flow CPAP. Without the heated humidifier, the absolute humidity was significantly higher with ventilator CPAP than with continuous low-flow and high-flow CPAP. The level of comfort was similar for all the three modes of ventilation and with or without the heated humidifier. The findings in healthy individuals were similar to those in the patients with acute respiratory failure. CONCLUSION: The fresh gas flowing through the helmet with continuous flow CPAP systems limited the possibility to increase the humidity. We suggest that a heated humidifier should be employed with continuous flow CPAP systems.