Background Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. Methods Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. Results The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P Conclusions In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.

The members of the Writing Committee background Most patients requiring mechanical ventilation for acute lung injury and the acute res- piratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ven- tilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients. methods We randomly assigned 549 patients with acute lung injury and ARDS to receive me- chanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen. results Mean (±SD) PEEP values on days 1 through 4 were 8.3±3.2 cm of water in the lower- PEEP group and 13.2±3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5±10.4 days in the lower-PEEP group and 13.8±10.6 days in the higher-PEEP group (P = 0.50). conclusions These results suggest that in patients with acute lung injury and ARDS who receive me- chanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical out- comes are similar whether lower or higher PEEP levels are used.

Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome

The acute respiratory distress syndrome (ARDS) is an important cause of acute respiratory failure that is often associated with multiple organ failure. Several clinical disorders can precipitate ARDS, including pneumonia, sepsis, aspiration of gastric contents, and major trauma. Physiologically, ARDS is characterized by increased permeability pulmonary edema, severe arterial hypoxemia, and impaired carbon dioxide excretion. Based on both experimental and clinical studies, progress has been made in understanding the mechanisms responsible for the pathogenesis and the resolution of lung injury, including the contribution of environmental and genetic factors. Improved survival has been achieved with the use of lung-protective ventilation. Future progress will depend on developing novel therapeutics that can facilitate and enhance lung repair.

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The acute respiratory distress syndrome.

Mechanical ventilation may cause injury to the ventilated lung. This article reviews the probable causes of such injury and ways to prevent it.

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Ventilator-Induced Lung Injury

Background In the acute respiratory distress syndrome (ARDS), positive end-expiratory pressure (PEEP) may decrease ventilator-induced lung injury by keeping lung regions open that otherwise would be collapsed. Since the effects of PEEP probably depend on the recruitability of lung tissue, we conducted a study to examine the relationship between the percentage of potentially recruitable lung, as indicated by computed tomography (CT), and the clinical and physiological effects of PEEP. Methods Sixty-eight patients with acute lung injury or ARDS underwent whole-lung CT during breath-holding sessions at airway pressures of 5, 15, and 45 cm of water. The percentage of potentially recruitable lung was defined as the proportion of lung tissue in which aeration was restored at airway pressures between 5 and 45 cm of water. Results The percentage of potentially recruitable lung varied widely in the population, accounting for a mean (±SD) of 13±11 percent of the lung weight, and was highly correlated with the percentage of lung tissue in which aeration was maintained after the application of PEEP (r 2 = 0.72, P<0.001). On average, 24 percent of the lung could not be recruited. Patients with a higher percentage of potentially recruitable lung (greater than the median value of 9 percent) had greater total lung weights (P<0.001), poorer oxygenation (defined as a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen) (P<0.001) and respiratory-system compliance (P = 0.002), higher levels of dead space (P = 0.002), and higher rates of death (P = 0.02) than patients with a lower percentage of potentially recruitable lung. The combined physiological variables predicted, with a sensitivity of 71 percent and a specificity of 59 percent, whether a patient’s proportion of potentially recruitable lung was higher or lower than the median. Conclusions In ARDS, the percentage of potentially recruitable lung is extremely variable and is strongly associated with the response to PEEP.

/pdf/lung-recruitment-in-patients-with-the-acute-respiratory-jbh1jtt49v.pdf

Lung Recruitment in Patients with the Acute Respiratory Distress Syndrome

ContextStudies have shown that an inflammatory response may be elicited by
mechanical ventilation used for recruitment or derecruitment of collapsed
lung units or to overdistend alveolar regions, and that a lung-protective
strategy may reduce this response.ObjectiveTo test the hypothesis that mechanical ventilation induces a pulmonary
and systemic cytokine response that can be minimized by limiting recruitment
or derecruitment and overdistention.Design and SettingRandomized controlled trial in the intensive care units of 2 European
hospitals from November 1995 to February 1998, with a 28-day follow-up.PatientsForty-four patients (mean [SD] age, 50 [18] years) with acute respiratory
distress syndrome were enrolled, 7 of whom were withdrawn due to adverse events.InterventionsAfter admission, volume-pressure curves were measured and bronchoalveolar
lavage and blood samples were obtained. Patients were randomized to either
the control group (n=19): tidal volume to obtain normal values of arterial
carbon dioxide tension (35-40 mm Hg) and positive end-expiratory pressure
(PEEP) producing the greatest improvement in arterial oxygen saturation without
worsening hemodynamics; or the lung-protective strategy group (n=18): tidal
volume and PEEP based on the volume-pressure curve. Measurements were repeated
24 to 30 and 36 to 40 hours after randomization.Main Outcome MeasuresPulmonary and systemic concentrations of inflammatory mediators approximately
36 hours after randomization.ResultsPhysiological characteristics and cytokine concentrations were similar
in both groups at randomization. There were significant differences (mean
[SD]) between the control and lung-protective strategy groups in tidal volume
(11.1 [1.3] vs 7.6 [1.1] mL/kg), end-inspiratory plateau pressures (31.0 [4.5]
vs 24.6 [2.4] cm H2O), and PEEP (6.5 [1.7] vs 14.8 [2.7] cm H2O) (P<.001). Patients in the control group
had an increase in bronchoalveolar lavage concentrations of interleukin (IL)
1β, IL-6, and IL-1 receptor agonist and in both bronchoalveolar lavage
and plasma concentrations of tumor necrosis factor (TNF) α, IL-6, and
TNF-α receptors over 36 hours (P<.05 for
all). Patients in the lung-protective strategy group had a reduction in bronchoalveolar
lavage concentrations of polymorphonuclear cells, TNF-α, IL-1β,
soluble TNF-α receptor 55, and IL-8, and in plasma and bronchoalveolar
lavage concentrations of IL-6, soluble TNF-α receptor 75, and IL-1 receptor
antagonist (P<.05). The concentration of the inflammatory
mediators 36 hours after randomization was significantly lower in the lung-protective
strategy group than in the control group (P<.05).ConclusionsMechanical ventilation can induce a cytokine response that may be attenuated
by a strategy to minimize overdistention and recruitment/derecruitment of
the lung. Whether these physiological improvements are associated with improvements
in clinical end points should be determined in future studies.

https://jamanetwork.com/journals/jama/articlepdf/190583/jce80051.pdf

Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial.

Effect of Mechanical Ventilation on Inflammatory Mediators in Patients with Acute Respiratory Distress Syndrome: A Randomized Controlled Trial

Background: Body weight (BW) loss is an essential therapeutic goal in type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists are effective in reducing BW, but their effect on body composition has not yet been fully explored. The study aim was to assess the impact of Semaglutide on body composition in patients with T2D. Methods: Forty patients with T2D were treated with subcutaneous Semaglutide and evaluated at the baseline (T0) and after three (T3) and six (T6) months. Body composition was assessed by a phase-sensitive bioimpedance analyzer. Visceral adipose tissue (VAT) thickness was also measured with an ultrasonographic method (US-VAT). Anthropometric variables, muscular strength, and laboratory tests were analyzed and compared. Results: A significant decrease in VAT, the fat mass index (FMI), and BW loss was observed at all observation times. US-VAT, the skeletal mass index (SMI), the fat-free mass index (FFMI), waist circumferences, and glycated hemoglobin had lessened after three months and remained stable at T6. No variations in muscle strength, the muscle quality index, and body water were found. Discussion: In a real-life setting, Semaglutide provided significant weight loss mainly due to a reduction in the FMI and VAT, with non-clinically relevant changes in the SMI, the FFMI, and muscle strength. Most importantly, the results were obtained after three months of treatment and persisted thereafter.

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Once-Weekly Semaglutide Induces an Early Improvement in Body Composition in Patients with Type 2 Diabetes: A 26-Week Prospective Real-Life Study

Abstract We evaluated the clinical impact, in daily clinical practice, of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) therapies in patients with type 2 diabetes. Data from 500 unselected consecutive patients were retrospectively analyzed. Only those with a full assessment at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment with SGLT2i or GLP1RA were included in the study (n = 167). At baseline, patients had a high mean body weight (BW), abdominal circumference (AC), body mass index (BMI), and HOMA index. Despite normal C-peptide values, 39 patients were being treated with insulin (up to 120 IU/day). During therapy, a progressive improvement in BW, BMI, and AC was observed with both the molecules. Fasting glucose and glycated Hb decrease was already significant at T3 in all patients, while the HOMA index selectively improved with SGLT2i therapy. Renal function parameters remained stable regardless of the drug used. Finally, SGLT2i reduced serum uric acid and improved the lipid profile, while GLP1RA reduced serum levels of liver enzymes. Both the therapeutic regimens allowed a significant reduction or complete suspension of unnecessary insulin therapies. Our real life data confirm the results obtained from randomized clinical trials and should be taken as a warning against inappropriate use of insulin in patients with preserved β-cell function.

/pdf/effectiveness-and-clinical-benefits-of-new-anti-diabetic-3dj619ai.pdf

Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience

BACKGROUND
The Italian population's habits changed dramatically during the "COVID-19 lockdown" due to physical distancing and self-isolation. Moreover, medical consultations of patients with chronic diseases, such as type 2 diabetes (T2D), were suspended or postponed, unless urgent or semi-urgent, for several consecutive months. Thus, it is expected that the lockdown could have affected glucometabolic control in T2D.


PURPOSE
The aim of the study was to assess changes in glucometabolic control in a cohort of T2D patients before (T1) and after (T2) the COVID-19 lockdown (March-May 2020).


METHODS
The study was approved by the Ethics Committee of the University of Bari, and all patients provided informed written consent to participate. Medical history, complete physical examination, and laboratory assessment were conducted as real-life clinical practice. Changes in clinical and laboratory variables between T1 and T2 were calculated.


RESULTS
In detail, 13 patients were on metformin as monotherapy, 36 on GLP-1RA, 12 on sodium-glucose transporter 2 inhibitors (SGLT-2i), and 2 on dipeptidyl-peptidase 4 inhibitors (DPP4i). The mean age was 65.3 years (43-83). Study participants were mainly men (73%). The body weight (BW) ranged from 56 to 145 kg, and the waist circumference ranged from 88 to 146 cm. The mean HbA1c was 51.0 mmol/mol. At T2, no statistically significant changes were observed from baseline except for BW [-1.6 (-2.60 to -0.62)] and HbA1c [-2.90 (-4.69; -1.12)].


CONCLUSION
We evaluated the effects of the COVID-19 lockdown on glucometabolic control in patients with background well-controlled T2D. We found that the lockdown had no adverse effects on metabolic profile regardless of background clinical characteristics and antihyperglycemic management. Despite limitations due to the nature of this study (sample size, retrospective observation, lack of data on lifestyle changes in our patients' everyday lives), T2D patients managed in our Diabetes Centers faced the lockdown-related restrictions without any detrimental consequence.

Cosimo Tortorella

Papers

Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial.

Effect of Mechanical Ventilation on Inflammatory Mediators in Patients with Acute Respiratory Distress Syndrome: A Randomized Controlled Trial

Once-Weekly Semaglutide Induces an Early Improvement in Body Composition in Patients with Type 2 Diabetes: A 26-Week Prospective Real-Life Study

Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience

The Impact of COVID-19 Lockdown on Patients with Type 2 Diabetes Mellitus: A Brief Report.