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  • 1
    In: Pancreatology, Elsevier BV, Vol. 22, No. 7 ( 2022-11), p. 902-916
    Type of Medium: Online Resource
    ISSN: 1424-3903
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2043694-4
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  • 2
    In: Updates in Surgery, Springer Science and Business Media LLC, Vol. 75, No. 3 ( 2023-04), p. 493-522
    Abstract: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension ( p  = 0.032; 95% CI 1.135–15.882; aOR 4.245), qSOFA ( p  = 0.005; 95% CI 1.359–5.879; aOR 2.828), renal failure ( p  = 0.022; 95% CI 1.138–5.442; aOR 2.489), and haemodynamic failure ( p  = 0.018; 95% CI 1.184–5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis ( p  = 0.003; 95% CI 1.598–9.930; aOR 3.983), abdominal compartment syndrome ( p  = 0.032; 95% CI 1.090–6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding ( p  = 0.009; 95% CI 1.286–5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality ( p   〈  0.001; 95% CI 1.912–7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis ( p  = 0.018; 95% CI 0.138–0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143–0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990). Graphical abstract
    Type of Medium: Online Resource
    ISSN: 2038-131X , 2038-3312
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2562178-6
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  • 3
    In: JAMA Surgery, American Medical Association (AMA), Vol. 158, No. 10 ( 2023-10-11), p. e233660-
    Abstract: Considering the lack of equipoise regarding the timing of cholecystectomy in patients with moderately severe and severe acute biliary pancreatitis (ABP), it is critical to assess this issue. Objective To assess the outcomes of early cholecystectomy (EC) in patients with moderately severe and severe ABP. Design, Settings, and Participants This cohort study retrospectively analyzed real-life data from the MANCTRA-1 (Compliance With Evidence-Based Clinical Guidelines in the Management of Acute Biliary Pancreatitis) data set, assessing 5304 consecutive patients hospitalized between January 1, 2019, and December 31, 2020, for ABP from 42 countries. A total of 3696 patients who were hospitalized for ABP and underwent cholecystectomy were included in the analysis; of these, 1202 underwent EC, defined as a cholecystectomy performed within 14 days of admission. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality and morbidity. Data analysis was performed from January to February 2023. Main Outcomes Mortality and morbidity after EC. Results Of the 3696 patients (mean [SD] age, 58.5 [17.8] years; 1907 [51.5%] female) included in the analysis, 1202 (32.5%) underwent EC and 2494 (67.5%) underwent delayed cholecystectomy (DC). Overall, EC presented an increased risk of postoperative mortality (1.4% vs 0.1%, P   & amp;lt; .001) and morbidity (7.7% vs 3.7%, P   & amp;lt; .001) compared with DC. On the multivariable analysis, moderately severe and severe ABP were associated with increased mortality (odds ratio [OR], 361.46; 95% CI, 2.28-57 212.31; P  = .02) and morbidity (OR, 2.64; 95% CI, 1.35-5.19; P  = .005). In patients with moderately severe and severe ABP (n = 108), EC was associated with an increased risk of mortality (16 [15.6%] vs 0 [0%] , P   & amp;lt; .001), morbidity (30 [30.3%] vs 57 [5.5%] , P   & amp;lt; .001), bile leakage (2 [2.4%] vs 4 [0.4%] , P  = .02), and infections (12 [14.6%] vs 4 [0.4%] , P   & amp;lt; .001) compared with patients with mild ABP who underwent EC. In patients with moderately severe and severe ABP (n = 108), EC was associated with higher mortality (16 [15.6%] vs 2 [1.2%] , P   & amp;lt; .001), morbidity (30 [30.3%] vs 17 [10.3%] , P   & amp;lt; .001), and infections (12 [14.6%] vs 2 [1.3%] , P   & amp;lt; .001) compared with patients with moderately severe and severe ABP who underwent DC. On the multivariable analysis, the patient’s age (OR, 1.12; 95% CI, 1.02-1.36; P  = .03) and American Society of Anesthesiologists score (OR, 5.91; 95% CI, 1.06-32.78; P  = .04) were associated with mortality; severe complications of ABP were associated with increased mortality (OR, 50.04; 95% CI, 2.37-1058.01; P  = .01) and morbidity (OR, 33.64; 95% CI, 3.19-354.73; P  = .003). Conclusions and Relevance This cohort study’s findings suggest that EC should be considered carefully in patients with moderately severe and severe ABP, as it was associated with increased postoperative mortality and morbidity. However, older and more fragile patients manifesting severe complications related to ABP should most likely not be considered for EC.
    Type of Medium: Online Resource
    ISSN: 2168-6254
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 4
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 124-124
    Abstract: Introduction Limited stage follicular lymphoma (FL) is usually managed with involved field radiotherapy (IFRT), although different approaches are currently carried out, ranging from watch and wait to combined treatment. RT on involved lymph nodes allows eradication of the disease only in 40-50% of patients. Anti-CD20 monoclonal antibodies (MoAb), widely used in advanced stage FL, are likely to be effective in reducing the relapse risk, although no scientific evidence of their role has been provided. The aim of this multicenter phase II prospective study was to evaluate the role of MRD in identifying patients unlikely to be cured by RT, for whom an immunotherapy-based consolidation could improve outcome. Methods 110 patients with stage I/II FL were enrolled. IFRT was administered to all patients at a dose of 24 Gy. Peripheral blood (PB) and bone marrow (BM) samples were centralized to the Italian FIL (Federazione Italiani Linfomi) MRD Network of EuroMRD-certified laboratories: the presence of a BCL2/IGH rearrangement was investigated at baseline in all patients by nested PCR (NEST) and RQ-PCR (RQ), the latter according to the EuroMRD guidelines. In patients BCL2/IGH+ at baseline by both NEST and RQ in BM and/or PB, MRD was analyzed in both tissues after IFRT and every 6 months over a three-year follow-up period. Patients with positive MRD by both NEST and RQ in BM and/or PB after IFRT or who became positive during the follow-up were treated with 8 weekly doses of the anti-CD20 MoAb ofatumumab. The primary objective of the study was to define the efficacy of immunotherapy in obtaining the disappearance of BCL2/IGH rearranged cells. Results Preliminary data are available for 107 patients, 57 males, 50 females. Median age was 55 years (29-83). 17% had G1 FL, 32% G2, 40% G3A, 11% NOS. The FLIPI score was 0 in 59% of patients, 1 in 35%, 2 in 6%. 69% of patients had inguinal site involvement. Despite a negative BM biopsy, at baseline 30% of patients (n=32) had a BCL2/IGH rearrangement (30 MBR, 1 MBR and mcr, 1 mcr) in the BM and/or PB; the concordance between compartments was 90%, with 10% of negative PB showing a positive BM. No significant differences were observed in relapse probability between patients with or without a molecular marker. All patients were submitted to IFRT and all obtained a clinical response, which was complete in 79 of the 101 evaluated patients (78%) and partial in 22 (22%). MRD evaluation after treatment revealed the persistence of BCL2/IGH rearranged cells in the PB and/or BM in 60% of patients. According to the design of the protocol, MRD-positive patients, either after IFRT (n=18) or in case of conversion to a positive signal during the follow-up (n=7), received 8 weekly administration of ofatumumab. A conversion to MRD negativity, evaluated in 23 treated patients, was obtained in 20 (87% - CI 65.1-97.1). This result was significantly superior to the expected 50%. One death occurred after IFRT, due to ischemic stroke. Adverse events likely correlated to ofatumumab occurred in 7/25 treated patients, consisting of infusion reactions in 5, leading to a permanent interruption of immunotherapy in 3. After a median follow-up of 18 months, all patients who achieved a MRD negativity with ofatumumab underwent a regular molecular follow-up and are still MRD-negative. Overall, clinical relapse or progression were observed in 17 patients: 13 (18%) among the 73 "no marker" patients; 2 relapses (16%) were observed among the 12 MRD-negative patients after IFRT and 2 relapses were observed among the 23 patients treated with the anti-CD20 MoAb (8.7%), 1 having achieved a MRD negativity and 1 not. No significant differences in event-free survival have so far been observed between the three groups. Conclusions The MRD data of this phase II trial for early stage FL indicate that RT alone is often insufficient to eradicate the disease, being capable of inducing a negative MRD only in 40% of evaluable cases, with a long-lasting effect only in half of them. The primary objective of this study - MRD negativity after immunotherapy - was achieved, obtaining the disappearance of BCL2/IGH rearranged cells in the majority of patients treated with ofatumumab. The strategy of an immunotherapy consolidation after IFRT in MRD-positive patients allowed to increase molecular responses. A longer follow-up and further studies on larger patient populations will allow to conclusively define the impact of this MRD-driven strategy also on clinical outcome. Disclosures Pulsoni: Roche: Consultancy, Speakers Bureau; Takeda: Consultancy; Pfizer: Consultancy; Sandoz: Consultancy; Gilead: Speakers Bureau; Merk: Consultancy; Bristol Meyer Squibb: Speakers Bureau. Ferrero:Servier: Speakers Bureau; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Gilead: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Luminari:ROCHE: Other: Role as Advisor ; CELGENE: Other: Role as Advisor & Travel Grant; TAKEDA: Other: Travel Grant; GILEAD: Other: Lecturer . Liberati:Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Celgene: Honoraria, Other: Clinical trial support; Bristol-Myers Squibb: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Janssen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Roche: Other: Clinical trial support; Novartis: Other: Clinical trial support. Ferreri:Roche: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Kite: Consultancy. Nassi:Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Corradini:Roche: Honoraria; Novartis: Honoraria; kite: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria. Mannina:Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Arcaini:Celgene: Speakers Bureau; Gilead Sciences: Research Funding; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses. Galimberti:Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau. Ladetto:AbbVie: Honoraria; Roche: Honoraria; ADC Therapeutics: Honoraria; Acerta: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; J & J: Honoraria; Celgene: Honoraria. Foà:Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: The anti-CD20 MoAb Ofatumomab is employed to eradicate Minimal Residual Disease in early stage Follicular Lymphoma(FL). The drug is registered for Chronic Lymphocytic Leukemia, not for FL.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Cancer Chemotherapy and Pharmacology, Springer Science and Business Media LLC, Vol. 79, No. 4 ( 2017-4), p. 767-773
    Type of Medium: Online Resource
    ISSN: 0344-5704 , 1432-0843
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 1458488-8
    SSG: 15,3
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  • 6
    In: European Journal of Heart Failure, Wiley
    Abstract: In the EXPLORER‐HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real‐world HOCM patients with those enrolled in EXPLORER‐HCM and assessing their eligibility to treatment. Methods and results We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.e. gradient ≥30 mmHg at rest or ≥50 mmHg after Valsalva manoeuvre or exercise) despite pharmacological or non‐pharmacological therapy. Pharmacological or non‐pharmacological therapy resolved LVOTO in 1044 (61.2%) of the 1706 HOCM patients under active follow‐up, whereas 662 patients (38.8%) had persistent LVOTO. Compared to the EXPLORER‐HCM trial population, these real‐world HOCM patients were older (62.1 ± 14.3 vs. 58.5 ± 12.2 years, p = 0.02), had a lower body mass index (26.8 ± 5.3 vs. 29.7 ± 4.9 kg/m 2 , p 〈 0.0001) and a more frequent history of atrial fibrillation (21.5% vs. 9.8%, p = 0.027). At echocardiography, they had lower left ventricular ejection fraction (LVEF, 66 ± 7% vs. 74 ± 6%, p 〈 0.0001), higher left ventricular outflow tract gradients at rest (60 ± 27 vs. 52 ± 29 mmHg, p = 0.003), and larger left atrial volume index (49 ± 16 vs. 40 ± 12 ml/m 2 , p 〈 0.0001). Overall, 324 (48.9%) would have been eligible for enrolment in the EXPLORER‐HCM trial and 339 (51.2%) for treatment with mavacamten according to European guidelines. Conclusions Real‐world HOCM patients differ from the EXPLORER‐HCM population for their older age, lower LVEF and larger atrial volume, potentially reflecting a more advanced stage of the disease. About half of real‐world HOCM patients were found eligible to mavacamten.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 1500332-2
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  • 7
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3951-3951
    Abstract: Introduction. Drug transporters, such as ABCB1, hOCT1, and ABCG2, control both intracellular and systemic plasma concentrations of BCR-ABL1 inhibitors. Our group previously reported that the hOCT1 c.480C 〉 G polymorphism significantly correlated with higher rates of adverse events and shorter event-free survival (EFS) of patients receiving imatinib. Even if nilotinib has less affinity than imatinib for the transmembrane transporters, no definitive data about the possible role of their polymorphisms are available from the "real life". Methods. Through an approach similar to the one previously used for imatinib, we investigated any possible influence of ABCB1 and hOCT1 polymorphisms on the nilotinib efficacy and toxicity in a series of 78 CML patients receiving nilotinib as first-line therapy in 8 Italian Centers from June 2012 to June 2016. Lack of CCyR at 12 months, stop of treatment for any cause, loss of MR3 or CCyR, appearance of mutations were computed as events in the EFS assessment. The following polymorphisms were tested by real-time PCR: hOCT1: rs683369[c.480C 〉 G]; ABCB1: rs1128503 [c.1236C 〉 T], rs2032582[c.2677G 〉 T/A], and rs1045642[c.3435C 〉 T]. Results. Forty-six patients were male and 32 female; the median age was 47 years (range, 18-79); Sokal score was low in 44%, intermediate in 37%, and high in 19% of cases; EUTOS was high in 30%. Efficacy: 97% of patients were in CHR and 82% in early molecular response (EMR) at 3 months; 85% achieved the CCyR at 6 months, and 88% the MR3 with a median time of 6.1 months; 78% achieved a deep molecular response (DMR), with 14% of MR5, with a median time of 26 months.With a median follow-up of 36 months, no patient lost CCyR and 9% lost MR3. All patients are still alive; 23% of patients stopped nilotinib (one third of them because of failure), and half of them reduced to 〈 600 mg/day at least once; 3-year EFS was 90%.Patients were grouped according to the absence or the presence of at least one polymorphic allele (heterozygous or polymorphic homozygous): concerning c.3435C 〉 T SNP, 56% of patients were heterozigous and 22% omozigous polymorphic; for the c1236 C 〉 T SNP, 54% of patients were heterozigous and 12% omozigous polymorphic; finally, for the hOCT1 c.480 C 〉 G, 41% of patients were heterozigous and 10% omozigous polymorphic.We found that ABCB1 and hOCT1 polymorphisms did not condition the achievement of CHR, CCyR, or MR3. Nevertheless, polymorphism of ABCB1 (c.3435C 〉 T) was associated with a higher probability of achieving DMR (90% vs 65%; p=0.04).A longer 3-year EFS was conditioned by the achievement of EMR (90% vs 75%; p=0.012) and of MR3 (90% vs 65%: p=0.04). We found that polymorphic or wild-type status of transporters did not impact on EFS.Toxicities were observed in 41% of cases, with 40% of grade 3 or 4; ABCB1 and hOCT1 polymorphisms did not condition toxicities or nilotinib discontinuation. Conclusions. Our previous studies showed that polymorphic hOCT1 negatively conditioned CCyR and EFS during imatinib treatment, and that the combination of ABCB1 and hOCT1 polymorphisms were related to higher levels of toxicity.On the contrary, the present study demonstrated that the same polymorphisms did not condition toxicity when patients received nilotinib as first-line treatment. About efficacy, even if in a multicentric "real life" setting, it resulted superimposable to that reported in literature. We found that hOCT1 polymorphism did not have any impact on the quality of response; on the contrary, the ABCB1 c.3435C 〉 T polymorphism (that induces a lower efflux from the leukemic cell and lower intestinal and renal excretion) was associated to a high rate of deep molecular response.On the basis of these results, we demonstrated that hOCT1 and ABCB1 polymorphisms, differently from the imatinib setting, are not relevant in patients receiving nilotinib, and that patients polymorphic for ABCB1 can even receive an advantage on DMR. Disclosures Saglio: Ariad: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 57, No. 2 ( 2016-02), p. 400-410
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2016
    detail.hit.zdb_id: 2030637-4
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  • 9
    In: Oncotarget, Impact Journals, LLC, Vol. 8, No. 50 ( 2017-10-20), p. 88021-88033
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2560162-3
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  • 10
    In: Critical Care, Springer Science and Business Media LLC, Vol. 25, No. 1 ( 2021-12)
    Abstract: Flow Index, a numerical expression of the shape of the inspiratory flow-time waveform recorded during pressure support ventilation, is associated with patient inspiratory effort. The aim of this study was to assess the accuracy of Flow Index in detecting high or low inspiratory effort during pressure support ventilation and to establish cutoff values for the Flow index to identify these conditions. The secondary aim was to compare the performance of Flow index,of breathing pattern parameters and of airway occlusion pressure ( P 0.1 ) in detecting high or low inspiratory effort during pressure support ventilation. Methods Data from 24 subjects was included in the analysis, accounting for a total of 702 breaths. Breaths with high inspiratory effort were defined by a pressure developed by inspiratory muscles ( P musc ) greater than 10 cmH 2 O while breaths with low inspiratory effort were defined by a P musc lower than 5 cmH 2 O. The areas under the receiver operating characteristic curves of Flow Index and respiratory rate, tidal volume,respiratory rate over tidal volume and P 0.1 were analyzed and compared to identify breaths with low or high inspiratory effort. Results P musc , P 0.1 , Pressure Time Product and Flow Index differed between breaths with high, low and intermediate inspiratory effort, while RR, RR/ V T and V T /kg of IBW did not differ in a statistically significant way. A Flow index higher than 4.5 identified breaths with high inspiratory effort [AUC 0.89 (CI 95% 0.85–0.93)], a Flow Index lower than 2.6 identified breaths with low inspiratory effort [AUC 0.80 (CI 95% 0.76–0.83)] . Conclusions Flow Index is accurate in detecting high and low spontaneous inspiratory effort during pressure support ventilation.
    Type of Medium: Online Resource
    ISSN: 1364-8535
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2051256-9
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