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Background: Sleep is a significant dimension of daily life. However, only a few studies have examined the sleep quality of asthmatics in a real-world clinical settings. Objective: This study is aimed to estimate the prevalence of sleep impairments among asthmatic patients and examine the relationship between sleep quality, asthma control, rhinitis symptoms, and sociodemographic characteristics. Methods: The present study adopted the observational cross-sectional research design that has been designed by the Italian Respiratory Society and used valid assessments to measure the study variables. Results: Data from 1150 asthmatic patients (mean age 51.01 years ± 16.03) were subjected to analysis. 58.3% of the patients had impaired sleep quality (Pittsburgh Sleep Quality Index [PSQI] total scores > 5), and their mean PSQI score was 5.68 (SD = 3.4). A significant correlation emerged between sleep quality and asthma control (p = 0.0001) and a significant albeit weak correlation emerged between PSQI total scores and Total 5 Symptoms Score (r = 0.24, p = 0.0001). Sleep quality was significantly associated health-related quality of life [HRQoL]. (r = 0.50, p < 0.001). After exclusion of patients at risk for Obstructive Sleep Apnea Syndrome (OSAS) and Gastro Esophageal Reflux Disease (GERD), the most important determinants of PSQI score were HRQoL, In the entire sample asthma control is the strongest predictor of both sleep quality and HRQoL. Conclusions: The results of this real-world study highlight the prevalence, impact and predictors of sleep disturbances in asthmatic patients and suggest the need for physicians to detect poor sleep quality.

The increasing need of collecting high quality blood components and of improving the overall productivity of a blood centre requires the utilisation of a new innovative process that combines high speed collection with an automated process and blood component tailoring to fit individual patient requirements. We collected dosed Red Blood Cell (dRBC) units on 64 donors, eligible as regular donors on the Gambro BCT TRIMA using the dRBC collection protocol. The collection target was set to 180 ml packed Red Blood Cells (pRBCs) in 225 ml total collection volume (n = 7), or 300 ml pRBCs in 375 ml total collection volume (n = 33) or 360 ml in 450 ml (n = 24), depending on donor's hematological profile and blood volemia. Saline was infused as the replacement fluid at a 120%) collection:infusion ratio. Donor per cent hematocrit was (mean +/- S.D.) 43.7 +/- 4.0% and TBV = 4.99 +/- 0.69 1. The procedures yielded 100 +/- 6% of predicted yield, with a hematocrit of 78.2 +/- 6.6% in 29 +/- 3 min. Hb content was 99.9 +/- 21.8 in all procedures, or 61.5-94.4-118.6 g in the three groups, respectively. After the addition of the SAG-M storage solution, the hematocrit was 56.3 +/- 6.2%. No adverse reactions have been reported by the donors and all pPRBC units were transfused to patients without any transfusion reaction being reported by clinicians. The dRBC protocol is well tolerated by donors without any side effects, other than normal effects of regular blood donation. Higher pRBC productivity can be reached with a safe and automated process in conjunction with a high and consistent product quality easily matching the donor collection criteria and pRBC unit standards. Tailoring of pRBC units can result in an improved patient transfusion support.

Efforts to improve the purity of blood products have mainly focused on reducing white blood cell (WBC) levels in cellular blood products. Relatively little attention has been given to the cellular purity of plasma. We evaluated plasma units collected on six apheresis systems: Dideco Excel, Haemonetics-MCS+, Fresenius-AS-Tech 204, Baxter-Amicus, Gambro BCT COBE Spectra and Gambro BCT-Trima. Collected plasma volumes averaged 300-350 ml for the various systems. Plasma samples were analyzed for platelet (PLT) content (Technicon H3, Bayer) and residual WBC (Imagn 2000). Results are given below. Platelet levels were consistently low for MCS+, COBE Spectra and Trima (all50 x 10(3) microl(-1)), and were highest with AS204. Residual WBC levels were relatively low in all systems except MCS+. Extremely low levels were observed in Trima plasma. All of the Trima and Spectra units contained1 x 10(6) WBC per product. With Excel, AS-Tech 204 and Amicus, 1 to 2 units were found to have1 x 10(6) WBC, while almost all units from MCS+ exceeded this limit. Different levels of plasma purity were obtained with different apheresis systems. The Gambro BCT COBE Spectra and Trima systems were found to achieve consistently low levels of both platelets and WBC.

Since 1989 we have been collecting dry-platelets on a routine basis. Dry-platelets are those collected along with 25–30 ml of contaminating plasma cell with separators such as the Amicus, AS 104 and the Excel Pro. Platelets are resuspended in non plasma media for storage and for at least 60 hours their viability and functionality are not impaired. In this article we report on two hemolytic crises determined by two O Rh D + units of single donor platelets (SPD) taken from the same donor in a double-apheresis session. The two split units were admistered to two A Rh D + patients suffering from metastatic breast cancer and severe aplastic anemia (SAA) respectively. In both cases the hemolytic reaction was of the intravascular type, with a drop in hemoglobin (Hgb) level from 8.6 to 5.4 and from 8.8 down to 5.3 g/dl respectively. From the patients’ RBC only α - agglutinins were eluted and donor's indirect antiglobulin test (IAT) was negative with extended panel RBCs. In the first case the clinical course after erythroexchange (Erex) was uneventful whereas in the second one, that suffering from SAA, after Erex, acute renal failure and shock did complicate the clinical course and the patient died seven days after the incriminated platelet transfusion.

TTP remains enigmatic both in terms of etiology and management. The most recent approach is aggressive plasma exchange (PE) employing cryopoor plasma for replacement, based on the pathogenetic relevance given to exceedingly large Von Willebrand (VWF) multimers in the determination of the syndrome with normalization during remission. PE with fresh frozen plasma (FFP) is better than FFP infusion as shown by a recent Canadian study, supporting the theory that to treat TTP an offending circulating agent needs to be removed from the patient's plasma in contrast to the hypothesis that a missing factor is to be given along with FFP. A more recent hypothesis is supported by the results of studies published by the end of 1998 [Moake J, Chintagumpala M, Turner N et al. Blood 1994;84:490-97; Moake J, McPherson PD. Am J Med 1989;87: 3-9N] which would show that TTP is mediated by auto-antibodies to VWF-cleaving protease, or is the result of deficiency of the protease ascribed to abnormalities in its production, function or survival. Plasmapheresis without plasma infusion is relatively ineffective perhaps because it does not increase the protease activity. Cascade filtration (CF) is the autologous counterpart of plasmapheresis. It has been used by our group since 1980 to remove from patients plasma macromolecules such as VWF, fibrinogen, LDL and circulatory immune complexes (CIC). After secondary filtration, the autologous plasma has a composition which is very similar to that of allogeneic plasma after cryoprecipitation, a product which used in the management of TTP. Based on this knowledge, in 1994 we began to use CF in the treatment of TTP patients. In the beginning (7 patients) CF was combined with a decreasing number of conventional PEs using allogeneic plasma for substitution. Lately only CF with some plasma supplementation has been used in the last 9 cases. From a clinical point of view our 16 patients achieved remission after a number of treatments (11 +/- 7) that compares sufficiently well with those required by our historical control group of 47 cases (14 +/- 13). Of course the patient's exposure to allogenic plasma was significantly lower for patients in the CF only group (1.4 +/- 1.2 plasma U/session) compared to the PE + CF group (4.4 +/- 2.3 plasma U/session) or for the controls treated by PE only (10.8 +/- 4.6 plasma U/session). There were no deaths in the CF or PE + CF groups and no untoward effect was observed. On the contrary there were 5 deaths (1 on the day of presentation) in the PE group, and 1 HBV and 2 HCV infections as well as 4 severe allergic reactions to plasma proteins (or passive antibody infusion). We conclude that CF is presently the best treatment to offer to patients suffering from sporadic TTP and that CF may contribute to expanding the knowledge of the pathogenetic mechanisms of this uncommon multisystem disorder.

In apheresis, leukodepletion by secondary filtration of the platelet components or by the primary use of special high efficiency apparatuses is widely used to meet current clinical practice. Leukodepletion of RBC is mandatory for hemato-oncological patients and new filters for plasma are progressively being introduced in the routine of European blood banks. However, since the monitoring of leukodepletion efficiency continues to be carried out manually using the Nageotte or the microdroplet fluorescence assay (MFA), inaccuracy and labour-intensity of counting will limit the possibility of satisfying the increasing demand for leukodepletion monitoring. Volumetric capillary cytometry (VCC) is a totally automated system that has been shown to correlate well with Nageotte, MFA and flow-cytometric countings of residual leukocytes in platelet and RBC product. In this article we describe the application of VCC in the quality control program of our hemapheresis unit in which all apheresis donations are of the multicomponent collection type.

BACKGROUND Collection of multiple products including plasma, packed red blood cells (PBRC) and double units of platelets, is increasingly improving donor utilisation and decreasing blood transfusion costs. Total apheresis is the new trend in blood banking and both industry and physicians are progressively expanding their involvement in this field. During 1998, at our hemapheresis unit, we used three new apparatuses for multicomponent collection (MCC). These apparatuses vary in terms of principle, operation and specific capabilities, and thus knowledge of them is essential to match their characteristics with plateletapheresis needs. STUDY DESIGN We reviewed all MCCs carried out in 1998 with MCS+, Trima and Excel-Pro cell separators. These apparatuses were evaluated in terms of platelet yield, white blood cell (WBC) contamination, efficiency per minute, platelet activation, and PBRC product quality. RESULTS The three machines are compared in the following table [table in text]. CONCLUSIONS MCC with the new apparatuses is well accepted by donors and personnel. There are no risks for the donors and, excluding ACD reactions and/or vaso/vagal attacks at the beginning of procedures, no severe reaction was seen. The quality and quantity of platelet products are good. When PRBC or a second platelets unit are collected, the cost of the kit is covered by this double product.

Collection of multiple products, including single and double units of platelets (SDP, DPP), plasma and RBC is progressively improving donor utilization and is leading to more cost-effective apheresis. Cell separators such as the Fresenius AS 204, the Dideco Excel version 97 and the Baxter Amicus are newcomers to the family of the last generation apparatuses used for MCC such as the AS 104, the Vivacell and the MCS 3p. The Cobe Spectra is for the moment the only apparatus unable to collect packed RBC along with platelets but Cobe too is moving in the direction of MCC. The next step is triple product apheresis.

Mobilized peripheral blood progenitor cells (PBPC) are increasingly used to reconstitute hematopoiesis in patients undergoing high-dose chemoradiotherapy. PBPC collections comprise a heterogeneous population containing both committed progenitors and pluripotent stem cells and can be harvested (i) in steady state, (ii) after chemotherapeutic conditioning, (iii) growth factor priming, or (iv) both. The use of PBPC has opened new therapeutic perspectives mainly related to the availability of large amounts of mobilized hematopoietic stem and progenitor cells. Extensive manipulation of the grafts, including the possibility of exploiting these cells as vehicles for gene therapy strategies, are now possible and will be reviewed.

There has been an increasing interest in recent years over the qualitative superiority of single-donor platelets in the management of hemato-oncologic patients. The reasonable desire of both patients and physicians to limit the risks of transfusion along with the need for limiting the costs involved in this kind of therapy have led to application of multicomponent donations both in terms of double platelet concentrates and double products such as red blood cells (RBC) and platelets from the same donor. Single donor platelets and RBC have been collected in a semi-automated mode and only the very recent introduction of the Haemonetics MCS 3p with its SDP/RBC protocol provides a totally closed-system automated protocol for this combined collection. Twenty procedures have been carried out so far at our unit. In a mean of 87 minutes (6–7 passes), a mean of 3.1 × 1011 platelets were collected along with ∼220 mL of packed RBC. The leukocyte contamination of the platelet product was in the range of 0.4–1.1 × 107 (99% lymphocytes), and the quality of platelets was very satisfactory as measured by the hypotonic shock response, aggregation induced by ADP, collagen and ristocetin, morphology score, and membrane glycoproteins modifications. Equally satisfactory was the quality of the RBC concentrate, suspended in 80 mL of SAG-M, with a total hemoglobin (Hb) content approaching 55 g as compared to the normal Hb content of a standard RBC concentrate that is approximately 62 g. No adverse effect has complicated the 20 procedures carried out so far, and the donors' evaluation of the procedure was favorable, except for the length of the procedure.

Background The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications. Methods A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period. Results Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay. Conclusion Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.

Background: The Fresenius AS 104® cell separator has recently met some popularity in European apheresis units for the quality of the platelets obtained with the totally automated double-needle procedure. Materials and Methods: Taking advantage of the machine’s flexibility we have developed a new automated procedure for single-needle thrombocytapheresis (SNP). So far 61 SNP were carried out. From donors having a platelet precount of 2.74 ×105 an average of 3.8 ×1011 cells were collected by processing 2.5 liters of blood in a run time of 83 min. Results and Conclusions: The leukocyte and erythrocyte contaminations were 2.7×107 and 3.5×107, respectively. Only 2 products did contain less than 3.5×1011 platelets, and 7 procedures were complicated by minor signs of hypocalcemia. With minor modifications this SNP is presently offered on a routine basis to our platelet donors.

A new CFC apparatus for intraoperative blood salvage (CATS) has been introduced by Fresenius and submitted to preliminary evaluation at our hemapheresis unit. The volume of shed blood submitted to washing was 1714 ± 496 with a hematocrit of 19% and the volume of PRBC ready for transfusion 297.9 ml with hematocrit of 64.3%. Elimination of contaminant activated platelets and WBC was 92% and 74% respectively. Elimination of contaminants such as protein, free hemoglobin, LDH and K ions was always over 95%. Regular application of CATS is warrented after our study.

The extensive application of IOBS has permitted a great reduction in the use of homoglous transfusion which presently represents the largest field of application of autologous systems. In cardiac and vascular surgery, IOBS is particularly useful to the goal of preventing the transmission of viral disorders and other adverse effects related to homologous transfusions. The apparatuses for IOBS may also be used to perform hemodilution and sequestration of a desired amount of platelet rich plasma. The appropriate usage of drugs in perioperative period and the promotion of hemostasis with IOBS are important costituents for the correct transfusional management of the patient. The feasibility and safety of IOBS is known and in expert hands it is an optimal method for the transfusional treatment of surgical patients

Optimal blood supply is critical to modern medical practice. Among the different possibilities of improving the quality and safety of blood, it is generally felt that autologous donation has played an important role and has contributed to changing transfusional practices, mainly since the appearance of HIV and HCV on the blood transfusion scene. At the San Martino Hospital Immunohematology Service, the autotransfusion era began in 1985. Autologous predeposit donation was the first to be introduced, followed by intentional perioperative hemodilution, intraoperative blood salvage with DFC apparatuses and lastly post-operative blood salvage. From about 200 autologous donations in 1985 we reached 5,372 in 1993 and more than 6,000 autologus donations are expected for 1994. Only 189 intraoperative blood salvages, were carried out in 1986, 593 in 1989, 1,207 in 1993 and more than 1,500 blood salvage sessions are anticipated for 1994. In the meantime, the total number of homologous RBC units employed in the Hospital dropped from 45,000 in 1985 to 18,000 in 1994, with the Onco-hematological Divisions using approximately 10,000 units of packed RBC.

Ten patients in first or second relapse with Philadelphia chromosome acute lymphoblastic leukaemia, ineligible for allogeneic sibling marrow transplantation, were treated with an intensive chemotherapy regimen including idarubicin, intermediate-dose arabinosylcytosine, etoposide and G-CSF. Peripheral blood stem cells were collected by leukapheresis during initial early WBC recovery from chemotherapy-induced aplasia. In 5/10 patients all metaphases in leukapheresis products were found to be Philadelphia-chromosome-negative and they have been used as autotransplants after conditioning with TBI/etoposide/cyclophosphamide (or idarubicin) and G-CSF. All five patients showed sustained engraftment and one of them is alive and well Philadelphia-chromosome-negative 18 months after transplant. These preliminary results suggest that it is possible to recover Philadelphia-chromosome-negative blood stem cells after intensive chemotherapy, even in advanced patients, and to perform autografting with these cells.

Autologous transfusion is playing an important role in modern transfusion medicine. At San Martino hospital we use a combination of manual and mechanical techniques in order to improve autotransfusion procedures, control the hypertransfusion and avoid waste. Our autotransfusion program has determined a 55% reduction in the red cell concentrates used (from 42,000 in 1985 down to 19,400 in 1992). Proper training, cultural improvements and new applications on autotransfusion procedures will permit a better use of blood with less transfusion related complications, until a suitable substitute for blood will be available.

The number of conditions that can benefit from Plasma-Exchange (PE) continues to grow. We have recently added to the list the Cyclosporin-A induced hypertrygliceridemia and myoglobinuric acute renal insufficiency. Such as any therapeutic measure for PE, four evolutive phases can be recognized: the discovery and research, the confirmation of indications, the routine applications and the decline, when new more powerful tools are offered by culture or technology. We have participated in the first three phases during the last 20 years. Not necessarily all experiences were favourable. Nonetheless, we feel that, for the time being, a hemapheresis unit is an absolute necessity for a medium - sized hospital even if only therapeutic procedures are carried out. The phase four, decline of interest and applications, cannot be foreseen. Finally the ability of PE to shorten substantially the length of hospital stays along with the ease with which procedure can be performed on ambulatory patients, substantiate a favourable cost/benefit ratio for this therapeutic modality.

Vascular involvement is presently considered a "common pathway" in a number of diseases that is mediated by circulating immune complexes (CIC). CIC are found in the circulation when the disease is active and in single patients their level may parallel disease activity. Lepromatous leprosis is characterized by the presence of CIC and deposits of immunoglobulins and complement in vascular lesions of the different organs and an Arthus-like mechanism is considered as the basis for the clinical picture. The same mechanism is considered to play an essential pathophysiologic role in Lucio's phenomenon, which is characterized by lymphohistiocytic vascular infiltrates with or without thrombosis and secondary cutaneous infarction. Lepromatous vascular involvement is mediated by CIC whose antigen composition is known, the same as it is with HCV mediated cryoglobulinemia, HBV positive panarteritis nodosa, rheumatoid vasculitis, or Wagner's granulomatosis, which are usually treated by PE [1-3]. PE has been employed for lepromatous vasculitis since 1979 [4] and other cases have been successfully treated afterwards [5,6]. We report on another patient successfully treated by plasma exchange.

We have performed 24 cascade filtration treatments in 8 patients with hyperviscosity syndrome (2 cases), essential mixed cryoglobulinemia, post-hepatitic cryoglobulinemia, Sjogrens disease, rheumatoid vasculitis, Miller-Fisher syndrome and chronic dysimmune polyneuropathy. New cellulose diacetate filters were employed, giving a satisfactory performance. At 1.5 L plasma treatment, the rejection rate for macromolecular plasma components was close to 90%, whereas albumin recovery was close to 70%. Treatments were clinically effective, confirming that cascade filtration is an alternative to conventional plasma exchange in patients with IgM or immune complex mediated diseases.

A new technique which allows lymphocytapheresis to be combined with cascade filtration (CF) is described in this paper. This therapeutical approach was applied for the treatment of patients affected by necrotizing vasculitis (1), inflammatory myopathies (5), Cryoglobulinemia (5), immune complex polyneuropathies (7), rheumatoid arthritis (3) and psoriasis (3 patients). Two cases of Waldenstrom's macroglobulinemia were also treated after the onset of the hyperviscosity syndrome. 78 procedures have been performed without any untoward effect. From a clinical point of view all patients had some improvement following treatment, thereby confirming not only the clinical safety of this therapeutical approach but also its effectiveness at least in the management of diseases which usually respond to plasma exchange treatment. Laboratory investigations showed that with CF it is possible to selectively remove IgM, immune complexes, fibrinogen, lipoproteins and high molecular weight plasma components, sparing most albumin and IgG globulins (85 and 71%, respectively).

A simple method for the study of kinetic solubility curves of cryoglobulins is presented. In its first application to the study of 21 patients with cryoglobulinemia, it was possible to ascertain that clinical condition roughly correlates with decreased solubility whereas no correlation is found with per cent cryocrit. In the group of patients we studied, 6 underwent plasma exchange treatment when glomerulonephritis, acute renal insufficiency, cerebritis and polyneuropathy appeared: in these patients, following 2 to 5 apheretic sessions, solubility increased showing a sort of correlation with clinical benefits determined by treatment. The preliminarity of this study is underlined.

In the treatment of Waldenstrom's macroglobulinemia (WM) and lipoprotein or immune complex mediated diseases, centrifugal and membrane plasma separation systems have been successfully employed over the past years. More recently, semiselective double filtration systems have been used in isolated cases. While it is hoped that cascade filtration (CF) will soon become a routine technique, a note of caution came from some investigators because of the lack of any evidence that CF does really deplete patients' plasma of known pathogenic macromolecules. The aim of this study was to test the efficacy of CF in the removal of IgM paraproteins in comparison with discontinuous flow centrifugation (DFC). Eight patients were treated by DFC and seven by CF; there were no significant differences between the two groups in terms of sex, age, clinical severity and IgM plasma concentration. After DFC or CF sessions, IgM concentration diminished by 50% and plasma viscosity by 60%, producing a comparable mean reduction in patients' clinical severity. Our in vivo results thus preliminarily answer the question whether CF is capable of removing known pathogenic macromolecules from patiets' plasma, and the technique appears to warrant further investigations.

Rebound after plasmapheresis is thought to be due to enhanced antibody and/or immune complex production. To prevent rebound a combination of steroids and immunosuppressive drugs has been used: lymphocytapheresis was employed in most patients, for not more than 10 sessions. 50 patients with myasthenia gravis, inflammatory myopathy, chronic dysimmune polyneuropathy and immune complex polyneuropathy have been treated and long-lasting benefits obtained in 35 patients. Rebound effects were observed only when cytotoxic drugs were not given or discontinued too soon. 8 patients who had been treated by plasmapheresis combined with steroids alone, after some recurrences of their disease, were switched to cytotoxic drugs, steroids and lymphocytapheresis combined with plasma exchange: in this group 7 patients eventually gained long lasting remissions. Our clinical experience strongly supports the hypothesis of a synergy between plasmapheresis and immuno-suppressive measures.

During the COVID-19 pandemic, a shortage of mechanical ventilators was reported and ventilator sharing between patients was proposed as an ultimate solution. Two lung simulators were ventilated by one anesthesia machine connected through two respiratory circuits and T-pieces. Five different combinations of compliances (30–50 mL × cmH2O−1) and resistances (5–20 cmH2O × L−1 × s−1) were tested. The ventilation setting was: pressure-controlled ventilation, positive end-expiratory pressure 15 cmH2O, inspiratory pressure 10 cmH2O, respiratory rate 20 bpm. Pressures and flows from all the circuit sections have been recorded and analyzed. Simulated patients with equal compliance and resistance received similar ventilation. Compliance reduction from 50 to 30 mL × cmH2O−1 decreased the tidal volume (VT) by 32% (418 ± 49 vs. 285 ± 17 mL). The resistance increase from 5 to 20 cmH2O × L−1 × s−1 decreased VT by 22% (425 ± 69 vs. 331 ± 51 mL). The maximal alveolar pressure was lower at higher compliance and resistance values and decreased linearly with the time constant (r² = 0.80, p &lt, 0.001). The minimum alveolar pressure ranged from 15.5 ± 0.04 to 16.57 ± 0.04 cmH2O. Cross-flows between the simulated patients have been recorded in all the tested combinations, during both the inspiratory and expiratory phases. The simultaneous ventilation of two patients with one ventilator may be unable to match individual patient’s needs and has a high risk of cross-interference.

Background Limited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m2] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS. Methods In this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012–2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015–2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring. Results The standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m2), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m2). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13–0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16–0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16–0.74). Conclusion Individualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.

Supplemental Digital Content is available in the text., OBJECTIVE: To investigate whether individualized optimization of mechanical ventilation through the implementation of a lung rescue team could reduce the need for venovenous extracorporeal membrane oxygenation in patients with obesity and acute respiratory distress syndrome and decrease ICU and hospital length of stay and mortality. DESIGN: Single-center, retrospective study at the Massachusetts General Hospital from June 2015 to June 2019. PATIENTS: All patients with obesity and acute respiratory distress syndrome who were referred for venovenous extracorporeal membrane oxygenation evaluation due to hypoxemic respiratory failure. INTERVENTION: Evaluation and individualized optimization of mechanical ventilation by the lung rescue team before the decision to proceed with venovenous extracorporeal membrane oxygenation. The control group was those patients managed according to hospital standard of care without lung rescue team evaluation. MEASUREMENT AND MAIN RESULTS: All 20 patients (100%) allocated in the control group received venovenous extracorporeal membrane oxygenation, whereas 10 of 13 patients (77%) evaluated by the lung rescue team did not receive venovenous extracorporeal membrane oxygenation. Patients who underwent lung rescue team evaluation had a shorter duration of mechanical ventilation (p = 0.03) and shorter ICU length of stay (p = 0.03). There were no differences between groups in in-hospital, 30-day, or 1–year mortality. CONCLUSIONS: In this hypothesis-generating study, individualized optimization of mechanical ventilation of patients with acute respiratory distress syndrome and obesity by a lung rescue team was associated with a decrease in the utilization of venovenous extracorporeal membrane oxygenation, duration of mechanical ventilation, and ICU length of stay. Mortality was not modified by the lung rescue team intervention.

BACKGROUND: Endotracheal suctioning is mandatory to prevent complications caused by the retention of tracheal secretions. Endotracheal suctioning is often performed late, when patients show signs of respiratory and hemodynamic alterations. We conceived a prototype device that, when synchronized with the ventilator, automatically removes secretions collected below the endotracheal tube (ETT) cuff, thus avoiding endotracheal suctioning. The aim of our investigation was to assess the performance of this novel prototype in vitro. METHODS: Three studies were performed to examine the characteristics of the prototype. We tested device9s ability to generate an effective artificial cough flow (artificial cough maneuver) > 1 L/s by rapidly deflating the ETT cuff within the time of a sustained inflation (at 30 and at 40 cm H2O) (cough flow study). We also tested the prototype9s ability to remove the fluid positioned below the ETT cuff using saline dye (fluid removal study), and to prevent the aspiration of saline dye from above the ETT cuff during the deflation phase of the ETT cuff (aspiration study). The trachea model was positioned at 45° in the aspiration study, and horizontally in the other two studies. RESULTS: In the cough flow study, the prototype provided an effective artificial cough maneuver, with a mean ± SD of 1.78 ± 0.19 L/s (range, 1.42–2.14 L/s). The tracheal pressure after ETT cuff deflation never decreased below the PEEP level. In the fluid removal study, the prototype cleared the fluid from below the ETT cuff and the experimental trachea. No fluid was aspirated from the area above the ETT cuff toward the lower airways. CONCLUSIONS: We conceived an system capable of automatically expelling fluid from below the ETT cuff outside an experimental trachea by generating an artificial cough maneuver. This system may decrease the use of endotracheal suctioning and its complications. Future in vivo studies are needed to confirm this first in vitro evaluation.

Background: Understanding the level of patients’ satisfaction with treatment and its determinants have the potential to impact therapeutic management and clinical outcome in chronic conditions such as chronic obstructive pulmonary disease (COPD). Methods: A national, multicenter, longitudinal, observational study of COPD from 20 Italian pulmonary centers to explore patients’ satisfaction to treatment [assessed by the Treatment Satisfaction Questionnaire, 9 items (TSQM-9)] and association with clinical parameters [including dyspnea score, COPD Assessment Test (CAT) score, exacerbation rate], adherence to treatment [Morisky Medication-Taking Adherence Scale (MMAS-4)], illness perception [evaluated by Brief Illness Perception Questionnaire (B-IPQ)] in a 1-year follow up. Results: A total of 401 COPD patients were enrolled [69.4% group B Global Initiative for COPD (GOLD), considering 366 patients with available GOLD 2017 classification at enrollment]. At enrollment, satisfaction with treatment was moderate, being TSQM-9 mean scores for effectiveness 64.2 [95% confidence interval (CI) 62.5–65.9], for convenience 75.8 (95% CI 74.2–77.3), and for global satisfaction 65.7 (95% CI 64.0–67.4). Global satisfaction was negatively associated with disease perception (β = −0.4709, p Conclusions: The results of this real-life study showed that the patients’ satisfaction with treatments is only moderate in COPD. A high grade of patients’ satisfaction is associated mainly with a low perception of the disease, high adherence to treatment and lower level of dyspnea. Trial Registration: Clinicaltrials.gov identifier: NCT02689492 The reviews of this paper are available via the supplemental material section.

The EGFR (epidermal growth factor receptor) a member of the family of transmembrane protein kinase receptors known as the erbB family shows a significant correlation with the presence of metastases and poorly differentiated oral cancer. Aim of the present work is to define the key-role of EGFR in oral cancer prognosis. We have analyzed the EGFR expression on 149 cases of oral squamous cell cancers (OSCC) and we have found that it was poorly expressed in normal oral epithelium, but its expression was significantly increased in OSCCs. Moreover, we have recorded that both pEGFR-Tyr 845 and pEGFR-Tyr 1068 were mainly distributed in high histological grading and in advanced stages. Western blotting has confirmed the total absence of EGFR phosphorylation in normal oral epithelium and the higher level of protein phosphorylation in representative cases of OSCCs. The EGF-R amplification was found by fluorescence in situ hybridization (FISH) in 14% of OSCC; interestingly, EGF-R amplification was mainly observed in OSCC with higher histological grading (G2 and G3) and advanced stage (pT4) sub-groups. Kaplan-Meyer survival analysis suggested that patients with positive pEGFR-Tyr 845 tumors had a worse prognosis and were bad responders to chemotherapy. These results confirm the central role of EGF-R activation status as a prognostic biomarker in OSCC The EGFR (epidermal growth factor receptor) a member of the family of transmembrane protein kinase receptors known as the erbB family shows a significant correlation with the presence of metastases and poorly differentiated oral cancer. Aim of the present work is to define the key-role of EGFR in oral cancer prognosis. We have analyzed the EGFR expression on 149 cases of oral squamous cell cancers (OSCC) and we have found that it was poorly expressed in normal oral epithelium, but its expression was significantly increased in OSCCs. Moreover, we have recorded that both pEGFR-Tyr 845 and pEGFR-Tyr 1068 were mainly distributed in high histological grading and in advanced stages. Western blotting has confirmed the total absence of EGFR phosphorylation in normal oral epithelium and the higher level of protein phosphorylation in representative cases of OSCCs. The EGF-R amplification was found by fluorescence in situ hybridization (FISH) in 14% of OSCC; interestingly, EGF-R amplification was mainly observed in OSCC with higher histological grading (G2 and G3) and advanced stage (pT4) sub-groups. Kaplan-Meyer survival analysis suggested that patients with positive pEGFR-Tyr 845 tumors had a worse prognosis and were bad responders to chemotherapy. These results confirm the central role of EGF-R activation status as a prognostic biomarker in OSCC. © 2012 Landes Bioscience.

HIV-1 gp120 interacts with IgE VH3+ on the surface of human basophils and mast cells (FcΕRI+ cells), acting as a viral immunoglobulin superantigen. gp120 from different clades induces mediator release from FcΕRI+ cells. gp120 also induces IL-4 and IL-13 synthesis in human basophils. The chemokine receptors CCR3 and CXCR4, which are coreceptors of HIV-1 infection, are expressed by human FcΕRI+ cells. HIV-1 Tat protein is a potent chemoattractant for basophils and lung mast cells, interacting with CCR3. Incubation of basophils with Tat protein upregulates the surface expression of the CCR3 receptor. There is evidence that human FcΕRI+ cells could be infected in vitro by M-tropic HIV-1 strains.

Mast cells and basophils (FcvarepsilonRI(+) cells) are classically involved in allergic disorders. HIV-1 glycoprotein gp120 acts as a viral superantigen by interacting with the heavy chain, variable 3 (V(H)3) region of IgE to induce cytokine release from FcvarepsilonRI(+) cells. The chemokine receptors CCR3 and CXCR4, co-receptors for HIV-1, are expressed by FcvarepsilonRI(+) cells. Via its interaction with CCR3, HIV-1 transactivation (Tat) protein is a potent chemoattractant for FcvarepsilonRI(+) cells. Incubation of basophils with Tat protein upregulates the surface expression of the CCR3 receptor. There is some evidence that human FcvarepsilonRI(+) cells could be infected in vitro by M-tropic HIV-1 strains.

Human heart mast cells (HHMC) have been identified in heart tissue, perivascularly, and in the intima of coronary arteries. In vitro activation of isolated HHMC induces the release of vasoactive and proinflammatory mediators (histamine, tryptase, and cysteinyl leukotriene C4[LTC4]). We investigated the effects of several bacterial proteins on HHMC activation in vitro. HHMC released histamine, tryptase, and LTC4in response toStaphylococcus aureusCowan 1 and the immunoglobulin (Ig)-binding protein A, but not toS. aureusWood 46, which does not synthesize protein A. The effect of protein A was inhibited by preincubation with monoclonal IgM VH3+. Some strains ofPeptostreptococcus magnusexpress an Ig light chain-binding surface protein called protein L. Such bacteria and soluble protein L stimulated the release of preformed and newly synthesized mediators from HHMC. Preincubation of HHMC with either protein A or protein L resulted in complete cross-desensitization to a subsequent challenge with the heterologous stimulus or anti-IgE. Monoclonal IgE (κ chains) blocked protein L-induced release, whereas IgE (λ chains) had no effect. Streptococcal protein G, formyl-containing tripeptide, and pepstatin A did not activate HHMC. Bacterial products protein A and protein L and intact bacteria (S. aureusandP. magnus) activate HHMC by acting as Ig superantigens.

In all mammalian species investigated so far, mast cells and basophils are the only cells that synthesize histamine and express plasma membrane receptors that bind IgE with high affinity (Fc epsilonRI). Human basophils and mast cells derive from distinct precursors that originate in the bone marrow and fetal liver and probably circulate in peripheral blood. There is extensive evidence that mast cells and basophils and their mediators are primary effectors of allergic inflammation. Immunologically activated human basophils release two cytokines: IL-4 and IL-13. Expression of several cytokines has been documented in a number of experimental models of human and rodent mast cells. However, to date few studies have analyzed the mechanisms of gene expression in human Fc epsilonRI+ cells. Some of these studies imply a role for NFAT and GATA family members in the IgE-mediated activation of cytokine gene transcription in basophils and mast cells. Studies of human basophils and mast cells isolated from different anatomic sites have established the different profiles of eicosanoids released by these cells. Recently, the characterization of arachidonic acid pools and the identification of novel enzymes involved in arachidonate remodeling and mobilization clarified in part how eicosanoid productions is regulated in mast cells and basophils. In addition to histamine, human mast cell secretory granules contain the neutral proteases tryptase, chymase and carboxypeptidase that possess several biochemical properties. In particular, tryptase may play a role as a fibrogenic factor and chymase might convert angiotensin I to angiotensin II. Mast cells are present in human heart and in human coronary arteries raising the possibility that local activation of cardiac mast cells might contribute to certain cardiovascular diseases. Recent evidence also suggests that mast cells and basophils can play a role during viral and bacterial infections. It is now evident that in man these two cells not only participate in inflammation associated with allergic disease, but also in chronic and fibrotic disorders affecting several organs and in host defense against bacterial and viral infections.