Clonal Hematopoiesis of Indeterminate Potential and Long-term Outcomes in Heart Transplantation.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) mutations, a trait of aging, has been associated with the progression of cardiovascular disease and the development of malignancy. Uncertainty prevails regarding a robust association between CHIP and heart-transplantation (HT) outcomes. OBJECTIVES: To determine the prevalence of CHIP mutations in HT and their association with long-term outcomes, including cardiac allograft vasculopathy (CAV), graft failure, malignancy, and all-cause mortality. METHODS: We conducted a mixed retrospective-prospective observational study of HT recipients with targeted sequencing for CHIP mutations (variant allele frequency [VAF] of ≥ 2%). The primary composite outcome was the first occurrence of CAV grade ≥ 2, graft failure, malignancy, cardiac retransplantation, or all-cause death. Secondary outcomes were the individual components of the composite primary outcome. Sensitivity analyses with base-case and extreme scenarios were performed. RESULTS: Among 95 HT recipients, 30 had CHIP mutations (31.6%). DNMT3A mutations were most common (44.7%), followed by PPM1D (13.2%), SF3B1 (10.5%), TET2 (7.9%), and TP53 (7.9%). The only significant independent predictor of CHIP was age at enrollment or age at transplantation. After multivariable adjustment, CHIP mutations were not associated with the primary outcome, which occurred in 44 (46.3%) patients (HR = 0.487; 95% CI:0.197-1.204; P = 0.119), nor were they associated with mlalignancy alone, or death. CONCLUSION: We demonstrated no association between CHIP mutations and post-transplant outcomes, including CAV, graft failure, malignancy, and all-cause mortality. In line with previously published data, our analysis provides additional evidence about the lack of clinical value of using CHIP mutations as a biomarker for surveillance in outcomes after HT.

Influence of Fractional Inspired Oxygen Tension on Lung Perfusion Distribution, Regional Ventilation, and Lung Volume during Mechanical Ventilation of Supine Healthy Swine.

BACKGROUND: Lower fractional inspired oxygen tension (Fio2) during general anesthesia can reduce lung atelectasis. The objectives are to evaluate the effect of two Fio2 (0.4 and 1) during low positive end-expiratory pressure (PEEP) ventilation over lung perfusion distribution, volume, and regional ventilation. These variables were evaluated at two PEEP levels and unilateral lung atelectasis. METHODS: In this exploratory study, 10 healthy female piglets (32.3 ± 3.4 kg) underwent mechanical ventilation in two atelectasis models: (1) bilateral gravitational atelectasis (n = 6), induced by changes in PEEP and Fio2 in three combinations: high PEEP with low Fio2 (Fio2 = 0.4), zero PEEP (PEEP0) with low Fio2 (Fio2 = 0.4), and PEEP0 with high Fio2 (Fio2 = 1); and (2) unilateral atelectasis (n = 6), induced by left bronchial occlusion, with the left lung aerated (Fio2 = 0.21) and low aerated (Fio2 = 1; n = 5 for this step). Measurements were conducted after 10 min in each step, encompassing assessment of respiratory mechanics, oxygenation, and hemodynamics; lung ventilation and perfusion by electrical impedance tomography; and lung aeration and perfusion by computed tomography. RESULTS: During bilateral gravitational atelectasis, PEEP reduction increased atelectasis in dorsal regions, decreased respiratory compliance, and distributed lung ventilation to ventral regions with a parallel shift of perfusion to the same areas. With PEEP0, there were no differences between low and high Fio2 in respiratory compliance (23.9 ± 6.5 ml/cm H2O vs. 21.9 ± 5.0; P = 0.441), regional ventilation, and regional perfusion, despite higher lung collapse (18.6 ± 7.6% vs. 32.7 ± 14.5%; P = 0.045) with high Fio2. During unilateral lung atelectasis, the deaerated lung had a lower shunt (19.3 ± 3.6% vs. 25.3 ± 5.5%; P = 0.045) and lower computed tomography perfusion to the left lung (8.8 ± 1.8% vs. 23.8 ± 7.1%; P = 0.007). CONCLUSIONS: PEEP0 with low Fio2, compared with high Fio2, did not produce significant changes in respiratory system compliance, regional lung ventilation, and perfusion despite significantly lower lung collapse. After left bronchial occlusion, the shrinkage of the parenchyma with Fio2 = 1 enhanced hypoxic pulmonary vasoconstriction, reducing intrapulmonary shunt and perfusion of the nonventilated areas.

Intraoperative individualization of positive-end-expiratory pressure through electrical impedance tomography or esophageal pressure assessment: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review of randomized-controlled trials (RCTs) with meta-analyses aimed to compare the effects on intraoperative arterial oxygen tension to inspired oxygen fraction ratio (PaO2/FiO2), exerted by positive end-expiratory pressure (PEEP) individualized trough electrical impedance tomography (EIT) or esophageal pressure (Pes) assessment (intervention) vs. PEEP not tailored on EIT or Pes (control), in patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach. METHODS: PUBMED®, EMBASE®, and Cochrane Controlled Clinical trials register were searched for observational studies and RCTs from inception to the end of August 2022. Inclusion criteria were: RCTs comparing PEEP titrated on EIT/Pes assessment vs. PEEP not individualized on EIT/Pes and reporting intraoperative PaO2/FiO2. Two authors independently extracted data from the enrolled investigations. Data are reported as mean difference and 95% confidence interval (CI). RESULTS: Six RCTs were included for a total of 240 patients undergoing general anesthesia for surgery, of whom 117 subjects in the intervention group and 123 subjects in the control group. The intraoperative mean PaO2/FiO2 was 69.6 (95%CI 32.-106.4 ) mmHg higher in the intervention group as compared with the control group with 81.4% between-study heterogeneity (p < 0.01). However, at meta-regression, the between-study heterogeneity diminished to 44.96% when data were moderated for body mass index (estimate 3.45, 95%CI 0.78-6.11, p = 0.011). CONCLUSIONS: In patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach, PEEP personalized by EIT or Pes allowed the achievement of a better intraoperative oxygenation compared to PEEP not individualized through EIT or Pes. PROSPERO REGISTRATION NUMBER: CRD 42021218306, 30/01/2023.

A strange case of pleuritic pain in the third trimester of pregnancy.

Pulmonary sequestration is an uncommon congenital malformation of the lung, generally diagnosed in childhood or adolescence, corresponding to dysplastic lung tissue not communicating with the rest of vascular or bronchial lung system but receiving an arterial blood supply from systemic arteries. Currently, surgical resection is usually indicated in order to prevent or treat related symptoms or complications, although controversy exists regarding its use in asymptomatic patients and adults. We present the case of a 32-year-old pregnant woman with acute chest pain and vomiting diagnosed with intralobar sequestration at 32+2 weeks of gestation and treated with pulmonary lobectomy after giving birth by cesarean section at 33+0 weeks of gestation.

Phrenic Nerve Block and Respiratory Effort in Pigs and Critically Ill Patients with Acute Lung Injury.

BACKGROUND: Strong spontaneous inspiratory efforts can be difficult to control and prohibit protective mechanical ventilation. Instead of using deep sedation and neuromuscular blockade, the authors hypothesized that perineural administration of lidocaine around the phrenic nerve would reduce tidal volume (VT) and peak transpulmonary pressure in spontaneously breathing patients with acute respiratory distress syndrome. METHODS: An established animal model of acute respiratory distress syndrome with six female pigs was used in a proof-of-concept study. The authors then evaluated this technique in nine mechanically ventilated patients under pressure support exhibiting driving pressure greater than 15 cm H2O or VT greater than 10 ml/kg of predicted body weight. Esophageal and transpulmonary pressures, electrical activity of the diaphragm, and electrical impedance tomography were measured in pigs and patients. Ultrasound imaging and a nerve stimulator were used to identify the phrenic nerve, and perineural lidocaine was administered sequentially around the left and right phrenic nerves. RESULTS: Results are presented as median [interquartile range, 25th to 75th percentiles]. In pigs, VT decreased from 7.4 ml/kg [7.2 to 8.4] to 5.9 ml/kg [5.5 to 6.6] (P < 0.001), as did peak transpulmonary pressure (25.8 cm H2O [20.2 to 27.2] to 17.7 cm H2O [13.8 to 18.8]; P < 0.001) and driving pressure (28.7 cm H2O [20.4 to 30.8] to 19.4 cm H2O [15.2 to 22.9]; P < 0.001). Ventilation in the most dependent part decreased from 29.3% [26.4 to 29.5] to 20.1% [15.3 to 20.8] (P < 0.001). In patients, VT decreased (8.2 ml/ kg [7.9 to 11.1] to 6.0 ml/ kg [5.7 to 6.7]; P < 0.001), as did driving pressure (24.7 cm H2O [20.4 to 34.5] to 18.4 cm H2O [16.8 to 20.7]; P < 0.001). Esophageal pressure, peak transpulmonary pressure, and electrical activity of the diaphragm also decreased. Dependent ventilation only slightly decreased from 11.5% [8.5 to 12.6] to 7.9% [5.3 to 8.6] (P = 0.005). Respiratory rate did not vary. Variables recovered 1 to 12.7 h [6.7 to 13.7] after phrenic nerve block. CONCLUSIONS: Phrenic nerve block is feasible, lasts around 12 h, and reduces VT and driving pressure without changing respiratory rate in patients under assisted ventilation.

Optimization of Extraction Conditions and Characterization of Volatile Organic Compounds of Eugenia klotzschiana O. Berg Fruit Pulp.

Eugenia klotzschiana O. Berg is a native species to the Cerrado biome with significant nutritional value. However, its volatile organic compounds (VOCs) chemical profile is not reported in the scientific literature. VOCs are low molecular weight chemical compounds capable of conferring aroma to fruit, constituting quality markers, and participating in the maintenance and preservation of fruit species. This work studied and determined the best conditions for extraction and analysis of VOCs from the pulp of Eugenia klotzschiana O. Berg fruit and identified and characterized its aroma. Headspace solid-phase microextraction (HS-SPME) was employed using different fiber sorbents: DVB/CAR/PDMS, PDMS/DVB, and PA. Gas chromatography and mass spectrometry (GC-MS) were employed to separate, detect, and identify VOCs. Variables of time and temperature of extraction and sample weight distinctly influenced the extraction of volatiles for each fiber. PDMS/DVB was the most efficient, followed by PA and CAR/PDMS/DVB. Thirty-eight compounds that comprise the aroma were identified among sesquiterpenes (56.4%) and monoterpenes (30.8%), such as α-fenchene, guaiol, globulol, α-muurolene, γ-himachalene, α-pinene, γ-elemene, and patchoulene.

Bioactive activities and chemical profile characterization using paper spray mass spectrometry of extracts of Eriobotrya japonica Lindl. leaves.

RATIONALE: The loquat (Eriobotrya japonica Lindl.) is a fruit tree that has been used in Chinese medicine for thousands of years for the treatment of various diseases. The loquat leaf extracts contain several bioactive compounds with antioxidant and antimicrobial properties, and identification of these substances using quick and simple methods has been an analytical trend. METHODS: The influence of dehydration of loquat leaves (without drying, at 40°C, and at 60°C), the type of solvent (ethanol and methanol), and the method of extraction (shaking and ultrasound) on obtaining extracts containing phenolic compounds and substances with antioxidant and antimicrobial properties was evaluated. The chemical constituents of an extract were identified using paper spray mass spectrometry (PS-MS). RESULTS: The extract obtained from the dehydrated leaves at 40°C presented the best results. The extracts obtained from these leaves and with ethanol had the highest values of total phenolics and antioxidant activities, but the methanolic extract subjected to ultrasound had the highest levels of chlorogenic, caffeic, and ellagic acids. All extracts evaluated inhibited the growth of Staphylococcus aureus. Using the PS-MS technique, it was possible to identify the presence of 49 substances such as organic acids, phenolic acids, flavonoids, sugars, quinones, and terpenes. CONCLUSIONS: In general, extracts of dehydrated leaves at 40°C and extracted with ethanol using ultrasound can be considered a good source of bioactive compounds with potential applications as functional ingredients or additives in the food and pharmaceutical industries. PS-MS was demonstrated to be a simple and ultrafast technique to obtain the chemical profile of the loquat leaf extract.

Beyond diversity loss and climate change: Impacts of Amazon deforestation on infectious diseases and public health.

Amazonian biodiversity is increasingly threatened due to the weakening of policies for combating deforestation, especially in Brazil. Loss of animal and plant species, many not yet known to science, is just one among many negative consequences of Amazon deforestation. Deforestation affects indigenous communities, riverside as well as urban populations, and even planetary health. Amazonia has a prominent role in regulating the Earth's climate, with forest loss contributing to rising regional and global temperatures and intensification of extreme weather events. These climatic conditions are important drivers of emerging infectious diseases, and activities associated with deforestation contribute to the spread of disease vectors. This review presents the main impacts of Amazon deforestation on infectious-disease dynamics and public health from a One Health perspective. Because Brazil holds the largest area of Amazon rainforest, emphasis is given to the Brazilian scenario. Finally, potential solutions to mitigate deforestation and emerging infectious diseases are presented from the perspectives of researchers in different fields.

High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious.

RATIONALE: In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious. OBJECTIVES: To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP). METHODS: Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS. MEASUREMENTS AND MAIN RESULTS: Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients). CONCLUSIONS: Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.

Individual Positive End-expiratory Pressure Settings Optimize Intraoperative Mechanical Ventilation and Reduce Postoperative Atelectasis.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Intraoperative lung-protective ventilation has been recommended to reduce postoperative pulmonary complications after abdominal surgery. Although the protective role of a more physiologic tidal volume has been established, the added protection afforded by positive end-expiratory pressure (PEEP) remains uncertain. The authors hypothesized that a low fixed PEEP might not fit all patients and that an individually titrated PEEP during anesthesia might improve lung function during and after surgery. METHODS: Forty patients were studied in the operating room (20 laparoscopic and 20 open-abdominal). They underwent elective abdominal surgery and were randomized to institutional PEEP (4 cm H2O) or electrical impedance tomography-guided PEEP (applied after recruitment maneuvers and targeted at minimizing lung collapse and hyperdistension, simultaneously). Patients were extubated without changing selected PEEP or fractional inspired oxygen tension while under anesthesia and submitted to chest computed tomography after extubation. Our primary goal was to individually identify the electrical impedance tomography-guided PEEP value producing the best compromise of lung collapse and hyperdistention. RESULTS: Electrical impedance tomography-guided PEEP varied markedly across individuals (median, 12 cm H2O; range, 6 to 16 cm H2O; 95% CI, 10-14). Compared with PEEP of 4 cm H2O, patients randomized to the electrical impedance tomography-guided strategy had less postoperative atelectasis (6.2 ± 4.1 vs. 10.8 ± 7.1% of lung tissue mass; P = 0.017) and lower intraoperative driving pressures (mean values during surgery of 8.0 ± 1.7 vs. 11.6 ± 3.8 cm H2O; P < 0.001). The electrical impedance tomography-guided PEEP arm had higher intraoperative oxygenation (435 ± 62 vs. 266 ± 76 mmHg for laparoscopic group; P < 0.001), while presenting equivalent hemodynamics (mean arterial pressure during surgery of 80 ± 14 vs. 78 ± 15 mmHg; P = 0.821). CONCLUSIONS: PEEP requirements vary widely among patients receiving protective tidal volumes during anesthesia for abdominal surgery. Individualized PEEP settings could reduce postoperative atelectasis (measured by computed tomography) while improving intraoperative oxygenation and driving pressures, causing minimum side effects.

Quantitative Dual-Energy Computed Tomography Predicts Regional Perfusion Heterogeneity in a Model of Acute Lung Injury.

OBJECTIVE: The aims of this study were to investigate the ability of contrast-enhanced dual-energy computed tomography (DECT) for assessing regional perfusion in a model of acute lung injury, using dynamic first-pass perfusion CT (DynCT) as the criterion standard and to evaluate if changes in lung perfusion caused by prone ventilation are similarly demonstrated by DECT and DynCT. METHODS: This was an institutional review board-approved study, compliant with guidelines for humane care of laboratory animals. A ventilator-induced lung injury protocol was applied to 6 landrace pigs. Perfused blood volume (PBV) and pulmonary blood flow (PBF) were respectively quantified by DECT and DynCT, in supine and prone positions. The lungs were segmented in equally sized regions of interest, namely, dorsal, middle, and ventral. Perfused blood volume and PBF values were normalized by lung density. Regional air fraction (AF) was assessed by triple-material decomposition DECT. Per-animal correlation between PBV and PBF was assessed with Pearson R. Regional differences in PBV, PBF, and AF were evaluated with 1-way analysis of variance and post hoc linear trend analysis (α = 5%). RESULTS: Mean correlation coefficient between PBV and PBF was 0.70 (range, 0.55-0.98). Higher PBV and PBF values were observed in dorsal versus ventral regions. Dorsal-to-ventral linear trend slopes were -10.24 mL/100 g per zone for PBV (P < 0.001) and -223.0 mL/100 g per minute per zone for PBF (P < 0.001). Prone ventilation also revealed higher PBV and PBF in dorsal versus ventral regions. Dorsal-to-ventral linear trend slopes were -16.16 mL/100 g per zone for PBV (P < 0.001) and -108.2 mL/100 g per minute per zone for PBF (P < 0.001). By contrast, AF was lower in dorsal versus ventral regions in supine position, with dorsal-to-ventral linear trend slope of +5.77%/zone (P < 0.05). Prone ventilation was associated with homogenization of AF distribution among different regions (P = 0.74). CONCLUSIONS: Dual-energy computed tomography PBV is correlated with DynCT-PBF in a model of acute lung injury, and able to demonstrate regional differences in pulmonary perfusion. Perfusion was higher in the dorsal regions, irrespectively to decubitus, with more homogeneous lung aeration in prone position.

Pd-M/C (M = Pd, Cu, Pt) Electrocatalysts for Oxygen Reduction Reaction in Alkaline Medium: Correlating the Electronic Structure with Activity.

The increasing global needs for clean and renewable energy have fostered the design of new and highly efficient materials for fuel cells applications. In this work, Pd-M (M = Pd, Cu, Pt) and Pt nanoparticles were prepared by a green synthesis method. The carbon-supported nanoparticles were evaluated as electrocatalysts for the oxygen reduction reaction (ORR) in alkaline medium. A comprehensive electronic and structural characterization of these materials was achieved using X-ray diffraction, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy. Their electrochemical properties were investigated by cyclic voltammetry, while their activities for the ORR were characterized using steady-state polarization experiments. The results revealed that the bimetallic nanoparticles consist of highly crystalline nanoalloys with size around 5 nm, in which the charge transfer involving Pd and M atoms affects the activity of the electrocatalysts. Additionally, the samples with higher ORR activity are those whose d-band center is closer to the Fermi level.

Spontaneous Effort During Mechanical Ventilation: Maximal Injury With Less Positive End-Expiratory Pressure.

OBJECTIVES: We recently described how spontaneous effort during mechanical ventilation can cause "pendelluft," that is, displacement of gas from nondependent (more recruited) lung to dependent (less recruited) lung during early inspiration. Such transfer depends on the coexistence of more recruited (source) liquid-like lung regions together with less recruited (target) solid-like lung regions. Pendelluft may improve gas exchange, but because of tidal recruitment, it may also contribute to injury. We hypothesize that higher positive end-expiratory pressure levels decrease the propensity to pendelluft and that with lower positive end-expiratory pressure levels, pendelluft is associated with improved gas exchange but increased tidal recruitment. DESIGN: Crossover design. SETTING: University animal research laboratory. SUBJECTS: Anesthetized landrace pigs. INTERVENTIONS: Surfactant depletion was achieved by saline lavage in anesthetized pigs, and ventilator-induced lung injury was produced by ventilation with high tidal volume and low positive end-expiratory pressure. Ventilation was continued in each of four conditions: positive end-expiratory pressure (low or optimized positive end-expiratory pressure after recruitment) and spontaneous breathing (present or absent). Tidal recruitment was assessed using dynamic CT and regional ventilation/perfusion using electric impedance tomography. Esophageal pressure was measured using an esophageal balloon manometer. MEASUREMENTS AND RESULTS: Among the four conditions, spontaneous breathing at low positive end-expiratory pressure not only caused the largest degree of pendelluft, which was associated with improved ventilation/perfusion matching and oxygenation, but also generated the greatest tidal recruitment. At low positive end-expiratory pressure, paralysis worsened oxygenation but reduced tidal recruitment. Optimized positive end-expiratory pressure decreased the magnitude of spontaneous efforts (measured by esophageal pressure) despite using less sedation, from -5.6 ± 1.3 to -2.0 ± 0.7 cm H2O, while concomitantly reducing pendelluft and tidal recruitment. No pendelluft was observed in the absence of spontaneous effort. CONCLUSIONS: Spontaneous effort at low positive end-expiratory pressure improved oxygenation but promoted tidal recruitment associated with pendelluft. Optimized positive end-expiratory pressure (set after lung recruitment) may reverse the harmful effects of spontaneous breathing by reducing inspiratory effort, pendelluft, and tidal recruitment.

Outcome of patients with high-risk Duke treadmill score and normal myocardial perfusion imaging on spect.

BACKGROUND: Annual mortality rate can range from <1% for patients with normal myocardial perfusion by SPECT to >5% based on a high-risk Duke treadmill score (DTS). Information on the prognosis of patients with the combination of HRDTS and normal SPECT is limited and is the purpose of this study. METHODS: Data from a large nuclear cardiology registry (n = 17,972 patients) were reviewed. A total of 340 had HRDTS (score ≤ -11) while undergoing SPECT. Combined cardiovascular mortality and non-fatal myocardial infarction (MI) and cardiovascular mortality alone were available in 310 patients at a mean follow-up of 4.01 ± 1.5 years. RESULTS: The majority of the patients had abnormal SPECT (n = 270, 71%). The abnormal SPECT patients compared to the normal were older (65.6 vs 62.8 years of age; P = .025), more likely to have abnormal left ventricular ejection fraction (26.1% vs 0%; P < .0001), known coronary artery disease (CAD, 35.9% vs 7.8%; P < .0001) and lower DTS (-14.5 vs -13.2; P = .0006), Kaplan-Meier survival analysis demonstrated a significantly lower cardiovascular mortality (5.4% vs 0%, P = .02) and combined outcome of MI and cardiovascular mortality (15% vs 4.4%, P = .009) in patients with normal versus abnormal SPECT. CONCLUSIONS: High-risk DTS is associated with abnormal perfusion SPECT in most patients, but nearly one-third of the patients had normal perfusion. Patients with a normal SPECT had a lower cardiovascular event rates.

Bleeding phenotype and correlation with factor XI (FXI) activity in congenital FXI deficiency: results of a retrospective study from a single centre.

Bleeding phenotype in factor XI (FXI)-deficient patients is variable, and not related to baseline FXI:Act. Aims of our study were to describe the characteristics and the management of surgery and deliveries in FXI-deficient patients, and to investigate the relationship between the haemorrhagic phenotype and the baseline FXI:Act. Ninety-five patients were diagnosed and followed in our centre for a median follow-up of 0.9 years (0.1-36.2); median FXI:Act of all patients: 38% (0.5-69%). Fifty-six patients (59%) experienced bleeding episodes not surgery-related. Prior to diagnosis, 64 patients underwent 132 surgeries, and after diagnosis, 23 patients underwent 36 surgeries. Globally 26 of 168 surgeries were prophylactically treated, whereas 142 of 168 were not. As regard as surgeries performed without prophylaxis, 30 bleeding events (21%) occurred in 21 patients. At diagnosis, the median FXI:Act of bleeding and non-bleeding patients was 28% and 37%, respectively, without statistically significant difference between the two groups (P = 0.26). As regard as surgeries performed under prophylactic treatment just 1 bleeding event occurred. Prior to diagnosis, 31 spontaneous deliveries (SD) and eight caesarian sections (CS) were performed without prophylaxis: 4 postpartum haemorrhages (10.5%) occurred (patients FXI:Act: 2%, 6%, 27%, 52.3% respectively). After diagnosis, four SD and five CS were performed with prophylaxis: no postpartum haemorrhages occurred. We confirm the wide bleeding phenotype variability in FXI-deficient patients, not related to the baseline FXI:Act levels. We highlight the importance of performing a correct diagnosis and follow-up, because a good management of prophylactic treatment, dramatically reduces the bleeding rate in case of surgery or deliveries.

Spontaneous effort causes occult pendelluft during mechanical ventilation.

RATIONALE: In normal lungs, local changes in pleural pressure (P(pl)) are generalized over the whole pleural surface. However, in a patient with injured lungs, we observed (using electrical impedance tomography) a pendelluft phenomenon (movement of air within the lung from nondependent to dependent regions without change in tidal volume) that was caused by spontaneous breathing during mechanical ventilation. OBJECTIVES: To test the hypotheses that in injured lungs negative P(pl) generated by diaphragm contraction has localized effects (in dependent regions) that are not uniformly transmitted, and that such localized changes in P(pl) cause pendelluft. METHODS: We used electrical impedance tomography and dynamic computed tomography (CT) to analyze regional inflation in anesthetized pigs with lung injury. Changes in local P(pl) were measured in nondependent versus dependent regions using intrabronchial balloon catheters. The airway pressure needed to achieve comparable dependent lung inflation during paralysis versus spontaneous breathing was estimated. MEASUREMENTS AND MAIN RESULTS: In all animals, spontaneous breathing caused pendelluft during early inflation, which was associated with more negative local P(pl) in dependent regions versus nondependent regions (-13.0 ± 4.0 vs. -6.4 ± 3.8 cm H2O; P < 0.05). Dynamic CT confirmed pendelluft, which occurred despite limitation of tidal volume to less than 6 ml/kg. Comparable inflation of dependent lung during paralysis required almost threefold greater driving pressure (and tidal volume) versus spontaneous breathing (28.0 ± 0.5 vs. 10.3 ± 0.6 cm H2O, P < 0.01; 14.8 ± 4.6 vs. 5.8 ± 1.6 ml/kg, P < 0.05). CONCLUSIONS: Spontaneous breathing effort during mechanical ventilation causes unsuspected overstretch of dependent lung during early inflation (associated with reciprocal deflation of nondependent lung). Even when not increasing tidal volume, strong spontaneous effort may potentially enhance lung damage.

Microplastic pollution in waters of the Antarctic coastal environment of Potter Cove (25 de Mayo Island/King George Island, South Shetlands).

Plastic pollution in the Southern Ocean around Antarctica is a growing concern, but many areas in this vast region remain unexplored. This study provides the first comprehensive analysis of marine microplastic (MPs) concentrations in Potter Cove, located near the Argentinian Carlini research station on 25 de Mayo/King George Island, Antarctica. Water samples were collected at 14 sites within the cove, representing various influences from the station's activities. Two sampling methods were used: a 5 L Niskin bottle and an in-situ filtering device called Microfilter, allowing for large water volumes to be filtered. MPs were found in 100 % of the samples. Microfilter samples ranged from 0.02 to 2.14 MPs/L, with a mean concentration of 0.44 ± 0.44 MPs/L. Niskin bottle samples showed concentrations from 0.40 to 55.67 MPs/L, with a mean concentration of 19.03 ± 18.21 MPs/L. The dominant types of MPs were anthropogenic black, transparent, and pink microfibers (MFs) measuring between 0.11 and 3.6 mm (Microfilter) and 0.06 to 7.96 mm (Niskin bottle), with a median length of 0.01 mm for both methods. Transparent and black irregular microfragments (MFRs) with diameters from 0.10 to 5.08 mm and a median diameter of 0.49 mm were also prevalent. FTIR-spectroscopy revealed the presence of 14 types of polymers. Cellulose-based materials and polyethylene terephthalate were the most abundant in MFs, while polyurethanes and styrene-based copolymers dominated in MFRs. MPs were more abundant near the Carlini station. Compared to other coastal Antarctic areas, the MPs in the cove were relatively abundant and mostly smaller than 1 mm. Local activities on the island were identified as the primary source of MPs in the cove, and the cyclonic water circulation likely affects the distribution of small-sized particles. To protect the ecosystem, reducing plastic usage, improving waste management, regulating MPs debris, and enhancing wastewater practices are essential.