Causes of Hypoxemia in COVID-19 Acute Respiratory Distress Syndrome: A Combined Multiple Inert Gas Elimination Technique and Dual-energy Computed Tomography Study.

BACKGROUND: Despite the fervent scientific effort, a state-of-the art assessment of the different causes of hypoxemia (shunt, ventilation-perfusion mismatch, and diffusion limitation) in COVID-19 acute respiratory distress syndrome (ARDS) is currently lacking. In this study, the authors hypothesized a multifactorial genesis of hypoxemia and aimed to measure the relative contribution of each of the different mechanism and their relationship with the distribution of tissue and blood within the lung. METHODS: In this cross-sectional study, the authors prospectively enrolled 10 patients with COVID-19 ARDS who had been intubated for less than 7 days. The multiple inert gas elimination technique (MIGET) and a dual-energy computed tomography (DECT) were performed and quantitatively analyzed for both tissue and blood volume. Variables related to the respiratory mechanics and invasive hemodynamics (PiCCO [Getinge, Sweden]) were also recorded. RESULTS: The sample (51 ± 15 yr; Pao2/Fio2, 172 ± 86 mmHg) had a mortality of 50%. The MIGET showed a shunt of 25 ± 16% and a dead space of 53 ± 11%. Ventilation and perfusion were mismatched (LogSD, Q, 0.86 ± 0.33). Unexpectedly, evidence of diffusion limitation or postpulmonary shunting was also found. In the well aerated regions, the blood volume was in excess compared to the tissue, while the opposite happened in the atelectasis. Shunt was proportional to the blood volume of the atelectasis (R2 = 0.70, P = 0.003). V˙A/Q˙T mismatch was correlated with the blood volume of the poorly aerated tissue (R2 = 0.54, P = 0.016). The overperfusion coefficient was related to Pao2/Fio2 (R2 = 0.66, P = 0.002), excess tissue mass (R2 = 0.84, P < 0.001), and Etco2/Paco2 (R2 = 0.63, P = 0.004). CONCLUSIONS: These data support the hypothesis of a highly multifactorial genesis of hypoxemia. Moreover, recent evidence from post-mortem studies (i.e., opening of intrapulmonary bronchopulmonary anastomosis) may explain the findings regarding the postpulmonary shunting. The hyperperfusion might be related to the disease severity.

Effect of dihydrotestosterone, 17-ß-estrogen, genistein and equol on remodeling and morphology of bone in osteoporotic male rats during bone healing.

INTRODUCTION: The aim of this study was to investigate the effect of dihydrotestosterone (DHT), 17-ß-estrogen (E2), genistein (GEN) and equol (EQ) on bone remodeling and bone morphology during healing of osteoporotic male rat tibiae. MATERIALS AND METHODS: 180 Sprague-Dawley male rats were divided in 5 groups of 36 animals. After orchidectomy (ORX) and development of osteoporosis, trepanation of the tibia was performed. Until the time of trepanation all groups received soya free food (SF), then food change occurred and treatment started. At day 95, 102 and 151, samples were taken and histomorphometry was performed to analyze changes in bone structure under treatment. At day 33 and 70 all animals received calcein respective alizarin for polychrome bone labeling. RESULTS: The cortical bone was particularly affected. Treatment with DHT and E2 led to a significant long-term expansion of the thickness of the diaphyseal cortical bone, while the phytoestrogens EQ and GEN only had a positive short-term effect in this area. Only E2 preserved the trabecular bone for a limited time. In all groups, periosteal and endosteal bone areas showed the highest bone formation activity. The osteoporotic male injured bone shows a shift in mineral apposition rate (MAR) from periosteal to endosteal bone in the SF, DHT and E2 groups but not in the GEN and EQ phytohormones groups. An MAR decrease in trabecular bone formation was observed at day 70 in all groups except the E2 group. CONCLUSION: We conclude from our results that healing of cortical bone defects in a rat model of male osteoporosis are mainly influenced by the estrogen pathway. Nevertheless, effects via purely androgenic mechanisms can also be demonstrated. The role of a phytohormone therapy is only marginal and if only useful for a short-term supportive approach. The role of the periosteal to endosteal shift during male osteoporotic bone healing needs to be further examined.

Temporal patterns in ecosystem services research: A review and three recommendations.

Temporal aspects of ecosystem services have gained surprisingly little attention given that ecosystem service flows are not static but change over time. We present the first systematic review to describe and establish how studies have assessed temporal patterns in supply and demand of ecosystem services. 295 studies, 2% of all studies engaging with the ecosystem service concept, considered changes in ecosystem services over time. Changes were mainly characterised as monotonic and linear (81%), rather than non-linear or through system shocks. Further, a lack of focus of changing ecosystem service demand (rather than supply) hampers our understanding of the temporal patterns of ecosystem services provision and use. Future studies on changes in ecosystem services over time should (1) more explicitly study temporal patterns, (2) analyse trade-offs and synergies between services over time, and (3) integrate changes in supply and demand and involve and empower stakeholders in temporal ecosystem services research.

Mechanical Ventilation Strategies Targeting Different Magnitudes of Collapse and Tidal Recruitment in Porcine Acid Aspiration-Induced Lung Injury.

Reducing ventilator-associated lung injury by individualized mechanical ventilation (MV) in patients with Acute Respiratory Distress Syndrome (ARDS) remains a matter of research. We randomly assigned 27 pigs with acid aspiration-induced ARDS to three different MV protocols for 24 h, targeting different magnitudes of collapse and tidal recruitment (collapse&TR): the ARDS-network (ARDSnet) group with low positive end-expiratory pressure (PEEP) protocol (permissive collapse&TR); the Open Lung Concept (OLC) group, PaO2/FiO2 >400 mmHg, indicating collapse&TR <10%; and the minimized collapse&TR monitored by Electrical Impedance Tomography (EIT) group, standard deviation of regional ventilation delay, SDRVD. We analyzed cardiorespiratory parameters, computed tomography (CT), EIT, and post-mortem histology. Mean PEEP over post-randomization measurements was significantly lower in the ARDSnet group at 6.8 ± 1.0 cmH2O compared to the EIT (21.1 ± 2.6 cmH2O) and OLC (18.7 ± 3.2 cmH2O) groups (general linear model (GLM) p < 0.001). Collapse&TR and SDRVD, averaged over all post-randomization measurements, were significantly lower in the EIT and OLC groups than in the ARDSnet group (collapse p < 0.001, TR p = 0.006, SDRVD p < 0.004). Global histological diffuse alveolar damage (DAD) scores in the ARDSnet group (10.1 ± 4.3) exceeded those in the EIT (8.4 ± 3.7) and OLC groups (6.3 ± 3.3) (p = 0.16). Sub-scores for edema and inflammation differed significantly (ANOVA p < 0.05). In a clinically realistic model of early ARDS with recruitable and nonrecruitable collapse, mechanical ventilation involving recruitment and high-PEEP reduced collapse&TR and resulted in improved hemodynamic and physiological conditions with a tendency to reduced histologic lung damage.

Accuracy of Navigation-Guided Dental Implant Placement with Screw Versus Hand Template Fixation in the Edentulous Mandible.

PURPOSE: Preoperative planning of the implant position as part of a coordinated prosthetic and surgical concept is becoming increasingly important regarding function and esthetics. The aim of this study was to investigate the transmission accuracy of template fixation during surgery in edentulous arches with hand fixation in comparison to intermediary screw fixation. MATERIALS AND METHODS: Preoperatively, 10 implant positions were planned using computed tomography (CT) with the system med3D for implant placement in four mandible models of the Goettingen study model, using a prosthetic diagnostic template. A total of 40 implant insertions were created. For every 20 insertions, the template was temporarily fixed with three screws and compared with the insertion using a hand-fixed template. The precision of the transmission was evaluated with and without screw fixation by re-evaluating the preimplant planning with additional CT scanning of the respective models. RESULTS: Compared with the hand-fixed procedure (HFG) in the model situation, there were no significant differences between the deviations of planned and final implant position in the screw-fixed group (FG). According to the study results, the fixed procedure leads to less depth deviation and lateral error of the implant base in relation to the HFG. Within both groups, there were significant differences between the radial deviation tendencies from the implant base to the implant apex (P = .033 for FG and P = .001 for HFG). CONCLUSION: The use of CT-based implant planning succeeds in fixed and hand-fixed surgical procedures with high precision in the atrophic, edentulous mandible model. According to the results of this study, in cases demanding high depth precision, screw-fixation of the template can be helpful.

The incidence of occult metastasis and the status of elective neck dissection in salivary adenoid cystic carcinoma: a single center study.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is characterized by a high rate of local recurrence and late distant metastasis. The status of an elective neck dissection (END) is controversial in the literature. STUDY DESIGN: In this study we retrospectively analyzed the surgical treatment and follow-up examinations of 59 patients with ACCs of a salivary gland treated in a single center between 1980 and 2016. RESULTS: The incidence of occult nodal metastases among all patients who underwent END was 20.6%. The overall survival and the disease-free survival of patients who underwent END versus patients without END had no significant differences. Even in the case of positive lymph nodes metastasis there was no significant benefit in survival or local recurrence control. CONCLUSION: The incidence of occult neck metastases in patients with ACC was 20.6%. There was no significant enhanced survival in the group of patients who underwent an END.

Repair of large saddle defects of the mandibular ridge using dual growth factor release-An experimental pilot study in minipigs.

AIM: To test the hypothesis that the addition of small amounts of rhVEGF to rhBMP2 in a polymer carrier can accomplish equivalent repair effect as a reduced dosage of rhBMP2 compared to rhBMP2 alone. MATERIALS AND METHODS: Defects were created bilaterally in the mandibles of 18 minipigs. In 12 test animals, defects were filled with 0.5 g particulate PDLLA/CaCO3 composite loaded with 400 µg rhBMP2/50 µg rhVEGF165 on one side and 800 µg rhBMP2 on the other. After 4 and 13 weeks, the animals were evaluated each for area of new bone formation (mm²) and bone density (area %). RESULTS: Area of newly formed bone was higher in defects with carriers loaded with 400 µg rhBMP2 50 µg VEGF165 than in defects with 800 µg rhBMP2 after 4 weeks (11.97 versus 7.97 mm²; p = 0.043) and 13 weeks (72.48 versus 62.2 mm²; p = .028). Defects filled with blank carrier exhibited less bone after 13 weeks (42.75 mm²; p = .039 and .020 respectively). CONCLUSIONS: Delivery of rhBMP2 from a polymer carrier can improve repair of large saddle defects of the mandibular ridge. Addition of small amounts of rhVEGF can increase bone formation and at the same time reduce the dosage of rhBMP2.

A review of ecosystem service benefits from wild bees across social contexts.

In order to understand the role of wild bees in both social and ecological systems, we conducted a quantitative and qualitative review of publications dealing with wild bees and the benefits they provide in social contexts. We classified publications according to several attributes such as services and benefits derived from wild bees, types of bee-human interactions, recipients of direct benefits, social contexts where wild bees are found, and sources of changes to the bee-human system. We found that most of the services and benefits from wild bees are related to food, medicine, and pollination. We also found that wild bees directly provide benefits to communities to a greater extent than individuals. In the social contexts where they are found, wild bees occupy a central role. Several drivers of change affect bee-human systems, ranging from environmental to political drivers. These are the areas where we recommend making interventions for conserving the bee-human system.

Clinical efficacy of grafting materials in alveolar ridge augmentation: A systematic review.

PURPOSE: To evaluate the efficacy of grafting materials in lateral and vertical ridge augmentations. MATERIALS AND METHODS: A systematic review of the literature on the clinical use of grafting materials of the years 1995 to April 2015 was conducted using electronic search of PubMed and Cochrane libraries and hand search of eight print journals. A total of 184 papers were included, comprising 6182 patients. Parameters evaluated were observation period [months], bone formation [histologic area%], defect fill [%], horizontal and vertical gain [mm], loss of augmented volume [mm], complication rate [%], and implant survival rate [%]. Results are expressed as weighted means ± SD. RESULTS: Results were obtained after a weighted mean observation period of 27.4 months (range 3-168 months). Bone formation in the augmented areas varied from 33.2 ± 14.9% for allogeneic grafts to 56.0 ± 25.6% for mixtures of autogenous and other grafting materials. Defect fill in dehiscence defects ranged from 51.0 ± 13.6% (synthetic) to 85.8 ± 13.4% (xenogeneic) for the different materials, with an overall weighted mean of 79.8 ± 18.7%. Weighted mean horizontal gain for all particulate grafting materials was 3.7 ± 1.2 mm, with variation between 2.2 ± 1.2 mm (synthetic) and 4.5 ± 1.0 mm (mixtures of autogenous bone with allogeneic/xenogeneic grafting material) without statistical significance. Weighted overall mean vertical gain was 3.7 ± 1.4 mm. Vertical gain was substantially higher when space-making barrier materials such as titanium meshes were used; however this was also associated with strong increase in complication rate. Block grafts achieved higher horizontal gain by approximately 1 mm. The use of block grafts achieved significantly increased vertical gain compared to particulate material only when autogenous block grafts from extraoral donor sites were used. CONCLUSION: Horizontal and vertical gain by 3.7 mm on average can be achieved using particulate materials. This can be increased by using titanium meshes. Substantial vertical gains beyond this dimension require the use of extraoral bone block grafts.

Bedside estimation of nonaerated lung tissue using blood gas analysis.

OBJECTIVES: Studies correlating the arterial partial pressure of oxygen to the fraction of nonaerated lung assessed by CT shunt yielded inconsistent results. We systematically analyzed this relationship and scrutinized key methodological factors that may compromise it. We hypothesized that both physiological shunt and the ratio between PaO2 and the fraction of inspired oxygen enable estimation of CT shunt at the bedside. DESIGN: : Prospective observational clinical and laboratory animal investigations. SETTING: ICUs (University Hospital Leipzig, Germany) and Experimental Pulmonology Laboratory (University of São Paulo, Brazil). PATIENTS, SUBJECTS AND INTERVENTIONS: Whole-lung CT and arterial blood gases were acquired simultaneously in 77 patients mechanically ventilated with pure oxygen. A subgroup of 28 patients was submitted to different Fio2. We also studied 19 patients who underwent repeat CT. Furthermore we studied ten pigs with acute lung injury at multiple airway pressures, as well as a theoretical model relating PaO2 and physiological shunt. We logarithmically transformed the PaO2/Fio2 to change this nonlinear relationship into a linear regression problem. MEASUREMENTS AND MAIN RESULTS: We observed strong linear correlations between Riley's approximation of physiological shunt and CT shunt (R = 0.84) and between logarithmically transformed PaO2/Fio2 and CT shunt (R = 0.86), allowing us to construct a look-up table with prediction intervals. Strong linear correlations were also demonstrated within-patients (R = 0.95). Correlations were significantly improved by the following methodological issues: measurement of PaO2/Fio2 during pure oxygen ventilation, use of logarithmically transformed PaO2/Fio2 instead of the "raw" PaO2/Fio2, quantification of nonaerated lung as percentage of total lung mass and definition of nonaerated lung by the [-200 to +100] Hounsfield Units interval, which includes shunting units within less opacified lung regions. CONCLUSION: During pure oxygen ventilation, logarithmically transformed PaO2/Fio2 allows estimation of CT shunt and its changes in patients during systemic inflammation. Relevant intrapulmonary shunting seems to occur in lung regions with CT numbers between [-200 and +100] Hounsfield Units.

Extrapolation in the analysis of lung aeration by computed tomography: a validation study.

INTRODUCTION: Computed tomography (CT) is considered the gold standard for quantification of global or regional lung aeration and lung mass. Quantitative CT, however, involves the exposure to ionizing radiation and requires manual image processing. We recently evaluated an extrapolation method which calculates quantitative CT parameters characterizing the entire lung from only 10 reference CT-slices thereby reducing radiation exposure and analysis time. We hypothesized that this extrapolation method could be further validated using CT-data from pigs and sheep, which have a different thoracic anatomy. METHODS: We quantified volume and mass of the total lung and differently aerated lung compartments in 168 ovine and 55 porcine whole-lung CTs covering lung conditions from normal to gross deaeration. Extrapolated volume and mass parameters were compared to the respective values obtained by whole-lung analysis. We also tested the accuracy of extrapolation for all possible numbers of CT slices between 15 and 5. Bias and limits of agreement (LOA) were analyzed by the Bland-Altman method. RESULTS: For extrapolation from 10 reference slices, bias (LOA) for the total lung volume and mass of sheep were 18.4 (-57.2 to 94.0) ml and 4.2 (-21.8 to 30.2) grams, respectively. The corresponding bias (LOA) values for pigs were 5.1 (-55.2 to 65.3) ml and 1.6 (-32.9 to 36.2) grams, respectively. All bias values for differently aerated lung compartments were below 1% of the total lung volume or mass and the LOA never exceeded ± 2.5%. Bias values diverged from zero and the LOA became considerably wider when less than 10 reference slices were used. CONCLUSIONS: The extrapolation method appears robust against variations in thoracic anatomy, which further supports its accuracy and potential usefulness for clinical and experimental application of quantitative CT.

Computed tomographic assessment of lung weights in trauma patients with early posttraumatic lung dysfunction.

INTRODUCTION: Quantitative computed tomography (qCT)-based assessment of total lung weight (Mlung) has the potential to differentiate atelectasis from consolidation and could thus provide valuable information for managing trauma patients fulfilling commonly used criteria for acute lung injury (ALI). We hypothesized that qCT would identify atelectasis as a frequent mimic of early posttraumatic ALI. METHODS: In this prospective observational study, Mlung was calculated by qCT in 78 mechanically ventilated trauma patients fulfilling the ALI criteria at admission. A reference interval for Mlung was derived from 74 trauma patients with morphologically and functionally normal lungs (reference). Results are given as medians with interquartile ranges. RESULTS: The ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen was 560 (506 to 616) mmHg in reference patients and 169 (95 to 240) mmHg in ALI patients. The median reference Mlung value was 885 (771 to 973) g, and the reference interval for Mlung was 584 to 1164 g, which matched that of previous reports. Despite the significantly greater median Mlung value (1088 (862 to 1,342) g) in the ALI group, 46 (59%) ALI patients had Mlung values within the reference interval and thus most likely had atelectasis. In only 17 patients (22%), Mlung was increased to the range previously reported for ALI patients and compatible with lung consolidation. Statistically significant differences between atelectasis and consolidation patients were found for age, Lung Injury Score, Glasgow Coma Scale score, total lung volume, mass of the nonaerated lung compartment, ventilator-free days and intensive care unit-free days. CONCLUSIONS: Atelectasis is a frequent cause of early posttraumatic lung dysfunction. Differentiation between atelectasis and consolidation from other causes of lung damage by using qCT may help to identify patients who could benefit from management strategies such as damage control surgery and lung-protective mechanical ventilation that focus on the prevention of pulmonary complications.