Cardiopulmonary exercise testing criteria for advanced therapies in patients with heart failure.

Many cardiology associations endorse the role of the cardiopulmonary exercise test (CPET) to define the severity of impairment of functional capacity in individuals with heart failure with reduced ejection fraction (HFrEF) and when evaluating the need for advanced therapies for these patients. The focus of the CPET within the cardiology community has been on peak volume of oxygen uptake (VO2). However, several CPET variables are associated with outcomes in individuals with and without chronic disease and can inform clinical decisions in individuals with HFrEF. In this manuscript, we will review the normal cardiopulmonary response to a graded exercise test and review current guideline recommendations relative to CPET in patients with HFrEF.

Serum Ferritin as a Predictor of Outcomes in Hospitalized Patients with Covid-19 Pneumonia.

Purpose: Elevated ferritin levels are associated with poor outcomes in Covid-19 patients. Optimal timing of ferritin assessment and the merit of longitudinal values remains unclear. Methods: Patients admitted to Henry Ford Hospital with confirmed SARS-CoV-2 were studied. Regression models were used to determine the relation between ferritin and mortality, need for mechanical ventilation, ICU admission, and days on the ventilator. Results: 2265 patients were evaluated. Patients with an initial ferritin of > 490 ng/mL had an increased risk of death (OR 3.4, P < .001), admission to the ICU (OR 2.78, P < .001) and need for mechanical ventilation (OR 3.9, P < .001). There was no difference between admission and Day 1 ICU ferritin levels (611.5 ng/mL vs. 649 ng/mL respectively; P = .07). The decline in ferritin over ICU days 1-4 was similar between survivors and non-survivors. A change in ferritin levels from admission to ICU Day 1 (P = .330), or from ICU Day 1 to 2 (P = .788), did not predict days on the ventilator. Conclusions: Initial Ferritin levels were highly predictive of ICU admission, the need for mechanical ventilation and in-hospital mortality. However, longitudinal measures of ferritin throughout the hospital stay did not provide additional predictive value.

Correction: A Neolithic Mega-Tsunami Event in the Eastern Mediterranean: Prehistoric Settlement Vulnerability Along the Carmel Coast, Israel.

[This corrects the article DOI: 10.1371/journal.pone.0243619.].

Racial Differences in a Detroit, MI, ICU Population of Coronavirus Disease 2019 Patients.

OBJECTIVES: To investigate the potential influence of racial differences in outcomes of patients infected by coronavirus disease 2019-positive patients who require intensive care in an urban hospital. DESIGN: Retrospective cohort study. SETTING: Henry Ford Health System Multidisciplinary ICU, a total of 156 beds spread throughout the hospital in Detroit, MI. PATIENTS: We obtained data from the electronic medical record of all adult severe acute respiratory syndrome coronavirus-2-positive patients managed in the ICU of Henry Ford Hospital in Detroit, MI, between March 13, 2020, and July 31, 2020. Included patients were divided into two groups: people of color (including Black, Asian, Hispanic/Latino, and Arab) and White. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 365 patients were evaluated: 219 were Black (60.0%), 129 were White (35.3%), two were Asian (0.6%), eight were Hispanic/Latino (2.2%), and seven were Arab (1.9%). People of color were younger (62.8 vs 67.1; p = 0.007), with equal distribution of sex. People of color had less coronary artery disease (34 [14.4%] vs 35 [27.1%]; p =0.003) and less self-reported use of regular alcohol consumption (50 [21.2%] vs 12 [9.3%]; p = 0.004) than Whites, with no differences in diabetes (125 [53.0%] vs 66 [51.2%]; p = 0.742), hypertension (188 [79.7%] vs 99 [76.8%]; p = 0.516), congestive heart failure (41 [17.4%] vs 32 [24.8%]; p = 0.090), or chronic kidney disease (123 [54.1%] vs 55 [42.6%]; p = 0.083).There was no difference in ICU length of stay between people of color (18 d [CI, 7-47 d]) and Whites (18 d [CI, 6-48 d]; p = 0. 0.979). Neither frequency (72.5% vs 71.3%; p = ns) nor median time to mechanical ventilation between people of color (9 d [CI, 6-15 d]) and Whites (10 d [CI, 5-16 d]; p = 0.733) was different. Overall, 188 patients (51.5 %) died in the hospital. The 28-day mortality was lower in people of color (107/236; 45.3%) versus Whites (73/129; 56.6%) (adjusted odds ratio 0.60; p = 0.034), and there was an increased median survival time in people of color (20 d) versus Whites (13.5 d; hazard ratio 0.62; p = 0.002). The inhospital mortality was lower in people of color versus White, but the difference was not statistically significant (113 [47.9%] vs 75 [58.1%], respectively; p = 0.061). Finally, there was no significant difference in days of symptoms prior to admission, frequency of presenting symptoms, or frequency or severity of acute respiratory distress syndrome between the two groups. CONCLUSIONS: In critically ill patients infected with coronavirus disease 2019, people of color had a lower 28-day mortality than Whites with no difference in hospital mortality, ICU length of stay, or rates of intubation. These findings are contrary to previously held beliefs surrounding the pandemic.

Role of Tissue Plasminogen Activator for Diffuse Pulmonary Microemboli in Coronavirus Disease 2019 Patient.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hypercoagulability has been of great interest in the pathophysiology of coronavirus disease 2019 (COVID-19). Many patients have clinical findings of dead-space ventilation, similar to pulmonary embolism. Herein, a patient who presented with COVID-19 pneumonia and whose condition rapidly deteriorated to respiratory failure requiring intubation is described. Tissue plasminogen activator (tPA) was administered because of concern of pulmonary microemboli, with improvement of respiratory status and extubation within 24 hours. Patients with COVID-19 infection have an increased risk of thrombus formation,1 and the administration of tPA may benefit these patients by immediately lysing diffuse thrombi and improving gas exchange.

A Neolithic mega-tsunami event in the eastern Mediterranean: Prehistoric settlement vulnerability along the Carmel coast, Israel.

Tsunami events in antiquity had a profound influence on coastal societies. Six thousand years of historical records and geological data show that tsunamis are a common phenomenon affecting the eastern Mediterranean coastline. However, the possible impact of older tsunamis on prehistoric societies has not been investigated. Here we report, based on optically stimulated luminescence chronology, the earliest documented Holocene tsunami event, between 9.91 to 9.29 ka (kilo-annum), from the eastern Mediterranean at Dor, Israel. Tsunami debris from the early Neolithic is composed of marine sand embedded within fresh-brackish wetland deposits. Global and local sea-level curves for the period, 9.91-9.29 ka, as well as surface elevation reconstructions, show that the tsunami had a run-up of at least ~16 m and traveled between 3.5 to 1.5 km inland from the palaeo-coastline. Submerged slump scars on the continental slope, 16 km west of Dor, point to the nearby "Dor-complex" as a likely cause. The near absence of Pre-Pottery Neolithic A-B archaeological sites (11.70-9.80 cal. ka) suggest these sites were removed by the tsunami, whereas younger, late Pre-Pottery Neolithic B-C (9.25-8.35 cal. ka) and later Pottery-Neolithic sites (8.25-7.80 cal. ka) indicate resettlement following the event. The large run-up of this event highlights the disruptive impact of tsunamis on past societies along the Levantine coast.

Earthquake damage as a catalyst to abandonment of a Middle Bronze Age settlement: Tel Kabri, Israel.

For years there has been much speculation surrounding the abandonment of the Middle Bronze Age IIB palace of Tel Kabri, ca. 1700 BCE. There are no weapons, hoards of money and jewelry, or visible evidence for fire, which rules out hostile attack or conquest. There are also no indications of drought or environmental degradation that might have forced the inhabitants to vacate the site, nor mass graveyards to indicate a pandemic. The current study uses micro-geoarchaeological methods to show that the demise of the palace was rapid, with walls and ceilings collapsing at once prior to abandonment. Macroscopic data (stratigraphic and structural) from five excavation seasons were reexamined, showing that at least nine Potential Earthquake Archaeological Effects (PEAEs) are found and associated with the last occupation phase of the site's palace. All lines of evidence point to the possibility that an earthquake damaged the palace, possibly to a point where it was no longer economically viable to repair. This conclusion is compounded by the discovery of a 1-3 m wide trench that cuts through the palace for 30 m, which may be the result of ground shaking or liquefaction caused by an earthquake. This study shows the importance of combining macro- and micro-archaeological methods for the identification of ancient earthquakes, together with the need to evaluate alternative scenarios of climatic, environmental, and economic collapse, as well as human-induced destruction before a seismic event scenario can be proposed.

Neotectonics of the Sea of Galilee (northeast Israel): implication for geodynamics and seismicity along the Dead Sea Fault system.

The Sea of Galilee in northeast Israel is a freshwater lake filling a morphological depression along the Dead Sea Fault. It is located in a tectonically complex area, where a N-S main fault system intersects secondary fault patterns non-univocally interpreted by previous reconstructions. A set of multiscale geophysical, geochemical and seismological data, reprocessed or newly collected, was analysed to unravel the interplay between shallow tectonic deformations and geodynamic processes. The result is a neotectonic map highlighting major seismogenic faults in a key region at the boundary between the Africa/Sinai and Arabian plates. Most active seismogenic displacement occurs along NNW-SSE oriented transtensional faults. This results in a left-lateral bifurcation of the Dead Sea Fault forming a rhomb-shaped depression we named the Capharnaum Trough, located off-track relative to the alleged principal deformation zone. Low-magnitude (ML = 3-4) epicentres accurately located during a recent seismic sequence are aligned along this feature, whose activity, depth and regional importance is supported by geophysical and geochemical evidence. This case study, involving a multiscale/multidisciplinary approach, may serve as a reference for similar geodynamic settings in the world, where unravelling geometric and kinematic complexities is challenging but fundamental for reliable earthquake hazard assessments.

Outcomes in Medical Intensive Care Patients Housed in Geographically Distant Units.

OBJECTIVE: The purpose of this study is to determine whether in patients admitted to a medical intensive care unit (ICU) service there are outcome differences between those in a medical ICU bed ("home") and a geographically distant subspecialty ICU bed ("overflow"). METHODS: We performed a retrospective cohort study of 4091 patients admitted to a medical ICU of a large tertiary-care urban teaching hospital. Depending on bed availability, some patients were housed in surgical or cardiac subspecialty ICUs while still being cared for by the primary medical ICU service. We assessed the association of these overflow patients with readmission rates and ICU and hospital length of stay (LOS). Potential differences in care was assessed by measuring the number of central line days, urinary catheter days, and ventilator days. RESULTS: Of the 4091 consecutive patients admitted to the medical ICU, 362 (9%) were housed in an overflow ICU and 3729 (91%) were home patients. There was no difference in demographics, patient characteristics, ICU admission diagnosis, or risk of mortality between the 2 groups. Compared to home patients, overflow patients had a higher rate of readmission to the ICU (10.5% vs 6.63% respectively P = .006), a slightly shorter ICU LOS (median 2 [interquartile range, IQR: 1-4] days versus home group of 2 [IQR: 1-5] days; P = .001), and a slightly longer hospital LOS (overflow 7 [IQR: 4-17] days vs home 7 [IQR: 4-13] days, P = .001). There was no differences in number of central venous catheter days, urinary catheter days, ventilator days, or mortality. CONCLUSIONS: Medical ICU patients who are housed in ICUs geographically distant from the primary team's location have increased morbidity when compared to patients admitted to the home ICU. However, there are no differences in number of central venous catheter days, urinary catheter days, ventilator days, or mortality.

Methane Bubble Ascent within Fine-Grained Cohesive Aquatic Sediments: Dynamics and Controlling Factors.

Methane (CH4) is a potent greenhouse gas. Its release from aquatic sediments to the water column and potentially to the atmosphere, is a subject of great concern. A coupled macroscopic single-bubble mechanical/reaction-transport numerical model was used to explore the ascent of a mature CH4 bubble toward the seafloor in muddy aquatic sediment. Two bubble ascent scenarios were demonstrated: stable and dynamic. For small effective overburden loads (≤11 kPa), stable ascent is followed by dynamic ascent (which has not been previously demonstrated to the best of the our knowledge). This ultimately leads to the bubble being released to the water column. Higher effective overburden loads induce only stable bubble ascent, which stops at the gas horizon frequently observed below the seafloor. The depth of the gas horizon increases, while bubble rise velocity decreases with an increase in the overburden load. It is shown that the bubble migration scenario is managed predominantly by inner bubble pressure, which defines a bubble solute exchange with ambient porewaters. Predicting a bubble ascent scenario in muddy sediment will further allow estimation of CH4 emission to the atmosphere and evaluation of changes in the effective mechanical properties of aquatic sediment due to the ascending bubbles.

An extensive pockmark field on the upper Atlantic margin of Southeast Brazil: spatial analysis and its relationship with salt diapirism.

We present new evidence for the existence of a large pockmark field on the continental slope of the Santos Basin, offshore southeast Brazil. A recent high-resolution multibeam bathymetric survey revealed 984 pockmarks across a smooth seabed at water depths of 300-700 m. Four patterns of pockmark arrays were identified in the data: linear, network, concentric, and radial. Interpretation of Two-dimensional multi-channel seismic reflection profiles that crosscut the surveyed area shows numerous salt diapirs in various stages of development (e.g. salt domes, walls, and anticlines). Some diapirs were exposed on the seafloor, whereas the tops of others (diapir heads) were situated several hundreds of meters below the surface. Extensional faults typically cap these diapirs and reach shallow depths beneath the seafloor. Our analysis suggests that these pockmark patterns are linked to stages in the development of underlying diapirs and their related faults. The latter may extend above salt walls, take the form of polygonal extensional faults along higher-level salt anticlines, or concentric faults above diapir heads that reach close to the seafloor. Seismic data also revealed buried pockmark fields that had repeatedly developed since the Middle Miocene. The close spatio-temporal connection between pockmark and diapir distribution identified here suggests that the pockmark field extends further across the Campos and Espírito Santo Basins, offshore Brazil. Spatial overlap between the pockmark field topping a large diapir field and a proliferous hydrocarbon basin is believed to have facilitated the escape of fluid/gas from the subsurface to the water column, which was enhanced by halokinesis. This provides a possible control on fossil gas contribution to the marine system over geological time.

Mindfulness treatment for substance misuse: A systematic review and meta-analysis.

High rates of relapse following substance misuse treatment highlight an urgent need for effective therapies. Although the number of empirical studies investigating effects of mindfulness treatment for substance misuse has increased dramatically in recent years, few reviews have examined findings of mindfulness studies. Thus, this systematic review examined methodological characteristics and substantive findings of studies evaluating mindfulness treatments for substance misuse published by 2015. The review also includes the first meta-analysis of randomized controlled trials of mindfulness treatments for substance misuse. Comprehensive bibliographic searches in PubMed, PsycInfo, and Web of Science, identified 42 pertinent studies. Meta-analytic results revealed significant small-to-large effects of mindfulness treatments in reducing the frequency and severity of substance misuse, intensity of craving for psychoactive substances, and severity of stress. Mindfulness treatments were also effective in increasing rates of posttreatment abstinence from cigarette smoking compared to alternative treatments. Mindfulness treatment for substance misuse is a promising intervention for substance misuse, although more research is needed examining the mechanisms by which mindfulness interventions exert their effects and the effectiveness of mindfulness treatments in diverse treatment settings.

Successful Ultrasound-Guided Femoral Nerve Blockade and Catheterization in a Patient with Von Willebrand Disease.

Peripheral nerve blockade (PNB) is superior to neuraxial anesthesia and/or opioid therapy for perioperative analgesia in total knee replacement (TKR). Evidence on the safety of PNB in patients with coagulopathy is lacking. We describe the first documented account of continuous femoral PNB for perioperative analgesia in a patient with Von Willebrand Disease (vWD). Given her history of opioid tolerance and after an informative discussion, a continuous femoral PNB was planned for in this 34-year-old female undergoing TKR. A Humate-P intravenous infusion was started and the patient was positioned supinely. Using sterile technique with ultrasound guidance, a Contiplex 18 Gauge Tuohy needle was advanced in plane through the fascia iliaca towards the femoral nerve. A nerve catheter was threaded through the needle and secured without complications. Postoperatively, a levobupivacaine femoral catheter infusion was maintained, and twice daily Humate-P intravenous infusions were administered for 48 hours; enoxaparin thromboprophylaxis was initiated thereafter. The patient was discharged uneventfully on postoperative day 4. Given documentation of delayed, unheralded bleeding from PNB in coagulopathic patients, we recommend individualized PNB in vWD patients. Multidisciplinary team involvement is required to guide factor supplementation and thromboprophylaxis, as is close follow-up to elicit signs of bleeding throughout the delayed postoperative period.

Dedicated multidisciplinary ventilator bundle team and compliance with sedation vacation.

BACKGROUND: How compliance with a ventilator bundle is monitored varies from institution to institution. Some institutions rely on the primary intensive care unit team to review the bundle during their rounds; others rely on a separate team of health care personnel that may include representatives from disciplines such as nursing, respiratory therapy, and pharmacy. OBJECTIVES: To compare rates of compliance with ventilator bundle components between a dedicated ventilator bundle rounding team and the primary intensive care unit rounding team in a 68-bed medical intensive care unit. METHODS: A query of the medical intensive care unit's database was used to retrospectively determine rates of compliance with specific ventilator bundle components at a tertiary care hospital in an urban community for 1 year. RESULTS: Compared with the intensive care unit rounding team, the ventilator bundle rounding team had better compliance with sedation vacation (61.7% vs 54.0%, P < .001). Rates of compliance with spontaneous breathing trials and prophylaxis of peptic ulcer disease were similar in both study groups. CONCLUSIONS: A dedicated ventilator bundle rounding team improves compliance with sedation vacation, but not with spontaneous breathing trials and prophylaxis of peptic ulcer disease. In a large-volume tertiary center, a dedicated ventilator bundle rounding team may be more effective than the primary rounding team in achieving compliance with some bundle components.

Outcomes of patients considered for, but not admitted to, the intensive care unit.

OBJECTIVE: The purpose of this study is to evaluate factors associated with decisions to reject patients from medical intensive care unit (MICU) admission and assess the outcome of these patients. DESIGN: Prospective, observational cohort study. SETTING: Large tertiary referral, teaching hospital. PATIENTS: Consecutive patients evaluated for MICU admission but not admitted. MEASUREMENTS: Patient characteristics and demographics, location of evaluation, clinical and laboratory data, major organ system dysfunction, 48-hr patient status, and 6-month mortality. MAIN RESULTS: A total of 1,302 patients were admitted to the MICU, 353 patients were evaluated for the MICU but were not admitted, and 324 patients were used in analysis. Mean age was 68.6 +/- 17.1 yrs, and 57.7% were women. Hospice care was instituted during or immediately after evaluation in 8.3% (n = 27) of cases. MICU care was declined by the patient in 5.2% (n = 17) of evaluations. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 17.4 +/- 6.0. Factors associated with death at 6 months included age, APACHE II score, entering hospice, and patient choice to decline care. Of the patients considered too well to benefit, 9% were admitted to the MICU within 48 hrs and 35.5% died within 6 months; however, no deaths occurred within 48 hrs. CONCLUSIONS: Patients who are considered for critical care are at very high risk of mortality within 6 months. Given that no deaths occurred within 48 hrs and that only 9% needed intensive care unit admission within 48 hrs, the house staff's decision process is safe at this one institution.

Heart failure reduces both the effects and interaction between cyclic GMP and cyclic AMP.

BACKGROUND: We tested the hypothesis that the negative functional effects of cyclic GMP would be attenuated by cyclic AMP and this interaction would be reduced in pacing-induced failure of hypertrophic hearts. MATERIALS AND METHODS: 8-Bromo-cGMP (2 microg/kg/min) was infused into a coronary artery in eight control, eight ventricular hypertrophy (HYP), and eight hypertrophic failure (HYP-FAIL) dogs. Then isoproterenol (0.1 microg/kg/min) was infused, followed by 8 Br-cGMP. Regional myocardial work (force*shortening/min), and O(2) consumption (VO(2)) (coronary blood flow*O(2) extraction) were measured. Cyclic GMP levels were determined by radioimmunoassay. RESULTS: 8-Br-cGMP significantly decreased regional work from 3812 +/- 839 g*mm/min by 17% and VO(2) by 29% in control, but not in HYP (1073 +/- 182 by -10%, VO(2) by -16%) or HYP-FAIL (495 +/- 145 by -9%, VO(2) by 0%). Isoproterenol increased work by 43% and VO(2) by 48% in controls and in HYP (work by 54%, VO(2) by 39%), but not in HYP-FAIL (work by -28%, VO(2) by -5%). Subsequently, 8-Br-cGMP had no effect on work or VO(2) in control (-2%, -13%), HYP (-12%, -30%), or HYP-FAIL (+13%, +14%). Cyclic AMP levels were elevated by isoproterenol in control (381 +/- 115 versus 553 +/- 119 pmol/g) and HYP (313 +/- 55 versus 486 +/- 227), but not in HYP-FAIL (300 +/- 60 versus 284 +/- 126). After isoproterenol, 8-Br-cGMP further elevated cyclic AMP in control (687 +/- 122), but not in HYP or HYP-FAIL. CONCLUSIONS: In controls, cyclic AMP attenuated cyclic GMPs negative functional and metabolic effects. The effects and the interaction were blunted in the HYP and HYP-FAIL groups.

Reduction in interaction between cGMP and cAMP in dog ventricular myocytes with hypertrophic failure.

Baseline function and signal transduction are depressed in hearts with hypertrophic failure. We tested the hypothesis that the effects of cGMP and its interaction with cAMP would be reduced in cardiac myocytes from hypertrophic failing hearts. Ventricular myocytes were isolated from control dogs, dogs with aortic valve stenosis hypertrophy, and dogs with pacing hypertrophic failure. Myocyte function was measured using a video edge detector. Cell contraction data were obtained at baseline, with 8-bromo-cGMP (10(-7), 10(-6), and 10(-5) M), with erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA; a cAMP phosphodiesterase (PDE(2)) inhibitor] plus 8-bromo-cGMP, or milrinone (a PDE(3) inhibitor) plus 8-bromo-cGMP. Baseline percent shortening and maximal rates of shortening (R(max)) and relaxation were slightly reduced in hypertrophic myocytes and were significantly lower in failing myocytes (R(max): control dogs, 95.3 +/- 17.3; hypertrophy dogs, 88.2 +/- 5.5; failure dogs, 53.2 +/- 6.4 mum/s). 8-Bromo-cGMP dose dependently reduced myocyte function in all groups. However, EHNA (10(-6) M) and milrinone (10(-6) M) significantly reduced the negative effects of cGMP on cell contractility in control and hypertrophy but not in failing myocytes (R(max) for control dogs: cGMP, -46%; +EHNA, -21%; +milrinone, -19%; for hypertrophy dogs: cGMP, -40%; +EHNA, -13%; +milrinone, -20%; for failure dogs: cGMP, -40%; +EHNA, -29%; +milrinone, -32%). Both combinations of EHNA-cGMP and milrinone-cGMP significantly increased intracellular cAMP in control, hypertrophic, and failing myocytes. These data indicated that the cGMP signaling pathway was preserved in hypertrophic failing cardiac myocytes. However, the interaction of cGMP with the cAMP signaling pathway was impaired in these failing myocytes.