Redox-Active Triazole-Derived Mesoionic Imines with Ferrocenyl Substituents and their Metal Complexes: Directed Hydrogen-Bonding, Unusual C-H Activation and Ion-Pair Formation.

We present herein the synthesis, characterization and complexation of ferrocenyl-substituted MIIs (mesoionic imines) and their metal complexes. In the free MIIs, strong hydrogen bonding interactions are observed between the imine-N and the C-H bonds of the ferrocenyl substituents both in the solid state and in solution. The influence of this hydrogen bonding is so strong that complexation of the MIIs with [IrCp*Cl2]2 yields unique six-membered iridacycles via C-H-activation of the corresponding C-H-site at the Fc-substituent and not the Ph-substituent. This result is in contrast to previous reports in which always a preferential C-H activation at the phenyl substituent is observed in competitive reactions in the presence of ferrocenyl substituents. The corresponding Ir complexes formed after in-situ halide exchange reaction exist in either [Ir-I] contact or as [Ir]+I- solvent separated ion-pairs depending on the solvent polarity. The iodide coordinated and solvent separated ion-pairs display drastically different physical properties. The TEP (Tolman-electronic-parameter) of these ligands was determined and lines up with previously reported MII-ligands. The redox properties were investigated by a combination of electrochemical and spectroelectrochemical methods. We show here how non-covalent interactions can have a drastic influence on the physical and chemical properties of these new class of compounds.

Air-Stable Dinuclear Complexes of Four-Coordinate ZnII and NiII Ions with a Radical Bridge: A Detailed Look at Redox Activity and Antiferromagnetic Coupling.

Air-stable dinuclear complexes [(bmsab)NiII(tmsab)NiII(bmsab)]3- and [(bmsab)ZnII(tmsab)ZnII(bmsab)]3- (bmsab = bis(methanesulfoneamido)benzene, tmsab = tetra(methanesulfonamido)benzene) were prepared via a synthetic route based on heteroleptic precursor complexes. The new complexes combine a distorted tetrahedral coordination environment with an open-shell bridging ligand. The ZnII species was subjected to a detailed investigation of the (spectro-)electrochemical processes. The NiII species is a rare example of a complex that combines strong exchange coupling (J > 440 cm-1) with pronounced positive zero-field splitting (D = +72 cm-1). Combining SQUID magnetometry and (HF)EPR spectroscopy with ab initio calculations allowed for accurate quantification of the exchange interaction.

Bronchoalveolar Lavage Fluid Cytology of Deployed Military Personnel With Chronic Respiratory Symptoms From the STAMPEDE III Study.

INTRODUCTION: Deployed military personnel may be at risk for developing acute and chronic lung disease. Prior studies of this patient population have revealed that unexplained exertional dyspnea is the most common diagnosis despite an extensive evaluation. There is a concern that an occult disorder may be affecting this population. This study evaluated the role for bronchoalveolar lavage (BAL) fluid analysis in the evaluation of chronic deployment-associated dyspnea. MATERIALS AND METHODS: Military personnel who reported chronic respiratory symptoms were evaluated as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Participants underwent bronchoscopy with BAL as part of a standardized evaluation. RESULTS: A total of 308 patients with a mean age of 38 ± 8.6 years underwent bronchoscopy with BAL. BAL cell-count percentages of macrophages, lymphocytes, neutrophils, and eosinophils were: 76.2 ± 17.0%, 16.3 ± 13.4%, 6.6 ± 8.9%, and 0.9 ± 3.2%, respectively. There was no clear differentiation between groups based on increases in lymphocyte counts (P = .640), although lymphocyte values were more elevated (21.4 ± 12.1%) in the interstitial lung disease category. Neutrophil counts (6.6 ± 8.9%) were elevated compared to the reported normal reference values and were increased in the isolated pulmonary function test abnormality (9.4 ± 11.6%), large airway disorder (10.0 ± 7.5%), miscellaneous (10.9 ± 20.2%), and obstructive lung disease (11.0 ± 15.6%) groups. Eosinophil counts were within normal limits (0.9 ± 3.2%) and showed no differences between groups (P = .545); asthma patients trended higher (1.6 ± 5.7%). BAL counts for the exertional dyspnea group were within normal reference values and showed no differences from the entire cohort. CONCLUSIONS: The addition of BAL cytology did not help differentiate those patients with unexplained dyspnea from other etiologies.

Correlation between positive airway pressure and medication adherence: the healthy user effect.

STUDY OBJECTIVES: Despite the efficacy of positive airway pressure (PAP) for the treatment of obstructive sleep apnea (OSA), adherence remains challenging and negatively impacts assessments of effectiveness. It is unclear if low adherence is due to intolerance of PAP, or if this reflects overall adherence with medical therapy. We sought to correlate PAP use with medication adherence to determine if poor adherence with PAP was specific to this treatment or represented global compliance with medical therapy. METHODS: 600 consecutive OSA patients treated with PAP. Objective measures of PAP use were correlated with medication adherence. We included all chronically used medications, defined as medications used daily for at least ninety days prior to PAP initiation. Medication use was verified using an electronic health record. PAP adherence ("regular use") was defined as PAP use for ≥4 hours/night on ≥70% of nights. Medication adherence was defined as >70% of pills taken as prescribed. RESULTS: Complete records were available for 566 patients, 361 (63.8%) utilized chronic medications. The cohort was primarily men (90.3%, age 44.6±10.2 years), with moderate OSA (AHI 18.1±13.9 events/h). In patients on chronic medications, PAP was used 55.8% of nights and 37.7% were regular users. Patients who were adherent with medications used PAP more hours/night (5.4 vs. 4.6, p<0.001) and were more likely to have regular PAP use compared to those non-adherent with medications (p=0.04). CONCLUSIONS: Adherence with PAP correlated with adherence to chronic medications. Low PAP adherence may reflect an individual's global adherence to medical care. This association may lead to better identification of patients who benefit from targeted therapy to improve overall healthcare adherence.

Overview of Methamphetamine-Associated Pulmonary Arterial Hypertension.

TOPIC IMPORTANCE: The global surge in methamphetamine use is a critical public health concern, particularly due to its robust correlation with methamphetamine-associated pulmonary arterial hypertension (MA-PAH). This association raises urgent alarms about the potential escalation of MA-PAH incidence, posing a significant and imminent challenge to global public health. REVIEW FINDINGS: This comprehensive review meticulously explores MA-PAH, offering insights into its epidemiology, pathophysiology, clinical presentation, diagnostic intricacies, and management strategies. The pathogenesis, yet to be fully described, involves complex molecular interactions, including alterations in serotonin signaling, reduced activity of carboxylesterase 1, oxidative stress, and dysregulation of pulmonary vasoconstrictors and vasodilators. These processes culminate in the structural remodeling of the pulmonary vasculature, resulting in pulmonary arterial hypertension. MA-PAH exhibits a more severe clinical profile in functional class and hemodynamics compared with idiopathic pulmonary arterial hypertension. Management involves a multifaceted approach, integrating pulmonary vasodilators, cessation of methamphetamine use, and implementing social and rehabilitation programs. These measures aim to enhance patient outcomes and detect potential relapses for timely intervention. SUMMARY: This review consolidates our understanding of MA-PAH, pinpointing knowledge gaps for future studies. Addressing these gaps is crucial for advancing diagnostic accuracy, unraveling mechanisms, and optimizing treatment for MA-PAH, thereby addressing the evolving landscape of this complex health concern.

Isolation, Characterization and Reactivity of Key Intermediates Relevant to Reductive (Electro)catalysis with Cp*Rh Complexes Containing Pyridyl-MIC (MIC=Mesoionic Carbene) Ligands.

In recent years, metal complexes of pyridyl-mesoionic carbene (MIC) ligands have been reported as excellent homogeneous and molecular electrocatalysts. In combination with group 9 metals, such ligands form highly active catalysts for hydrogenation/transfer hydrogenation/hydrosilylation catalysis and electrocatalysts for dihydrogen production. Despite such progress, very little is known about the structural/electrochemical/spectroscopic properties of crucial intermediates for such catalytic reactions with these ligands: solvato complexes, reduced complexes and hydridic species. We present here a comprehensive study involving the isolation, crystallographic characterization, electrochemical/spectroelectrochemical/theoretical investigations, and in-situ reactivity studies of all the aforementioned crucial intermediates involving Cp*Rh and pyridyl-MIC ligands. A detailed mechanistic study of the precatalytic activation of [RhCp*] complexes with pyridyl-MIC ligands is presented. Intriguingly, amphiphilicity of the [RhCp*]-hydride complexes was observed, displaying the substrate dependent transfer of H+ , H or H- . To the best of our knowledge, this study is the first of its kind targeting intermediates and reactive species involving metal complexes of pyridyl-MIC ligands and investigating the interconversion amongst them.

9-Month observational Dia-Vacc study of vaccine type influence on SARS-CoV-2 immunity in dialysis and kidney transplant patients.

BACKGROUND: SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients. METHODS: We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. FINDINGS: Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively. Seroconversion remained positive in 100 % of AP and 99·2 % of MP, but 86 %/81 % of DP/KTR, respectively. Compared to MP, DP but not KTR or AP were at risk for a strong RBD decline, while KTR kept lowest RBD values over time. By multivariate analysis, BNT162b2mRNA versus 1273-mRNA vaccine type was an independent risk factor for a strong decline of RBD antibodies. Within the DP group, only time on dialysis was another (inverse) risk factor for the DP group. Compared to humoral immunity, T-cell immunity decline was less prominent. INTERPRETATION: While seroconverted KTR reach lowest RBD values over time, DP are at specific risk for a strong decline of RBD antibodies after successful SARS-CoV-2mRNA vaccination, which also depends on the vaccine type being used. Therefore, booster vaccinations for DP should be considered earlier compared to normal population.

Methamphetamine-associated pulmonary arterial hypertension: data from the national biological sample and data repository for pulmonary arterial hypertension (PAH Biobank).

OBJECTIVE: This study compares the clinical and haemodynamic severity of methamphetamine-associated pulmonary arterial hypertension (MA-PAH) with idiopathic pulmonary arterial hypertension (IPAH) and connective tissue-associated pulmonary arterial hypertension (CTD-PAH). It also examines sex differences in clinical and physiological parameters among those with MA-PAH. DESIGN: This is a cross-sectional study using clinically derived data from the National Biological Sample and Data Repository for Pulmonary Arterial Hypertension (PAH biobank), a US-based registry, to compare clinical and physiological characteristics between males and females with MA-PAH. POPULATION: The analysis included 1830 patients enrolled in the PAH biobank, with a diagnosis of MA-PAH (n=42), IPAH (n=1073), or CTD-PAH (n=715). MAIN OUTCOME MEASURES: The study assessed and compared the clinical and haemodynamic parameters of patients with MA-PAH, IPAH and CTD-PAH. RESULTS: Among the patients analysed, 42 had MA-PAH, with 69.1% being female. There were no statistically significant differences in functional class among patients with MA-PAH, IPAH and CTD-PAH. The per cent predicted 6-min walk distance (6MWD) was comparable between the three groups. Patients with MA-PAH had similar mean pulmonary artery pressure and pulmonary vascular resistance to patients with IPAH but higher compared with patients with CTD-PAH. Male patients with MA-PAH exhibited a worse functional class and lower per cent predicted 6MWD, but no significant differences in haemodynamic findings were observed between the sexes. CONCLUSION: There were no differences in haemodynamic between MA-PAH and IPAH but we found that MA-PAH differed from CTD-PAH. The study did not find evidence of sex differences in MA-PAH. Further research is necessary to identify risk factors and underlying mechanisms of MA-PAH, particularly considering the increasing prevalence of methamphetamine use. Such investigations will contribute to the development of effective prevention and treatment strategies for this condition.

The Best of Both Worlds: Combining the Power of MICs and WCAs To Generate Stable and Crystalline CrI -Tetracarbonyl Complexes with π-Accepting Ligands.

Invited for the cover of this issue are Biprajit Sarkar and co-workers at the University of Stuttgart and University of Freiburg. In the image, the solar flare represents the non-innocence (fluorine-specific interactions) of the counterion, and the black hole at the metal center illustrates the oxidation/electron deficiency of the Cr-center, while the electron "gets lost" in the space (oxidation agent). Read the full text of the article at 10.1002/chem.202301205.

Impact of Bidentate Pyridyl-Mesoionic Carbene Ligands: Structural, (Spectro)Electrochemical, Photophysical, and Theoretical Investigations on Ruthenium(II) Complexes.

We present here new synthetic strategies for the isolation of a series of Ru(II) complexes with pyridyl-mesoionic carbene ligands (MIC) of the 1,2,3-triazole-5-ylidene type, in which the bpy ligands (bpy = 2,2'-bipyridine) of the archetypical [Ru(bpy)3]2+ have been successively replaced by one, two, or three pyridyl-MIC ligands. Three new complexes have been isolated and investigated via NMR spectroscopy and single-crystal X-ray diffraction analysis. The incorporation of one MIC unit shifts the potential of the metal-centered oxidation about 160 mV to more cathodic potential in cyclic voltammetry, demonstrating the extraordinary σ-donor ability of the pyridyl-MIC ligand, while the π-acceptor capacities are dominated by the bpy ligand, as indicated by electron paramagnetic resonance spectroelectrochemistry (EPR-SEC). The replacement of all bpy ligands by the pyridyl-MIC ligand results in an anoidic shift of the ligand-centered reduction by 390 mV compared to the well-established [Ru(bpy)3]2+ complex. In addition, UV/vis/NIR-SEC in combination with theoretical calculations provided detailed insights into the electronic structures of the respective redox states, taking into account the total number of pyridyl-MIC ligands incorporated in the Ru(II) complexes. The luminescence quantum yield and lifetimes were determined by time-resolved absorption and emission spectroscopy. An estimation of the excited state redox potentials conclusively showed that the pyridyl-MIC ligand can tune the photoredox activity of the isolated complexes to stronger photoreductants. These observations can provide new strategies for the design of photocatalysts and photosensitizers based on MICs.

Cancer-Associated Fibroblasts Influence Survival in Pleural Mesothelioma: Digital Gene Expression Analysis and Supervised Machine Learning Model.

The exact mechanism of desmoplastic stromal reaction (DSR) formation is still unclear. The interaction between cancer cells and cancer-associated fibroblasts (CAFs) has an important role in tumor progression, while stromal changes are a poor prognostic factor in pleural mesothelioma (PM). We aimed to assess the impact of CAFs paracrine signaling within the tumor microenvironment and the DSR presence on survival, in a cohort of 77 PM patients. DSR formation was evaluated morphologically and by immunohistochemistry for Fibroblast activation protein alpha (FAP). Digital gene expression was analyzed using a custom-designed CodeSet (NanoString). Decision-tree-based analysis using the "conditional inference tree" (CIT) machine learning algorithm was performed on the obtained results. A significant association between FAP gene expression levels and the appearance of DSR was found (p = 0.025). DSR-high samples demonstrated a statistically significant prolonged median survival time. The elevated expression of MYT1, KDR, PIK3R1, PIK3R4, and SOS1 was associated with shortened OS, whereas the upregulation of VEGFC, FAP, and CDK4 was associated with prolonged OS. CIT revealed a three-tier system based on FAP, NF1, and RPTOR expressions. We could outline the prognostic value of CAFs-induced PI3K signaling pathway activation together with FAP-dependent CDK4 mediated cell cycle progression in PM, where prognostic and predictive biomarkers are urgently needed to introduce new therapeutic strategies.

Beyond Trauma: High-Volume Critical Care Medicine in a Military Medical Center-Based Military-Civilian Partnership.

INTRODUCTION: Critical Care Internal Medicine (CCIM) is vital to the U.S. Military as evidenced by the role CCIM played in the COVID-19 pandemic response and wartime operations. Although the proficiency needs of military surgeons have been well studied, this has not been the case for CCIM. The objective of this study was to compare the patient volume and acuity of military CCIM physicians working solely at Military Treatment Facilities (MTFs) with those at MTFs also working part-time in a military-civilian partnership (MCP) at the University Medical Center of Southern Nevada (UMC). MATERIALS AND METHODS: We analyzed FY2019 critical care coding data from the Military Health System and UMC comparing the number of critical care encounters, the number of high-acuity critical care encounters, and the Abilities/Activity component of the Knowledge, Skills, and Abilities/Clinical Activity (KSA) score. This analysis was restricted to critical care encounters defined by Current Procedural Terminology codes for critical care (99291 and 99292). A critical care encounter was considered high acuity if the patient had ICD-10 codes for shock, respiratory failure, or cardiac arrest or had at least three codes for critical care in the same episode. RESULTS: The five AF CCIM physicians in the MCP group performed 2,019 critical care encounters in 206 days, with 63.1% (1,273) being defined as high acuity. The total number of MTF critical care encounters was 16,855 across all providers and services, with 28.9% (4,864) of encounters defined as high acuity. When limited to CCIM encounters, MTFs had 6,785 critical care encounters, with 32.0% being high acuity (2,171). Thus, the five AF CCIM physicians, while working 206 days at the UMC, equated to 12.0% (2,019/16,855) of the total critical care MTF encounters, 27.2% (1,273/4,684) of the total high-acuity MTF critical care encounters, and 29.8% (2,019/6,785) of the MTF CCIM encounters, with 58.6% (1,273/2,171) of the MTF CCIM high-acuity encounters.The USAF CCIM physicians in the MCP group performed 454,395 KSAs in 206 days, with a KSA density per day of 2,206. In the MTF group, CCIM providers generated 2,344,791 total KSAs over 10,287 days, with a KSA density per day of 227.9. Thus, the five CCIM physicians at the UMC accounted for 19.38% of the MTF CCIM KSAs, with a KSA density over 10 times higher (2,206 vs. 227.9). CONCLUSIONS: The volume and acuity of critical care at MTFs may be insufficient to maintain CCIM proficiency under the current system. Military-civilian partnerships are invaluable in maintaining clinical proficiency for military CCIM physicians and can be done on a part-time basis while maintaining beneficiary care at an MTF. Future CCIM expeditionary success is contingent on CCIM physicians and team members having the required CCIM exposure to grow and maintain clinical proficiency.Limitations of this study include the absence of off-duty employment (moonlighting) data and difficulty filtering military data down to just CCIM physicians, which likely caused the MTF CCIM data to be overestimated.

Design and rationale of the CHILL phase II trial of hypothermia and neuromuscular blockade for acute respiratory distress syndrome.

The Cooling to Help Injured Lungs (CHILL) trial is an open label, two group, parallel design multicenter, randomized phase IIB clinical trial assessing the efficacy and safety of targeted temperature management with combined external cooling and neuromuscular blockade to block shivering in patients with early moderate-severe acute respiratory distress syndrome (ARDS). This report provides the background and rationale for the clinical trial and outlines the methods using the Consolidated Standards of Reporting Trials guidelines. Key design challenges include: [1] protocolizing important co-interventions; [2] incorporation of patients with COVID-19 as the cause of ARDS; [3] inability to blind the investigators; and [4] ability to obtain timely informed consent from patients or legally authorized representatives early in the disease process. Results of the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial informed the decision to mandate sedation and neuromuscular blockade only in the group assigned to therapeutic hypothermia and proceed without this mandate in the control group assigned to a usual temperature management protocol. Previous trials conducted in National Heart, Lung, and Blood Institute ARDS Clinical Trials (ARDSNet) and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks informed ventilator management, ventilation liberation and fluid management protocols. Since ARDS due to COVID-19 is a common cause of ARDS during pandemic surges and shares many features with ARDS from other causes, patients with ARDS due to COVID-19 are included. Finally, a stepwise approach to obtaining informed consent prior to documenting critical hypoxemia was adopted to facilitate enrollment and reduce the number of candidates excluded because eligibility time window expiration.

The Best of Both Worlds: Combining the Power of MICs and WCAs To Generate Stable and Crystalline CrI -Tetracarbonyl Complexes with π-Accepting Ligands.

Here we present stable and crystalline chromium(I) tetracarbonyl complexes with pyridyl-MIC (MIC=mesoionic carbene) ligands and weakly coordinating anions (WCA=[Al(ORF )4 ]- , RF =C(CF3 )3 and BArF =[B(ArF )4 ]- , ArF =3,5-(CF3 )2 C6 H3 ). The complexes were fully characterized via crystallographic, spectroscopic and theoretical methods. The influence of counter anions on the IR and EPR spectroscopic properties of the CrI complexes was investigated, and the electronic innocence versus non-innocence of WCAs was probed. These are the first examples of stable and crystalline [Cr(CO)4 ]+ complexes with a chelating π - ${\pi -}$ accepting ligand, and the data presented here are of relevance for both the photochemical and the electrochemical properties of these classes of compounds.

Azide-Substituted 1,2,3-Triazolium Salts as Useful Synthetic Synthons: Access to Triazenyl Radicals and Staudinger Type Reactivity.

Mesoionic carbenes (MIC) are a popular class of compound that are heavily investigated at the moment. The access to cationic MICs, and the ability of MICs to stabilize radicals are two highly attractive fields that have hardly been explored until now. Here the synthesis and characterisation of three different cationic azide-substituted 1,2,3-triazolium salts, used as building blocks for studying their reactivity towards triphenylphosphine are reported, where the reactivity is dependent on the nature of the starting triazolium salt. Furthermore, the cationic triazolium salts were used to develop a series of unsymmetrical MIC-triazene-NHC/MIC' compounds, which can be readily converted to the radical form either by electrochemical or chemical methods. These radicals, which display NIR electrochromism, were investigated using a battery of techniques such as electrochemistry, UV/Vis/NIR and EPR spectroelectrochemistry, and theoretical calculations. Interestingly, the MIC plays an important role in the stabilization of the triazenyl radical, particularly in a competitive role vis-à-vis their NHC counterparts. These results shed new light on the ability of MICs to stabilize radicals, and possibly also on their π-accepting ability.

Remote patient monitoring to facilitate same-day discharge after laparoscopic sleeve gastrectomy: a pilot evaluation.

BACKGROUND: Limited hospital inpatient capacity, exacerbated by SARS-CoV-2 (COVID-19) and associated staffing shortages, has driven interest in converting surgeries historically done as inpatient procedures to same-day surgeries (SDS). Remote patient monitoring (RPM) has the potential to increase safety and confidence in SDS but has had mixed success in a bariatric population. OBJECTIVES: Assess the feasibility of and adherence to a protocol offering patients same-day laparoscopic sleeve gastrectomy (SG) supported by RPM with an updated wearable device. Secondary outcomes were readmissions, costs, adherence, and clinical alarm rates. SETTING: Academic, military tertiary referral center (United States). METHODS: A single-center, retrospective case control study of patients undergoing SG, comparing SDS with RPM to patients admitted to the hospital for SG during this time. Patients for SDS were selected by set inclusion/exclusion criteria and patient/surgeon preference, and perioperative management was standardized. RESULTS: Twenty patients were enrolled in the SDS group, then compared with 53 inpatients. Inpatients were older (46 versus 39, P = .006), but with no significant differences in sex, preoperative body mass index, or co-morbidities. RPM wearable and blood pressure adherence was found to be 97% and 80%, respectively. Readmission rates were similar (10% versus 7.5%, P > .05). RPM alarm rates were .5 (0-1.3) per patient for each 24-hour home monitoring period. SDS patients also demonstrated the potential for cost savings over inpatient SG, depending on the number of patients monitored per day as well as the healthcare setting. CONCLUSIONS: SG as SDS with RPM was a feasible approach. It should be evaluated in other surgical procedures and higher-risk patient populations.

Spin State in Homoleptic Iron(II) Terpyridine Complexes Influences Mixed Valency and Electrocatalytic CO2 Reduction.

Two homoleptic Fe(II) complexes in different spin states bearing superbasic terpyridine derivatives as ligands are investigated to determine the relationship between spin state and electrochemical/spectroscopic behavior. Antiferromagnetic coupling between a ligand-centered radical and the high-spin metal center leads to an anodic shift of the first reduction potential and results in a species that shows mixed valency with a moderately intense intervalence-charge-transfer band. The differences afforded by the different spin states extend to the electrochemical reactivity of the complexes: while the low-spin species is a precatalyst for electrocatalytic CO2 reduction and leads to the preferential formation of CO with a Faradaic efficiency of 37%, the high-spin species only catalyzes proton reduction at a modest Faradaic efficiency of approximately 20%.

Ruthenium Complexes of Polyfluorocarbon Substituted Terpyridine and Mesoionic Carbene Ligands: An Interplay in CO2 Reduction.

In recent years terpyridines (tpy) and mesoionic carbenes (MIC) have been widely used in metal complexes. With the right combination with a metal center, both of these ligands are individually known to generate excellent catalysts for CO2 reduction. In this study, we combine the potentials of PFC (PFC=polyfluorocarbon) substituted tpy and MIC ligands within the same platform to obtain a new class of complexes, which we investigated with respect to their structural, electrochemical and UV/Vis/NIR spectroelectrochemical properties. We further show that the resulting metal complexes are potent electrocatalysts for CO2 reduction in which CO is exclusively formed with a faradaic efficiency of 92 %. A preliminary mechanistic study, including the isolation and characterization of a key intermediate is also reported.

Single-Center Experience With the Seraph-100® Microbind® Affinity Blood Filter in Patients With SARS-CoV-2 Infection and Septic Shock at a Military Treatment Facility.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) infection is characterized by a dysregulated inflammatory response, which may result in severe hemodynamic instability and septic shock. The Seraph-100® Microbind® Affinity Blood Filter is a commercially available extracorporeal pathogen absorbent device with the ability to bind pathogens and cytokines present within the blood. Our study aimed to evaluate the efficacy of the Seraph-100® for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and septic shock. MATERIALS AND METHODS: A retrospective review was performed to evaluate the use of the Seraph-100® blood filter at a Single Center tertiary-care facility at Brooke Army Medical Center from 2020 to 2021. Nine patients (11 treatments) were completed with the Seraph-100® blood filter in patients with SARS-CoV-2 infection and septic shock. The Seraph-100® blood filter was used in combination with continuous renal replacement therapy and slow low-efficiency dialysis or directly in parallel with the extracorporeal membrane oxygenation circuit. RESULTS: Within this cohort, there was a statistically significant improvement in the following clinical parameters comparing values to before and after treatment with the Seraph-100® blood filter: Mean arterial pressure (mmHg) (64.2 ± 2.36 vs. 76.2 ± 2.68; P < .001), heart rate (beats per minute) (128 ± 6.6 vs. 100.3 ± 6.07; P < .001), administered fraction of oxygen (%) (74.4 ± 10.58 vs. 60.3 ± 10.35; P < .001), serum lactate (mmol/L) (6.14 ± 1.25 vs. 2.8 ± 1.14; P = .0095), and pH (7.29 ± 0.03 vs. 7.39 ± 0.04; P = .0203). There were statistically significant improvements in vasopressor requirements: norepinephrine (mcg/min) (36.3 ± 4.74 vs. 8.3 ± 3.92; P < .001), vasopressin (units/min) (0.04 ± 0.004 vs. 0.02 ± 0.003; P < .001), dobutamine (mcg/kg/min) (2.3 ± 1.00 vs. 0.2 ± 0.75; P = .006) and angiotensin II (ng/kg/min) (34.5 ± 6.4 vs. 3.3 ± 5.26; P < .001). CONCLUSIONS: The use of the Seraph-100® blood filter was associated with statistically and clinically significant improvements in hemodynamic parameters and decreased vasopressor requirements in patients with septic shock and SARS-CoV-2 infection.

Financial and Clinical Impact of Virtual Care During the COVID-19 Pandemic: Difference-in-Differences Analysis.

BACKGROUND: Virtual care (VC) and remote patient monitoring programs were deployed widely during the COVID-19 pandemic. Deployments were heterogeneous and evolved as the pandemic progressed, complicating subsequent attempts to quantify their impact. The unique arrangement of the US Military Health System (MHS) enabled direct comparison between facilities that did and did not implement a standardized VC program. The VC program enrolled patients symptomatic for COVID-19 or at risk for severe disease. Patients' vital signs were continuously monitored at home with a wearable device (Current Health). A central team monitored vital signs and conducted daily or twice-daily reviews (the nurse-to-patient ratio was 1:30). OBJECTIVE: Our goal was to describe the operational model of a VC program for COVID-19, evaluate its financial impact, and detail its clinical outcomes. METHODS: This was a retrospective difference-in-differences (DiD) evaluation that compared 8 military treatment facilities (MTFs) with and 39 MTFs without a VC program. Tricare Prime beneficiaries diagnosed with COVID-19 (Medicare Severity Diagnosis Related Group 177 or International Classification of Diseases-10 codes U07.1/07.2) who were eligible for care within the MHS and aged 21 years and or older between December 2020 and December 2021 were included. Primary outcomes were length of stay and associated cost savings; secondary outcomes were escalation to physical care from home, 30-day readmissions after VC discharge, adherence to the wearable, and alarms per patient-day. RESULTS: A total of 1838 patients with COVID-19 were admitted to an MTF with a VC program of 3988 admitted to the MHS. Of these patients, 237 (13%) were enrolled in the VC program. The DiD analysis indicated that centers with the program had a 12% lower length of stay averaged across all COVID-19 patients, saving US $2047 per patient. The total cost of equipping, establishing, and staffing the VC program was estimated at US $3816 per day. Total net savings were estimated at US $2.3 million in the first year of the program across the MHS. The wearables were activated by 231 patients (97.5%) and were monitored through the Current Health platform for a total of 3474 (median 7.9, range 3.2-16.5) days. Wearable adherence was 85% (IQR 63%-94%). Patients triggered a median of 1.6 (IQR 0.7-5.2) vital sign alarms per patient per day; 203 (85.7%) were monitored at home and then directly discharged from VC; 27 (11.4%) were escalated to a physical hospital bed as part of their initial admission. There were no increases in 30-day readmissions or emergency department visits. CONCLUSIONS: Monitored patients were adherent to the wearable device and triggered a manageable number of alarms/day for the monitoring-team-to-patient ratio. Despite only enrolling 13% of COVID-19 patients at centers where it was available, the program offered substantial savings averaged across all patients in those centers without adversely affecting clinical outcomes.