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.

Use of a Chemotherapy Toxicity Prediction Tool to Decrease Risks for Hospitalization in Older Patients.

Objectives Performance status (PS) scales such as the Eastern Cooperative Oncology Group (ECOG) PS and the Karnofsky Performance Index have limited utility in selecting therapies and predicting related adverse events in older patients with cancer. In July 2016, medical oncologists at our institution adopted the Cancer and Aging Research Group toxicity prediction score (CARG), a toxicity prediction tool, to identify patients who are "fit" for chemotherapy versus those who are "frail" and may experience severe complications. Methods Our retrospective review included referrals of beneficiaries 75 years of age and older who received standard systemic therapy and patients of the same age whose treatment was modified due to CARG. We compared the score's utilization six months before and after its incorporation and then assessed how its application impacted admissions, emergency department (ED) visits, and medical management. Results Thirty-eight patients with a mean age of 81 years met the inclusion criteria. Their diagnoses included gastrointestinal (37%), lung (21%), hematologic (18%), breast (10.5%), genitourinary (3%), and other (10.5%) malignancies. CARG was documented for 12.5% of systemic therapy recipients before its adoption and 41% of recipients after adoption. Its use was limited by the reliance on physicians to perform scoring during time-constrained patient encounters. Patients had fewer mean inpatient admissions (0.7 versus 2.3), admission days (4.3 versus 8), and ED visits (1.1 versus 2.5) when management was modified based on the score. Conclusion CARG assessment may facilitate a safer and more tailored approach to cancer care in older patients than conventional PS scales alone. Its integration into patient screening would increase its application and better define its potential predictive capacity to decrease risks for hospitalization.

Metastatic Cardiac Tumor Presenting as an Anteroseptal ST-Segment Elevation Myocardial Infarction in a Young Male.

In the appropriate clinical context, ST-segment elevation on electrocardiogram (ECG) necessitates prompt evaluation for coronary artery occlusion requiring reperfusion with percutaneous coronary intervention. Conversely, the etiology of ST-segment elevation may be representative of an alternative diagnosis other than myocardial infarction. We report the case of a patient with a history of primary bone sarcoma who presented for further evaluation of a large pericardial effusion identified on an outpatient echocardiogram and was found to have ST-segment elevation on ECG in the absence of any cardiopulmonary symptoms. The ECG abnormalities were attributed to a likely persistent current of injury resulting from a mass in the interventricular septum, likely representative of a metastatic lesion of his known malignancy. This case highlights the importance of maintaining a broad differential for ST-segment elevation, particularly in patients without symptoms of angina and those with a history of aggressive or relapsing cancer to minimize the morbidity and mortality of invasive procedures.

A Non-Hereditary Case of Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is believed to result from an autosomal dominant mutation in the fumarate hydratase (FH) gene on chromosome 1. It is characterized by leiomyomas, mainly uterine or cutaneous, and renal cell carcinoma (RCC). The most common type of RCC associated with HLRCC is type II papillary RCC although other types are seen. Of note, chromophobe RCC has not been described in previously documented cases of HLRCC. HLRCC is typically associated with germline mutations with occasional somatic mutations reported, however, to the best of our knowledge, none have yielded the full phenotype until now. Herein, we report a case of a 45-year-old woman who underwent a hysterectomy following a year of heavy vaginal bleeding, yielding a diagnosis of uterine leiomyomas. Eight months later, the patient presented with hematuria and was subsequently found to have a left renal mass. Following a left radical nephrectomy, histologic exam revealed a chromophobe RCC with FH deficiency.

Effusive-Constrictive Pericarditis in a Young Active Duty Male.

Effusive-constrictive pericarditis (ECP) is a rare clinical entity resulting from accumulating pericardial fluid within a stiff, non-compliant pericardium. There are a number of etiologies for ECP, which include malignancy, radiation, post-surgical causes, infectious, and collagen disorders. Clinically, ECP often presents as right-sided heart failure, or in advanced cases, cardiac tamponade. Symptoms may persist despite treatment with pericardiocentesis, and may warrant consideration for pericardiectomy for more definitive management. Invasive hemodynamic evaluation with cardiac catheterization remains the gold standard for diagnosis of ECP; however, echocardiography can provide a definitive diagnosis with high sensitivity and specificity. Echocardiographic features suggestive of ECP include ventricular septal motion abnormalities, such as interdependence, accentuated longitudinal motion of the heart, and altered respirophasic ventricular filling. While these features have been well established and can lead to the diagnosis of ECP, they are rarely observed in clinical practice. We present a case of ECP in a 25-year-old active duty male with a history of chest wall myoepithelial carcinoma who clearly demonstrated such echocardiographic findings of ECP.

Solid-State Characterization of Three Polymorphs of an Orally Available Analog of Diethylenetriaminepentaacetic Acid.

The present work investigated the physical and thermal characteristics of three polymorphic forms (namely, PF1, PF2, and PF3) of a diethyl ester analog of diethylenetriaminepentaacetic acid (C2E2) produced under varying conditions. The identity of each form of C2E2 was confirmed by 1H-NMR, 13C-NMR, and mass spectroscopy. The different polymorphic forms exhibited solubilities ranging from 40 to 150 mg/mL. Powder X-ray diffraction (PXRD) and electron microscopy confirmed that all three forms were crystalline, two of which being scaly, and the third being well-formed. Infrared and Raman spectroscopy revealed differences in the C = O bonding region while differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) showed widely different melting points with only one thermal event for each compound. The comparison of the melting points and heats of fusion show that the PF1 is monotropically related to both PF2 and PF3, while PF2 and PF3 are enantropically related. Our finding indicates that PF3 is the thermodynamically stable polymorph and will be used for in vitro and in vivo experiments.

Exploring Molecular Speciation and Crystallization Mechanism of Amorphous 2-Phenylamino Nicotinic Acid.

PURPOSE: Molecular understanding of phase stability and transition of the amorphous state helps in formulation and manufacturing of poorly-soluble drugs. Crystallization of a model compound, 2-phenylamino nicotinic acid (2PNA), from the amorphous state was studied using solid-state analytical methods. Our previous report suggests that 2PNA molecules mainly develop intermolecular -COOH∙∙∙pyridine N (acid-pyridine) interactions in the amorphous state. In the current study, the molecular speciation is explored with regard to the phase transition from the amorphous to the crystalline state. METHODS: Using spectroscopic techniques, the molecular interactions and structural evolvement during the recrystallization from the glassy state were investigated. RESULTS: The results unveiled that the structurally heterogeneous amorphous state contains acid-pyridine aggregates - either as hydrogen-bonded neutral molecules or as zwitterions - as well as a population of carboxylic acid dimers. Phase transition from the amorphous state results in crystal structures composed of carboxylic acid dimer (acid-acid) synthon or acid-pyridine chains depending on the crystallization conditions employed. CONCLUSIONS: The study underlines the structural evolvement, as well as its impact on the metastability, of amorphous samples from local, supramolecular assemblies to long-range intermolecular ordering through crystallization.

Gaining Thermodynamic Insight From Distinct Glass Formation Kinetics of Structurally Similar Organic Compounds.

Thermodynamic and kinetic aspects of crystallization of 12 structurally similar organic compounds were investigated from the supercooled liquid state by calorimetric and rheologic measurements. Based on their crystallization behaviors, these compounds were divided into 3 categories: stable glass formers, poor glass formers, and good glass formers with poor stability on reheating. Correlation was sought between thermodynamic quantities and glass formation based on nucleation and crystal growth theories. Larger values of enthalpy of fusion and melting point were found to correlate with poor glass-forming ability. Conversely, lower entropy of fusion was found to correlate with glass formation. Examination of kinetic aspects of glass formation revealed 2 important facets of good glass formers, that is, rapid increase in viscosity on supercooling and high melting point viscosity compared with non-glass formers. A broader relationship was sought between entropy of fusion and glass formation by including several glass formers from literature. Our analysis indicated that good glass formers tend to have an entropy of fusion closer to 0.3 J cm-3 K-1. The structural similarity of the compounds in this study provides insights regarding the nature of intermolecular interactions responsible for the observed effect on entropy of fusion, viscosity, and crystallization kinetics.

Impact of Supramolecular Aggregation on the Crystallization Kinetics of Organic Compounds from the Supercooled Liquid State.

Despite numerous challenges in their theoretical description and practical implementation, amorphous drugs are of growing importance to the pharmaceutical industry. One such challenge is to gain molecular level understanding of the propensity of a molecule to form and remain as a glassy solid. In this study, a series of structurally similar diarylamine compounds was examined to elucidate the role of supramolecular aggregation on crystallization kinetics from supercooled liquid state. The structural similarity of the compounds makes it easier to isolate the molecular features that affect crystallization kinetics and glass forming ability of these compounds. To examine the role of hydrogen-bonded aggregation and motifs on crystallization kinetics, a combination of thermal and spectroscopic techniques was employed. Using variable temperature FTIR, Raman, and solid-state NMR spectroscopies, the presence of hydrogen bonding in the melt and glassy state was examined and correlated with observed phase transition behaviors. Spectroscopic results revealed that the formation of hydrogen-bonded aggregates involving carboxylic acid and pyridine nitrogen (acid-pyridine aggregates) between neighboring molecules in the melt state impedes crystallization, while the presence of carboxylic acid dimers (acid-acid dimers) in the melt favors crystallization. This study suggests that glass formation of small molecules is influenced by the type of intermolecular interactions present in the melt state and the kinetics associated with the molecules to assemble into a crystalline lattice. For the compounds that form acid-pyridine aggregates, the formation of energy degenerate chains, produced due to conformational flexibility of the molecules, presents a kinetic barrier to crystallization. The poor crystallization tendency of these aggregates stems from the highly directional hydrogen-bonding interactions needed to form the acid-pyridine chains. Conversely, for the compounds that form acid-acid dimers, the nondirectional van der Waals forces needed to construct a nucleus promote rapid assembly and crystallization.