Monitoring carbon dioxide tension and arterial oxygen saturation by a single earlobe sensor in patients with critical illness or sleep apnea

OBJECTIVES: The purpose of the study was to evaluate a novel, combined sensor for transcutaneous monitoring of arterial oxygen saturation and carbon dioxide tension. DESIGN: The new monitoring technique was compared to established reference methods. SETTING: ICU and sleep laboratory of a university hospital. PATIENTS: Eighteen critically ill adult patients with acute respiratory failure or heart failure, and 12 patients with sleep apnea (mean [+/- SD] apnea/hypopnea index, 43 +/- 24 events per hour). MEASUREMENTS: Continuous measurements were performed over several hours by the novel heated (temperature, 42 degrees C) earlobe sensor (TOSCA; Linde Medical Sensors; Basel, Switzerland), incorporating electrochemical and optical elements for carbon dioxide measurement (PtcCO2) and pulse oximetry (SpO2), respectively. The data were compared to the results of repeated arterial blood gas analyses in critically ill patients and to simultaneous nocturnal pulse oximetry performed with different devices with earlobe or finger sensors in sleep apnea patients. RESULTS: In critically ill patients, the mean difference and limits of agreement (bias +/- 2 SDs) of transcutaneous PtcCO2 vs arterial PaCO2 were 3 +/- 7 mm Hg; the corresponding values for changes in PtcCO2 vs PaCO2 were 1 +/- 6 mm Hg. The bias +/- 2 SDs for pulse oximetric SpO2 vs arterial oxygen saturation (SaO2) were 1 +/- 4%. In sleep apnea patients, the combined earlobe sensor identified more transient oxygen desaturations, and the rate of change in oxygen saturation during events was greater compared to those with other tested pulse oximeters, indicating a faster response. CONCLUSIONS: Due to its ability to accurately assess both ventilation and oxygenation by a single transcutaneous sensor, the described noninvasive monitoring technique is a valuable tool for respiratory monitoring with potential applications in critical care and sleep medicine.     

Nosocomial transmission of tuberculosis associated with a draining abscess

Nine secondary cases of tuberculosis and 59 tuberculin skin test conversions occurred after exposure to a hospitalized patient with a large tuberculous abscess of the hip and thigh. Among 442 tuberculin-negative hospital employees, the relative risk of skin test conversion associated with recalled exposure to the patient was 14.0 (95% confidence limits, 6.8, 28.7). Four of 5 surgical suite employees who assisted with incision and debridement of the abscess had skin test conversions, as did 85% of 33 employees on a general medical floor who recalled exposure to the patient and 30% of 20 intensive care unit employees who recalled exposure. The prevalence of tuberculin reactivity in visitors and other patients on two floors also showed a strong association with exposure to the patient. A high concentration of Mycobacterium tuberculosis in the abscessed tissue, disturbance of the surface of liquid drainage from the abscess by irrigations and by the agitated behavior of the patient, and positive air pressure in the patient's room are factors that appear to have contributed to the high risk of tuberculosis transmission.     

Nitric oxide synthase expression and role during cardiomyogenesis

OBJECTIVE: The aim of the present study was the investigation of the expression of NOS during cardiomyogenesis and its functional role. DESIGN: The qualitative and quantitative expression of NOS isoforms during different stages of cardiac development was evaluated using immunocytochemistry and dot blots, respectively. The functional relevance of NOS expression during cardiomyogenesis was investigated using the in vitro ES cell-differentiation model and selective pharmacological agents. RESULTS: On day 7.5 of embryonic development (E7.5) none of the NOS isoforms were expressed in the embryo, whereas the inducible (iNOS), as well as the endothelial (eNOS) isoforms were detected in the extraembryonic parts. In contrast, starting from E9.5 rat and murine embryos displayed prominent iNOS and eNOS expression. This was correlated with high expression of soluble guanylylcyclase (sGC) as well as high cyclic GMP (cGMP) content. During further development after E14.5 both, iNOS as well as eNOS, started to be downregulated and shortly prior to birth reduced staining for eNOS was found, whereas iNOS was hardly detectable. We further investigated whether NO plays a role for cardiomyogenesis, using in vitro ES cell-derived cardiomyocytes differentiating within embryoid bodies (EBs). The NOS expression pattern in these cells paralleled the one detected in vivo. We demonstrate that continuous incubation of EBs with the NOS inhibitors L-NMMA (2-10 mM) or L-NA (2-10 mM) for 4 to 9 days after plating resulted in a pronounced differentiation arrest of cardiomyocytes, whereas this effect could be reversed by coapplication of the NO-donor spermine-NONOate (10 microM). CONCLUSIONS: Both, iNOS and eNOS isoforms are prominently expressed during early stages of cardiomyogenesis. Around E14.5 NOS expression starts to decline. Moreover, the NO-generation is required for cardiomyogenesis since NOS inhibitors prevent the maturation of terminally differentiated cardiomyocytes using the ES cell system.     

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

SARS-CoV-2 (CoV2) antibody therapies, including COVID-19 convalescent plasma (CCP), monoclonal antibodies, and hyperimmune globulin, are among the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the 4 endemic human coronavirus (HCoV) genomes in 126 CCP donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies against CoV2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a 2-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting desired therapeutics and understanding the complex immune responses elicited by CoV2 infection.     

Powassan virus: What is the risk to the blood supply?

Powassan virus (POWV) is an emerging tick-borne arbovirus that is found widely in Canada, the Northeastern and Northcentral United States, and the Russian Far East. While still rare, there has been an increase in reported cases of POWV disease over the last decade; most (>90%) cases have been neuroinvasive and the associated fatality rate is high (>10%). Transfusion-associated risk of POWV remains uncertain; while no intervention is likely indicated, one probable case of transfusion-transmitted POWV in the context of an increase in the incidence of POWV and other tick-borne infections, merits vigilance.     

Immunohistochemical detection of proluteinizing hormone-releasing hormone peptides in neurons in the human hypothalamus.

To determine the presence of LHRH prohormone products in the human hypothalamus, antisera raised against LHRH and GnRH-associated peptide (GAP) were used to search for the presence of the corresponding antigens in the human adult and fetal hypothalamus by an immunohistochemical approach. The comparison of immunostaining on adjacent sections shows that all of the cells labeled with LHRH antiserum are also labeled with GAP antiserum and vice versa. Labeled cells are detectable during the 9th week of fetal life, this being the earliest time evaluated. At this time, the LHRH/GAP-positive cells frequently have a neuroblastic appearance. The first detectable fibers appear during the 11th week, and these were observed in the lamina terminalis cinerea and median eminence. In the adult brain, fibers and endings labeled with LHRH or GAP antiserum in the median eminence demonstrate the same topography and morphological characteristics, which are distinct from fibers labeled with other neuropeptide antisera. These results show that the LHRH precursor molecule is produced throughout life in the human hypothalamus, including the earliest stages of development of the peptidergic neurons. Moreover, the detection of LHRH- and GAP-positive fibers in the median eminence by the 11th week of fetal life suggests the possibility of an early role of LHRH and, possibly, other LHRH prohormone-derived peptides in the development of anterior pituitary function during the fetal period.     

Screening for primary aldosteronism in a cohort of Brazilian patients with resistant hypertension

The objective was to estimate the prevalence of plasma aldosterone concentration:plasma renin activity ratio >30 ng/dL:ng/mL/h in patients with resistant hypertension and to describe the computed tomography findings of adrenal glands in those with elevated ratios. In a cross-sectional design, 492 patients were enrolled. All patients with plasma aldosterone concentration:plasma renin activity ratio >or=30 ng/dL:ng/mL/h (n=77) underwent abdominal computed tomography. Patients with an adrenal image of possible aldosterone-producing adenoma underwent a saline-loading test. The prevalence of elevated plasma aldosterone concentration:plasma renin activity ratio was 15.7% (95% confidence interval, 12.6-19.2). Twelve patients showed adrenal abnormalities on computed tomography. The level of renin was low in 50% of the sample. Results indicate a low prevalence of aldosterone-producing adenoma. Our evidence points out the importance of confirming the hypothesis that essential hypertension, low-renin hypertension, and idiopathic hyperaldosteronism could be the same disease, but at different neurohormonal stages, and aldosterone-producing adenoma may be yet another disease.