Constrictive pericarditis: portal, splenic, and femoral venous Doppler pulsatility: a case series.

PURPOSE: Pulsatile flow of the portal vein has been implicated as an indicator of right ventricular dysfunction in cardiac patients. In patients with significantly elevated right atrial pressure, pulsatile venous flow may be transmitted to the portal, splenic, renal, and femoral veins. We describe the evolution of these echocardiographic findings in four patients with constrictive pericarditis (CP) undergoing pericardiectomy with simultaneous hemodynamic waveform and cerebral oximetry monitoring in the operating room and in the intensive care unit. CLINICAL FEATURES: Patient 1 presented classic signs of CP, including equalization of left and right diastolic pressures, a "square root" sign on the diastolic portion of the right ventricular pressure curve, and elevated right atrial pressure. Preoperative transesophageal echocardiography showed a hyperdynamic left ventricle and dilated right ventricle with abnormal pulsatile waveforms in the portal and splenic veins. Surgical decompression of the pericardium gradually normalized the Doppler waveforms. Increased venous return following pericardiectomy during surgery in patients 2 and 3 and during the postoperative period in patient 4 resulted in right ventricular (RV) failure due to significantly increased preload. Venous pulsatility was also observed in the portal, splenic, and femoral veins. CONCLUSION: In patients with CP, changes in hemodynamic and echocardiographic signs of RV dysfunction are rapidly reflected by changes in peripheral venous velocities. Identifying signs of splanchnic and peripheral vascular venous congestion could help identify patients at higher risk of developing postoperative complications following pericardiectomy.

RéSUMé: OBJECTIF : Le flux pulsatile de la veine porte a été impliqué comme indicateur de dysfonctionnement ventriculaire droit chez les patients de chirurgie cardiaque. Le flux veineux pulsatile pourrait être transmis aux veines porte, splénique, rénale et fémorale chez les patients présentant une pression auriculaire droite significativement élevée. Nous décrivons l'évolution de ces observations échocardiographiques chez quatre patients atteints de péricardite constrictive (PC) bénéficiant d'une péricardectomie avec monitorage simultané de la forme d'onde hémodynamique et de l'oxymétrie cérébrale en salle d'opération et à l'unité de soins intensifs. CARACTéRISTIQUES CLINIQUES: Le patient 1 présentait des signes classiques de PC, y compris l'égalisation des pressions diastoliques gauche et droite, un signe de « racine carrée ¼ sur la partie diastolique de la courbe de pression ventriculaire droite, et une pression auriculaire droite élevée. L'échocardiographie transœsophagienne préopératoire a montré un ventricule gauche hyperdynamique et un ventricule droit dilaté, avec des formes d'onde pulsatiles anormales dans les veines porte et splénique. La décompression chirurgicale du péricarde a progressivement normalisé les formes d'onde Doppler. L'augmentation du retour veineux suivant une péricardectomie, survenue pendant la chirurgie chez les patients 2 et 3 et en période postopératoire chez le patient 4, a entraîné une défaillance ventriculaire droite (VD) due à l'augmentation significative de la précharge. La pulsatilité veineuse a également été observée dans les veines porte, splénique et fémorale. CONCLUSION: Chez les patients atteints de péricardite constrictive, les changements dans les signes hémodynamiques et échocardiographiques de dysfonctionnement du VD sont rapidement reflétés par des changements dans la vélocité veineuse périphérique. L'identification des signes de congestion veineuse splanchnique et vasculaire périphérique pourrait aider à identifier les patients présentant un risque plus élevé de manifester des complications postopératoires après une péricardectomie.

Effect of Body Mass Index on the Clinical Outcomes of Adult Patients Treated With Venoarterial ECMO for Cardiogenic Shock.

OBJECTIVE: Current guidelines consider obesity to be a relative contraindication to venoarterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. The authors investigated the effect of body mass index (BMI) on clinical outcomes in patients treated with VA-ECMO for cardiogenic shock. DESIGN: This was a retrospective and observational study. SETTING: University hospital. PARTICIPANTS: The study comprised 150 adult patients who underwent VA-ECMO for cardiogenic shock. MEASUREMENTS AND MAIN RESULTS: The primary outcome was intensive care unit (ICU) mortality. Of the 150 included patients, 10 were underweight (BMI < 18.5 kg/m²), 62 were normal weight (BMI = 18.5-24.9 kg/m²), 34 were overweight (BMI = 25.0-29.9 kg/m²), 34 were obese class I (BMI = 30.0-34.9 kg/m²), and 10 were obese class II (BMI = 35.0-39.9 kg/m²). All-cause ICU mortality was 62% (underweight, 70%; normal weight, 53%; overweight, 65%; class I obese, 71%; class II obese, 70%). After multivariate logistic regression, BMI was not associated with ICU mortality (adjusted odds ratio [aOR] 0.99 [0.92-1.07], p = 0.8). Analysis by BMI category showed unfavorable mortality trends in underweight patients (aOR 3.58 [0.82-19.6], p = 0.11) and class I obese patients (aOR 2.39 [0.95-6.38], p = 0.07). No statistically significant differences were found among BMI categories in the incidences of complications. CONCLUSION: The results suggested that BMI alone should not be considered an exclusion criterion for VA-ECMO. The unfavorable trend observed in underweight patients could be the result of malnutrition.

Epidemiological Characterization of Patients in the First Eight Weeks Following Detection of SARS-CoV-2 B.1.1.529 (omicron) Variant in Cuba.

INTRODUCTION: In November 2021, omicron-a new SARS-CoV-2 variant-was identified in South Africa and almost immediately, WHO declared it a 'variant of concern'. In view of its rapid worldwide spread and its imminent introduction in Cuba, genomic surveillance was strengthened. OBJECTIVE: Describe cases during the first eight epidemiological weeks (epiweeks) of SARS-CoV-2 infection attributable to omicron variant in Cuba by clinical and epidemiological variables. METHODS: From epiweek 48, 2021 to epiweek 4, 2022, 288 nasopharyngeal swabs were processed for sequencing of a 1836 bp fragment of the S gene. Variants were identified according to GISAID database and confirmed by phylogenetic analysis. Variants' association with clinical and epidemiological outcomes was assessed. RESULTS: The first cases of omicron variant were imported, mostly from African countries and the United States. During the period studied, omicron was detected in 83.0% (239/288) of cases processed, while the delta variant was found in 17.0% (49/288). Most persons infected with omicron were symptomatic (63.2%; 151/239) and fully vaccinated (65.3%; 156/239); severe cases and deaths occurred mainly among patients aged ≥65 years (92.9%; 13/14), and 12 of these deaths occurred in fully vaccinated persons (92.3%; 12/13). Omicron spread rapidly throughout the country (from 10% of cases in epiweek 48, 2021, to 100% by epiweek 4, 2022), displacing the formerly predominant delta variant. CONCLUSIONS: Omicron's rapid expansion in Cuba was associated with increased incidence but not with a higher case fatality rate. The relatively milder disease in those infected with this variant could be influenced by the high vaccination coverage, along with the natural immunity acquired as a consequence of previous virus infection.

Interest of new alkylsulfonylhydrazide-type compound in the treatment of alcohol use disorders.

RATIONALE: Recent preclinical research suggested that histone deacetylase inhibitors (HDACIs) and specifically class I HDAC selective inhibitors might be useful to treat alcohol use disorders (AUDs). OBJECTIVE: The objective of this study was to find a new inhibitor of the HDAC-1 isoenzyme and to test its efficacy in an animal model of AUDs. METHODS: In the present study, we prepared new derivatives bearing sulfonylhydrazide-type zinc-binding group (ZBG) and evaluated these compounds in vitro on HDAC-1 isoenzyme. The most promising compound was tested on ethanol operant self-administration and relapse in rats. RESULTS: We showed that the alkylsulfonylhydrazide-type compound (ASH) reduced by more than 55% the total amount of ethanol consumed after one intracerebroventricular microinjection, while no effect was observed on motivation of the animals to consume ethanol. In addition, one ASH injection in the central amygdala reduced relapse. CONCLUSIONS: Our study demonstrated that a new compound designed to target HDAC-1 is effective in reducing ethanol intake and relapse in rats and further confirm the interest of pursuing research to study the exact mechanism by which such inhibitor may be useful to treat AUDs.

Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial.

PURPOSE: Hospital-acquired bacterial pneumonia (HABP) is a critical concern in hospitals with ventilator-associated bacterial pneumonia (VABP) remaining the most common infection in the ICU, often due to Staphylococcus aureus, an increasingly difficult to treat pathogen. Anti-infective monoclonal antibodies (mAb) may provide new, promising treatment options. This randomized, double-blinded, placebo-controlled study aimed at assessing the safety and pharmacokinetics of AR-301, an S. aureus alpha toxin-neutralizing mAb, and exploring its clinical and microbiologic outcomes when used adjunctively with standard-of-care antibiotics. METHODS: Eligibility in this trial required microbiologically confirmed severe S. aureus pneumonia, including HABP, VABP or CABP, treated in the ICU and an APACHE II score ≤ 30. Standard-of-care antibiotics selected by the investigators were administered to all patients in the study following clinical and microbiologic confirmation of S. aureus pneumonia. Adjunctive treatment of AR-301 was to start < 36 h after onset of severe pneumonia. AR-301 was administered to four sequentially ascending dose cohorts. The placebo cohort received antibiotics and a placebo buffer. Clinical outcomes were adjudicated by a blinded committee. S. aureus eradication was declared based on a negative follow-up culture and presumed to be negative when no culture was obtained in the presence of clinical improvement. RESULTS: Thirteen ICUs enrolled 48 patients, with pneumonia attributable to MRSA in six subjects. The study drug displayed a favorable safety profile: Of 343 AEs reported, 8 (2.3%) were deemed related, none serious. In a post hoc subgroup analysis of VABP patients receiving AR-301, ventilation duration was shorter for AR-301-treated patients compared with the placebo group. Overall, there was a trend toward a better and faster microbiologic eradication at day 28. The PK profile of AR-301 is consistent with that of a human IgG1 mAb, with a plasma half-life of about 25 days. CONCLUSIONS: Adjunctive treatment of severe S. aureus HABP with anti-staphylococcal mAbs appears feasible and suggests some clinical benefits, but larger randomized studies are needed to better define its safety and efficacy.

Inactivación del virus Zika con medio de transporte de ácidos nucleicos, potencialmente aplicable a muestras clínicas para el diagnóstico molecular de SARS-CoV-2 / Inactivation of Zika virus with nucleic acids transport media, potentially applicable to clinical samples for the molecular diagnosis of SARS-CoV-2

RESUMEN Introducción: Los medios de colecta de muestras clínicas con capacidad de desnaturalizar virus reducen los riesgos de contagio durante el transporte y procesamiento. Objetivo: Emplear el medio de transporte de ácidos nucleicos (TAN) en muestras de exudado nasofaríngeo colectadas para el diagnóstico de SARS-CoV-2. Métodos: Se realizó un estudio experimental para demostrar la capacidad del medio de inactivar la infectividad viral. Se tomó como modelo de virus envuelto el virus Zika (VZk), cuyo nivel de bioseguridad es 2. Se evaluó el desempeño clínico del medio TAN para el diagnóstico de SARS-CoV-2. Se empleó una cepa del VZk propagada en la línea celular Vero y, previo a la infección de las células, el VZk se puso en contacto a intervalos de tiempo diferentes (2; 15 y 30 min) con el medio TAN puro; y luego se realizaron diluciones seriadas (10-1-10-4). La inactivación viral se evaluó por RT-PCR, en el sobrenadante y células colectadas, al culminar el periodo de propagación. El desempeño clínico del medio TAN se estimó tomando como referencia el CITOSWAB® VTM, en 30 exudados nasofaríngeos colectados para diagnóstico de la infección por SARS-CoV-2. Resultados: El VZk preservó su infectividad a diluciones del inóculo ≥ 10-2, independientemente del tiempo de contacto. La sensibilidad y especificidad clínica del medio TAN para el diagnóstico de SARS-CoV-2 fueron del 100 %, respectivamente. Conclusiones: Los resultados sugieren que muestras clínicas positivas a VZk en diluciones ≤ 10-1 del medio TAN pueden ser manipuladas de forma segura, lo que pudiera aplicarse potencialmente al diagnóstico molecular del SARS-CoV-2.

ABSTRACT Introduction: Collection media of clinical samples with the capacity to denature viruses reduce the risk of contagion during transportation and processing. Objective: To use the nucleic acids transport media (NATM) in nasopharyngeal swab samples collected for the diagnosis of SARS-CoV-2. Methods: An experimental study was conducted to demonstrate the medium capacity to inactivate viral infectivity. Zika virus (ZIKV), of biosafety level 2, was used as an enveloped virus model. The clinical performance of the NATM for the diagnosis of SARS-CoV-2 was evaluated. A ZIKV strain propagated in the Vero cell line was used and, prior to cells infection, ZIKV was in contact at different intervals (2; 15, and 30 min) with pure NATM; subsequently, serial dilutions (10-1-10-4) were performed. Viral inactivation was evaluated by RT-PCR in the supernatant and the collected cells when the propagation period was completed. CITOSWAB® VTM was used as reference to estimate the clinical performance of the NATM in 30 nasopharyngeal swabs collected for the diagnosis of SARS-CoV-2 infection. Results: ZIKV remained infectious at inoculum dilutions of ≥ 10-2, regardless of contact time. Clinical specificity and sensitivity of the NATM for the diagnosis of SARS-CoV-2 were 100%, respectively. Conclusions: Results suggest that ZIKV positive clinical samples at dilutions ≤ 10-1 of the NATM can be safely handled, which could potentially be applied to the molecular diagnosis of SARS-CoV-2.

Prognostic impact of left ventricular diastolic function in patients with septic shock.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is highly prevalent in the general population and associated with a significant morbidity and mortality. Its prognostic role in patients sustaining septic shock in the intensive care unit (ICU) remains controversial. Accordingly, we investigated whether LV diastolic function was independently associated with ICU mortality in a cohort of septic shock patients assessed using critical care echocardiography. METHODS: Over a 5-year period, patients hospitalized in a Medical-Surgical ICU who underwent an echocardiographic assessment with digitally stored images during the initial management of a septic shock were included in this retrospective single-center study. Off-line echocardiographic measurements were independently performed by an expert in critical care echocardiography who was unaware of patients' outcome. LV diastolic dysfunction was defined by the presence of a lateral E' maximal velocity <10 cm/s. A multivariate analysis was performed to determine independent risk factors associated with ICU mortality. RESULTS: Among the 540 patients hospitalized in the ICU with septic shock during the study period, 223 were studied (140 men [63 %]; age 64 ± 13 years; SAPS II 55 ± 18; SOFA 10 ± 3; Charlson 3.5 ± 2.5) and 204 of them (91 %) were mechanically ventilated. ICU mortality was 35 %. LV diastolic dysfunction was observed in 31 % of patients. The proportion of LV diastolic dysfunction tended to be higher in non-survivors than in their counterparts (28/78 [36 %] vs. 41/145 [28 %]: p = 0.15). Inappropriate initial antibiotic therapy (OR 4.17 [CI 95 % 1.33-12.5]: p = 0.03), maximal dose of vasopressors (OR 1.38 [CI 95 % 1.16-1.63]: p = 0.01), SOFA score (OR 1.16 [CI 95 % 1.02-1.32]: p = 0.02) and lateral E' maximal velocity (OR 1.12 [CI 95 % 1.01-1.24]: p = 0.02) were independently associated with ICU mortality. After adjusting for the SAPS II score, inappropriate initial antibiotic therapy and maximal dose of vasopressors remained independent factors for ICU mortality, whereas a trend was only observed for lateral E' maximal velocity (OR 1.11 [CI 95 % 0.99-1.23]: p = 0.07). CONCLUSION: The present study suggests that LV diastolic function might be associated with ICU mortality in patients with septic shock. A multicenter prospective study assessing a large cohort of patients using serial echocardiographic examinations remains required to confirm the prognostic value of LV diastolic dysfunction in septic shock.