Effect of high versus low dose of dexamethasone on clinical worsening in patients hospitalised with moderate or severe COVID-19 Pneumonia: an open-label, randomised clinical trial

BackgroundLow dose dexamethasone demonstrated clinical improvement in patients with coronavirus disease 2019 (COVID-19) needing oxygen therapy; however, evidence on the efficacy of high dose of dexamethasone is limited.MethodsWe performed a randomised, open-label, controlled trial involving hospitalised patients with confirmed COVID-19 pneumonia needing oxygen therapy. Patients were randomly assigned in a 1:1 ratio to receive low dose dexamethasone (6 mg once daily for 10 days) or high dose dexamethasone (20 mg once daily for 5 days, followed by 10 mg once daily for additional 5 days). The primary outcome was clinical worsening within 11 days since randomisation. Secondary outcomes included 28-day mortality, time to recovery, and clinical status at day 5, 11, 14 and 28 on an ordinal scale ranging from 1 (discharged) to 7 (death).ResultsA total of 200 patients (mean (sd) age, 64 (14) years; 62% male) were enrolled. Thirty-two patients of 102 (31.4%) enrolled in the low dose group and 16 of 98 (16.3%) in the high dose group showed clinical worsening within 11 days since randomisation (rate ratio, 0.427; 95% CI, 0.216–0.842; p=0.014). The 28-day mortality was 5.9% in the low dose group and 6.1% in the high dose group (p=0.844). There was no significant difference in time to recovery, and in the 7-point ordinal scale at day 5, 11, 14 and 28.ConclusionsAmong hospitalised COVID-19 patients needing oxygen therapy, high dose of dexamethasone reduced clinical worsening within 11 days after randomisation as compared with low dose.

Clinical impact of SARS-CoV-2 infection among patients with vulvar cancer: the Gemelli Vul.Can multidisciplinary team

Background‘Severe acute respiratory syndrome coronavirus-2’ (SARS-CoV-2) infection has dramatically affected the management of patients with cancer, who are most vulnerable to the consequences of the infection. Patients with vulvar cancer are frequently elderly and affected by multiple co-morbidities, thus representing a particularly frail population.ObjectiveTo assess the clinical impact of the SARS-CoV-2 infection among patients scheduled for treatment for active vulvar cancer.MethodsData on patients with vulvar tumors referred to Fondazione Policlinico Universitario Agostino Gemelli IRCCS between February 2020 and July 2021 were retrospectively analyzed. Patients with a positive reverse transcription polymerase chain reaction in nasopharyngeal swab were considered as positive for SARS-Cov-2.ResultsOne hundred and ninety-one patients with vulvar cancer were evaluated and scheduled for treatment. The median age was 72 years (range 35–94). Seven (3.7%) patients were diagnosed with SARS-Cov-2 infection: three (42.9%) had their treatment delayed, with no apparent consequences, two (28.6%) had their treatment delayed and later abandoned because of clinical worsening due to oncologic disease progression, and two (28.6%) contracted the infection in the post-operative period and died due to respiratory complications.ConclusionsIn most cases the infection had major clinical implications, being associated with significant delays in oncologic treatments and extremely high mortality when contracted in the post-operative period.

Clinical Relevance of Right Atrial Functional Response to Treatment in Pulmonary Arterial Hypertension

Background: Right atrial (RA) function has emerged as an important determinant of outcome in pulmonary arterial hypertension (PAH). However, studies exploring RA function after initiation of specific pulmonary vascular treatment and its association with outcome in patients with incident PAH are lacking.Methods: RA peak longitudinal strain (PLS), passive strain (PS), and peak active contraction strain (PACS) were retrospectively assessed in 56 treatment-naïve patients with PAH at baseline and during follow-up after initiation of specific monotherapy or combination therapy. Patients were grouped according to their individual RA functional response to treatment, based on change from baseline (Δ): worsened (first Δ-tertile), stable (second Δ-tertile), and improved (third Δ-tertile). The Spearman's rho correlation and linear regression analysis were used to determine associations. Time to clinical worsening (defined as deterioration of functional class or 6-min walking distance, disease-related hospital admission, or death) was measured from the follow-up assessment. The association of RA functional treatment response with time to clinical worsening was assessed using the Kaplan–Meier and the Cox regression analyses.Results: Median (interquartile range) time to echocardiographic follow-up was 11 (9–12) months. Of the 56 patients, 37 patients (66%) received specific dual or triple combination therapy. Δ RA PLS during follow-up was significantly associated with changes in key hemodynamic and echocardiographic parameters. The change of pulmonary vascular resistance, right ventricular (RV) end-systolic area, and global longitudinal strain were independently associated with Δ RA PLS. The median time to clinical worsening after echocardiographic follow-up was 6 (2–14) months [17 events (30%)]. In the multivariate Cox regression analysis, worsening of RA PLS was significantly associated with clinical deterioration (hazard ratio: 4.87; 95% CI: 1.26–18.76; p = 0.022). Patients with worsened RA PLS had a significantly poorer prognosis than those with stable or improved RA PLS (log-rank p = 0.012). By contrast, PS and PACS did not yield significant prognostic information.Conclusion: Treatment-naïve patients with PAH may show different RA functional response patterns to PAH therapy. These functional patterns are significantly associated with clinically relevant outcome measures. Improvements of RA function are driven by reductions of afterload, RV remodeling, and RV dysfunction.

Heart Rate Recovery at 1 Min after Exercise Is a Marker of Disease Severity and Prognosis in Chronic Thromboembolic Pulmonary Hypertension

<b><i>Background:</i></b> Attenuated heart rate recovery at 1 min (HRR1) was demonstrated to correlate with poor prognosis in patients with pulmonary arterial hypertension, whereas its role in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. <b><i>Objectives:</i></b> The aim of this study was to investigate the correlations between HRR1 and functional status, echocardiography, hemodynamics, and prognosis of CTEPH. <b><i>Methods:</i></b> We retrospectively enrolled patients with CTEPH who underwent right heart catheterization and cardiopulmonary exercise test between June 2014 to October 2020 in Fuwai hospital. The primary outcome was clinical worsening. Linear regression was performed to assess the association between HRR1 and established markers of CTEPH severity. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff of HRR1. Cox regression models were used to assess the association between HRR1 and clinical worsening. <b><i>Results:</i></b> A total of 211 patients with CTEPH were included in the study. After adjusting for confounders, HRR1 positively correlated with 6-min walk distance, mixed venous oxygen saturation, and peak oxygen consumption, and negatively correlated with NT-proBNP, pulmonary vascular resistance, and ventilatory equivalent of carbon dioxide. Compared with patients with HRR1 ≥16 beats, patients with HRR1 &#x3c;16 beats had approximately a 3-fold risk of experiencing clinical worsening and the risk escalated with time. <b><i>Conclusion:</i></b> HRR1 could reflect disease severity and was independently associated with prognosis in patients with CTEPH.

COVID-19 pandemic challenges: on the way to overcome obstacles in realization of PAH-specific therapy treatment goals

Our observation demonstrates a case of a 40-year-old female with idiopathic pulmonary arterial hypertension World Health Organization functional class III, who was admitted to NMRC of Cardiology repeatedly due to disease progression including dyspnea worsening and exercise tolerance decrease after previous COVID-19 infection on riociguat (7.5 mg daily), macitentan (10 mg daily) and selexipag (1600 mcg daily) therapy. Clinical examination demonstrated high-risk status according to the expected 1-year mortality. Due to unreleased treatment goals and high-risk status, we performed transition from selexipag to inhale iloprost. After therapy escalation the patient demonstrated a significant improvement in clinical condition, dyspnea reduction and exercise tolerance increase. The current treatment strategy for pulmonary arterial hypertension is based on regular multiparametric risk stratification approach in PAH patients. The impact of COVID-19 may become an important cause of clinical worsening in PAH patients during COVID-19 pandemic. Directed on vasodilatation and antiproliferation mechanisms of action of PAH-specific drugs are supposed to be protective in COVID-19 patients. However, the probability of clinical worsening in PAH patients despite PAH-specific therapy intake needs to be closely monitored to perform timely treatment correction in order to achieve low-risk status and to improve the prognosis of PAH patients.

Prognostic Accuracy of the Modified CHA2DS2-VASc Score in COVID-19 Patients Admitted to the Emergency Department Due to Clinical Worsening

Introduction: Risk factors comprising the CHA2DS2VASc score are recognized as risk factors for venous thromboembolism and mortality in COVID-19 patients. A modified CHA2DS2VASc score (M-CHA2D2VASc), developed by changing gender criteria from female to male, has been proposed to predict in-hospital mortality in COVID-19 patients. The aim of this study was to evaluate the prognostic accuracy of M-CHA2D2VASc for adverse clinical outcomes and short-term mortality in COVID-19 patients admitted to the Emergency Department.Material and Methods: Retrospective study of patients admitted to the ED who underwent computed tomography pulmonary angiography due to suspected pulmonary embolism or clinical worsening. Patients were stratified into three M-CHA2DS2-VASc risk-categories: low (0 - 1 points), intermediate (2 - 3 points) and high-risk (≥ 4 points).Results: We included 300 patients (median age 71 years, 59% male). The overall mortality was 27%. The M-CHA2DS2-VASc score was higher in non-survivors compared to survivors [4 (IQR:3 - 5) vs 2 (IQR: 1 - 4), respectively, p < 0.001). The M-CHA2DS2-VASc score was identified as an independent predictor of mortality in a multivariable logistic regression model (OR 1.406, p = 0.007). The Kaplan-Meier survival curves showed that the M-CHA2DS2-VASc score was associated with short-term mortality (log-rank test < 0.001), regardless of hospitalization (log-rank test p < 0.001 and p = 0.007, respectively). The survival proportion was 92%, 80% and 63% in the lower, intermediate, and higher risk-groups. As for the risk-categories, no difference was found in pulmonary embolism, Intensive Care Unit admission, and invasive mechanical ventilation.Discussion: This is the first study to validate M-CHA2DS2-VASc score as a predictor of short-term mortality in patients admitted to the Emergency Department.Conclusion: The M-CHA2DS2-VASC score might be useful for prompt risk-stratification in COVID-19 patients during admission to the Emergency Department.

Agrobacterium radiobacter Endophthalmitis Associated with Baerveldt Tube Exposure

<i>Agrobacterium radiobacter</i> is a Gram-negative bacillus and a rare cause of endophthalmitis. An 85-year-male presented with late-onset endophthalmitis associated with exposure of an inferonasal Baerveldt tube. The patient was initially treated with anterior chamber paracentesis and intravitreal antibiotics. Aqueous humor culture revealed <i>A. radiobacter</i> resistant to cefazolin, ceftazidime, amikacin, tobramycin, and trimethoprim-sulfamethoxazole. Subsequently, the patient underwent explantation of the glaucoma drainage implant (GDI). After initial improvement, the patient had clinical worsening and was diagnosed with recurrence. Subsequent treatment involved explantation of the second GDI in addition to pars plana vitrectomy with silicone oil infusion, intraocular lens removal, and administration of intravitreal antibiotics. Visual acuity improved but remained at count fingers at 2 weeks. This is the first reported patient with <i>A. radiobacter</i> endophthalmitis associated with an exposed GDI. This report illustrates the resistant nature of this organism in addition to the efficacy of silicone oil administration and intraocular prosthesis explantation.

Acute worsening of clinical presentation in CRPS after SARS-CoV-2 (COVID-19) vaccination: a case series

We present the acute worsening of clinical presentation in complex regional pain syndrome (CRPS), following mRNA-based COVID-19 vaccination. We report the case series of three patients diagnosed with CRPS type I who presented with acute worsening of symptoms after mRNA-based COVID-19 vaccination and their medical management. The acute clinical worsening after mRNA-based COVID-19 vaccination was transient and effectively managed with adjustment of individualized therapy in all three patients. The mortality and morbidity of COVID-19 infection are serious, and vaccination is recommended in the general population, including patients with a diagnosis of CRPS. However, clinicians should be aware of the possibility that there may be a clinical worsening CRPS after mRNA-based COVID-19 vaccination.

A Real-world Experience of Atrioventricular Synchronous Pacing with Leadless Ventricular Pacemakers

Aims: The MicraTM transcatheter pacing system (TPS) (Medtronic) is the only leadless pacemaker that promotes atrioventricular (AV) synchrony via accelerometer-based atrial sensing. Data regarding the real-world experience with this novel system are currently lacking. We sought to characterize patients undergoing MicraTM -AV implants, describe percentage AV synchrony achieved, and analyze the causes for suboptimal AV synchrony. Methods: In this retrospective cohort study, electronic medical records from 56 consecutive patients undergoing MicraTM -AV implants at the Mayo Clinic sites in Minnesota, Florida, and Arizona with a minimum follow-up of 3 months were reviewed. Demographic data, comorbidities, echocardiographic data, and clinical outcomes were compared among patients with and without atrial synchronous-ventricular pacing (AsVP) ≥70%. Results: Fifty-six percent of patients achieved AsVP ≥70%. Patients with adequate AsVP had smaller body mass indices, a lower proportion of congestive heart failure and pulmonary hypertension. Echocardiographic parameters and procedural characteristics were similar across the two groups. Active device troubleshooting was associated with higher AsVP. The likely reasons for low AsVP were persistent atrial arrhythmias, small A4-wave amplitude, and inadequate device reprogramming. Importantly, in patients with low AsVP, subjective clinical worsening was not noted during follow-up. Conclusion: With the increasing popularity of leadless PM, it is paramount for device implanting teams to be familiar with common predictors of AV synchrony and troubleshooting with MicraTM -AV devices.

Laryngotracheomalacia in a Patient with Mosaic Trisomy 8

Mosaic trisomy 8 is a condition characterized by a great phenotypic and cytogenetic variability whose incidence ranges around 1 in 25,000 to 50,000 live births. Here, we report a mosaic trisomy 8 patient presenting laryngotracheomalacia, an uncommon finding, analyzing its possible role over morbidity, and mortality. The patient was a boy who, after birth, had tachypnea and paleness. He presented periods of respiratory dysfunction with need of ventilatory support. Respiratory syncytial virus test was positive. Naso fibrobronchoscopy showed moderate laryngotracheomalacia. He also had recurrent episodes of pneumonia and difficulty in withdrawing continuous positive airway pressure. The patient also presented leucoma, abnormal and low-set ears, pectus excavatum, clenched fists with overlapping fingers, cryptorchidism, clubfeet, and deep longitudinal plantar creases. G-bands by Trypsin using giemsa (GTG-banding) karyotype from a peripheral blood sample revealed a mosaic trisomy 8: mos 47,XY, + 8[15]/46,XY[7]. At 4 months, the patient developed respiratory failure, and a chest computed tomography scan showed areas of atelectasis and gross fibroatelectatic striae. He ended up presenting clinical worsening and died at 4 months and 8 days. In our literature review, we found some reports describing patients with mosaic trisomy 8 and laryngotracheomalacia. However, we cannot rule out the possibility that this association could be casual, since laryngotracheomalacia is a relatively common finding in children. Therefore, more studies are still necessary to understand the possible relation between both conditions and the role of laryngotracheomalacia over morbidity and prognosis of mosaic trisomy 8 patients.