Tocilizumab Is Associated with Increased Risk of Fungal Infections among Critically Ill Patients with COVID-19 and Acute Renal Failure: An Observational Cohort Study.

RESEARCH QUESTION: Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19? BACKGROUND: Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has found a role as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections. We sought to assess the risk of invasive fungal disease and the therapeutic impact of tocilizumab on the hospital length of stay, duration of mechanical ventilation, and intensive-care-unit length of stay in critically ill patients with severe coronavirus-19 pneumonia. METHODS: Records of critically ill patients with coronavirus-2019 admitted from March to September 2020 at our institution were reviewed. The risk for fungal infections, intensive-care-unit length of stay, hospital length of stay, and duration of mechanical ventilation in those that received tocilizumab in addition to standard coronavirus-2019 treatments was assessed. RESULTS: Fifty-six critically ill patients treated with dexamethasone and remdesivir for coronavirus-2019 were included, of which 16 patients also received tocilizumab. The majority of the cohort was African American, Asian, or of other ethnic minorities (53.6%). Invasive fungal infections occurred in 10.7% of all patients, and infection rates were significantly higher in the tocilizumab group than in the control group (31.2% vs. 2.5%, risk difference [RD] = 28.8%, p < 0.01). The increased risk in the tocilizumab group was strongly associated with renal replacement therapy. There was a dose-response relationship between the risk of fungal infection and number of tocilizumab doses received, with 2.5% of infections occurring with zero doses, 20% with a single dose (RD = 17.5%), and 50% with two doses (RD = 47.5%) (trend test p < 0.001). In addition, ICU LOS (23.4 days vs. 9.0 days, p < 0.01), the duration of mechanical ventilation (18.9 vs. 3.5 days, p = 0.01), and hospital length of stay (LOS) (29.1 vs. 15.5, p < 0.01) were increased in patients that received tocilizumab. CONCLUSIONS: Repurposed immunomodulator therapies, such as tocilizumab, are now recommended treatments for severe coronavirus-2019 pneumonia, but safety concerns remain. In this early pandemic cohort, the addition of tocilizumab to dexamethasone was associated with an increased risk of fungal infection in those that were critically ill and received renal replacement therapy. Tocilizumab use was also associated with increased ICU and hospital LOSs and duration of mechanical ventilation.

Influence of Iron Deficiency on Clinical and Haemodynamic Parameters in Pulmonary Arterial Hypertension Cohorts.

BACKGROUND: Iron deficiency (Fedef) has been shown to be common in patients with group 1 or pulmonary arterial hypertension (PAH). Several studies have shown a negative impact of Fedef on clinical and haemodynamic parameters of the disease, but data from individual studies have not been strong enough to lead to incorporation of the finding of Fedef into prognostic or therapeutic algorithms. The goal of this meta-analysis was to combine data from available studies to better define any associations between Fedef and established variables of prognostic importance in PAH. METHODS: A literature search identified nine studies with extractable data relevant to the study questions. The impact of Fedef upon the following parameters was evaluated: 6-minute walk distance (6MWD), WHO-functional class, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, echocardiography, and findings from right heart catheterisation (RHC). Pooled results were reported as mean difference or risk difference with 95% confidence intervals utilising a random effects modeling approach. RESULTS: Fedef in the PAH population was common (47% of cases) and was associated with cardiovascular dysfunction (lower tricuspid annular plane systolic excursion [TAPSE], elevated NT-proBNP, and lower mixed venous oxygen saturation) and with reduction in functional capacity (lower 6MWD and higher functional class). CONCLUSION: This meta-analysis strengthens the relationships between Fedef and several markers of poor outcome in PAH. Fedef in patients with PAH warrants further scrutiny and merits consideration as a cause of clinical deterioration. Even though causation and longitudinal relationships between Fedef and PAH could not be identified, effect of Fedef on factors that affect disease prognosis is noteworthy and worthy of more focussed studies.

A Rare Case of Pulmonary Emboli Presenting With ST Elevation on ECG.

Pulmonary embolism is a common medical emergency and often life threatening but can be misdiagnosed frequently leading to fatal outcomes. Changes in electrocardiogram (ECG) are common in pulmonary embolism and rarely they can present with ST elevation. We here describe a 79-year-old woman who presented after a cardiac arrest and was found have ST-segment elevation on ECG with normal coronary angiogram while CT scan revealing pulmonary embolism.

Personal Protective Equipment Efficiency in Healthcare Emergencies: A Single-Center Experience.

Coronavirus disease 2019 (COVID-19) has dramatically shifted the healthcare landscape since 2020. Measures against it includes universal masking in the healthcare areas and the community, viral testing before aerosolizing procedures, and ambulatory elective surgical procedures. Some hospitals have had mandated viral testing policies even before admission to the hospital. Healthcare workers (HCWs) have been cautiously modifying all pertinent practices to avoid the transmission of the virus. Personal protective equipment (PPE), including gowns, gloves, eye protection, and properly fitted N95 respirator or powered air-purifying respirators (PAPR) while treating the suspected and confirmed COVID-19 patients were made mandatory. Similarly, we changed our aerosol-generating procedures (AGPs) protocols based on available limited data. We amended our approach to in-hospital cardiopulmonary resuscitation (basic life support (BLS)/advanced cardiovascular life support (ACLS)), given the risk of aerosol generation and transmission during the process. This article shares our experience and outcomes of PPE use in healthcare emergencies at our tertiary care academic center.

Acute Influenza Infection Presenting with Cardiac Tamponade: A Case Report and Review of Literature.

INTRODUCTION: Cardiac complications associated with influenza infection can occur either via a direct effect of the virus on the heart or through exacerbation of preexisting cardiovascular disease. We present a case of a 57-year-old man with acute influenza infection complicated by pericardial effusion and cardiac tamponade. CASE PRESENTATION: A 57-year-old white man presented to the Emergency Department with sudden onset of severe, nonexertional, retrosternal, pressure-like chest pain for a few hours and with fever and muscle aches for 2 days. The patient was initially admitted because of suspected acute coronary syndrome. The next morning, he complained of acute-onset shortness of breath and had hypotension and tachycardia. On examination, his peripheral extremities were cold and heart sounds were distant. Pulsus paradoxus was 20 mmHg. The electrocardiogram showed low-voltage QRS complex with electrical alternans. An urgently performed bedside echocardiogram showed moderate pericardial effusion with a small right ventricular cavity with diastolic collapse. Emergent pericardiocentesis was performed, with removal of 250 mL of fluid from the pericardial space. The patient's hemodynamic status immediately improved. Analyses of pericardial fluid demonstrated no bacteria, acid-fast bacilli, or malignant cells. The result of a rapid influenza diagnostic test with polymerase chain reaction was positive for influenza A virus, with other viral panels yielding normal results. The patient was treated with oseltamivir for 5 days. DISCUSSION: Pericardial involvement is a rare and perhaps underreported complication of influenza infection. Early recognition of cardiac symptoms and appropriate diagnostic workup in a patient presenting with influenza-like symptoms is important to avoid life-threatening complications.

Noncystic fibrosis bronchiectasis management: opportunities and challenges.

PURPOSE OF REVIEW: Noncystic fibrosis bronchiectasis is a challenging disease which carries a heavy healthcare burden and significant mortality and morbidity. This review highlights the challenges in the diagnosis of bronchiectasis and discusses the management strategies and research opportunities in this field. RECENT FINDINGS: The challenges in the management of bronchiectasis appear to be multifactorial, arising from both etiological heterogeneity and disease-specific management. Frequent inflammation and infections not only lead to progressive respiratory failure but also increase the risk of cardiovascular complications. No therapies are approved specifically for adult bronchiectasis, but new guidelines and recent studies outline strategies for control of infection and inflammation and for prevention of frequent exacerbations to improve overall prognosis. SUMMARY: Recent studies in the management of bronchiectasis are encouraging. Advances have been made in understanding both disease heterogeneity and best practices for care; interventions such as daily mucociliary clearance, eradication of colonized microbial organisms, and control of inflammation may result in favorable outcomes.

Prevalence and predictors of readmissions among adults with cystic fibrosis in the United States.

INTRODUCTION: Patients with Cystic Fibrosis (CF) have increasing rates of hospitalization. We analyzed the burden and predictors of thirty-day readmission among patients with CF in the U.S. MATERIAL AND METHODS: Nationwide Readmission Database (NRD) 2013 was used to identify adults with CF who were hospitalized. These individuals were followed to determine the prevalence of readmission within thirty days of index discharge. Cox proportional hazard regression was used to identify independent predictors of readmission. RESULTS: There were 14,616 index admissions of adults with CF in 2013. Of these, 2,606 (17.8%) patients were readmitted within 30 days of discharge. Female sex and chronic anemia were independent predictors of readmission. The most common causes of readmission were pulmonary exacerbation (31%), lung transplant complications (5.2%), and septicemia (3.4%). CONCLUSION: Readmissions are frequent among adults with CF and contribute to significant healthcare burden and cost among this population.

A Rare Cause of Pulmonary Edema in the Postoperative Period.

With the increasing longevity of the population, the annual rates of hip arthroplasties performed have been steadily increasing over the past decade. Given the presence of medical comorbidities in the older patients, the peri-operative care of these individuals requires multi-specialty care, now more than ever. Hip arthroplasty is generally well tolerated, with early mortality after the procedure being <1%. Bone cement implantation syndrome (BCIS) is an entity that is occasionally encountered during or after the surgery. It is characterized by hypoxemia, hypotension, cardiac arrhythmias, and cardiac arrest leading to death, in severe cases. We report a case of a middle-aged female who developed refractory hypotension and pulmonary edema while undergoing hemiarthroplasty for a pathological femoral neck fracture and experienced cardiac arrest in the immediate postoperative period. Critical care physicians must familiarize themselves with promptly diagnosing and managing BCIS.

Contemporary national trends of cystic fibrosis hospitalizations and co-morbidities in the United States.

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting multisystemic genetic disease. Patients with CF have a high rate of hospitalization. We attempt to ascertain national trends of inpatient stays, prevalence of various co-morbidities during hospitalizations, outcomes and discharge disposition among CF patients. MATERIAL AND METHODS: Data from the National Inpatient Sample (NIS) was used to identify all hospitalizations of patients with CF and their demographic characteristics from 2003 to 2013. Prevalence and effects of various co-morbidities like acute kidney injury (AKI) were determined. Detailed sub-group analysis was performed for individuals with lung transplant. RESULTS: The annual rate of hospitalization per 1,000 CF patients in the U.S. increased from 994 in 2003 to 1,072 in 2013. The overall in-hospital mortality was 1.5%; median age at death was 27 years. In-hospital mortality trended down from 1.9% to 1.2% from 2003 to 2013 (p-value for trend: 0.002). The median length of stay was 7 days. The prevalence of chronic liver disease and AKI was 3.7% and 3.8% respectively. Multivariate adjusted odds of mortality for AKI was 1.74 (95% CI 1.57-1.93, p < 0.001). Patients with prior lung transplantation accounted for 6.5% of hospitalizations. These patients had a significantly higher prevalence of AKI. CONCLUSIONS: The annual hospitalization rates of CF patients is increasing over the years. Females with CF constitute a higher proportion of hospitalized patients despite a higher male preponderance of males with CF in the community. AKI is associated with a significantly higher in-hospital mortality. Lung transplant recipients have a higher prevalence of AKI and mortality.

Delay in diagnosis of chronic obstructive pulmonary disease: reasons and solutions.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a crippling disease with a high worldwide prevalence. It is the fifth-leading cause of death worldwide and estimated to become the third-leading cause of death by 2030. This review highlights recent studies that discuss reasons for and possible solutions to the delay in diagnosis of COPD. RECENT FINDINGS: Delay in COPD diagnosis is multifactorial and can be grouped into healthcare provider-related factors, patient-related factors, and heterogeneity in the disease itself. The current literature strongly supports the lack of awareness and knowledge about COPD among healthcare providers as an important factor in misdiagnosis and/or delays in diagnosis. Ironically, COPD is both underdiagnosed and overdiagnosed. SUMMARY: Achieving the goal of early diagnosis in COPD needs a major overhaul and culture change in primary care settings. Respiratory symptoms in a smoker 40 years or above should trigger automatic health alert and spirometry indications. Awareness of tobacco-related injury is the first building block in prevention and cure.

Acute thyrotoxic bulbar myopathy with encephalopathic behaviour: an uncommon complication of hyperthyroidism.

Objective. Acute thyrotoxic bulbar palsy is rare, severe, and rapidly progressive. We describe a case of thyrotoxicosis with bulbar palsy, encephalopathy, and pyramidal tract dysfunction. Case Report. 64-year-old white male with toxic multinodular goiter presented with rapid atrial fibrillation. He had mild tremor, normal cranial nerve examination, 4/5 strength in all extremities, normal reflexes, and down going plantars. TSH was low at 0.09 (normal: 0.34-5.6 uIU/mL), and free T4 was high at 5.22 (normal: 0.47-1.41 ng/dL). Despite optimal AV nodal blockade, he had persistent rapid atrial fibrillation. He later developed cervical dystonia, rigidity, clonus, dysarthria, dysphagia, vocal cord palsy, and absent gag reflex. Thyroid storm was suspected. Neuroimaging and cerebrospinal fluid cultures were nondiagnostic. Acetylcholine receptor antibodies were negative. Swallow ability was impaired with heavy secretions. Remarkable improvement in symptoms was noted after initiation of treatment for thyroid storm. Conclusion. Pyramidal tract symptoms and bulbar palsy may occur with thyrotoxicosis. Cranial nerve involvement and encephalopathy raise a question of primary brain mechanism causing bulbar palsy. This is reversible with prompt treatment of thyroid storm.