Tocilizumab challenge: A series of cytokine storm therapy experiences in hospitalized COVID-19 pneumonia patients

To recognize the period of exaggerated cytokine response in patients with coronavirus disease 2019 (COVID-19) pneumonia, and to describe the clinical outcomes of using tocilizumab as a treatment option. The data of 12 adult COVID-19 pneumonia patients who were followed in the inpatient clinics of Biruni University Medical Faculty Hospital (Istanbul, Turkey) were retrospectively analyzed. Diagnostic tests, laboratory examinations, clinical findings, and computed tomography of the thorax imaging results were evaluated. A dramatic laboratory and clinical improvement was observed in 83% (10 out of 12) of patients after tocilizumab. In 17% (2 out of 12) of our patients, short-term ventilator support was required in the intensive care unit. The longest hospital stay was 18 days. However, in the end, all of our patients were discharged home with good health. Although arterial oxygen saturations (87.58 ± 3.12%) dropped in room air in the pre-tocilizumab period, post-tocilizumab they normalized in all patients (94.42 ± 1%). None of them had fever after tocilizumab treatment and the levels of C-reactive protein (13.08 ± 12.89) were almost within normal limits. Eosinophil values were quite low at the time of diagnosis (10 ± 17.06), but increased significantly post-tocilizumab (155.33 ± 192.69). There is currently no proven treatment for COVID-19 induced by novel coronavirus SARS-CoV-2. Based on our experience with twelve adult COVID-19 pneumonia patients, we can say that tocilizumab, an IL-6 inhibitor, is more beneficial in preventing the damage caused by excessive cytokine response in the body if administered at the right time and provides clinical and radiological recovery.     

Clinical Heterogeneity of Immunodysregulation,Polyendocrinopathy, Enteropathy,X-linked: Pulmonary Involvement as a Non-Classical Disease Manifestation

Purpose

IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) is a rare X-linked recessive life-threatening disorder characterized by autoimmunity and early death. Pulmonary complication related with IPEX has not been elucidated exactly. Here, we report 4 IPEX patients, 3 of which died from severe pulmonary disease.

Methods

Clinical data and laboratory findings including autoantibodies, immunoglobulin levels as well as number of T, B and NK cells were evaluated. FOXP3 expression and T reg activity were analyzed. The FOXP3 gene was sequenced and RNA analysis was performed.

Results

Patient I (PI) presented with nephrotic syndrome at 3 years of age and then developed autoimmune hepatitis without eczema, enteropathy or high IgE and died at 9 years of age due to acute respiratory distress syndrome (ARDS). Two cousins of PI had the same hypomorphic splice site mutation leading to a deletion of 27 amino acids, but normal FOXP3 protein expression and normal suppressive capacity of T reg in a proliferation inhibition assay. However, they exhibited typical symptoms such as eczema, diabetes and enteropathy with eosinophilia at early age (PII, PIII) and were transplanted in infancy. One of them had severe respiratory distress right after birth (PIII). Patient IV from another family presented with chronic diarrhea without autoimmune manifestations and died due to ARDS.

Conclusion

Lung disease related to IPEX syndrome has not been reported before and this entity could be a critical factor in disease outcome.     

The assessment of cardiac autonomic functions in adolescents with a family history of premature atherosclerosis

OBJECTIVES:Subclinical atherosclerosis has been recently detected in adolescents with a family history of premature atherosclerosis. However, no studies in the literature have assessed the cardiac autonomic functions of these adolescents. The aim of this study was to evaluate the cardiac autonomic functions of adolescents with a family history of premature atherosclerosis compared with those of age- and gender-matched adolescents without a family history of atherosclerosis.METHOD:We evaluated the cardiac autonomic functions of 36 adolescents with a family history of premature atherosclerosis (Group 1) and compared them with those of 31 age- and gender-matched adolescents whose parents did not have premature atherosclerosis (Group 2). Twenty-four-hour time domain (standard deviation of all normal sinus RR intervals [SDNN], standard deviation of the mean of normal RR intervals in each 5-minute segment [SDANN], root-mean-square differences in successive RR intervals) and frequency domain (very low frequency, low frequency, high frequency, low frequency/high frequency) parameters of heart rate variability were used for the evaluation of cardiac autonomic functions.RESULTS:There were no differences in the time and frequency domain parameters of heart rate variability between the two groups. Heart rate was negatively correlated with SDNN (r = -0.278, p = 0.035), while age was significantly correlated with root-mean-square differences in successive RR intervals, high frequency, low frequency and low frequency/high frequency (r = -0.264, -0.370, 0.265 and 0.374, respectively; p<0.05 for all).CONCLUSION:We found that the cardiac autonomic functions of adolescents with a family history of premature atherosclerosis were not different compared with those of adolescents without a positive family history of premature atherosclerosis. It appears that subclinical atherosclerosis does not reach a critical value such that it can alter cardiac autonomic functions in adolescence.     

The role of baseline and post‐procedural frontal plane QRS‐T angles for cardiac risk assessment in patients with acute STEMI

Background

To our knowledge, no study so far investigated the importance of post‐procedural frontal QRS‐T angle f(QRS‐T) in ST segment elevation myocardial infarction (STEMI). The aim of our study was to investigate the role of baseline and post‐procedural f(QRS‐T) angles for determining high risk STEMI patients, and the success of reperfusion.

Methods

A total of 248 patients with first acute STEMI that underwent primary percutaneous coronary intervention (pPCI) or thrombolytic therapy (TT) between 2013 and 2014 were included in this study. Baseline f(QRS‐T) angle was defined as the angle which measured from the first ECG at the time of hospital admission. Post‐procedural (QRS‐T) angle was defined according to the treatment strategy as follows: the angle which measured from the post‐PCI ECG in patients treated with pPCI; the angle which measured from the ECG taken 90 min after onset of therapy in patients treated with TT.

Results

The baseline (101.9° ± 48.0 vs. 72.1° ± 49.1, p = 0.014) and post‐procedural f(QRS‐T) angles (95.7° ± 48.1 vs. 58.1° ± 47.1, p = 0.002) were significantly higher in patients who developed in‐hospital mortality than the patients who did not develop in‐hospital mortality. Also, f(QRS‐T) angle measured at 90 min was significantly lower in patients with successful thrombolysis group compared to failed thrombolysis group (53.2° ± 42.8 vs. 77.3° ± 52.9, p = 0.033), whereas baseline f(QRS‐T) angle was similar between two groups (78.6° ± 53.4 vs. 78.9° ± 54.0, p = 0.976). Multivariate analysis showed that post‐procedural f(QRS‐T) angle ≥89.6° (odds ratio: 3.541, 95% confidence interval: 1.235–10.154, p = 0.019), but not baseline f(QRS‐T) angle, was independent predictor of in‐hospital mortality.

Conclusion

f(QRS‐T) angle may be used as a beneficial tool for determining high risk patients in acute STEMI. Unlike previous studies, we showed for the first time that that post‐procedural f(QRS‐T) can predict in‐hospital mortality and TT failure.