Compassionate use of anti-IL6 receptor antibodies in critically ill patients with acute respiratory distress syndrome due to SARS-CoV-2.

BACKGROUND: COVID-19 patients developing the acute respiratory distress syndrome (ARDS) show increased production of pro-inflammatory cytokines, including interleukin-6 (IL-6). The use of humanized monoclonal antibody against interleukin-6 receptor (IL-6R) may represent a potential treatment strategy. We analyzed the effects of compassionate use of tocilizumab and sarilumab on clinical outcome of patients affected by ARDS due COVID-19. METHODS: This single-center, observational, exploratory study was performed during the acute phase of COVID-19 outbreak, between March 7th and April 21st, 2020 in a University Hospital in Rome, Italy. All consecutive adult patients admitted to the intensive care unit with laboratory-confirmed COVID-19 and fulfilling ARDS criteria were enrolled. Patients who were treated with anti-IL-6R therapy were compared to those who were not, as per clinical decision. Inverse probability weights were applied to weight individual's contribution to survival curves and in the multivariate regression model. RESULTS: Among 105 ARDS patients, 65 received compassionate treatment with anti-IL-6R therapy (43 [66%] Tocilizumab [Hoffmann-La Roche, Basel, Switzerland] and 22 [34%] Sarilumab, respectively], with oxygenation improvement. In the multivariable Cox proportional regression hazards model with propensity score inverse probability weighting, patients who received anti-IL-6R treatment had lower risk of death compared to those who did not, with a hazard ration of 0.34 [95% confidence interval 0.17-0.74], P=0.001. CONCLUSIONS: Our data suggested that immune modulator therapy based on anti-human IL-6 receptor monoclonal antibodies might lead to improved outcome in patients with ARDS due to COVID-19. These data support the need for confirmatory randomized trials to assess the effect of immune modulator therapies on mortality.

Hemoglobin levels and circulating blasts are two easily evaluable diagnostic parameters highly predictive of leukemic transformation in primary myelofibrosis.

To predict leukemic transformation (LT), we evaluated easily detectable diagnostic parameters in 338 patients with primary myelofibrosis (PMF) followed in the Latium region (Italy) between 1981 and 2010. Forty patients (11.8%) progressed to leukemia, with a resulting 10-year leukemia-free survival (LFS) rates of 72%. Hb (<10g/dL), and circulating blasts (≥1%) were the only two independent prognostic for LT at the multivariate analysis. Two hundred-fifty patients with both the two parameters available were grouped as follows: low risk (none or one factor)=216 patients; high risk (both factors)=31 patients. The median LFS times were 269 and 45 months for the low and high-risk groups, respectively (P<.0001). The LT predictive power of these two parameters was confirmed in an external series of 270 PMF patients from Tuscany, in whom the median LFS was not reached and 61 months for the low and high risk groups, respectively (P<.0001). These results establish anemia and circulating blasts, two easily and universally available parameters, as strong predictors of LT in PMF and may help to improve prognostic stratification of these patients particularly in countries with low resources where more sophisticated molecular testing is unavailable.

Association of epicardial fat thickness with the severity of obstructive sleep apnea in obese patients.

BACKGROUND: The correlation between obesity and severity of obstructive sleep apnea (OSA) is controversial. Although fat excess is a predisposing factor for the development of OSA, it has not been determined whether fat distribution rather than obesity per se is associated with OSA severity. Epicardial fat thickness (EFT) is an independent index of visceral adiposity and cardiometabolic risk. We investigated the relation between fat distribution and cardiometabolic risk factors, including EFT and common carotid intima-media thickness (cIMT), with the severity of OSA in obese patients. METHODS: One hundred and fifteen obese patients (56 males, 59 females) with polysomnographic evidence of OSA (≥ 5 apnea/hypopnea events per hour) of various degrees, without significant differences in grade of obesity as defined by body mass index (BMI), were evaluated. The following parameters were measured: BMI, body composition by dual energy X-ray absorptiometry, EFT, right ventricular end-diastolic diameter (RVEDD) and cIMT by ultrasound, and parameters of metabolic syndrome (waist circumference, arterial blood pressure, fasting glucose, HDL-cholesterol and triglycerides). RESULTS: EFT, RVEDD, cIMT and trunk/leg fat mass ratio showed a positive correlation with OSA severity in univariate analysis (r=0.536, p<0.001; r=0.480, p<0.001; r=0.345, p<0.001; r=0.330, p<0.001, respectively). However, multiple linear regression analysis showed that EFT was the most significant independent correlate of the severity of OSA (R(2)=0.376, p=0.022). CONCLUSIONS: The present study suggests that, in obese patients, EFT may be included among the clinical parameters associating with OSA severity. The association of EFT with OSA, both cardiovascular risk factors, is independent of obesity as defined by classical measures.

Supracricoid partial laryngectomy in the treatment of laryngeal cancer: univariate and multivariate analysis of prognostic factors.

OBJECTIVES: To evaluate the oncological results of supracricoid partial laryngectomy as a treatment for selected glottic and supraglottic cancer in a large series of patients who had undergone uniform treatment over a 16-year period and to determine the different prognostic factors that may influence local control and survival. DESIGN: Retrospective clinical study. SETTING: Academic tertiary referral medical center. PATIENTS: The study population comprised 253 consecutive patients (234 men and 19 women) with glottic and supraglottic squamous cell carcinoma. The mean age was 58 years for men and 59.2 years for women. INTERVENTION: Supracricoid partial laryngectomy: 180 patients had undergone cricohyoidopexy and 73 had undergone cricohyoidoepiglottopexy. MAIN OUTCOME MEASURES: Local control and overall survival. Potential prognostic factors for local control and survival were evaluated with univariate and multivariate models. RESULTS: The 3-, 5-, 10-, and 16-year overall survival rates in this group of 253 patients were 85.8%, 79.1%, 57.6%, and 57.6%, respectively. With regard to local control, univariate and multivariate analyses showed that a positive resection margin was the only important predictor of local control and that a dysplastic lesion at the margin of resection is just as aggressive as the presence of invasive carcinoma. When considering the prognostic factors influencing survival, univariate analysis showed that the tumor category, lymph node category, tumor stage, and recurrence all had a significant influence on the survival rate. Multivariate analysis showed that the most important predictor of survival was recurrence. CONCLUSIONS: Supracricoid partial laryngectomy is a valid choice in the treatment of selected glottic and supraglottic cancer while maintaining laryngeal functions and achieving a high rate of local control. T category, N category, tumor stage, positive resection margins, and recurrence are the most important predictors of oncological outcome.

The influence of lifestyle on cardiovascular risk factors. Analysis using a neural network.

The cardiovascular pathologies are the most common causes of death in the elderly patient. To single out the main risk factors in order to effectively prevent the onset of the disease, the authors experimented a special computerized tool, the neural network, that works out a mathematical relation that can obtain certain data (defined as output) as a function of other data (defined as input). Data were processed from a sample of 276 subjects of both sexes aged 26-69 years old. The output data were: high/low cholesterolemia, HDL cholesterol, triglyceridemia with respect to an established cut-off; the input data were: sex, age, build, weight, married/single, number of children, number of cigarettes smoked/day, amount of wine and number of cups of coffee. We conclude that: (i) a relationship exists, deduced from a neural network, between a set of input variables and a dichotomous output variable; (ii) this relationship can be expressed as a mathematical function; (iii) a neural network, having learned the data on a sufficiently large population, can provide valid predictive data for a single individual with a high probability (up to 93.33%) that the response it gives is correct. In this study, such a result is found for two of the three cardiovascular risk indicators considered (cholesterol and triglycerides); (iv) the repetition of the neural network analysis of the cases in question after a "pruning" operation provided a somewhat less good performance; (v) a statistical analysis conducted on those same cases has confirmed the existence of a strong relationship between the input and the output variables. Therefore the neural network is a valid instrument for providing predictive in a single subject on cardiovascular pathology risks.

Prognostic value of resection margins in supracricoid laryngectomy.

OBJECTIVES: The objective was to assess the prognostic value of surgical margin involvement in patients treated for squamous cell carcinoma of the larynx. STUDY DESIGN: Retrospective study. METHODS: A review was made of 253 patients treated with supracricoid laryngectomy between 1984 and 2001. A histopathological study on the surgical resection margins was performed in all cases. The incidence of local recurrence was correlated with the histological features of resection margins. RESULTS: Forty patients (15.8%) were identified as having positive margins: 29 had invasive carcinoma and 11 had dysplastic lesions. The remaining 213 patients (84.2%) had negative margins. Subsequent follow-up showed that 19 of 253 patients developed local recurrence and 3 patients developed regional recurrence. Nine of these patients had positive resection margins (six with invasive carcinoma and three with dysplastic lesions), and 10 had negative resection margins. Overall survival at 3 years was significantly higher for patients without recurrence than for patients with local or regional failure (89.9% vs. 45.5% [P <.05]). CONCLUSION: According to results of the study, patients with positive resection margins developed local recurrence more frequently than those with clear resection margins (P <.05).

Decreased habituation of the R2 component of the blink reflex in migraine patients.

OBJECTIVE: Activation of the trigemino-vascular system as well as of brainstem trigeminal nuclei are thought to play an important role in migraine. The aim of this study was to investigate the habituation phenomenon of the blink reflex in 30 headache-free migraine patients and 30 control subjects. METHODS: An electromyographic device with a specific habituation test program was used to elicit and record blink reflex responses on both the right and left sides, and to randomly repeat the stimulations at different time intervals in order to induce habituation. RESULTS: Whereas the R1 and R2 latencies, amplitudes and areas in the basal assessment were similar in patients and control subjects, the blink reflex habituation responses were markedly reduced in migraine patients who had a migraine attack within 72 h after testing (group A). In these patients, the differences between the R2 areas, obtained when stimuli were delivered at subsequent time intervals ranging between 10-5, 5-4, 4-3 and 3-2 s, were statistically different (P<0.001) from those of the patients who had a migraine attack after a longer time interval (group B) and control subjects. CONCLUSIONS: Our data suggest that the brainstem pathways involved in the blink reflex may be activated in the premonitory phase of migraine attacks, probably through mechanisms that involve dopaminergic function.