The optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still undefined. In the absence of randomised studies, we retrospectively analysed:

NCPB was associated with a reduction in analgesic drug administration and drug-related adverse effects, representing an effective tool in the treatment of pancreatic cancer pain.

Since the beginning of the SARS-CoV-2 pandemic, COVID-19 appeared as a unique disease with unconventional tissue and systemic immune features. Here we show a COVID-19 immune signature associated with severity by integrating single-cell RNA-seq analysis from blood samples and broncho-alveolar lavage fluids with clinical, immunological and functional ex vivo data. This signature is characterized by lung accumulation of naïve lymphoid cells associated with a systemic expansion and activation of myeloid cells. Myeloid-driven immune suppression is a hallmark of COVID-19 evolution, highlighting arginase-1 expression with immune regulatory features of monocytes. Monocyte-dependent and neutrophil-dependent immune suppression loss is associated with fatal clinical outcome in severe patients. Additionally, our analysis shows a lung CXCR6+ effector memory T cell subset is associated with better prognosis in patients with severe COVID-19. In summary, COVID-19-induced myeloid dysregulation and lymphoid impairment establish a condition of ‘immune silence’ in patients with critical COVID-19.

Spontaneous oscillations of heart period and arterial pressure can be analysed by mathematical tools to extract the main frequency-related information. This is generally contained within three principal bands: a high-frequency (HF) band, related to the respiratory rate, a low-frequency (LF) band, centred around 0.1 Hz and a very-low-frequency (VLF) band, spanning the leftmost part of the spectrum.Pressure oscillations at the respiratory frequency are linked to rhythmic changes of intrathoracic pressure due to respiratory mechanics, while low-frequency fluctuations, often identified as Mayer's waves, are the result of efferent sympathetic activity (Polosa, 1984;Cevese et al. 1995). The interpretation of heart period fluctuations is more problematic, because it has to account for the interplay of sympathetic and vagal Baroreflex and oscillation of heart period at 0.1 Hz studied by a-blockade and cross-spectral analysis in healthy humansAntonio Cevese, Giosuè Gulli, Enrico Polati *, Leonardo Gottin * and Renato Grasso † 1. Parameters derived from frequency-domain analysis of heart period and blood pressure variability are gaining increasing importance in clinical practice. However, the underlying physiological mechanisms in human subjects are not fully understood. Here we address the question as to whether the low frequency variability (›0.1 Hz) of the heart period may depend on a baroreflex-mediated response to blood pressure oscillations, induced by the a-sympathetic drive on the peripheral resistance.2. Heart period (ECG), finger arterial pressure (Finapres) and respiratory airflow were recorded in eight healthy volunteers in the supine position with metronome respiration at 0.25 Hz. We inhibited the vascular response to the sympathetic vasomotor activity with a peripheral a-blocker (urapidil) and maintained mean blood pressure at control levels with angiotensin II.3. We performed spectral and cross-spectral analysis of heart period (RR) and systolic pressure to quantify the power of low-and high-frequency oscillations, phase shift, coherence and transfer function gain.4. In control conditions, spectral analysis yielded typical results. In the low-frequency range, cross-spectral analysis showed high coherence (> 0.5) and a negative phase shift (_65.1 ± 18 deg) between RR and systolic pressure, which indicates a 1-2 s lag in heart period changes in relation to pressure. In the high-frequency region, the phase shift was close to zero, indicating simultaneous fluctuations of RR and systolic pressure. During urapidil + angiotensin II infusion the low-frequency oscillations of both blood pressure and heart period were abolished in five cases. In the remaining three cases they were substantially reduced and lost their typical cross-spectral characteristics.5. We conclude that in supine rest conditions, the oscillation of RR at low frequency is almost entirely accounted for by a baroreflex mechanism, since it is not produced in the absence of a 0.1 Hz pressure oscillation.6. The results provide physiological support fo...

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Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

Background-Aortic

Although overall values did not change after TAVI, iFR presented significant and mostly erratic individual variations after valve replacement. Delta iFR was influenced by the extent of the transaortic gradient drop induced by TAVI. Therefore, caution is advisable in the interpretation of iFR in the presence of AS.