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Background Laboratory data and computed tomography (CT) have been used during the COVID-19 pandemic, mainly to determine patient prognosis and guide clinical management. The aim of this study was to evaluate the association between CT findings and laboratory data in a cohort of COVID-19 patients. Methods This was an observational cross-sectional study including consecutive patients presenting to the Reggio Emilia (Italy) province emergency rooms for suspected COVID-19 for one month during the outbreak peak, who underwent chest CT scan and laboratory testing at presentation and resulted positive for SARS-CoV-2. Results Included were 866 patients. Total leukocytes, neutrophils, C-reactive protein (CRP), creatinine, AST, ALT and LDH increase with worsening parenchymal involvement; an increase in platelets was appreciable with the highest burden of lung involvement. A decrease in lymphocyte counts paralleled worsening parenchymal extension, along with reduced arterial oxygen partial pressure and saturation. After correcting for parenchymal extension, ground-glass opacities were associated with reduced platelets and increased procalcitonin, consolidation with increased CRP and reduced oxygen saturation. Conclusions Pulmonary lesions induced by SARS-CoV-2 infection were associated with raised inflammatory response, impaired gas exchange and end-organ damage. These data suggest that lung lesions probably exert a central role in COVID-19 pathogenesis and clinical presentation.

Objective The aims of this study were to develop a multiparametric prognostic model for death in COVID-19 patients and to assess the incremental value of CT disease extension over clinical parameters. Methods Consecutive patients who presented to all five of the emergency rooms of the Reggio Emilia province between February 27 and March 23, 2020, for suspected COVID-19, underwent chest CT, and had a positive swab within 10 days were included in this retrospective study. Age, sex, comorbidities, days from symptom onset, and laboratory data were retrieved from institutional information systems. CT disease extension was visually graded as < 20%, 20–39%, 40–59%, or ≥ 60%. The association between clinical and CT variables with death was estimated with univariable and multivariable Cox proportional hazards models; model performance was assessed using k-fold cross-validation for the area under the ROC curve (cvAUC). Results Of the 866 included patients (median age 59.8, women 39.2%), 93 (10.74%) died. Clinical variables significantly associated with death in multivariable model were age, male sex, HDL cholesterol, dementia, heart failure, vascular diseases, time from symptom onset, neutrophils, LDH, and oxygen saturation level. CT disease extension was also independently associated with death (HR = 7.56, 95% CI = 3.49; 16.38 for ≥ 60% extension). cvAUCs were 0.927 (bootstrap bias-corrected 95% CI = 0.899–0.947) for the clinical model and 0.936 (bootstrap bias-corrected 95% CI = 0.912–0.953) when adding CT extension. Conclusions A prognostic model based on clinical variables is highly accurate in predicting death in COVID-19 patients. Adding CT disease extension to the model scarcely improves its accuracy. Key Points • Early identification of COVID-19 patients at higher risk of disease progression and death is crucial; the role of CT scan in defining prognosis is unclear. • A clinical model based on age, sex, comorbidities, days from symptom onset, and laboratory results was highly accurate in predicting death in COVID-19 patients presenting to the emergency room. • Disease extension assessed with CT was independently associated with death when added to the model but did not produce a valuable increase in accuracy. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-021-07993-9.

Objective To assess sensitivity/specificity of CT vs RT-PCR for the diagnosis of COVID-19 pneumonia in a prospective Italian cohort of symptomatic patients during the outbreak peak. Methods In this cross-sectional study, we included all consecutive patients who presented to the ER between March 13 and 23 for suspected COVID-19 and underwent CT and RT-PCR within 3 days. Using a structured report, radiologists prospectively classified CTs in highly suggestive, suggestive, and non-suggestive of COVID-19 pneumonia. Ground-glass, consolidation, and visual extension of parenchymal changes were collected. Three different RT-PCR-based reference standard definitions were used. Oxygen saturation level, CRP, LDH, and blood cell counts were collected and compared between CT/RT-PCR classes. Results The study included 696 patients (41.4% women; age 59 ± 15.8 years): 423/454 (93%) patients with highly suggestive CT, 97/127 (76%) with suggestive CT, and 31/115 (27%) with non-suggestive CT had positive RT-PCR. CT sensitivity ranged from 73 to 77% and from 90 to 94% for high and low positivity threshold, respectively. Specificity ranged from 79 to 84% for high positivity threshold and was about 58% for low positivity threshold. PPV remained ≥ 90% in all cases. Ground-glass was more frequent in patients with positive RT-PCR in all CT classes. Blood tests were significantly associated with RT-PCR and CT classes. Leukocytes, lymphocytes, neutrophils, and platelets decreased, CRP and LDH increased from non-suggestive to suggestive CT classes. Conclusions During the outbreak peak (in a high-prevalence setting), CT presented high PPV and may be considered a good reference to recognize COVID-19 patients while waiting for RT-PCR confirmation. Key Points • During the epidemic peak, CT showed high positive predictive value and sensitivity for COVID-19 pneumonia when compared with RT-PCR. • Blood tests were significantly associated with RT-PCR and CT classes. Electronic supplementary material The online version of this article (10.1007/s00330-020-07050-x) contains supplementary material, which is available to authorized users.

A b s t r ac t Background Current treatment recommendations for patients with polycythemia vera call for maintaining a hematocrit of less than 45%, but this therapeutic strategy has not been tested in a randomized clinical trial. Methods We randomly assigned 365 adults with JAK2-positive polycythemia vera who were being treated with phlebotomy, hydroxyurea, or both to receive either more intensive treatment (target hematocrit

Affinchè l'omeostasi corporea possa essere mantenuta, il numero di cellule che costituisce un organo od un tessuto deve essere complessivamente controllato mediante il mantenimento dell'equilibrio tra entrata in ciclo di nuove cellule ed eliminazione di cellule invecchiate o danneggiate. È ormai largamente accettato che alla normale omeostasi rissutale contribuiscono in egual misura due termini: la proliferazione e la morte cellulare per apoptosi. Wyllie ha proposto una elegante teoria per spiegare il contributo di entrambe le variabili nella regolazione dell'omeostasi tissutale. Le cellule staminali, nell'ambito di un dato compartimento, normalmente non sono molto numerose e si dividono relativamente poco. La loro progenie forma però un compartimento di "amplificazione" a livello del quale le dimensioni della popolazione cellulare si espandono rapidamente mediante divisioni cellulari ripetute (high turnover state). Solamente una parte della progenie viene tuttavia selezionata per sopravvivere ed andare incontro a differenziamento terminale. La selezione può essere operata da stimoli di "rescue" diversi fra di loro a seconda del tipo cellulare interessato (presenza di fattori di crescita specifici, affinità per l'antigene da parte delle immunoglobuline di membrana o del recettore dei linfociti T, formazione di sinapsi). Le cellule non selezionate vanno invece incontro ad apoptosi, essendo la loro proporzione variabile a seconda del tessuto o del momento. Solo le cellule in bigb turnover state, sono competenti per andare incontro ad apoptosi e diventano perciò suscettibili ad un ampio range di stimoli (anche non fisiologici). Le cellule selezionate al contrario diventano temporaneamente non competenti ma sono destinate a morire per apoptosi successivamente, al termine del processo di differenziamento terminale. In questa ottica quindi il processo apoptotico interviene nella regolazione dell'omeostasi tissutale a due livelli: limitando l'espansione della popolazione derivante direttamente dalle cellule staminali e rimuovendo le cellule al termine del loro lifespan. Da quanto enunciato risulta inoltre evidente che la suscettibilità all'apoptosi è strettamente correlata alla capacità di proliferare. Non è un caso quindi che sia stato proposto che la regolazione del processo apoptotico e quella del processo proliferativo siano fra di loro strettamente collegate. L'identificazione di meccanismi molecolari deputati alla regolazione reciproca dei due processi è di particolare importanza per la comprensione dei meccanismi che portano all'insorgenza ed all'espansione delle popolazioni tumorali. In queste ultime infatti la normale omeostasi tissutale è compromessa a causa non solo dell'aumentata capacità proliferativa ma anche di una diminuzione della mortalità. Inoltre, la disregolazione o la inibizione del processo apoptotico portando alla mancata eliminazione di cellule danneggiate che possono eventualmente espandersi (in seguito per esempio ad inappropriati stimoli di rescue) può essere cruciale nel corso della trasformazione neoplastica. Da diversi anni nel nostro laboratorio ci siamo dedicati allo studio del processo apoptotico utilizzando vari tipi di approcci metodologici e di modelli sperimentali. In particolare, ci siamo fecalizzati sulle seguenti linee di ricerca: i) caratterizzazione molecolare del processo apoptotico e suoi rapporti con il processo proliferativo; ii) ruolo del mitocondrio nel processo apoptotico; iii) importanza del processo apoptotico durante l'invecchiamento.

In recent decades, major theoretical and technological advances have been achieved in the field of immunology. These have allowed the scientific community to analyse the immune system in a much more sophisticated manner than was possible even 20 years ago. Moreover, great theoretical changes have also occurred in gerontology - in particular, the hypothesis has been put forward that ageing and diseases are two different phenomena, and that successful ageing, i.e. ageing in good psychophysical conditions, is really possible for most humans and animals. Immunosenescence was then carefully investigated, either in selected healthy people of advanced age or in the oldest old people, such as healthy centenarians. The main results showed that most immune parameters are indeed well preserved even at this far advanced age. This paper deals with some of the most important theoretical problems of immunosenescence. An immunological tenet was that the most important phenomenon of immunosenescence is the involution of the thymus. In most textbooks and papers it is taken for granted that the thymus starts its involution immediately after puberty. When people aged 60-65 were considered old, it was not difficult to think that they could live for the rest of their life with a fully involuted thymus. The findings on centenarians challenge this tenet, as they have only a small reduction of T lymphocytes, and a relatively normal number of virgin and memory T cells, together with a functional T cell repertoire. Other observations reported here on centenarians, concerning the activity of B lymphocytes and the cytokine network, as well as those on the well-preserved innate immunity and the cells' capability of undergoing proliferation after appropriate stimuli, suggest that complex immune changes occur with age, but also indicate that we have to modify our attitude, to grasp the new scenario which is emerging. Immunosenescence can no longer be considered as a unidirectional deterioration, and this complex phenomenon is much better described by terms such as 'remodelling', 'reshaping' or 'retuning'.