Interstitial pneumonia is a severe complication induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several treatments have been proposed alone or, more often, in ...combination, depending, also, on the presence of other organ disfunction. The most frequently related, well-described, and associated phenomenon is pan-lymphopenia with circulating, high levels of cytokines. We report, here, on two patients with COVID-19 and lymphoproliferative disorders treated with Tocilizumab (a humanized monoclonal antibody against the interleukin-6 receptor) and followed by an
FFDG PET/CT to early evaluate the therapy's efficacy.
One patient with angioimmunoblastic T-lymphoma (A), one with Hodgkin lymphoma (A), and both with positive RT-PCR for SARS-CoV-2 and with similar clinical findings of interstitial pneumonia at the CT scan, were imaged by
FFDG PET/CT before and 14 days after a single dose of Tocilizumab.
In both patients, the basal
FFDG PET/CT showed a diffused lung parenchyma uptake, corresponding to the hyperdense areas at the CT scan. After 2 weeks of a Tocilizumab infusion, patient B had an improvement of symptoms, with normalization of the
FFDG uptake. By contrast, patient A, who was still symptomatic, showed a persisting and abnormal distribution of
FFDG. Interestingly, both patients showed a low bone marrow uptake of
FFDG at the diagnosis and after 15 days, while the spleen uptake was low only in lymphopenic patient A; both are indirect signs of an immune deficiency.
In conclusion, in these two patients, interstitial pneumonia was efficiently treated with Tocilizumab, as demonstrated by the
FFDG PET/CT. Our results confirm that interleukin-6 (IL6) has a role in the COVID-19 disease and that anti-cytokine treatment can also be performed in patients with lymphoproliferative disorders.
The crosstalk between human gut microbiota and intestinal wall is essential for the organ's homeostasis and immune tolerance. The gut microbiota plays a role in healthy and pathological conditions ...mediated by inflammatory processes or by the gut-brain axes, both involving a possible role for S100B protein as a diffusible cytokine present not only in intestinal mucosa but also in faeces. In order to identify target proteins for a putative interaction between S100B and the microbiota proteome, we developed a bioinformatics workflow by integrating the interaction features of known domains with the proteomics data derived from metataxonomic studies of the gut microbiota from healthy and inflammatory bowel disease (IBD) subjects. On the basis of the microbiota composition, proteins putatively interacting with S100B domains were in fact found, both in healthy subjects and IBD patients, in a reduced number in the latter samples, also exhibiting differences in interacting domains occurrence between the two groups. In addition, differences between ulcerative colitis and Crohn disease samples were observed. These results offer the conceptual framework for where to investigate the role of S100B as a candidate signalling molecule in the microbiota/gut communication machinery, on the basis of interactions differently conditioned by healthy or pathological microbiota.
Highlights ► Resting-state EEG rhythms show peculiar frequency/spatial features in naïve human subjects with human immunodeficiency virus (HIV). ► Topography and frequency of the cortical sources ...estimated by low-resolution electromagnetic tomography (LORETA) can distinguish groups of HIV and control subjects. ► The LORETA approach provides clinically useful information for an early detection of the effect of HIV infection on brain and cognitive functions.
Many unsolved practical issues, from technical and scientific to ethical, legal and economic topics, are slowing down the translation of Personalized Medicine principles into medical practice. The ...Italian Society of Personalized Medicine exposes here its point of view, based on the real-world practice of precision medicine carried-out in Italian healthcare structures.
Background & Aims: Inadequate data are available about retreatment of nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the efficacy and tolerability of a 48-week therapy ...with pegylated IFN-α-2b plus high-dose ribavirin in patients who have failed to respond to the combination. Treatment up to 48 weeks also in patients who have failed to clear hepatitis C virus (HCV) RNA by week 24 was also evaluated. Methods: One hundred forty-one patients who previously did not respond to IFN and ribavirin, 86% with genotype 1 or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis, were retreated with pegylated IFN-α-2b 1.5 μg/kg per week and ribavirin 1000–1200 mg/day for 48 weeks and followed up for 24 weeks. Results: By intent-to-treat analysis, 20% of patients achieved a sustained virologic response (SVR). SVR of genotype 1 patients was 19%. Independent predictors of SVR were low γ-glutamyltransferase levels (OR, 22.9; 95% CI: 6.6–79.6) and low viral load (OR, 3.8; 95% CI: 1.1–12.6). Twelve (23%) out of 51 patients who were HCV RNA positive after 24 weeks of therapy achieved a late virologic response (after week 24) and 5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not associated with response (P = .2) or with early response (P = .3). Conclusions: Retreatment with pegylated IFN-α-2b and ribavirin of multiexperienced and “difficult to treat” nonresponder patients produced a very promising SVR. Accurate selection of patients, such as those with low viral load and low γ-glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in HCV RNA-positive patients may further increase the rate of SVR.
Here we tested the effect of combined antiretroviral therapy (cART) on deviant electroencephalographic (EEG) source activity in treatment-naïve HIV individuals.
Resting state eyes-closed EEG data ...were recorded before and after 5 months of cART in 48 male HIV subjects, who were naïve at the study start. The EEG data were also recorded in 59 age- and sex-matched healthy subjects as a control group. Frequency bands of interest included delta, theta, alpha1, alpha2 and alpha3, based on alpha frequency peak specific to each individual. They also included beta1 (13-20 Hz) and beta2 (20-30 Hz). Low-resolution brain electromagnetic tomography (LORETA) estimated EEG cortical source activity in frontal, central, temporal, parietal, and occipital regions.
Before the therapy, the HIV group showed greater parietal delta source activity and lower spatially diffuse alpha source activity compared to the control group. Thus, the ratio of parietal delta and alpha3 source activity served as an EEG marker. The z-score showed a statistically deviant EEG marker (EEG +) in 50% of the HIV individuals before therapy (p < 0.05). After 5 months of cART, delta source activity decreased, and alpha3 source activity increased in the HIV subjects with EEG + (about 50% of them showed a normalized EEG marker).
This procedure detected a deviant EEG marker before therapy and its post-therapy normalization in naïve HIV single individuals.
The parietal delta/alpha3 EEG marker may be used to monitor cART effects on brain function in such individuals.
Background
To investigate the cause of lymphopenia in patients with newly diagnosed COVID-19, we measured
18
FFDG uptake in several tissues, including the ileum, right colon, and caecum at diagnosis ...and after recovery and correlated these measurements with haematological parameters.
Methods
We studied, by
18
FFDG PET/CT, 18 newly diagnosed patients with COVID-19. Regions of interest were drawn over major organs and in the terminal ileum, caecum, and right colon, where the bowel wall was evaluable. Five patients were re-examined after recovery, and three of them also performed a white blood cell scan with
99m
Tc-HMPAO-WBC on both occasions. Complete blood count was performed on both occasions, and peripheral blood lymphocyte subsets were measured at diagnosis. Data were analysed by a statistician.
Results
Patients had moderate severity COVID-19 syndrome. Basal
18
FFDG PET/CT showed focal lung uptake corresponding to hyperdense areas at CT. We also found high spleen, ileal, caecal, and colonic activity as compared to 18 control subjects. At recovery, hypermetabolic tissues tended to normalize, but activity in the caecum remained higher than in controls. Regression analyses showed an inverse correlation between CD4 + lymphocytes and
18
FFDG uptake in the caecum and colon and a direct correlation between CD8 + lymphocytes and
18
FFDG uptake in lungs and bone marrow. WBC scans showed the presence of leukocytes in the caecum and colon that disappeared at recovery.
Conclusions
These findings indicate that lymphopenia in COVID-19 patients is associated with large bowel inflammation supporting the hypothesis that CD4 + lymphocytes migrate to peripheral lymphoid tissues in the bowel.
Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive ...inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention.
•The Kynurenine:Tryptophan ratio is an activation biomarker of the kynurenine pathway.•The kynurenine pathway has a key role in the regulation of the immune system.•The Kyn:Trp ratio is significantly increased in SARS-CoV2-postive patients.•The increase is more prominent in males than in females' SARS-CoV2-positive patients.•Increased Kyn:Trp ratio is associated with lymphopenia and COVID-19 severity.
The Coronavirus Disease (Covid-19) pandemic is rapidly spreading across the world, representing an unparalleled challenge for health care systems. There are differences in the estimated fatality ...rates, which cannot be explained easily. In Italy, the estimated case fatality rate was 12.7% in mid-April, while Germany remained at 1.8%. Moreover, it is to be noted that different areas of Italy have very different lethality rates. Due to the complexity of Covid-19 patient management, it is of paramount importance to develop a well-defined clinical workflow in order to avoid the inconsistent management of patients. The Integrated Care Pathway (ICP) represents a multidisciplinary outline of anticipated care to support patient management in the Sant'Andrea Hospital, Rome. The main objective of this pilot study was to develop a new ICP evaluated by care indicators, in order to improve the COVID-19 patient management. The suggested ICP was developed by a multi-professional team composed of different specialists and administrators already involved in clinical and management processes. After a review of current internal practices and published evidences, we identified (1) the activities performed during care delivery, (2) the responsibilities for these activities, (3) hospital structural adaptation needs and potential improvements, and (4) ICP indicators. The process map formed the basis of the final ICP document; 160 COVID-19 inpatients were considered, and the effect of the ICP implementation was evaluated over time during the exponential phase of the COVID-19 pandemic. In conclusion, a rapid adoption of ICP and regular audits of quality indicators for the management of COVID-19 patients might be important tools to improve the quality of care and outcomes.
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