The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p < 0.001) and be vaccinated (37% vs. 12.7%, p < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p < 0.001) and immune suppressed (66.4% vs. 35.2%, p < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

Ruolo della chemioembolizzazione intra-arteriosa (TACE) con microsfere a rilascio di Irinotecano (DEBIRI) nel trattamento delle metastasi epatiche da melanoma dell\u2019uvea

Scopo: Il 50% circa dei pazienti con melanoma dell\u2019uvea (UV) svilupper\ue0 metastasi, in prevalenza epatiche. La prognosi dei melanomi uveali metastatici (mUM) \ue8 severa e, ad oggi, non vi \ue8 una terapia standard. Materiali e metodi: Sono stati analizzati in modo prospettico i dati di 141 pazienti con mUM sottoposti, come approccio iniziale, a TACE con DEBIRI (12,1%), terapia sistemica (39,7%), entrambe (33,3%) o nessuna delle due (14,9%) da Settembre 1990 a Settembre 2013. Risultati: Il tempo medio libero da malattia \ue8 stato di 23,1 mesi, la sopravvivenza media dei pazienti in IV stadio \ue8 stata di 18,1 mesi. La percentuale di coinvolgimento epatico (RR 1.3), la presenza di malattia multi organo (RR 2.0), l\u2019incremento dei livelli di LDH (RR 1.8) ed un performance status secondo i criteri WHO pari a 1 (RR 1.6) o 2-3 (RR 4,7) sono stati associati ad una prognosi peggiore. In presenza di lunghi intervalli liberi da malattia (RR 0.9), il ricorso a TACE con DEBIRI nel trattamento delle metastasi epatiche ha determinato un incremento della sopravvivenza (22,6 mesi) rispetto alle sole chemioterapie sistemiche (14.4 mesi). In particolare la combinazione di DEBIRI TACE con fotemustina per via sistemica ha determinato il maggiore incremento della sopravvivenza (RR 0,5). Conclusioni: La prognosi dei melanomi uveali metastatici \ue8 influenzata da: percentuale di coinvolgimento epatico, presenza di malattia multiorgano, livelli di LDH, performance status, intervallo libero da malattia e dalla terapia loco regionale con DEBIRI

Transarterial Chemoembolization with Small Drug-Eluting Beads in Patients with Hepatocellular Carcinoma: Experience from a Cohort of 421 Patients at an Italian Center

To assess the safety, tolerability, and efficacy of small drug-eluting embolic (DEE) agents (70-150 \u3bcm) for chemoembolization of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This single-center, single-arm, retrospective study involved 421 patients (mean age, 66.1 y \ub1 9.8 [standard deviation]) with Barcelona Clinic Liver Cancer (BCLC) stage A (n = 88), B (n = 140), or C (n = 193) HCC and Child-Pugh class A (n = 233) or B (n = 188) cirrhosis. Patients had a mean of 7.2 lesions \ub1 4.8 (range, 1-21; mean diameter of target lesion, 21.4 cm \ub1 8.1; unilobar, n = 132; bilobar, n = 289; portal vein involvement, n = 193). One (n = 320) or 2 (n = 101) vials of small DEEs loaded with doxorubicin 50 mg per vial were delivered selectively (ie, segmentally) or superselectively (ie, directly into the tumor-feeding vessel) until complete delivery or stasis/near-stasis. Treatment was repeated in patients with partial response or stable disease at 1- or 3-month follow-up (mean, 2.0 cycles \ub1 0.9). Adverse events within 30 days of chemoembolization, response per modified Response Evaluation Criteria In Solid Tumors (mRECIST), and survival were assessed. RESULTS: Within 30 days after treatment, no deaths or bleeding events occurred, but all patients had at least 1 episode of postembolization syndrome (pain, fever, and/or nausea/vomiting; 27.1% grade 3/4 per National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0) and increased bilirubin and liver aminotransferase levels (0.2% and 5.9% grade 3/4, respectively). Overall response rates were 94.5% at 3 months and 99.5% at 6 months. Median overall survival was 42.0 months (95% confidence interval, 38.0-43.0 mo). CONCLUSIONS: Chemoembolization with small DEE agents is well tolerated and an effective treatment for a broad range of patients with liver-confined HCC

Sarcopenia and Cognitive Decline in Older Adults: Targeting the Muscle–Brain Axis

Declines in physical performance and cognition are commonly observed in older adults. The geroscience paradigm posits that a set of processes and pathways shared among age-associated conditions may also serve as a molecular explanation for the complex pathophysiology of physical frailty, sarcopenia, and cognitive decline. Mitochondrial dysfunction, inflammation, metabolic alterations, declines in cellular stemness, and altered intracellular signaling have been observed in muscle aging. Neurological factors have also been included among the determinants of sarcopenia. Neuromuscular junctions (NMJs) are synapses bridging nervous and skeletal muscle systems with a relevant role in age-related musculoskeletal derangement. Patterns of circulating metabolic and neurotrophic factors have been associated with physical frailty and sarcopenia. These factors are mostly related to disarrangements in protein-to-energy conversion as well as reduced calorie and protein intake to sustain muscle mass. A link between sarcopenia and cognitive decline in older adults has also been described with a possible role for muscle-derived mediators (i.e., myokines) in mediating muscle–brain crosstalk. Herein, we discuss the main molecular mechanisms and factors involved in the muscle–brain axis and their possible implication in cognitive decline in older adults. An overview of current behavioral strategies that allegedly act on the muscle–brain axis is also provided

Bone metastases from neuroendocrine tumors: clinical and biological considerations

We considered 351 patients affected by neuroendocrine tumors, followed at the University Hospital of Padua and at the Veneto Oncological Institute. Of these, 72 (20.5%) suffered from bone metastases. The sample was divided according to the timing of presentation of bone metastases into synchronous (within 6 months of diagnosis of primary tumor) and metachronous (after 6 months). We collected data on the type and grading of the primary tumor, and on the features of bone metastases. Our analysis shows that the group of synchronous metastases generally presents primary tumors with a higher degree of malignancy rather than the ones of the metachronous group. This is supported by the finding of a Ki-67 level in GEP-NETs, at the diagnosis of bone metastases, significantly higher in the synchronous group. Moreover, in low-grade NETs, Chromogranin A values are higher in the patients with synchronous metastases, indicating a more burden of disease. The parameters of phospho-calcium metabolism are within the normal range, and we do not find significant differences between the groups. Serious bone complications are not frequent and are not correlated with the site of origin of the primary tumor. From the analysis of the survival curves of the total sample, a cumulative survival rate of 33% at 10 years emerges. The average survival is 80 months, higher than what reported in the literature, while the median is 84 months. In our observation period, synchronous patients tend to have a worse prognosis than metachronous ones with 52-months survival rates of 58% and 86%

Specific antibodies reacting with simian virus 40 capsid protein mimotopes in serum samples from healthy blood donors

Simian virus 40 (SV40), a small DNA tumor virus, was inadvertently administered to human populations with the use of contaminated vaccines. SV40 sequences have mainly been detected in healthy individuals and cancer patients using polymerase chain reaction techniques. However, some studies have failed to reveal the presence of SV40 in human specimens. These conflicting results indicate the need for new research to verify whether SV40 is circulating in humans. Mimotopes from SV40 structural peptides were tested to investigate for specific reactions to human sera antibodies. An indirect enzyme-linked immunosorbent assay with synthetic peptides from SV40 viral capsid proteins 1-2-3 (VPs 1-2-3) was set up and employed to test 855 serum samples from healthy blood donors. Data from immunologic assays indicate that serum antibodies against SV40 VP mimotopes are detectable, although with a low titer, in blood donors 18 to 65 years old. The overall prevalence of serum samples that reacted with the 2 SV40 VP peptides was 18%. The strong points for this novel method include the simplicity of its approach and the potential to discriminate between SV40-specific antibody responses and to draw correlations between responses to the 2 independent SV40 peptides. These data suggest that SV40, or a yet undetected closely related polyomavirus, is circulating in human populations, but with lower prevalence than that of the ubiquitous BK and JC human polyomaviruses