A Real-World Nationwide Study on COVID-19 Trend in Italy during the Autumn-Winter Season of 2020 (before Mass Vaccination) and 2021 (after Mass Vaccination) Integrated with a Retrospective Analysis of the Mortality Burden per Year.

SARS-CoV-2 virulence is known to increase with lowering of environmental temperature and solar ultraviolet radiation; therefore, we have focused our real-world nationwide study concerning with COVID-19 trend and dynamics on the coldest seasons of the year in Italy, the Western country hardest hit at the onset of the pandemic, comparing the autumn-winter of 2020 (before mass vaccination but when the emergency machinery was fully operative in terms of tracing and swabs) with the autumn-winter of 2021 (after mass vaccination), and analyzing the mortality burden by age groups and life stages in the years 2019 (pre-COVID-19), 2020 (before mass vaccination), and 2021 (after mass vaccination). METHODS: During the state of national health emergency, the Civil Defense Department released the aggregate data coming from the Higher Institute of Health, the Ministry of Health, the Italian Regions, and the Independent Provinces, to inform the population about the pandemic situation, daily. Among these data, there were the number of contagions, performed swabs, hospitalizations in Intensive Care Units (ICU), non-ICU patients, and deaths. By means of a team effort, we have collected and elaborated all these data, comparing the COVID-19 pandemic in Italy during the autumn-winter of 2020 with the autumn-winter of 2021. Moreover, we have extracted from the database of the National Institute of Statistics the total number of annual deaths in Italy during the years 2019, 2020, and 2021, comparing them to each other in order to evaluate the mortality burden attributable to COVID-19. RESULTS: From the autumn-winter of 2020 to the autumn-winter of 2021, the contagions increased by ≈285%, against a ≈290% increase in the performed swabs; therefore, the mean positivity rate passed from 8.74% before mass vaccination to 8.59% after mass vaccination. The unprecedent vaccination campaign allowed a ≈251% abatement in COVID-19 deaths, and a reduction of ≈224% and ≈228% in daily ICU and non-ICU hospitalizations due to COVID-19, respectively. Regarding COVID-19 deaths, in 2020, there was a mortality excess of ≈14.3% quantifiable in 105,900 more deaths compared to 2019, the pre-COVID-19 year; 103,183 out of 105,900 deaths occurred in older adults (≥60 years), which is equivalent to ≈97.4%, while in adults over 50, the segment of population just below older adults, in 2020, there were 2807 more deaths than in 2019. Surprisingly, from the analysis of our data, it is emerged that in people under the age of 40 in the years 2019, 2020, and 2021, there were 7103, 6808, and 7165 deaths, respectively. This means that in subjects under 40 during 2020, there were 295 fewer deaths than in 2019, while during 2021, there were 357 more deaths than in 2020, equivalent to ≈5.2% more. CONCLUSIONS: COVID-19 is a potential life-threatening disease mainly in older adults, as they are the most vulnerable due to inherent immunosenescence and inflammaging. Extensive vaccination in this segment of population with up-to-date vaccines is the means to reduce deaths, hospitalizations, and ICU pressure in the public interest. In the event of future threats, a new mass vaccination campaign should not be implemented without taking into account the individual age; it should primarily be aimed at people over 60 and at patients of any age with immune deficits, and secondly at people over 50. COVID-19 vaccination shows a favorable benefit-risk ratio in older adults, while the balance steps down under the age of 40; this younger segment of the population should be therefore exempt from any mandatory vaccination.

Trends in the COVID-19 Pandemic in Italy during the Summers of 2020 (before Mass Vaccination), 2021 (after Primary Mass Vaccination) and 2022 (after Booster Mass Vaccination): A Real-World Nationwide Study Based on a Population of 58.85 Million People.

Like all RNA viruses, SARS-CoV-2 shows a high mutation rate, which has led to the emergence of new variants. Among them, Gamma and Delta developed at the turn of 2020-2021 in Amazonas and India, two ecoregions characterized by hot-humid weather, very similar to that of the summer season in Italy due to climate change, the first Western country to be hit hard by COVID-19 and to experience lockdown restrictions in a democratic framework of 58.85 million people. The aim of our research has been to evaluate the impact of climate on the COVID-19 pandemic in Italy during the summers of 2020 (before mass vaccination), 2021 (after primary mass vaccination) and 2022 (after booster mass vaccination), also taking into account the emergence of these two variants. METHODS: During the state of national health emergency and the Draghi government, the Civil Defense Department released the aggregate data coming from the Ministry of Health, the Higher Institute of Health, the Independent Provinces and the Italian Regions daily, in order to inform about the pandemic situation in Italy. Among these data there were the number of deaths, hospitalizations in intensive care units (ICU), non-ICU patients, contagions and performed swabs. By means of a team effort, we have collected and elaborated all these data, comparing the COVID-19 pandemic in Italy during the summers of 2020 (following the nationwide lockdown), 2021 and 2022. RESULTS: from the summer of 2020 to the summers of 2021 and 2022 all pandemic trend indicators have shown a sharp worsening in Italy. COVID-19 deaths increased by ≈298% and ≈834%, ICU hospitalizations by ≈386% and ≈310%, non-ICU hospitalizations by ≈224% and ≈600%, contagions by ≈627% and ≈6850% (i.e., ≈68.50 times), swabs by ≈354% and ≈370%, and the mean positivity rate passed from ≈1% to ≈2% and ≈20%, respectively. CONCLUSIONS: SARS-CoV-2 can be transmitted in any climate, including areas with hot and humid weather, and the emergence of variants adapted to hot-humid climates may result in summer COVID-19 outbreaks, even in neither tropical nor subtropical countries. Although COVID-19 vaccines can confer cross-protection against newly emerging variants, this cross-immunity is naturally not absolute but limited, considering that vaccine protection wanes significantly after 6 months. It follows that a subject vaccinated at the beginning of the winter will not be completely covered in the height of the summer, and we should not forget the unvaccinated. As a final remark, the long and strict nationwide lockdown made it possible to flatten SARS-CoV-2 circulation and, therefore, its negative impact on Italy during the summer of 2020.

SARS-CoV-2 Induced Herpes Virus Reactivations and Related Implications in Oncohematology: When Lymphocytopenia Sets in and Immunosurveillance Drops Out.

The severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), is a positive-sense single-stranded ribonucleic acid (RNA) virus contagious in humans and responsible for the ongoing coronavirus disease 2019 (COVID-19) [...].

PEG-Asparaginase Single-Agent Rescue in an Advanced Case of Monomorphic Epitheliotropic Intestinal T Cell Lymphoma.

PURPOSE: MEITL is a very rare and highly aggressive peripheral T cell lymphoma with poor prognosis and for which there is no standard treatment. Treatment options for patients patients with relapsed/refractory disease are scarce and the choice of an appropriate rescue still represents an unmet need. METHODS: Here, we report the case of a 65-year-old woman affected by MEITL, progressing after initial treatment with an anthracycline-based chemotherapy and surgery, who received single-agent PEG-asparaginase salvage therapy at our institution. RESULTS: PEG-asparaginase single-agent rescue proved to be rapidly effective in controlling the disease and its associated paraneoplastic features. Nevertheless, toxicity was high and the patient died due to a treatment-related complication. CONCLUSION: The case we described brings new evidences on the effectiveness of PEG-asparaginase therapy in MEITL patients. Whether PEG-asparaginase should be included in the treatment course of MEITL patients could be the subject of future studies.

Pituitary apoplexy following adenoviral vector-based COVID-19 vaccination.

Pituitary apoplexy (PA) may complicate the course of coronavirus disease 2019 (COVID-19), posing a potential threat to life. Among vaccines designed to prevent COVID-19, there are those adenoviral vector-based, such as Vaxzevria® (formerly COVID-19 Vaccine AstraZeneca). The product insert states that it can cause very rare coagulation disorders, in particular thrombosis with thrombocytopenia syndrome in some cases accompanied by bleeding, cerebrovascular venous or sinus thrombosis, and thrombocytopenia, including immune thrombocytopenia, also associated with bleeding. Here, we report the onset of PA after Vaxzevria® in a 28-year-old healthy Caucasian female, who experienced long-lasting tension-type headache, hyperprolactinemia and menstrual changes, without thrombocytopenia or thrombosis.

Apropos of menstrual changes and abnormal uterine bleeding after COVID-19 vaccination.

It is news of 28 October 2022 that the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency has recommended to add heavy menstrual bleeding among the side effects of unknown frequency inside the package insert of nucleoside-modified messenger ribonucleic acid vaccines to prevent coronavirus disease 2019 (COVID-19). The decision has been made in the light of the numerous reports of unexpected menstrual changes or abnormal uterine bleeding following COVID-19 vaccination. Here we advance a possible involvement of the particular adenohypophyseal microcirculation in these strange and still unexplained events.

Advances in Diagnosis and Treatment of Gynecological Malignancies: A Special Issue in Line with 2030 Agenda.

Among the 17 Sustainable Development Goals (SDG) of the United Nations 2030 Agenda, "good health and well-being" is point number 3 (SDG3), and all our efforts must be calibrated in this direction worldwide [...].

A Three-Case Series of Thrombotic Deaths in Patients over 50 with Comorbidities Temporally after modRNA COVID-19 Vaccination.

Coronavirus disease 2019 (COVID-19) is the most dramatic pandemic of the new millennium; to counteract it, specific vaccines have been launched in record time under emergency use authorization or conditional marketing authorization by virtue of a favorable risk/benefit balance. Among the various technological platforms, there is that exploiting a nucleoside-modified messenger RNA (modRNA), such as Comirnaty®, and that which is adenoviral vector-based. In the ongoing pharmacovigilance, the product information of the latter has been updated about the risk of thrombotic thrombocytopenia, venous thromboembolism without thrombocytopenia and immune thrombocytopenia without thrombosis. However, from an in-depth literature review, the same adverse events can rarely occur with modRNA vaccines too. In support of this, we here report a three-case series of thrombotic deaths in patients over 50 with comorbidities temporally after Comirnaty®, investigated by means of post-mortem histopathology and immunohistochemistry. In two out of three cases, the cause of death is traced back to pulmonary microthromboses rich in activated platelets, quite similar morphologically to those described in patients who died from severe COVID-19. Even if remote in the face of millions of administered doses, clinicians should be aware of the possible thrombotic risk also after Comirnaty®, in order to avoid a misdiagnosis with potentially lethal consequences. Since COVID-19 vaccines are inoculated in subjects to be protected, maximum attention must be paid to their safety, and prophylactic measures to increase it are always welcome. In light of the evidence, the product information of modRNA COVID-19 vaccines should be updated about the thrombotic risk, as happened for adenoviral vector-based vaccines.

Cubital Tunnel Syndrome Temporally after COVID-19 Vaccination.

Coronavirus disease 2019 (COVID-19) is the most dramatic pandemic of the new millennium. To counter it, specific vaccines have been launched in record time under emergency use authorization or conditional marketing authorization and have been subjected to additional monitoring. The European Medicines Agency recommend reporting any suspected adverse reactions during this additional monitoring phase. For the first time in the available medical literature, we report a left cubital tunnel syndrome in a 28-year-old right-handed healthy male after seven days from the first dose of Spikevax® (formerly Moderna COVID-19 Vaccine). Histochemistry for Alcian Blue performed on the tissue harvested from the cubital site reveals myxoid degeneration of the small nerve collaterals, a clear sign of nerve injury. It still remains unclear why the syndrome occurs in a localized and not generalized form to all osteofibrous tunnels. Today, modified messenger ribonucleic acid vaccines as Spikevax® represent an avantgarde technological platform with a lot of potential, but one which needs careful monitoring in order to identify in advance those patients who may experience adverse events after their administration.

Chemical characterization of non-psychoactive Cannabis sativa L. extracts, in vitro antiproliferative activity and induction of apoptosis in chronic myelogenous leukaemia cancer cells.

In this study, extracts from non-psychoactive Cannabis sativa L. varieties were characterized by means of ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) and their antiproliferative activity was assessed in vitro. The human chronic myelogenous leukaemia cell line K562 was chosen to investigate the mechanism of cell death. The effect on the cell cycle and cell death was analysed by flow cytometry. Proteins related to apoptosis were studied by western blotting. Mechanical properties of cells were assessed using the Micropipette Aspiration Technique (MAT). The results indicated that the cannabidiol (CBD)-rich extract inhibited cell proliferation of K562 cell line in a dose-dependent manner and induced apoptosis via caspase 3 and 7 activation. A significant decrease in the mitochondrial membrane potential was detected, together with the release of cytochrome c into the cytosol. The main apoptotic markers were not involved in the mechanism of cell death. The extract was also able to modify the mechanical properties of cells. Thus, this hemp extract and its pure component CBD deserve further investigation for a possible application against myeloproliferative diseases, also in association with other anticancer drugs.