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Background: Heart failure (HF)-related mortality has been exacerbated by the COVID-19 pandemic; however, it is unclear how healthcare reassessment has contributed to the excess mortality versus SARS-CoV-2 infection itself. We aimed to assess how the pandemic affected the therapeutic management and prognosis of HF patients. Methods: We retrospectively reviewed the healthcare utilization databases of the Lombardy region (Italy) to identify all newly-diagnosed HF patients from January 2018 to December 2021. Outcomes were the utilization of HF therapies (Sacubitril/Valsartan; cardiac resynchronization therapy [CRT] and/or implantable cardioverter-defibrillator [ICD]; mechanical circulatory support [MCS]; heart transplantation [HTX]) and mortality. Cox regression models were fitted to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with the pandemic. Results: 36,130 and 17,263 patients were identified in the pre-pandemic and pandemic eras, respectively. The pandemic reduced Sacubitril/Valsartan utilization (HR = 0.77, 95% CI: 0.65-0.91) and CRT/ICD implantation (HR = 0.85, 95% CI: 0.78-0.92), but not MCS (HR = 1.11, 95% CI: 0.86-1.43) and HTX (HR = 0.88, 95% CI: 0.70-1.09). An increased mortality risk was observed during the pandemic (HR = 1.19, 95% CI: 1.15-1.23), which was attributable to SARS-CoV-2 infection (HR for non-COVID-19-related mortality = 1.01, 95% CI: 0.97-1.04). Conclusions: The COVID-19 pandemic was associated with a reduction in medical and interventional therapies for HF and an increase in mortality for HF patients.

The actual incidence of bone marrow infiltration of human melanoma in clinical practice is underestimated, given it is found in only 7% of in vivo staging procedures, whereas this percentage increases up to 45% of autopsy cases. We performed a systematic review, in order to highlight the main clinico-pathologic features of melanoma bone marrow metastases (BMM), by reviewing 2.526 studies; seventy-three reports were included in the analysis,reporting a total amount of 146 patients. Moreover, as clinical exemples, we also present a collection of three BMM cases, extracted from our Institutional casistic. We found a slight male prevalence, with a median age at the time of BMM of 56.6 years (range: 3-81 years). The skin was the primary site of involvement in most cases (52%), followed by mucosa in 6 cases (8.8%) and uvea in 14 cases (20.5%), while in 13 cases (19%) the primary site of melanoma was not detected. In 36% of cases, BMM were preceded by lymph node involvement, while 64% of cases did not show nodal metastases, but directly to bone marrow (23%), as well as to other anatomical sites (41%). Presenting symptoms of BMM mostly included pain (60.7%), while anemia was the main laboratory alteration (80%), followed by thrombocytopenia, leukoerythroblastosis, pancytopenia, and leukopenia. A disseminated intravascular coagulation (DIC) was detected in 6 (11%) cases. In 12 cases (23.6%) BMM were amelanotic. The prognosis for BMM is poor, with a median time of survival of only 2 months, since currently conventional therapies for this anatomical site of metastasis are still not very successful, therefore, we stress the importance to evaluate bone marrow as a possible metastatic site in melanoma patients.

The occurrence of bone marrow metastases (BMM) in melanoma patients is often underestimated, with only 7% detected during in-vivo staging procedures but rising to 45% in autopsy cases. This systematic review aims to shed light on the clinical and laboratory features of BMM in melanoma by analyzing 73 studies selected from 2 482 initially retrieved from PubMed, Embase, and Cochrane CENTRAL databases. Our findings reveal a slight male predominance, with a median age at BMM diagnosis of 56 years. Primary melanoma sites included the skin (52%), mucosa (8.8%), uvea (20.5%) and unidentified (19%). BMM was preceded by lymph node involvement in 36.5% of cases, whereas 63% showed no nodal metastases, with direct BMM occurring in 22.5% and metastases to other sites in 41%. Common BMM symptoms included pain (60.7%), anemia (80%), thrombocytopenia, leukoerythroblastosis, pancytopenia and leukopenia, while disseminated intravascular coagulation was detected in 11% of cases. In 23.6% of cases, BMM was amelanotic. The prognosis for BMM is grim, with a median survival of only 2 months. Conventional therapies for BMM remain largely ineffective, emphasizing the importance of considering bone marrow as a potential metastatic site in melanoma patients.

Objectives: The aim of this study was to assess the clinical course and outcomes of all heart transplant recipients affected by coronavirus disease-2019 (COVID-19) who were followed at the leading heart transplant centers of Northern Italy. Background: The worldwide severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has created unprecedented challenges for public health, demanding exceptional efforts for the successful management and treatment of affected patients. Heart transplant patients represent a unique cohort of chronically immunosuppressed subjects in which SARS-CoV-2 may stimulate an unpredictable clinical course of infection. Methods: Since February 2020, we enrolled all 47 cases (79% male) in a first cohort of patients, with a mean age of 61.8 ± 14.5 years, who tested positive for SARS-CoV-2, out of 2,676 heart transplant recipients alive before the onset of the COVID-19 pandemic at 7 heart transplant centers in Northern Italy. Results: To date, 38 patients required hospitalization while 9 remained self-home quarantined and 14 died. Compared to the general population, prevalence (18 vs. 7 cases per 1,000) and related case fatality rate (29.7% vs. 15.4%) in heart transplant recipients were doubled. Univariable analysis showed older age (p = 0.002), diabetes mellitus (p = 0.040), extracardiac arteriopathy (p = 0.040), previous PCI (p = 0.040), CAV score (p = 0.039), lower GFR (p = 0.004), and higher NYHA functional classes (p = 0.023) were all significantly associated with in-hospital mortality. During the follow-up two patients died and a third patient has prolonged viral-shedding alternating positive and negative swabs. Since July 1st, 2020, we had 6 new patients who tested positive for SARS-CoV-2, 5 patients asymptomatic were self-quarantined, while 1 is still hospitalized for pneumonia. A standard therapy was maintained for all, except for the hospitalized patient. Conclusions: The prevalence and mortality of SARS-CoV-2 should spur cl

Hematopoietic stem cells (HSCs) are regulated by signals from the bone marrow (BM) niche that tune hematopoiesis at steady state and in hematologic disorders. To understand HSC-niche interactions in altered nonmalignant homeostasis, we selected b-thalassemia, a hemoglobin disorder, as a paradigm. In this severe congenital anemia, alterations secondary to the primary hemoglobin defect have a potential impact on HSC-niche cross talk. We report that HSCs in thalassemic mice (th3) have an impaired function, caused by the interaction with an altered BM niche. The HSC self-renewal defect is rescued after cell transplantation into a normal microenvironment, thus proving the active role of the BM stroma. Consistent with the common finding of osteoporosis in patients, we found reduced bone deposition with decreased levels of parathyroid hormone (PTH), which is a key regulator of bone metabolism but also of HSC activity. In vivo activation of PTH signaling through the reestablished Jagged1 and osteopontin levels correlated with the rescue of the functional pool of th3 HSCs by correcting HSC-niche cross talk. Reduced HSC quiescence was confirmed in thalassemic patients, along with altered features of the BM stromal niche. Our findings reveal a defect in HSCs in b-thalassemia induced by an altered BM microenvironment and provide novel and relevant insight for improving transplantation and gene therapy approaches.