The primary objective of this article is to provide an overview of studies in humans that evaluate and compare the effects of heated tobacco products (HTPs) with those of conventional cigarette smoking on cardiovascular and respiratory diseases. To address this research question, a scoping review methodology was employed. A comprehensive literature search was conducted in the PubMed, Scopus, Web of Science, and Cochrane Library databases to identify relevant articles published between January 2014 and March 2025. Two reviewers independently screened all articles. This process resulted in the identification of 34 articles deemed appropriate to the aims of this scoping review. Despite the heterogeneity of the available data, the current evidence suggests that HTPs are associated with a lower harmful impact on the cardiovascular and respiratory systems as compared to conventional cigarettes. However, considering the relatively recent introduction of HTPs, in contrast to the long latency periods typically required for the development of smoking-related chronic diseases, as well as the evolving design and composition of these products, it is not surprising that definitive conclusions regarding their clinical, and public health impact bring up the need to be integrated by long-term evidence derived from independently conducted studies.

Background Serum thromboxane B-2 (sTXB(2)) is a validated biomarker of low-dose aspirin pharmacodynamics. In the original method, nonanticoagulated blood samples must be incubated at 37 degrees C immediately after withdrawal, centrifuged and serum supernatant should be frozen until assayed. Timely completion of all preanalytical steps may affect the feasibility and quality of sTXB(2) measurements. The storage duration of frozen serum can also affect sTXB(2) stability. Objectives We assessed the stability of sTXB(2) in clotted blood samples stored at 4 degrees C before further processing and in sera stored at -40 degrees C for over a decade. Methods Venous whole blood withdrawn from individuals on chronic low-dose aspirin was dispensed in different tubes and immediately incubated at 37 degrees C for 1 hour. The reference tube was promptly processed following the original protocol; the remaining tubes were stored at 4 degrees C for 12 to 72 hours before further processing. Sera stored at a controlled -40 degrees C temperature for <1 to 15 years were reassayed. Values within the interassay variation limits (+/- 9%) vs baseline were considered acceptable. Results Baseline sTXB(2) values (median, 5.4 ng/mL; IQR, 2.4-13.4 ng/mL; n = 40) were comparable with those in samples at 4 degrees C up to 48 hours (median, 97% [IQR, 86%-104%] of the reference; n = 26), but at 72 hours, the variability exceeded the interassay variation. Thromboxane B-2 levels were stable in frozen sera for up to 10 years (median, 101% [IQR, 87%-108%] of the reference; n = 32) but decreased significantly afterward (median, 87% [IQR, 74%-109%] at 15 years; P = .005; n = 32). Conclusion Thromboxane B-2 is stable in clotted blood samples stored at 4 degrees C for up to 48 hours before further processing and in serum samples stored at -40 degrees C over 10 years.

The association of cigarette smoking with several severe and very severe diseases (oncological, cardiovascular, respiratory) which have dramatic epidemiological, medical, and financial impact, is a well-known public threat. Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent diseases in Italy, posing significant public health challenges. Tobacco smoking, a primary risk factor for COPD and a common asthma trigger, remains a critical preventable public health issue. While universally acknowledged that quitting smoking drastically reduces the risk of smoking-related health issues, a significant portion of smokers and patients find quitting challenging or undesirable, hence a need for new ways to deal with it. A worth considering alternative might be the switch to electronic cigarettes (e-cig), and heat-not-burn/heated tobacco products (HnB/HTP). Emerging evidence suggests potential benefits in asthma and COPD management when transitioning from traditional smoking to e-cigs or HnB devices. However, the effectiveness of these products in facilitating smoking cessation is still debated, alongside concerns about their role in promoting smoking initiation among non-smokers. Internists are among the physicians who most frequently assist patients with smoking-related diseases, and in this perspective they cannot avoid paying attention to the progressive diffusion of smoking products alternative to the traditional cigarette, and to the controversies with respect to their use. In this context, the Italian Society of Internal Medicine, also recognizing a growing need for clarity for healthcare providers, has undertaken a comprehensive analysis of existing literature to offer an informed perspective on the health impact of e-cigs and HnB/HTP on asthma and COPD.

The presence of anaemia in patients with chronic kidney disease (CKD) is associated with decreased quality of life, along with increased morbidity, mortality, and hospitalization rates. This, in turn, affects healthcare costs and the utilization of medical resources. The mechanisms involved in anaemia of CKD are diverse and complex. They include reduced production of endogenous erythropoietin (EPO), absolute and/or functional iron deficiency (due to inflammation leading to elevated levels of hepcidin), the diminished response of the bone marrow to EPO due to uraemic toxins, the shortened lifespan of red blood cells (RBC), and deficiencies in vitamin B12 or folic acid. [...]

Clinical trials are an essential source of high-quality evidence for the assessment of efficacy and safety of healthcare interventions. Nowadays the main criticality of the traditional clinical trial model is perhaps the need to improve patient selection and management, in terms of initial identification, recruitment and retention. Digital technology offers operational solutions that can facilitate many of the activities involved in clinical investigation. Decentralized Clinical Trials (DCTs) could be a new option that provides for the use of remote instruments/methods/activities in the different stages of a clinical trial, so that a range of procedures (such as informed consent, medical visits, administration of a drug or use of a medical device, measurement of clinical parameters, diagnostic testing etc.) can be moved from the research hospital to the patient’s home. Also in Italy the interest in DCTs is progressively growing, and thanks to their potential benefits DCTs can lead to significant advantages not only for patients, but also for the National Health Service and for the country as a whole. It is important that this interest should act as a stimulus, prompting timely initiatives in order to promote and regulate this new methodology for conduct of clinical trials to avoid the risk that, while other countries will be actively involved in the promotion and leading of DCTs, Italy will be selected only as “control arm”.

Decentralized clinical trials (DCTs) are studies in which the need for patients to physically access hospital-based trial sites is reduced or eliminated. The CoViD-19 pandemic has caused a significant increase in DCT: a survey shows that 76% of pharmaceutical companies, device manufacturers, and Contract Research Organizations adopted decentralized techniques during the early phase of the pandemic. The implementation of DCTs relies on the use of digital tools such as e-consent, apps, wearable devices, Electronic Patient-Reported Outcomes (ePRO), telemedicine, as well as on moving trial activities to the patient's home (e.g., drug delivery) or to local healthcare settings (i.e., community-based diagnosis and care facilities). DCTs adapt to patients' routines, allow patients to participate regardless of where they live by removing logistical barriers, offer better access to the study and the investigational product, and permit the inclusion of more diverse and more representative populations. The feasibility and quality of DCTs depends on several requirements including dedicated infrastructures and staff, an adequate regulatory framework, and partnerships between research sites, patients and sponsors. The evaluation of Ethics Committees (ECs) is crucial to the process of innovating and digitalizing clinical trials: adequate assessment tools and a suitable regulatory framework are needed for evaluation by ECs. DCTs also raise issues, many of which are of considerable ethical significance. These include the implications for the relationship between patients and healthcare staff, for the social dimension of the patient, for data integrity (at the source, during transmission, in the analysis phase), for personal data protection, and for the possible risks to health and safety. Despite their considerable growth, DCTs have only received little attention from bioethicists. This paper offers a review on some ethical implications and requirements of DCTs in order to encourage further ethical reflection on this rapidly emerging field.

The aim of the study was to explore the effects of Intentional Rounding, a regular-based proactive patient monitoring, on falls and pressure ulcers in internal medicine units. This is a cluster-randomised controlled study, where units were assigned (1:1) to Intentional Rounding (intervention group) or Standard of Care (control group). The primary outcome was the cumulative incidence of falls and new pressure ulcers. These events were considered separately as secondary endpoints, together with the number of bell calls and the evaluation of patient satisfaction. Primary analyses were carried out on the modified intention-to-treat population (hospitalisation of at least 10 days). Recruitment occurred between October 2019 and March 2020, at which time the study was prematurely closed due to the COVID-19 pandemic. Enrolment totalled 1822 patients at 26 sites; 779 patients were included in the modified intention-to-treat analysis. The intervention group had a lower risk of falls (adjusted incidence rate ratio 0.14; 95% confidence interval, 0.02–0.78; p = 0.03). There were no statistical differences in new pressure ulcers or the cumulative incidence of both adverse events. Mean bell calls for each patient were 15.4 ± 24.1 in the intervention group and 13.7 ± 20.5 in the control group (p = 0.38). Additionally, patient satisfaction in the intervention group was almost at the maximum level. Our study supports the usefulness of Intentional Rounding in a complex and vulnerable population such as that hospitalised in internal medicine units.

BACKGROUND:Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment-related bleeding, but the correlation of these risks with the cancer stage is unclear. METHODS:We evaluated the risks of VTE recurrence and treatment-related major bleeding according to the cancer stage in patients with VTE and solid cancer randomised to apixaban or dalteparin in the Caravaggio study. Cancer stage was categorised by expert cancer physicians according to pre-specified criteria, and study outcomes were adjudicated by an independent committee unaware of cancer stage and treatment allocation. RESULTS:Of the 1034 patients included in this analysis, 217 (21.0%) had localised cancer, 279 (27.0%) locally advanced cancer and 503 (48.7%) metastatic cancer. Cancer stage was undetermined in 35 patients (3.4%). VTE recurrence and major bleeding rates were 2.8% and 3.2% in patients with localised cancer, respectively. In comparison to patients with localised cancer, the VTE recurrence rate was higher in patients with locally advanced cancer (7.5%, hazard ratio [HR] = 2.8, 95% confidence interval [CI] = 1.1-6.9) and metastatic cancer (8.7%, HR = 3.3, CI = 1.4-7.7, CI). Patients with metastatic cancer had numerically increased major bleedings compared to those with localised cancer (5.2%, HR = 1.65, CI = 0.7-3.8). The efficacy and safety of apixaban and dalteparin across patients with different cancer stages were consistent with the findings observed in the overall patients with cancer randomised in the study. CONCLUSIONS:Patients with locally advanced and metastatic cancer have a higher rate of VTE recurrence than patients with localised cancer with no statistically significant difference in treatment-related major bleeding.

In Italy, Internal Medicine Units hospitalize approximately 1,300,000 patients, often elderly and comorbid. The prevalent diagnoses are respiratory diseases, heart failure, or pneumonia. As a matter of fact, anemia is probably underestimated in the compilation of the official discharge forms (SDO) according to ICD-9 diagnostic codes. We promoted a survey among the Members the Italian Scientific Society of Internal Medicine (FADOI) with the aim to investigate the prevalence of anemia and iron deficiency, over than certain aspects related to the therapeutic management of patients with anemia. Furthermore, we performed a review summarizing current evidence for iron intravenous therapy in these patients. According to the survey, anemia is present in around half of the patients hospitalized in Internal Medicine, and about a quarter of them shows iron metabolism alterations. In the evaluation of iron metabolism, the dosage of ferritin is the most requested exam, whereas transferrin saturation is less considered. By focusing on some categories of patients, the awareness of the usefulness of intravenous iron therapy in patients with heart failure seems to be sufficiently common (76% of physicians), while it seems lower (60%) in the management of patients with chronic kidney disease (CKD) and anemia. Finally, more than 75% of the physicians answered that, in their hospital, there are few outpatients’ offices or diagnostic pathways dedicated to patients with anemia. Anemia due to absolute or functional iron deficiency is particularly prevalent in Internal Medicine inpatients. For this reason, an accurate evaluation of iron profile and an adequate iron therapy is mandatory in these patients. Recent studies show that, in patients with heart failure, intravenous iron therapy is an effective way of improving patients’ health, regardless of the presence of anemia. Similarly, iron therapy results fundamental to optimize erythropoiesis-stimulating agent efficacy in patients with chronic renal failure. In the next future, other therapeutic aspects of intravenous iron therapy will be probably clarified by several interesting ongoing studies focused on these patients.

(1) Background: The objective of this rapid review is to assess whether new potassium binders (NPBs) could enable the optimization of RAASi therapy more than usual care or placebo in patients with or at risk of heart failure and hyperkalemia. (2) Methods: We searched for RCTs that included patients with or at risk of hyperkalemia and patients treated with Patiromer or sodium zirconium cyclosilicate (ZSC). The comparators were placebo, usual care, and potassium binders with different doses or different treatment protocols. We searched the Cochrane CENTRAL, MEDLINE, and ClinicalTrials.gov databases. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs. Data were pooled using the random effects model, and the fixed effects model was used for sensitivity analysis. (3) Results: We included 12 studies with 2800 enrolled patients. Only three of these trials (412 patients) were included in the meta-analysis. NPBs seemed to have an effect on the optimization of MRA therapy, with an RR (95% CI) of 1.24 (1.09, 1.42) (moderate certainty evidence); Patiromer seemed to have an effect on MRA optimization, with an RR (95% CI) or 1.25 (1.08, 1.45) (high certainty evidence). ZSC seemed to have no effect on enabling MRA therapy, with an RR (95% CI) of 1.19 (0.89, 1.59) (low certainty evidence). The AEs in HF patients with hyperkalemia treated with Patiromer were GI disorders and hypomagnesemia. ZSC The AEs included chronic cardiac failure, hypokalemia, and edema. (4) Conclusions: This meta-analysis included three studies with a small number of patients and a short follow-up period (1–3 months). The evidence of the effect of NPBs on MRA optimization had a moderate certainty for imprecision. Data on the effect on MRA optimization and less severe AEs in long-term treatment seem to suggest the use of Patiromer for the optimization of MRA therapy in patients with or at risk of heart failure and hyperkalemia. Future adequately powered RCTs are needed to assess the benefits and potential harms of potassium binders.

The progressive cutting of hospital beds in some health systems, together with the increased needs related to the aging population, has led to the phenomenon of patients hospitalized outside the appropriate ward (outliers). This is particularly relevant in the context of Internal Medicine. Despite its relevance in daily clinical practice, available evidence for the potential impact of this phenomenon is limited. The aim of this study is to evaluate the effects of this situation on patients’ outcomes and possibly identify organizational and managerial aspects related to the presence of outliers. The multicenter, observational, prospective Study Protocol of Safety Issues and SurvIval For Medical Outliers (SISIFO) was promoted by the Italian Federation of Associations of Hospital Doctors on Internal Medicine (FADOI). The primary study endpoint is the evaluation of in-hospital mortality in outliers versus controls. A sample size of 2400 patients has been estimated by assuming a mortality rate of 12% and 8% in outliers and controls, respectively. By virtue of the multicentric dimension, the expected number of patients, and the controlled design, the FADOI-SISIFO study might provide interesting and useful findings to better manage the phenomenon of outliers.

Biorąc pod uwage, ze wielu pacjentow z przewleklą obturacyjną chorobą pluc (POChP) pali papierosy pomimo objawow, wazne jest zrozumienie dlugofalowego wplywu zdrowotnego zastepowania tradycyjnych papierosow poprzez podgrzewane produkty tytoniowe (HTP, heated tobacco products). Przez 3 lata monitorowano parametry zdrowotne pacjentow z POChP, ktorzy znacznie ograniczyli palenie lub zaprzestali palenia papierosow po przejściu na HTP. Zmiany w liczbie codziennie wypalanych papierosow, rocznej czestości zaostrzen choroby, wskaźnikach czynności pluc, wyniku kwestionariusza ciezkości POChP wedlug oceny wlasnej pacjentow (wskaźnik CAT) i wyniku testu 6-minutowego marszu (6MWD) w stosunku do wartości wyjściowych byly mierzone u pacjentow z POChP stosujących HTP w 12., 24. i 36. miesiącu. Porownano je z grupą pacjentow z POChP dopasowanych pod wzgledem wieku i plci, ktorzy nadal palili papierosy. Kompletne zestawy danych byly dostepne u 38 pacjentow (po 19 w kazdej grupie). U osob stosujących HTP odnotowano znaczne zmniejszenie średniej (± SD) rocznej czestości zaostrzen POChP z 2,1 (± 0,9) na początku badania do 1,4 (± 0,8), 1,2 (± 0,8) i 1,3 (± 0,8) po 12, 24 i 36 miesiącach obserwacji (p < 0,05 dla wszystkich wizyt). Ponadto we wszystkich trzech punktach czasowych w kohorcie HTP stwierdzono znaczną i klinicznie istotną poprawe wynikow CAT i 6MWD. Nie zaobserwowano istotnych zmian u pacjentow z POChP, ktorzy kontynuowali palenie. Niniejsze badanie jestpierwszym, w ktore opisano dlugoterminowe skutki zdrowotne stosowania HTP u pacjentow z POChP. Poprawe objawow ze strony ukladu oddechowego, tolerancji wysilku, jakości zycia i czestości zaostrzen choroby zaobserwowano konsekwentnie u pacjentow z POChP, ktorzy powstrzymali sie od palenia lub znacznie ograniczyli palenie papierosow poprzez przestawienie sie na stosowanie HTP. Slowa kluczowe: zaprzestanie palenia, podgrzewane produkty tytoniowe, IQOS, glo, POChP, zmniejszenie szkod związanych z paleniem tytoniu

Given that many patients with chronic obstructive pulmonary disease (COPD) smoke despite their symptoms, it is important to understand the long-term health impact of cigarette substitution with heated tobacco products (HTPs). We monitored health parameters for 3 years in COPD patients who substantially attenuated or ceased cigarette consumption after switching to HTPs. Changes in daily cigarette smoking, annualized disease exacerbations, lung function indices, patient-reported outcomes (CAT scores) and 6-minute walk distance (6MWD) from baseline were measured in COPD patients using HTPs at 12, 24 and 36 months. These were compared to a group of age- and sex-matched COPD patients who continued smoking. Complete data sets were available for 38 patients (19 in each group). Subjects using HTPs had a substantial decrease in annualized COPD exacerbations within the group mean (± SD) from 2.1 (± 0.9) at baseline to 1.4 (± 0.8), 1.2 (± 0.8) and 1.3 (± 0.8) at 12-, 24- and 36-month follow-up (p < 0.05 for all visits). In addition, substantial and clinically significant improvements in CAT scores and 6MWD were identified at all three time points in the HTP cohort. No significant changes were observed in COPD patients who continued smoking. This study is the first to describe the long-term health effects of HTP use in COPD patients. Consistent improvements in respiratory symptoms, exercise tolerance, quality of life, and rate of disease exacerbations were observed in patients with COPD who abstained from smoking or substantially reduced their cigarette consumption by switching to HTP use.

The coronavirus disease 2019 (COVID-19) pandemic has stressed the importance of health research as never before. In the specific domain of clinical research, the effort to rapidly find responses to health challenges and therapeutic hypotheses has highlighted the need for efficient, timely, ethically correct research. The guidelines published by the Agenzia Italiana del Farmaco have shown that some useful changes are feasible: simple and rapid methods have been implemented to conduct clinical research in the emergency conditions of the pandemic, maintaining high levels of quality. In this perspective, four Italian scientific associations operating in clinical research have worked together to evaluate which measures, among the ones implemented during the pandemic, have been particularly significant and potentially effective under normal conditions or in case of emergencies, and that therefore will be useful in the future as well.

An amendment to this paper has been published and can be accessed via the original article.

Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE recurrence and major bleeding and the relative efficacy and safety of 6-month treatment with oral apixaban or subcutaneous dalteparin in patients with different cancer sites randomized in the Caravaggio study. Primary cancer was located at gastrointestinal sites in 375 patients (32.5%), lung in 200 (17.3%), breast in 155 (13.4%), genitourinary sites in 139 (12%), gynecological sites in 119 (10.3%), and was hematological in 85 patients (7.4%). Rates of VTE recurrence were 10.9% in patients with gynecological, 8.8% with gastrointestinal, 6.5% with genitourinary, and 5.5% with lung cancer with lower rates in the other sites of cancer. Rates of major bleeding were 7.2% in patients with genitourinary and 4.8% with gastrointestinal cancer, with lower rates in patients with other sites of cancer. The observed absolute risk difference in VTE recurrence in favor of apixaban was 11.9% in patients with gynecological, 5.5% with lung, 3.7% with genitourinary cancer, and 0.6% with gastrointestinal cancer. None of the risk differences was statistically significant. The rates of major bleeding in patients treated with apixaban or dalteparin was similar across patients with different cancer sites. In conclusion, recurrences appear to be more common in patients with gastrointestinal and gynecological cancer and major bleedings in patients with genitourinary and gastrointestinal cancer. Oral apixaban is a valid oral alternative to subcutaneous dalteparin for the treatment of a large spectrum of patients with cancer-associated VTE.

Background Direct oral anticoagulants are recommended for the treatment of cancer-associated thrombosis (CAT) as an alternative to low-molecular-weight heparin (LMWH), but an increased bleeding risk in patients with gastrointestinal cancer was reported. The Caravaggio study compared apixaban and dalteparin for the treatment of patients with CAT. Here we describe sites of bleeding, associated cancer sites, clinical presentation, and course of major bleeding in patients included in the Caravaggio study. Methods The Caravaggio study was a multinational, randomized, open-label, noninferiority study. Bleeding events and the severity of major bleedings were adjudicated by a committee unaware of treatment allocation using predefined criteria; for the purpose of this analysis, data were analyzed in the safety population. Results Major bleeding occurred in 22 of 576 patients on apixaban (3.8%) and in 23 of 579 patients on dalteparin (4.0%). The sites of major bleeding and their distribution according to the type of cancer were similar between the two treatment groups. Major bleeding occurred in nine patients with gastrointestinal cancer in each treatment group. The clinical presentation of major bleeding was severe or fatal in 6 patients on apixaban and in 5 patients on dalteparin, while the clinical course was severe in 5 patients on apixaban and in 7 patients on dalteparin. Conclusion Apixaban is a safe alternative to LMWH for the treatment in patients with CAT. No excess in gastrointestinal bleeding was observed in patients who received apixaban, including those with gastrointestinal cancer.

Invasive candidiasis (IC) is a challenging clinical condition, burdened by relevant mortality and morbidity. There is limited knowledge on the occurrence and management of IC in Internal Medicine Units (IMUs). Aim of this study was to provide real-world data on this topic. Consecutive objectively diagnosed cases of IC were collected in this prospective registry, which involved 18 IMUs in Italy. Patients were followed-up to 90 days from the diagnosis of candidemia. A total of 111 patients were observed (median age 78, IQR 67–83) for an overall incidence of infection of 1.89 cases/1000 hospital admissions. Candida albicans was the most frequent isolated species (62%), followed by Candida parapsilosis (17%) and Candida glabrata (13%). Echinocandins and fluconazole were used as initial therapy in 56.8 and 43.2% of patients, respectively. Antifungal therapy was started within 24 h in 18.9% of patients, in 40.6% in the period 1–3 days, and in 40.5% of patients more than 3 days after blood cultures. Death rate was 19.8% at 30 days and 40.5% at 90 days. At multivariable analysis concomitant bacteremia (i.e. polymicrobial sepsis), and fluconazole as the initial therapy were associated with an increased risk of death at 90 days. The incidence of IC is not negligible, and our registry confirmed that these patients have a relevant mortality rate at 90 days. Concomitant bacteremia, featuring polymicrobial sepsis, and starting antifungal treatment with fluconazole instead of echinocandins independently increase the risk of death. Efforts are needed to improve the awareness and management of IC in IMUs.