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Despite the innovations introduced in the 2022 European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, risk discrimination and management of pulmonary arterial hypertension (PAH) patients at intermediate risk still represents a grey zone. Additionally, clinical evidence derived from currently available studies is limited. This expert panel survey intends to aid physicians in choosing the best therapeutic strategy for patients at intermediate risk despite ongoing oral therapy. An expert panel of 24 physicians, specialized in cardiology and/or pulmonology with expertise in handling all drugs available for the treatment of PAH participated in the survey. All potential therapeutic options for patients at intermediate risk were explored and analyzed to produce graded consensus statements regarding: the switch from endothelin receptor antagonist (ERA) or phosphodiesterase 5 inhibitor (PDE5i) to another oral drug of the same class; the addition of a drug targeting the prostacyclin pathway administered by different routes; the switch from PDE5i to riociguat., Competing Interests: Declaration of competing interest S. Ghio reports personal fees from MSD and Ferrer, outside the submitted work. R. Badagliacca reports personal fees from UT, Dompè, Ferrer, Bayer, MSD and AOP Orphan Pharmaceuticals, outside the submitted work. R. Benza reports receiving grants from Actelion, Bayer AG, Bellerophon Therapeutics and Eiger Biopharmaceuticals, outside the submitted work. C. D. Vizza reports personal fees from GSK, UT, Dompè, Bayer and MSD, outside the submitted work. Other authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Subtalar arthrodesis (SA) is a common procedure to treat end-stage subtalar osteoarthritis. We set out in order to determine whether a combined direct fixation of both anterior and posterior facets during SA might influence union and complications compared to isolated fixation of the posterior facet. Our hypothesis was that a combined fixation increases the union rate and reduces the complication rate., Methods: In this PRISMA-compliant PROSPERO-registered systematic review, we included studies reporting data after SA stabilized with screws in adults. The characteristics of the cohort, study design, surgical details, nonunion and complication rate at the longest follow-up were recorded. The modified Coleman Methodology Score (mCMS) was applied to appraise the quality of studies. Two groups were compared: an ANT/POST group (screws positioned both in the anterior and posterior facet) and an ONLY POST group (isolated posterior facet fixation)., Results: Eighteen series (685 feet: ANT/POST = 96, ONLY POST = 589) were selected. The median follow-up was 28 months (IQR, 12-42). The pooled proportion showed a similar nonunion rate (6% vs 10%; p = 0.46) and complication rate (14% vs 19%, p = 0.47) in the ANT/POST group as compared to the ONLY POST group. The pooled proportion of reoperation was not different either (ANT/POST: 7% vs ONLY POST: 10%, p = 0.37). Kernel regression suggested a correlation between the proportion of open/arthroscopic procedures and the nonunion rate (p = 0.025) with a median nonunion rate at 10.9% and 5.9% for open and arthroscopic procedures, respectively. Mean CMS was 40.4 points (poor quality)., Conclusion: This proportional meta-analysis suggested that a combined direct fixation of anterior and posterior facets during subtalar arthrodesis does not significantly influence the risk of nonunion nor affects the risk of complication and reoperation as compared to isolated posterior facet fixation., Level of Evidence: IV; review of Level I-IV studies., Competing Interests: Declaration of competing interest Alessio Bernasconi declares leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for CURVEBEAM AI. Other authors have no conflict to declare., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools., Methods: Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n = 152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n = 143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n = 201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n = 519 patients). Risk stratification was based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 3-strata model and Registry to Evaluate Early and Long-Term PAH disease Management (REVEAL) 2.0 score., Results: These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% CI 1.6-2.8, p < 0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% CI 0.18-0.47, p < 0.001)., Conclusions: Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Introduction: The 2021 European Society of Cardiology (ESC) Guidelines recommend the use of four different classes of drugs for heart failure with reduced ejection fraction (HFrEF): beta blockers (BB), sodium-glucose cotransporter-2 inhibitors (SGLT2i), angiotensin receptor/neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRAs). Moreover, the 2023 ESC updated Guidelines suggest an intensive strategy of initiation and rapid up-titration of evidence-based treatment before discharge, based on trials not using the four-pillars. We hypothesized that an early concomitantly administration and up-titration of four-pillars, compared with a conventional stepwise approach, may impact the vulnerable phase after hospitalization owing to HF., Methods: This prospective, single center, observational study included consecutive in-hospital patients with HFrEF. After performing propensity score matching, they were divided according to treatment strategy into group 1 (G1), with predischarge start of all four-pillars, with their up-titration within 1 month, and group 2 (G2) with the pre Guidelines update stepwise four-pillars introduction. HF hospitalization, cardiovascular (CV) death, and the composite of both were evaluated between the two groups at 6-month follow-up., Results: The study included a total of 278 patients who completed 6-month follow-up (139 for both groups). There were no differences in terms of baseline features between the two groups. At survival analysis, HF hospitalization risk was significantly lower in G1 compared with G2 (p < 0.001), while no significant differences were observed regarding CV death (p = 0.642) or the composite of CV death and HF hospitalization (p = 0.135)., Conclusions: In our real-world population, patients with HF treated with a predischarge and simultaneous use of four-pillars showed a reduced risk of HF hospitalization during the vulnerable phase after discharge, compared with  a conventional stepwise approach., (© 2024. The Author(s).)

Introduction: Gliflozins are recommended as first-line treatment in patients with heart failure and/or cardiovascular comorbidities and are demonstrated to reduce atrial fibrillation (AF) occurrence. However, it is not well known which gliflozin yields the larger cardioprotection in terms of AF occurrence reduction. Hence, we aimed to compare data regarding AF recurrence associated with different gliflozins., Methods: An accurate search of online scientific libraries (from inception to June 1, 2023) was performed. Fifty-nine studies were included in the meta-analysis involving 108 026 patients, of whom 60 097 received gliflozins and 47 929 received placebo., Results: Gliflozins provided a statistically significant reduction of AF occurrence relative to standard of care therapy in the overall population (relative risks [RR]: 0.8880, 95% CI: [0.8059; 0.9784], p = .0164) and in patients with diabetes and cardiorenal diseases (RR: 0.8352, 95% CI: [0.7219; 0.9663], p = .0155). Dapagliflozin significantly decreased AF occurrence as compared to placebo (0.7259 [0.6337; 0.8316], p < .0001) in the overall population, in patients with diabetes (RR: 0.2482, 95% CI: [0.0682; 0.9033], p = .0345), with diabetes associated with cardiorenal diseases (RR: 0.7192, 95% CI: [0.5679; 0.9110], p = .0063) and in the subanalysis including studies with follow-up ≥1 year (RR: 0.7792, 95% CI: [0.6508; 0.9330], p = .0066). No significant differences in terms of AF protection were found among different gliflozins., Conclusions: Dapagliflozin use was associated with significant reduction in AF risk as compared to placebo in overall population and patients with diabetes, whereas the use of other gliflozins did not significantly reduce AF occurrence., (© 2024 Wiley Periodicals LLC.)

Quality of life of patients suffering from chronic diseases is inevitably conditioned by the number of pills taken during the day. To improve patients' tolerability, compliance and quality of life and reduce healthcare costs, pharmaceutical companies are focusing on the commercialization of fixed-dose combination (FDC) therapies. The last ESC/ERS guidelines for the treatment of pulmonary arterial hypertension (PAH) recommend initial dual combination therapy for newly diagnosed patients at low or intermediate mortality risk. In this regard, polypills including an endothelin receptor antagonist (ERA) and a phosphodiesterase 5 inhibitor (PDE5-i) could represent an useful therapeutic strategy, although with some limitations. To date, evidence about the use of FDCs in PAH is limited but future studies evaluating their safety and efficacy are welcome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

At the core of what defines us as humans is the concept of theory of mind: the ability to track other people's mental states. The recent development of large language models (LLMs) such as ChatGPT has led to intense debate about the possibility that these models exhibit behaviour that is indistinguishable from human behaviour in theory of mind tasks. Here we compare human and LLM performance on a comprehensive battery of measurements that aim to measure different theory of mind abilities, from understanding false beliefs to interpreting indirect requests and recognizing irony and faux pas. We tested two families of LLMs (GPT and LLaMA2) repeatedly against these measures and compared their performance with those from a sample of 1,907 human participants. Across the battery of theory of mind tests, we found that GPT-4 models performed at, or even sometimes above, human levels at identifying indirect requests, false beliefs and misdirection, but struggled with detecting faux pas. Faux pas, however, was the only test where LLaMA2 outperformed humans. Follow-up manipulations of the belief likelihood revealed that the superiority of LLaMA2 was illusory, possibly reflecting a bias towards attributing ignorance. By contrast, the poor performance of GPT originated from a hyperconservative approach towards committing to conclusions rather than from a genuine failure of inference. These findings not only demonstrate that LLMs exhibit behaviour that is consistent with the outputs of mentalistic inference in humans but also highlight the importance of systematic testing to ensure a non-superficial comparison between human and artificial intelligences., (© 2024. The Author(s).)

Background: Ischemic heart disease (IHD) represents the main cause of heart failure (HF). A prognostic stratification of HF patients with ischemic etiology, particularly those with acute coronary syndrome (ACS), may be challenging due the variability in clinical and hemodynamic status. The aim of this study is to assess the prognostic power of the HLM score in a population of patients with ischemic HF and in a subgroup who developed HF following ACS. Methods: This is an observational, prospective, single-center study, enrolling consecutive patients with a diagnosis of ischemic HF. Patients were stratified according to the four different HLM stages of severity, and the occurrence of CV death, HFH, and worsening HF events were evaluated at 6-month follow-up. A sub-analysis was performed on patients who developed HF following ACS at admission. Results: The study included 146 patients. HLM stage predicts the occurrence of CV death ( p = 0.01) and CV death/HFH ( p = 0.003). Cox regression analysis confirmed HLM stage as an independent predictor of CV death (OR: 3.07; 95% IC: 1.54-6.12; p = 0.001) and CV death/HFH (OR: 2.45; 95% IC: 1.43-4.21; p = 0.001) in the total population of patients with HF due to IHD. HLM stage potentially predicts the occurrence of CV death ( p < 0.001) and CV death/HFH ( p < 0.001) in patients with HF following ACS at admission. Conclusions: Pathophysiological-based prognostic assessment through HLM score is a potentially promising tool for the prediction of the occurrence of CV death and CV death/HFH in ischemic HF patients and in subgroups of patients with HF following ACS at admission.

Pulmonary hypertension (PH) is a frequent pathological condition worldwide, mainly secondary to cardiovascular and respiratory diseases, with a poor prognosis. Pulmonary arterial hypertension (PAH) is a rare form that affects the arterial pulmonary vasculature. PH and PAH are characterized by non-specific symptoms and a progressive increase of pulmonary vascular resistance that results in progressive, sometimes irreversible, right ventricular dysfunction. In recent years, a growing medical and social commitment on this disease allowed more accurate diagnosis in shorter times. However, the gap between guidelines and clinical practice remains a challenge for all medical doctors involved in the disease management. Considering the needs to share and describe diagnostic and therapeutic pathways, to measure the results obtained and to address the economical and organizational problems of this disease, all involved figures should collaborate to improve its prognostic impact and health expenses. In this consensus document, the PH experts of the Italian Association of Hospital Cardiologists (ANMCO) together with those of the Italian Society of Cardiology (SIC), address 1) definition, classification and unmet needs of PH and PAH; 2) classification and characteristics of centers involved in the diagnosis and treatment of the disease; 3) proposal of organization of a diagnostic-therapeutic pathway, based on robust and recent scientific evidence.

Background: Oral prostanoids are recommended in patients with pulmonary arterial hypertension (PAH) and an unsatisfactory response to first-line therapy., Objective: To compare the effectiveness of oral therapies targeting the prostacyclin pathway in PAH patients., Methods: An online search of Medline, Cochrane Registry, Scopus and EMBASE libraries (from inception to May, 12,020) was conducted. Eight randomized controlled studies were included in the meta-analysis involving 3023 patients, with 828 receiving oral treprostinil, 607 patients receiving selexipag, 125 patients receiving beraprost, and 1463 patients receiving placebo., Results: Compared to placebo, oral treprostinil (WMD 9.05, 95% CI 3.0280-15.0839, p = 0.0032) and beraprost (WMD 21.98, 95% CI 5.0536-38.9063, p = 0.0109) were associated with a significant increase in 6-min walking distance (6MWD) at follow-up from baseline, whereas selexipag use was associated with a non-significant increase in 6MWD (WMD 15.41, 95% CI -0.6074; 31.4232, p = 0.0593). Compared to placebo, the risk of clinical worsening was significantly lowered by selexipag (RR 0.47, 95% CI 0.35-0.65, p < 0.001) and oral treprostinil (RR 0.65, 95% CI 0.46-0.90, p 0.012), whereas a non-significant reduction of the outcome was related to beraprost use (RR 0.70, 95% CI 0.36-1.38, p 0.31). No significant difference in 6MWD change and clinical worsening reduction were found among oral treprostinil and selexipag. Beraprost use less frequently caused adverse events as compared to selexipag and oral treprostinil., Conclusions: No differences in 6MWD change, clinical worsening reduction and adverse events rates were found among oral treprostinil and selexipag, resulting in similar efficacy and safety profiles., Competing Interests: Declaration of competing interest R. Badagliacca received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Bayer, Dompè, Ferrer, GSK, MSD. C.D. Vizza received fees for serving as a speaker, consultant and an advisory board member, from the following Companies: Actelion, Dompè, GSK, Italfarmaco, Lilly, Pfizer, United Therapeutics. The other authors reported no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: Oral prostanoids are recommended in patients with pulmonary arterial hypertension (PAH) and a unsatisfactory response to first-line therapy., Objective: To compare effectiveness of oral therapies targeting the prostacyclin pathway in PAH patients., Methods: An online search of Medline, Cochrane Registry, Scopus and EMBASE libraries (from inception to May, 12020) was performed. Eight randomized controlled studies were included in the meta-analysis involving 3023 patients, of whom 828 receiving oral treprostinil, 607 patients receiving selexipag, 125 patients receiving beraprost, and 1463 patients received placebo., Results: As compared to placebo, oral treprostinil (WMD 9.05, 95% CI 3.0280-15.0839, p = 0.0032) and beraprost (WMD 21.98, 95% CI 5.0536-38.9063, p = 0.0109) arms significantly increased 6 min walking distance (6MWD) at follow-up from baseline, whereas selexipag use was associated with a non-significant increase in 6MWD (WMD 15.41, 95% CI -0.6074; 31.4232, p = 0.0593). Compared to placebo, the risk of clinical worsening was significantly lowered by selexipag (RR 0.47, 95% CI 0.35-0.65, p < 0.001) and oral treprostinil (RR 0.65, 95% CI 0.46-0.90, p 0.012), whereas a non-significant reduction of the outcome was related to beraprost use (RR 0.70, 95% CI 0.36-1.38, p 0.31). No significant difference in 6MWD change and clinical worsening reduction were found among oral treprostinil and selexipag. Beraprost use less frequently caused adverse events as compared to selexipag and oral treprostinil., Conclusions: No differences in 6MWD change, clinical worsening reduction and adverse events rates were found among oral treprostinil and selexipag, resulting in similar efficacy and safety profile., (Copyright © 2023. Published by Elsevier B.V.)

Parenteral prostanoids are being recommended in pulmonary arterial hypertension (PAH) treatment, but the prognostic relevance of delayed treatment initiation is still debated. This study assessed the impact of the timing of prostacyclin treatment initiation on reducing PVR and achieving a low-risk profile in PAH patients. The study enrolled 151 patients who started on parenteral prostanoids with different treatment strategies. All patients underwent right heart catheterization, clinical evaluation, and risk assessments at baseline and after 1-year follow-up. Patients with an upfront strategy including parenteral prostanoid plus one oral drug had -5.3 ± 6.2 WU (-50 ± 19%) reduction in PVR, patients with an upfront strategy including parenteral prostanoid plus double oral drug had -12.8 ± 5.9 WU (-68 ± 17%) reduction in PVR, while patients with an add-on strategy including parenteral prostanoid after oral drugs had -3.9 ± 3.5 WU (-23 ± 19%) reduction in PVR. An upfront strategy including parenteral prostanoids was independently associated with an increased likelihood of achieving the greater reduction of PVR compared with an add-on strategy. Additionally, the greater the severity of PH at the time of diagnosis, in terms of PVR and RV reverse remodeling, the higher the probability of treatment failure. An upfront strategy including a parenteral prostanoid is associated with the highest likelihood of achieving a low-risk profile and a greater reduction of PVR compared with parenteral prostanoid as an add-on to oral treatment.

The study of sexual dimorphism in human crania has important applications in the fields of human evolution and human osteology. Current, the identification of sex from cranial morphology relies on manual visual inspection of identifiable anatomical features, which can lead to bias due to user's expertise. We developed a landmark-based approach to automatically map the sexual dimorphism signal on the human cranium. We used a sex-known sample of 228 individuals from different geographical locations to identify which cranial regions are most sexually dimorphic taking into account shape, form and size. Our results, which align with standard protocols, show that glabellar and supraciliary regions, the mastoid process and the nasal region are the most sexually dimorphic traits (with an accuracy of 73%). The accuracy increased to 77% if they were considered together. Surprisingly the occipital external protuberance resulted to be not sexually dimorphic but mainly related to variations in size. Our approach here applied could be expanded to map other variable signals on skeletal morphology., (© 2023. Springer Nature Limited.)

Population size history is essential for studying human evolution. However, ancient population size history during the Pleistocene is notoriously difficult to unravel. In this study, we developed a fast infinitesimal time coalescent process (FitCoal) to circumvent this difficulty and calculated the composite likelihood for present-day human genomic sequences of 3154 individuals. Results showed that human ancestors went through a severe population bottleneck with about 1280 breeding individuals between around 930,000 and 813,000 years ago. The bottleneck lasted for about 117,000 years and brought human ancestors close to extinction. This bottleneck is congruent with a substantial chronological gap in the available African and Eurasian fossil record. Our results provide new insights into our ancestry and suggest a coincident speciation event.

Purpose of Review: The purpose of this review is to overview the most relevant and recent knowledge regarding medical management in pulmonary arterial hypertension (PAH)., Recent Findings: Evidence has shown that PAH patients' quality of life and prognosis depend on the capability of the RV to adapt to increased afterload and to fully recover in response to substantially reduced pulmonary vascular resistance obtained with medical therapy. Data from recent clinical studies show that more aggressive treatment strategies, especially in higher risk categories, determine larger afterload reductions, consequentially increasing the probability of achieving right heart reverse remodeling, therefore improving the patients' survival and quality of life. Remarkable progress has been observed over the past decades in the medical treatment of PAH, related to the development of drugs that target multiple biological pathways, strategies for earlier and more aggressive treatment interventions. New hopes for treatment of patients who are unable to achieve low-risk status have been derived from the phase 2 trial PULSAR and the phase 3 trial STELLAR, which show improvement in the hemodynamic status of patients treated with sotatercept on top of background therapy. Promising results are expected from several ongoing clinical trials targeting new pathways involved in the pathophysiology of PAH., (© 2023. The Author(s).)

Objectives: To explore: (1) self-care behaviors in children and young people (range: 6 months-24 years) with complex chronic conditions, characterized by the diagnosis of a severe chronic condition, substantial family-identified needs, functional limitations associated with technology dependence, and intensive use of healthcare services; (2) the contribution to self-care of family members and other persons involved in the child's health and daily life context (e.g., health professionals and teachers), and (3) the principal factors that might have influenced the self-care process associated with developmental age., Methods: A qualitative descriptive study was conducted in an Italian academic tertiary pediatric hospital between September 2020 and May 2021. Overall, 25 focus groups and 7 online interviews were conducted via videoconferencing. Textual data were analyzed using Emotional Text Mining to identify three levels of communication: the factors, the main themes (clusters), and the sub-themes., Results: A total of 104 participants were enrolled, including 27 patients with complex chronic conditions (12 males, mean age = 11.1 ± 4.40), 33 parents, 6 siblings, 33 health professionals, and 5 teachers. Participants described the process of self-care through four main factors: "self-care", "external settings", "family", and "management". Five clusters (themes) were identified: (1) Self-care management (device; consulting); (2) Shift of agency (influencing factors; parents; school); (3) Self-care support (normal life and personal development; multidisciplinary support); (4) Daily self-care maintenance/monitoring; (5) Treatment adherence. Self-care management was mostly relevant for parents of children aged between 6 months and 3 years., Conclusion: The self-care process varies according to the needs related to the specific developmental age and the evolution of the clinical condition over time. The contribution of the family, health professionals, and social networks is fundamental for adequate self-care. To help families manage the unstable condition of their children at home, it is necessary to strengthen support networks implement home care, and ensure continuity of care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Spitaletta, Biagioli, Greco, Mascolo, Liburdi, Manzi, Gawronski, Ricci, Tiozzo, Vellone, Grimaldi Capitello, Salata, Raponi, Dall'Oglio and Self-care CYP Study Group.)

Heart failure (HF) represents a major health and economic issue, with increasing morbidity and mortality in spite of novel therapeutic weapons. The disappointing results of HF management may be due to the current therapeutic approach based on the paradigm "one fits all", that cannot apply to a complex and multifaceted syndrome as HF. At this regard, the European Union is developing policies to move from reductionism to precision medicine, in order to identify specific disease biomarkers and develop targeted therapeutic strategies. The institution of biobanks may represent the game changer in HF scenario, providing a collection of human biological materials with the related medical and epidemiological data fueling the development of personalized therapeutic approach and fostering current and/or future research projects., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. R. Badagliacca received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Bayer, Dompè, Ferrer, GSK, MSD. C.D. Vizza received fees for serving as a speaker, consultant and an advisory board member, from the following Companies: Actelion, Dompè, GSK, Italfarmaco, Lilly, Pfizer, United Therapeutics. The other authors reported no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pulmonary hypertension is a clinical syndrome that may include multiple clinical conditions and can complicate the majority of cardiovascular and respiratory diseases. Pulmonary hypertension secondary to left heart disease is the prevalent clinical condition and accounts for two-thirds of all cases. Type 2 diabetes mellitus, which affects about 422 million adults worldwide, has emerged as an independent risk factor for the development of pulmonary hypertension in patients with left heart failure. While a correct diagnosis of pulmonary hypertension secondary to left heart disease requires invasive hemodynamic evaluation through right heart catheterization, several scores integrating clinical and echocardiographic parameters have been proposed to discriminate pre- and post-capillary types of pulmonary hypertension. Despite new emerging evidence on the pathophysiological mechanisms behind the effects of diabetes in patients with pre- and/or post-capillary pulmonary hypertension, no specific drug has been yet approved for this group of patients. In the last few years, the attention has been focused on the role of antidiabetic drugs in patients with pulmonary hypertension secondary to left heart failure, both in animal models and in clinical trials. The aim of the present review is to highlight the links emerged in the recent years between diabetes and pre- and/or post-capillary pulmonary hypertension and new perspectives for antidiabetic drugs in this setting., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Complete Neanderthal skeletons are almost unique findings. A very well-preserved specimen of this kind was discovered in 1993 in the deepest recesses of a karstic system near the town of Altamura in Southern Italy. We present here a detailed description of the cranium, after we virtually extracted it from the surrounding stalagmites and stalactites. The morphology of the Altamura cranium fits within the Neanderthal variability, though it retains features occurring in more archaic European samples. Some of these features were never observed in Homo neanderthalensis, i.e. in fossil specimens dated between 300 and 40 ka. Considering the U-Th age we previously obtained (>130 ka), the morphology of Altamura suggests that the archaic traits it retains may have been originated by geographic isolation of the early Neanderthal populations from Southern Italy., (© 2023. The Author(s).)

Rationale: Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting., Methods: The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144-363 days) right heart catheterisation and risk assessment after initial oral combination therapy., Results: Group A included 96 (53.0%) patients without cardiac comorbidities; Group B included 54 (29.8%) patients with one cardiac comorbidity; Group C included 31 (17.1%) patients with two cardiac comorbidities or more. Group C patients were older with a balanced sex distribution. There was a significant difference in PVR reduction moving from the absence to one or at least two cardiac comorbidities, respectively: median -45.0%, -30.3%, -24.3%. A European Respiratory Society/European Society of Cardiology low-risk status was present at first follow-up in 50 (52.0%) patients in Group A, 19 (35.1%) in Group B and 9 (29.0%) in Group C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group A, 15 (27.7%) in Group B and 7 (22.6%) in Group C. Group A patients were 2.3 times more likely to achieve/maintain a low-risk status compared with Group B and C (OR 2.27, 95% CI 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities., Conclusion: Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR., Competing Interests: Conflict of interest: R. Badagliacca reports personal fees from UT, Dompè, Ferrer, Bayer, MSD and AOP Orphan Pharmaceuticals, outside the submitted work. M. D'Alto reports personal fees from Bayer, Dompè, GSK, MSD and Ferrer, outside the submitted work. C.D. Vizza reports personal fees from GSK, UT, Dompè, Bayer and MSD, outside the submitted work. The other authors have nothing to disclose., (Copyright ©The authors 2022.)

Objective: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19., Materials and Methods: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019., Results: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019., Conclusion: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools., Competing Interests: Conflict of Interest: All authors have nothing to disclose., (Copyright ©The authors 2022.)

Background: Over the past two decades randomized controlled trials of combination treatments for Pulmonary Arterial Hypertension (PAH) have demonstrated improvements of clinical status but only modest reductions in mean pulmonary arterial pressure (mPAP). Recent experiences with upfront combination treatments including parenteral prostacyclins have shown more substantial mPAP reductions, and have provided grounds for reconsiderations of treatment., Objectives: To evaluate the possibility of achieving mPAP <25 mmHg with current treatments, its determinants and the prognostic impact of mPAP reduction., Methods: 267 consecutive idiopathic, hereditary and drug and toxin-induced PAH patients treated with targeted therapies from three expert centers were followed with periodic clinical and hemodynamic assessments for survival detection., Results: Fifty-four (20.2%) patients achieved a mPAP <25 mmHg over 58 months (IQR 27-90) of treatment. Determinants of mPAP <25 mmHg were mPAP at diagnosis (HR 0.96, 95C.I. 0.93-0.98, p = 0.002) and an upfront combination strategy (double oral combination: HR 2.3, 95C.I. 1.10-4.76, p = 0.02; one oral plus parenteral prostanoid: HR 3.6, 95C.I. 1.39-9.37, p = 0.008; triple combination employing parenteral prostanoids: HR 12.9, 95C.I. 4.9-33.2, p = 0.0001). Seventy-three patients (27.3%) died. Survival rates were 90%, 79%, 70%, 55%, and 42% at 1, 3, 5, 10, and 15 years, respectively. Mean PAP during follow-up, days from diagnosis to prostanoid initiation and prostanoid maximum dose emerged as independent predictors of survival (Uno-C-index: 0.85). A mPAP ≤35 mmHg during follow-up was identified as the best cutoff value for prediction of survival., Conclusions: Reduction to a mean PAP ≤ 35 mmHg appears to be a meaningful treatment target in idiopathic, hereditary and drug and toxin-induced pulmonary arterial hypertension., Competing Interests: Declaration of Competing Interest R. Badagliacca received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Bayer, Dompé, AOP, Ferrer, GSK, MSD. C.D. Vizza received fees for serving as a speaker, consultant and an advisory board member, from the following Companies: Actelion, Dompè, GSK, Italfarmaco, Lilly, Pfizer, United Therapeutics. I. Lang reports grants and personal fees from Actelion-Janssen and AOP Orphan Pharma, personal fees from Medtronic, Ferrer and United Therapeutics, outside the submitted work. A. Ogawa reports personal fees from Nippon Shinyaku Co., Ltd., outside the submitted work. H. Matsubara reports personal fees from Actelion, AOP orphan Pharmaceuticals AG, Bayer, GlaxoSmithKline, Pfizer Japan, Inc., United Therapeutics, Nippon Shinyaku, Co., Ltd., and Kaneka Medix Corporation, outside the submitted work. H. Shimokawahara reports grants from Nippon shinyaku co.,ltd.; grants from Kaneka Corporation, grants from Bayer Taiwan Co., Ltd., grants from Bayer Yakuhin, Ltd., grants from Daiichi Sankyo company, Limited, grants from Japan Lifeline Co.,Ltd., grants from Actelion Pharmaceuticals Ltd., grants from Pfizer Inc., grants from Mochida Pharmaceutical Co.,Ltd., outside the submitted work. The other authors reported no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

One of the consequences of the big data revolution is that data are more heterogeneous than ever. A new challenge appears when mixed-type data sets evolve over time and we are interested in the comparison among individuals. In this work, we propose a new protocol that integrates robust distances and visualization techniques for dynamic mixed data. In particular, given a time t∈T={1,2,…,N}, we start by measuring the proximity of n individuals in heterogeneous data by means of a robustified version of Gower's metric (proposed by the authors in a previous work) yielding to a collection of distance matrices {D(t),∀t∈T}. To monitor the evolution of distances and outlier detection over time, we propose several graphical tools: First, we track the evolution of pairwise distances via line graphs; second, a dynamic box plot is obtained to identify individuals which showed minimum or maximum disparities; third, to visualize individuals that are systematically far from the others and detect potential outliers, we use the proximity plots, which are line graphs based on a proximity function computed on {D(t),∀t∈T}; fourth, the evolution of the inter-distances between individuals is analyzed via dynamic multiple multidimensional scaling maps. These visualization tools were implemented in the Shinny application in R, and the methodology is illustrated on a real data set related to COVID-19 healthcare, policy and restriction measures about the 2020-2021 COVID-19 pandemic across EU Member States.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is the most serious long-term complication of acute pulmonary embolism (PE) though it is the only potentially reversible form of pulmonary hypertension (PH). Its incidence is mainly limited to the first 2 years following the embolic event, however it is often underdiagnosed or misdiagnosed., Methods: This is a multicenter observational cross-sectional and prospective study. Patients with a prior diagnosis of PE will be enrolled and undergo baseline evaluation for prevalent PH detection through a clinical examination and an echocardiogram as first screening exam. All cases of intermediate-high echocardiographic probability of PH will be confirmed by right heart catheterization and then identified as CTEPH through appropriate imaging and functional examinations in order to exclude other causes of PH. A CTEPH Risk Score will be created using retrospective data from this prevalent cohort of patients and will be then validated on an incident cohort of patients with acute PE., Results: One thousand retrospective and 218 prospective patients are expected to be enrolled and the study is expected to be completed by the end of 2021. Up to now 841 patients (620 retrospective and 221 prospective) have been enrolled., Conclusions: This study is the first large prospective study for the prediction of CTEPH development in patients with PE. It aims to create a comprehensive scoring tool that includes echocardiographic data which may allow early detection of CTEPH and the application of targeted follow-up screening programs in patients with PE.

Background: COVID-19 pandemic severely affected national health systems, altering the modality and the type of care of patients with acute and chronic diseases. To minimize the risk of exposure to SARS-CoV2 for patients and health professionals, face-to-face visits were cancelled or postponed and the use of telemedicine was strongly encouraged. This reorganization involved especially patients with rare diseases needing periodic comprehensive assessment, such as pulmonary arterial hypertension (PAH)., Main Body: The paper reports a proposal of strategy adopted for patients followed at our PAH center in Rome, where patients management was diversified based on clinical risk according to the European Society of Cardiology/European Respiratory Society PH guidelines-derived score and the REVEAL 2.0 score. A close monitoring and support of these patients were made possible by policy changes reducing barriers to telehealth access and promoting the use of telemedicine. Synchronous/asynchronous modalities and remote monitoring were used to collect and transfer medical data in order to guide physicians in therapeutic-decision making. Conversely, the use of implantable monitors providing hemodynamic information and echocardiography-mobile devices wirelessly connecting was limited by the poor experience existing in this setting. Large surveys and clinical trials are welcome to test the potential benefit of the optimal balance between traditional PAH management and telemedicine opportunities., Conclusion: Italy was found unprepared to manage the dramatic effects caused by COVID-19 on healthcare systems. In this emergency situation telemedicine represented a promising tool especially in rare diseases as PAH, but was limited by its scattered availability and legal and ethical issues. Cohesive partnership of health care providers with regional public health officials is needed to prioritize PAH patients for telemedicine by dedicated tools., Competing Interests: Declaration of Competing Interest R. Badagliacca received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Bayer, Dompè, Ferrer, GSK, MSD. C.D. Vizza received fees for serving as a speaker, consultant and an advisory board member, from the following Companies: Actelion, Dompè, GSK, Italfarmaco, Lilly, Pfizer, United Therapeutics. The other authors reported no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The scenario of Homo sapiens origin/s within Africa has become increasingly complex, with a pan-African perspective currently challenging the long-established single-origin hypothesis. In this paper, we review the lines of evidence employed in support of each model, highlighting inferential limitations and possible terminological misunderstandings. We argue that the metapopulation scenario envisaged by pan-African proponents well describes a mosaic diversification among late Middle Pleistocene groups. However, this does not rule out a major contribution that emerged from a single population where crucial derived features-notably, a globular braincase-appeared as the result of a punctuated, cladogenetic event. Thus, we suggest that a synthesis is possible and propose a scenario that, in our view, better reconciles with consolidated expectations in evolutionary theory. These indicate cladogenesis in allopatry as an ordinary pattern for the origin of a new species, particularly during phases of marked climatic and environmental instability., (© 2022 The Authors. Evolutionary Anthropology published by Wiley Periodicals LLC.)

Purpose: A hypercoagulable state has been reported to cause potential sight-threatening ischemia in patients suffering from Coronavirus disease 2019 (COVID-19). This study aimed to determine whether vessel density (VD), as measured by optical coherence tomography angiography (OCT-A), has insights into retinal and choriocapillaris vascular changes in patients affected by SARS-CoV-2 infection., Methods: Hundred and fifty two patients positive for SARS-CoV-2 infection were enrolled in this observational, retrospective, controlled study. A control group of 60 healthy subjects was selected for statistical comparisons. Raw OCT and OCT-A data were exported and 3D datasets were analyzed to determine VD., Results: Hundred and forty eyes (92.1%) were included for final analysis. The VD of the superficial capillary plexus (SCP) did not differ between the two groups. The mean VD of the deep capillary plexus (DCP) and the choriocapillaris (CC) was significantly lower in the foveal sector of the COVID-19 group compared to healthy controls. Within the post-COVID-19 group, the lowest DCP and CC foveal VD values were recorded in patients treated with antiviral therapy; no differences were observed among COVID-19 patients with other comorbidities (hypertension, diabetes, thyroid disease) or taking antiplatelet therapy. DCP and CC foveal VD were significantly lower in patients hospitalized in an intensive care unit (ICU) than asymptomatic patients., Conclusion: Foveal vessel density at the level of DCP and CC was reduced in post-COVID-19 patients. Further studies evaluating these changes over time will be needed to corroborate the hypothesis of a microvascular retinal impairment in individuals who have recently recovered from SARS-CoV-2 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chiosi, Campagna, Rinaldi, Manzi, dell'Omo, Fiorentino, Toro, Tranfa, D'Andrea, Rejdak and Costagliola.)

A comprehensive PAH echocardiographic examination of patients with pulmonary arterial hypertension (PAH) should include a set of parameters resembling the pathophysiological changes occurring in the course of the disease. This approach could help clinicians build a complete picture of the patient, test the effects of targeted therapies and identify patients who need a more aggressive therapeutic approach to achieve a low risk-status.

Background: Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing in this setting remains undefined., Methods: Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n = 124) and externally validate (n = 143) the prognostic model. Cross-validation on the overall population was used to strengthen the results of the analysis. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. Discrimination and calibration were assessed., Results: A risk score was constructed based on the beta-coefficient of the cross-validated model, including the stroke volume index (SVI) and the peak oxygen uptake (VO 2 peak). Patients were grouped based on cutoff values of the risk score allowing the highest discrimination in the overall cohort. Group 1, score ≤2 (101 patients) with VO 2 peak ≥14 ml/kg/min and SVI >30 ml/m 2 ; Group 2, score between 2 and 5 (112 patients) with VO 2 peak between 9 and 14 ml/kg/min, and SVI between 20 and 50 ml/m 2 ; Group 3, score >5 (46 patients) with VO 2 peak <10 ml/kg/min and SVI <30 ml/m 2 . The event-free survival rates at 1, 2 and 3 years, were 96%, 83% and 79% for Group 1, respectively; 82%, 67% and 52% for Group 2; 69%, 50% and 41% for Group 3., Conclusions: Combinations of VO 2 peak and SVI may provide important information to further stratify intermediate-risk prevalent patients with idiopathic PAH., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The response to the COVID-19 pandemic has been highly variable. Governments have applied different mitigation policies with varying effect on social and economic measures, over time. This article presents a methodology for examining the effect of mobility restriction measures and the association between health and population activity data. As case studies, we refer to the pre-vaccination experience in Italy and Israel. Facing the pandemic, Israel and Italy implemented different policy measures and experienced different population behavioral patterns. Data from these countries are used to demonstrate the proposed methodology. The analysis we introduce in this paper is a staged approach using Bayesian Networks and Structural Equations Models. The goal is to assess the impact of pandemic management and mitigation policies on pandemic spread and population activity. The proposed methodology models data from health registries and Google mobility data and then shows how decision makers can conduct scenario analyses to help design adequate pandemic management policies.

Background: To investigate the effects of a fixed combination of Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) on vascular parameters in mild to moderate diabetic macular edema (DME). Design: Prospective, case-control study. Methods: Fifty-six patients affected by diabetes mellitus type II were enrolled in the study. Twenty-eight patients with DME received 2 tablets/day, before meals of a dietary complementary supplement containing in fixed combination Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) (Intravit®, OFFHEALTH Spa, Firenze, Italy) for 6 months. Twenty-eight age-matched subjects affected by diabetes mellitus type II were given placebo and served as control group. Patients underwent best correct visual acuity (BCVA), swept optical coherence tomography (OCT), and OCT-Angiography (OCTA). OCTA images of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were obtained for each eye. By the end of the follow-up patients were defined responder to the therapy when a decrease of more than 30 μm was registered in central retinal thickness (CRT) measurement, while a poor responder was determined by the absence of reduction or an increase in central retinal thickness at 6 months. We assessed the foveal avascular zone (FAZ) area, vessel density and quantified the number of microaneurysms in each layer. Results: A significant improvement of BCVA and CRT reduction was recorded at 6 months follow-up in the dietary complementary supplementation group compared to control (respectively p = 0.028 and p = 0.0003). VD of the total capillary plexus, microaneurysms count, glycaemia and HbA1c did not vary over the follow-up period between groups. Within the Intravit® group, poor responders tended to show a larger FAZ area, more microaneurysms, and a lower VD in the DCP compared to the good responders group (p < 0.0001). Conclusions: A fixed combination of Curcumin, Artemisia, Bromelain, and Black pepper oral administration may have a positive impact on central retinal thickness, visual acuity, and VD of the DCP in compensated type 2 diabetic patients with mild DME.

Several porcupine taxa are reported from the middle Miocene to the early Holocene in the Old World. Among these, five species of the subfamily Hystricinae occurred in Africa approximately in the last 6 Ma: the extinct Hystrix makapanensis , Hystrix leakeyi , and Xenohystrix crassidens and the still living Hystrix africaeaustralis and Hystrix cristata . The large-sized H. makapanensis is reported from numerous sites in East and South Africa between the early Pliocene and Early Pleistocene. In this paper, we describe a new mandible of H. makapanensis from the world-renowned Tanzanian paleontological and archeological site of Olduvai Gorge (HWK West; lowermost Bed II; ca. 1.8-1.7 Ma). The discovery of the new mandible triggered a comprehensive review of the entire African record of H. makapanensis . In particular, we describe or re-analyze the samples from South Africa (Makapansgat Limeworks, Gondolin, Kromdraai, Swartkrans, and Sterkfontein), Tanzania (Olduvai and Laetoli), Ethiopia (Omo Shungura and Hadar), and Kenya (Chemeron), enriching the quantity of specimens confidently referable to this species and above all improving the information on its craniodental anatomy. On this basis, we: (1) propose an emended diagnosis of H. makapanensis ; (2) point out the morphological and biometric differences between H. makapanensis and other African Hystricinae (also in terms of body mass); and (3) broaden the knowledge on the geographical and chronological distribution of this extinct species., Supplementary Information: The online version contains supplementary material available at 10.1007/s10914-021-09588-z., Competing Interests: Conflict of InterestThe authors declare that they have no known competing financial interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Precision medicine, providing the right therapeutic strategy for the right patient, could revolutionize management and prognosis of patients affected by cardiovascular diseases. Big data and artificial intelligence are pivotal for the realization of this ambitious design. In the setting of pulmonary arterial hypertension (PAH), the use of computational models and data derived from ambulatory implantable hemodynamic monitors could provide useful information for tailored treatment, as requested by precision medicine.

The Fuegians, ancient inhabitants of Tierra del Fuego, are an exemplary case of a cold-adapted population, since they were capable of living in extreme climatic conditions without any adequate clothing. However, the mechanisms of their extraordinary resistance to cold remain enigmatic. Brown adipose tissue (BAT) plays a crucial role in this kind of adaptation, besides having a protective role on the detrimental effect of low temperatures on bone structure. Skeletal remains of 12 adult Fuegians, collected in the second half of XIX century, were analyzed for bone mineral density and structure. We show that, despite the unfavorable climate, bone mineral density of Fuegians was close to that seen in modern humans living in temperate zones. Furthermore, we report significant differences between Fuegians and other cold-adapted populations in the frequency of the Homeobox protein Hox-C4 (HOXC4) rs190771160 variant, a gene involved in BAT differentiation, whose identified variant is predicted to upregulate HOXC4 expression. Greater BAT accumulation might therefore explain the Fuegians extreme cold-resistance and the protection against major cold-related damage. These results increase our understanding of how ecological challenges have been important drivers of human-environment interactions during Humankind history., (© 2021. The Author(s).)

Purpose: Gastrocnemius recession has been described in the treatment of gastrocnemius contracture. The aims of this study were: (1) to assess the change in ankle dorsiflexion after isolated medial gastrocnemius recession performed according to L.S. Barouk's technique; (2) to compare ankle dorsiflexion after isolated medial head with complete proximal gastrocnemius recession., Methods: A cadaveric study was performed on 15 lower limb adult specimens. Isolated medial gastrocnemius head recession was initially performed, followed by an additional recession of the lateral gastrocnemius head. Ankle dorsiflexion torque was applied with 2 and 4 kg forces on second metatarsal head. Ankle dorsiflexion was measured with the knee both in extension and at 90° of flexion and values were recorded before surgery (T0), after medial head recession (T1) and after both heads recession (T2). Normality of data was assessed using the Shapiro-Wilk test, then measurements were compared in the three conditions with appropriate statistical tests., Results: After isolated medial gastrocnemius recession (Δ = T1-T0), ankle dorsiflexion assessed with the knee in extension significantly increased by 5° ± 3 (range, -2 to 10) with a 2-kg torque (p = 0.02) and by 4.5° ± 3 (range, -4 to 10) with a 4-kg torque (p = 0.04). No significant difference was observed with the knee flexed at 90° (p > 0.05 for all measurements). After both gastrocnemius heads recession (Δ = T2-T1), although a further increase in dorsiflexion was noticed, statistical significance was not reached neither with the knee in extension nor at 90° of flexion (p > 0.05 for all measurements)., Conclusion: In this study, isolated medial gastrocnemius head recession performed according to LS Barouk's technique was effective in improving ankle dorsiflexion, whereas the additional release of the lateral head did not produce any significant change., Level of Evidence: Level V, cadaveric study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The arrival of the Longobards in Italy represents one of the most significant periods of the Early Middle Ages. Such arrival had social and political implications, particularly in relation to cultural admixture with local communities. One way to understand this is through the reconstruction of paleodiet via stable isotope analysis. So far, the subsistence strategy of this population in central Italy remains poorly explored. Stable carbon and nitrogen isotope analyses are presented here on a total of 19 human bone collagen samples from the cemetery of Castel Trosino. This isotopic investigation contributes to the dietary reconstruction of Early Medieval populations in Italy, providing a crucial isotopic dataset for an area still poorly explored., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2021 The Authors. Published by Elsevier Inc.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe and under-recognized complication of acute pulmonary embolism (PE). Forty consecutive patients with acute PE (Group 1), predominantly female (22, 55%) with a mean age of 69 ± 15 years, were matched for demographic data with 40 healthy subjects (Group 2), 40 systemic hypertension patients (Group 3) and 45 prevalent idiopathic pulmonary arterial hypertension (IPAH) patients (Group 4). The baseline evaluation included physical examination, NYHA/WHO functional class, right heart catheterization (RHC) limited to IPAH patients, echocardiographic assessment and systemic arterial stiffness measurement by cardio-ankle vascular index (CAVI). Patients with PE underwent an echocardiographic evaluation within 1 month from hospital discharge (median 27 days; IQR 21-30) to assess the echo-derived probability of PH. The CAVI values were significantly higher in the PE and IPAH groups compared with the others (Group 1 vs. Group 2, p < 0.001; Group 1 vs. Group 3, p < 0.001; Group 1 vs. Group 4, p = ns; Group 4 vs. Group 2, p < 0.001; Group 4 vs. Group 3, p < 0.001; Group 2 vs. Group 3, p = ns). The predicted probability of echocardiography-derived high-risk criteria of PH increases for any unit increase of CAVI (OR 9.0; C.I.3.9-20.5; p = 0.0001). The PE patients with CAVI ≥ 9.0 at the time of hospital discharge presented an increased probability of PH. This study highlights a possible positive predictive role of CAVI as an early marker for the development of CTEPH.

In this paper, we develop a forecasting model for the spread of COVID-19 infection at a provincial (i.e., EU NUTS-3) level in Italy by using official data from the Italian Ministry of Health integrated with data extracted from daily official press conferences of regional authorities and local newspaper websites. This data integration is needed as COVID-19 death data are not available at the NUTS-3 level from official open data channels. An adjusted time-dependent SIRD model is used to predict the behavior of the epidemic; specifically, the number of susceptible, infected, deceased, recovered people and epidemiological parameters. Predictive model performance is evaluated using comparison with real data.

Objective: This study aims to investigate parasitic infection in Italy during the Roman period (27 BCE-476 CE) and subsequent Longobard (Lombard) period (6th-8th CE)., Materials: Sediment samples from drains and burials from Roman Imperial-period sites in Italy (Lucus Feroniae, Oplontis, Vacone, and Vagnari), Late Antique and Longobard-period burials at Selvicciola (ca. 4th-8th CE), and Longobard-period burials at Vacone and Povegliano Veronese., Methods: Microscopy was used to identify helminth eggs and enzyme-linked immunosorbent assay (ELISA) to detect protozoan antigens., Results: Roundworm and whipworm were found in pelvic sediment from Roman-period burials, while roundworm and the protozoan Giardia duodenalis were identified in Roman-period drains. In pelvic sediment from the Late Antique through Longobard periods, roundworm and Taenia tapeworm eggs were identified., Conclusions: Fecal-oral parasites were found throughout Imperial Roman Italy, suggesting that gastrointestinal infections caused a significant disease burden. In the Longobard period we see continuity in transmission of fecal-oral parasites, and the appearance of zoonotic parasites acquired from eating undercooked meat., Significance: A wealth of information exists about certain diseases in the Roman period, but relatively little is known about intestinal parasites in Italy during the Roman and Longobard periods. This is the first evidence for Giardia in Roman period Italy, and for any parasites in the Longobard period in Italy., Limitations: Low egg concentrations and lack of controls for some samples makes it difficult to differentiate true infections from environmental contamination in some cases., Suggestions for Future Research: Continual study of samples from Roman and Longobard period Italy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The coronavirus disease 2019 (COVID-19) epidemic is an infectious disease which was declared a pandemic and hit countries worldwide from the beginning of the year 2020. Despite the emergency vigilance plans, health systems in all countries experienced a different ratio of lethality, amount of admissions to intensive care units and quarantine management of positive patients. The aim of this study is to investigate whether some epidemiological estimates could have been useful in understanding the capacity of the Italian Regional Health Services to manage the COVID-19 epidemic., Methods: We have compared data between two different Italian regions in the Northern part of Italy (Lombardy and Veneto) and the national data to determine whether different health strategies might be significant in explaining dissimilar patterns of the COVID-19 epidemic in Italy. Data have been extracted from a public database and were available only in an aggregated form., Results: The regions in question displayed two different health policies to face the COVID-19 epidemic: while Veneto's health service was largely territorially oriented, Lombardy's strategy was more hospital-centered., Discussion: The key to facing epidemics like this one consists in identifying solutions outside of hospitals. This however requires there be well-trained general practitioners and enough healthcare personnel working outside hospitals., Competing Interests: Prof. Dr Massimo Galli reports grants, personal fees, non-financial support from MSD, GS, ViiV, AbbVie, JC, outside the submitted work. The authors declare that the research was conducted in the absence of any other commercial or financial relationships that could be construed as a potential conflict of interest., (© 2021 Castaldi et al.)