[The Italian law 219/2017: informed consent and advance directives. When the patient-doctor communication time is law, but it is forgotten]. / Legge 219/2017: consenso informato e disposizioni anticipate di trattamento. Quando il tempo della comunicazione medico-paziente è legge, ma viene dimenticato.

The Italian law 217/2019 on "Informed consent and advance directives" is an important step forward in the redefinition of patient-doctor relationships. The law points out the principles of the decisional autonomy and freedom of the patient to choose the treatment options. However, it is underestimated and largely unapplied by the Italian cardiologists. The main elements of patient-doctor communication are present in the law. The most important is the time devoted to the patient-doctor relationship, necessary to ease the disease awareness. This time is clearly emphasized in the law, but the healthcare institutions did not arrange for the appropriate organizational procedures. Through the advance directives (ADs) the patients may express their own wishes about healthcare treatments, as well as their consent or refusal regarding the diagnostic or therapeutical doctors' suggestions, allowing their respect in case they become incompetent. This right is supported by the patients' designation of a healthcare proxy, who can interact for them with the healthcare team. However, after 6 years since the law enactment, only 0.4% of the Italian citizens signed ADs, due to insufficient information and organization by the healthcare authorities. In the Law, the advance care planning is closely related to ADs. In this process, the adults can understand and share their personal values, life goals and preferences, in order to define the potential future medical care and to discuss all the issues with family and physicians. These processes can be integrated in a broader shared decision-making, a strong tool of the patient-doctor alliance.

Reproductive and obstetric outcomes in TESE-ICSI cycles: A comparison between obstructive and non-obstructive azoospermia.

PURPOSE: Comparison of intracytoplasmic sperm injection cycles with testicular sperm extraction in obstructive azoospermia and non-obstructive azoospermia are limited, and few studies have addressed obstetric and neonatal outcomes. DESIGN: This study analyzed couples who underwent testicular sperm extraction-intracytoplasmic sperm injection cycles for obstructive azoospermia and non-obstructive azoospermia to determine whether impaired spermatogenesis in non-obstructive azoospermia patients would lead to worse reproductive outcomes and higher rates of pregnancy complications and fetal anomalies. This study is a retrospective, single-center analysis of all testicular sperm cycles performed between January 1, 2001 and December 31, 2020. RESULTS: A total of 392 couples were considered in the study, leading to 1066 induction cycles, 620 (58.2%) from patients with obstructive azoospermia and 446 (41.8%) from non-obstructive azoospermia. The cumulative delivery rate did not significantly differ between the two groups (34% vs. 31%; p = 0.326). The miscarriage rate was similar between obstructive azoospermia and non-obstructive azoospermia patients. Fertilization rate instead showed a statistically significant difference (obstructive azoospermia: 66.1 ± 25.7 vs. non-obstructive azoospermia: 56.1 ± 27.0; p < 0.001). The overall maternal complication rate in the non-obstructive azoospermia group was higher (10.7% vs. 18.4%; p = 0.035), but there was no statistical significance for each pathology. There was no statistical difference in gestational age between the two groups for both single and twin pregnancies. Seven cases of congenital defects occurred in the obstructive azoospermia group, while two cases occurred in the non-obstructive azoospermia group. CONCLUSIONS: Despite impaired spermatogenesis in non-obstructive azoospermia patients, there were no substantial differences in reproductive outcomes compared to patients with obstructive azoospermia, even in terms of obstetric safety and neonatal well-being.

High sperm DNA fragmentation: do we have robust evidence to support antioxidants and testicular sperm extraction to improve fertility outcomes? a narrative review.

To date, infertility affects 10% to 15% of couples worldwide. A male factor is estimated to account for up to 50% of cases. Oral supplementation with antioxidants could be helpful to improve sperm quality by reducing oxidative damage. At the same time, there is a growing interest in the literature on the use of testicular sperm in patients with high DNA fragmentation index (DFI). This narrative review aims to evaluate the effectiveness of supplementation of oral antioxidants in infertile men with high DFI compared to testicular sperm retrieval. The current evidence is non-conclusive because of serious risk of bias due to small sample sizes and statistical methods. Further large well-designed randomised placebo-controlled trials are still required to clarify the exact role of these to different therapeutic approaches.

Ten Questions and Some Reflections about Palliative Care in Advanced Heart Failure Patients.

Heart failure is a clinical syndrome with increasing prevalence, high morbidity and mortality. It is characterized by high symptom burden, poor quality of life and high economic costs. This implies that the heart failure (HF) patients who receive palliative care (PC) have needs similar to cancer patients, but which are often unmet. This paper analyzes the main unresolved issues regarding the relationship between HF patients and the referral to an early PC program. These issues are presented as ten questions related to which patients should be admitted to PC and at what stage of their disease. Furthermore, the barriers opposing to referral to PC, the role of cardiologists and PC physicians within the care team, the gap between the scientific societies' suggestions and the real world, the right time to promote patients' awareness and shared decision making, regarding prognosis, end of life wishes and choices, with reference also to cardiac implantable devices' deactivation, are discussed. These unresolved questions support the need to reevaluate programs and specific models in achieving equal access to palliative care interventions for HF patients, which is still mainly offered to patients with cancer.

Palliative Care for Patients with End-Stage, Non-Oncologic Diseases-A Retrospective Study in Three Public Palliative Care Departments in Northern Italy.

Patients with irreversible malignant and non-malignant diseases have comparable mortality rates, symptom burdens, and quality of life issues; however, non-cancer patients seldom receive palliative care (PC) or receive it late in their disease trajectory. To explore the characteristics of non-cancer patients receiving PC in northern Italy, as well as the features and outcomes of their care, we retrospectively analyzed the charts of all non-cancer patients initiating PC regimens during 2019 in three publicly funded PC departments in Italy's populous Lombardy region. We recorded the baseline variables (including data collected with the NECPAL CCOMS-ICO-derived questionnaire used since 2018 to evaluate all admissions to the region's PC network), as well as treatment features (setting and duration) and outcomes (including time and setting of death). Of the 2043 patients admitted in 2019, only 12% (243 patients­131 females; mean age 83.5 years) had non-oncological primary diagnoses (mainly dementia [n = 78], heart disease [n = 55], and lung disease [n = 30]). All 243 had Karnofsky performance statuses ≤ 40% (10−20% in 64%); most (82%) were malnourished, 92% had ≥2 comorbidities, and 61% reported 2−3 severe symptoms (pain, dyspnea, and fatigue). Fifteen withdrew or were discharged from the study PCN; the other 228 remained in the PCN and died in hospice (n = 133), at home (n = 9), or after family-requested transfer to an emergency department (n = 1). Most deaths (172/228, 75%) occurred <3 weeks after PC initiation. These findings indicate that the PCN network we studied cares for few patients with life-limiting non-malignant diseases. Those admitted have advanced-stage illness, heavy symptom burdens, low performance statuses, and poor survival. Additional efforts are needed to improve PCN accessibility for non-cancer patients.

[ANMCO Position paper: Care pathway for advanced heart failure patients candidate for heart transplantation/ventricular assist device]. / Position paper ANMCO: Percorso assistenziale del paziente con insufficienza cardiaca avanzata candidabile a trapianto/assistenza ventricolare meccanica.

Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.

Is the lack of prior exposure to sperm antigens associated with worse neonatal and maternal outcomes? A 10-year single-center experience comparing ICSI-TESE pregnancies to ICSI pregnancies.

BACKGROUND: Nowadays, pathogenesis of preeclampsia (PE) is still unknown. Among the different etiological hypotheses, some authors proposed that it might be because of an abnormal immunologic response to a foreign fetal antigen derived from the father's spermatozoa. Indeed, the fetus is considered a semi-allograft, being one half paternally derived in its antigenicity, and the first pathogenic insult of PE may be an abnormal maternal immune response toward this semi-allogenic implant. In the context of artificial reproductive techniques, it has been shown that the use of donor and surgically retrieved spermatozoa (e.g., testicular sperm extraction [TESE]) increases the risk of PE, confirming the protective effect of sperm exposure on maternal complications. OBJECTIVE: Determining whether the lack of exposure to sperm antigens is associated with worse maternal and neonatal outcomes in pregnancies obtained through intracytoplasmic sperm injection after TESE (ICSI-TESE) for obstructive azoospermia (OA). MATERIALS AND METHODS: This is a single-center case-control retrospective study, focusing on all first pregnancies obtained through ICSI-TESE for OA at Humanitas Fertility Center between January 1, 2010 and December 31, 2019. Controls included patients that achieved their first pregnancy with ICSI and ejaculated spermatozoa, for a diagnosis other than azoospermia, in the same time period. Cases were matched with controls in a 1:2 ratio, considering female age, female BMI, and year of controlled ovarian stimulation. The primary outcome measure was the delivery rate, defined as the number of deliveries divided by the total number of clinical pregnancies. Secondary outcome measures focused on maternal and neonatal complications, such as miscarriage rate, rate of main obstetric complications, prematurity rate, and rate of congenital malformations. RESULTS: By analyzing overall 113 pregnancies among cases and 214 pregnancies among controls, this study showed that the delivery rate was higher in controls with respect to cases (92.06% vs. 84.07%, p = 0.026); among deliveries, live births were 98.95% and 100%, respectively, whereas only one stillbirth occurred in cases. The first trimester miscarriage rate was higher in the cases than controls (13.27% vs. 6.07%, p = 0.027), whereas no difference was found among the rate of second trimester miscarriages, therapeutic abortions, and ectopic pregnancies. There was no difference regarding the rate of maternal complications, including gestational hypertension, PE, HELLP syndrome, gestational diabetes, placenta previa, placental abruption, and premature rupture of the membranes. Considering neonatal complications, it was shown that twins belonging to controls had a higher prematurity rate with respect to cases (65.79% vs. 50.00%) but without a statistical relevance. Lastly, the rate of congenital malformations did not differ among the two groups. DISCUSSION: This study showed that, once couples diagnosed with OA achieve a pregnancy, they have a much higher risk of miscarriage in the first trimester in respect to non-azoospermic patients. Moreover, controls had a higher delivery rate in respect to cases; however, when the fetal status at birth was compared, no difference was found between live births and stillbirths. CONCLUSIONS: Differently from the findings in the literature, no association with PE was found. This might be related to a collider bias/left truncation bias: As azoospermic patients are at higher risk of early termination of pregnancy, it results that they do not have the possibility to develop PE and other adverse outcomes.

Influence of inguinal hernia repair on sperm autoimmunity: The largest single center experience.

BACKGROUND: Studies on immunological infertility after inguinal hernia correction are few and not very representative. Anti-sperm antibodies have been shown to reduce male fertility. Although the extent of infertility due to anti-sperm antibodies alone is not very clear, data indicates that about 8%-10% of infertile patients have immunological infertility DESIGN: This retrospective study includes all infertile male patients (n = 2258) who underwent mixed antiglobulin reaction tests and urologic examination from 2000 to 2020. Sperm quality (assessed by the number of spermatozoa, their motility, vitality, and normal form) was also evaluated. Among these patients, 191 had previously undergone unilateral or bilateral inguinal hernia surgery repair. The aim of the study is to evaluate if there is a higher incidence of positive mixed antiglobulin reaction test among patients undergoing inguinal hernioplasty compared to the unselected infertile population. RESULTS: Anti-sperm antibodies would seem to increase in both patients who performed general andrological surgery and groin hernia correction, respectively 3.48 (95% Confidence Interval: 1.70-7.10; p < 0.001) and 2.45 (95% Confidence Interval: 1.01-5.99; p < 0.05) times more than the unselected infertile population. CONCLUSIONS: Mixed antiglobulin reaction test could be useful in patients undergone previous scrotal surgery or hernia correction men, to avoid false unexplained infertility diagnoses and to direct the couple to assisted reproductive technology procedures. Basal evaluation of spermatozoa does not actually consider andrological surgery as an indication to autoimmunity investigation.

[Between intensive care and palliative care at the time of CoViD-19.] / Fra cure intensive e cure palliative ai tempi di CoViD-19.

The pandemic infection caused by the virus SARS-CoV-2 has determined a severe imbalance between demand and actual supply of intensive care. The shortage of intensive care units (ICU) beds and ventilators for the treatment of patients with severe respiratory failure produced angst in the clinicians/intensivists who have to decide which patients admit to ICU and in which patients to implement palliative care. They have to apply specific clinical and ethical criteria, in emergency conditions. Proportionality and appropriateness criteria should be integrated with equity, equality, utility criteria, widening the distributive justice concept from the right of the patient to receive all available therapies to a right resources allocation during shortage, guided by public health ethic. The clinical criteria should include the disease severity, the number and severity of comorbidities, frailty, the organ failures and their stage, the patient's age, the functional autonomy and cognitive status. Consequently the first come-first served rule to ICU admission should not be applied. The patients not admitted to ICU due to clinical reasons and advanced stage diseases should receive a high quality palliative care, to obtain a good symptoms control (mainly dyspnea, anxiety and delirium) and to implement palliative sedation at the end of life. Finally particular attention should be paid to the bereavement management of the family/caregivers and in the right approach of psychological problems and Post-Traumatic Stress Disorder of health workers involved in the pandemia.

[Selection criteria to cardiac surgery, transcatheter valvular interventions, electrophysiology and pacing procedures in patients with advanced heart failure]. / Criteri per la selezione del paziente con scompenso cardiaco avanzato alle procedure di cardiochirurgia, interventistica valvolare, elettrofisiologia ed elettrostimolazione.

Prognosis of advanced heart failure (HF) patients, often elderly, frail and with multiple comorbidities, has significantly improved due to recent advancements in interventional cardiology. A multidisciplinary approach is essential in order to better identify patients that could benefit from invasive procedures, avoiding futility. For patients with HF, the Multidimensional Prognostic Index could help the clinician in predicting not only the prognosis but also future quality of life. For cardiac surgical candidates, predictive scores should combine traditional mortality scores with geriatric parameters including nutritional status, screening of delirium, disabilities and comorbidities, in order to help the Heart Team in taking the right approach (i.e. conservative vs invasive strategies). Similarly, the indication to the implantation of a cardioverter-defibrillator or to ablative procedures should consider both the complication rates and the real impact on the quality of life considering the expected net clinical benefit.In the terminal stages of HF the therapeutic target should be oriented to a palliative care approach. In this perspective, the figure of the palliativist plays a role of growing interest and should be integrated into the HF multidisciplinary team.

[Implantable cardiac device deactivation at the end of life]. / La disattivazione dei dispositivi cardiaci impiantabili alla fine della vita.

Treatment of patients with heart failure is based on drugs, cardiac surgery and implantable cardiac devices to prevent sudden cardiac death (implantable cardioverter-defibrillator [ICD]), to reverse left ventricular dysfunction associated with left bundle branch block (cardiac resynchronization therapy) or mechanical circulatory support in more advanced phases of heart failure (left ventricular assist devices [LVAD]).During the follow-up, patients may die from progression of their underlying heart disease or from non-arrhythmic causes, such as malignancies, multi-organ failure, stroke, etc., without benefits by implanted devices. Patients implanted with ICD could die from non-arrhythmic causes, without appropriate shocks until the last few days or weeks of their life. These events occur roughly in 30% of patients, mainly in the last 24 h before death. LVAD therapy may induce significant complications, such as infections, hemorrhagic stroke, thromboembolism, right ventricular failure. In these cases, inappropriate and even appropriate shock deliveries by ICD can no longer prolong life and may simply lead to pain and reduced quality of life, as well as LVAD may prolong life with painful distress due to complications. Therefore, it appears important to discuss early with the patients and their relatives about deactivation of ICD or LVAD at the end of life. The goal of this paper is to provide an overview of the ethical, clinical and communication issues of cardiac implanted device deactivation, with a special focus on issues associated with advance care planning, which require shared decision-making, including those related to end of life decisions (advance directives). Palliative care should be early implemented, particularly in patients with LVAD.

[Palliative care and heart failure: some remarks about cost-effectiveness and clinical results]. / Cure palliative e scompenso cardiaco: considerazioni su costo-efficacia e risultati clinici.

Early palliative care (PC) clearly demonstrated its efficacy in patients with heart failure (HF), reducing symptom burden, mainly pain and depression, improving quality of life, and reducing the access to the health care system. However, there are not conclusive data on economic cost reduction. The reasons are related to the few patients involved in the studies dedicated to this topic, to the different clinical settings, different modalities of provision and funding of PC, and different timing of PC implementation. PC was not shown to reduce mortality nor hospital readmissions in randomized trials.The unanswered questions will be clarified only in larger studies, defining specific clinical settings, goals to achieve and standardizing the provision and funding modalities in the different countries.

[Information to be provided to patients and their caregivers. The Italian Law 219/2017 on informed consent, advance directives, and do not attempt resuscitation order]. / Informazione al malato e alla famiglia. Legge 219/2017: pianificazione condivisa delle cure, disposizioni anticipate di trattamento, "do not attempt resuscitation order".

The Italian law 219/2017, enacted on January 31, 2018, regulates patients' informed consent, personalized care planning and advance directives. The law provides for patient's self-determination in all phases of life. This also applies to patients suffering from chronic, progressive, terminal disease such as heart failure. In fact, the clinical and psychosocial trajectory for heart failure patients demands an interdisciplinary, systemic approach. Advance directives should be tailor-made to patient's needs and dynamically updated through the course of the disease according to patient's and family informed and shared decision-making. Healthcare professionals will require education and training to stay up to the task both clinically, psychologically and emotionally.

Barriers to Early Utilization of Palliative Care in Heart Failure: A Narrative Review.

Palliative care is indicated in patients with heart failure since the early phases of the disease, as suggested by international guidelines. However, patients are referred to palliative care very late. Many barriers could explain the gap between the guidelines' indications and clinical practice. The term palliative is perceived as a stigma by doctors, patients, and family members because it is charged with negative meanings, a poor prognosis, and no hope for improvement. Many authors prefer the term supportive care, which could facilitate a discussion between doctors, patients, and caregivers. There is substantial variation and overlap in the meanings assigned to these two terms in the literature. Prognosis, as the main indication to palliative care, delays its implementation. It is necessary to modify this paradigm, moving from prognosis to patients' needs. The lack of access to palliative care programs is often due to a lack of palliative care specialists and this shortage will be greater in the near future. In this study, a new model is proposed to integrate early over the course of the disease the palliative care (PC) specialist in the heart failure team, allowing to overcome the barriers and to achieve truly simultaneous care in the treatment of heart failure (HF) patients.

Facilitating supportive care in cardiac intensive care units.

PURPOSE OF REVIEW: The number of patients who die in the hospital in the Western world is high, and 20-30% of them are admitted to an ICU in the last month of life, including those in cardiac ICUs (CICUs) where invasive procedures are performed and mortality is high. Palliative consultation is provided in only a few cases. The ethical and decisional aspects associated with the advanced stages of illness are very rarely discussed. RECENT FINDINGS: The epidemiological and clinical landscape of CICUs has changed in the last decade; the incidence of acute coronary syndromes has decreased, whereas noncardiovascular diseases, comorbidities, the patients' age and clinical and therapeutic complexity have increased. The use of advanced and invasive treatments, such as mechanical ventilation, mechanical circulatory support and renal replacement therapies, has increased. This evolution increases the possibility of developing a life-threatening clinical event. SUMMARY: This review aimed to analyze the main epidemiological, clinical, ethical and training aspects that can facilitate the introduction of supportive/palliative care programs in the CICU to improve symptom management during the advanced/terminal stages of illness, and address such issues as advance care planning, withdrawing/withholding life-sustaining treatments, deactivation of implantable defibrillators and palliative sedation.

Cardiopulmonary exercise testing and echocardiographic exam: an useful interaction.

Cardiopulmonary exercise test (CPET) is a functional assessment that helps to detect disorders affecting the system involved in oxygen transport and utilization through the analysis of the gas exchange during exercise. The clinical application of CPET is various, it including training prescription, evaluation of treatment efficacy and outcome prediction in a broad spectrum of conditions. Furthermore, in patients with shortness of breath it provides pivotal information to bring out an accurate differential diagnosis between physical deconditioning, cardiopulmonary disease and muscular diseases. Modern software allows the breath-by-breath analysis of the volume of oxygen intake (VO2), volume of carbon dioxide output (VCO2) and expired air (VE). Through this analysis, CPET provides a series of additional parameters (peak VO2, ventilatory threshold, VE/VCO2 slope, end-tidal carbon dioxide exhaled) that characterize different patterns, helping in diagnosis process. Limitations to the routine use of CPET are mainly represented from the lack of measurement standardization and limited data from randomized multicentric studies. The integration of CPET with exercise stress echocardiography has been recently introduced in the clinical practice by integrating the diagnostic power offered by both the tools. This combined approach has been demonstrated to be valuable for diagnosing several cardiac diseases, including heart failure with preserved or reduced ejection fraction, cardiomyopathies, pulmonary arterial hypertension, valvular heart disease and coronary artery disease. Future investigations are needed to further promote this intriguing combination in the clinical and research setting.

The Role of Palliative Care in the Cardiac Intensive Care Unit.

In the last few years, important changes have occurred in the clinical and epidemiological characteristics of patients that were admitted to cardiac intensive care units (CICU). Care has shifted from acute coronary syndrome patients towards elderly patients, with a high prevalence of non-ischemic cardiovascular diseases and a high burden of non-cardiovascular comorbid conditions: both increase the susceptibility of patients to developing life-threatening critical conditions. These conditions are associated with a significant symptom burden and mortality rate and an increased length of stay. In this context, palliative care programs, including withholding/withdrawing life support treatments or the deactivation of implanted cardiac devices, are frequently needed, according to the specific guidelines of scientific societies. However, the implementation of these recommendations in clinical practice is still inconsistent. In this review, we analyze the reasons for this gap and the main cultural changes that are required to improve the care of patients with advanced illness.

[Wearable cardioverter-defibrillators: clinical experience and future perspectives]. / Il defibrillatore indossabile: evidenze cliniche e prospettive future.

Sudden cardiac death (SCD) can affect patients with ischemic or non-ischemic left ventricular dysfunction. Automatic implantable cardioverter-defibrillator (ICD) implantation is the most effective option for the treatment of malignant ventricular tachyarrhythmias; however, the procedure is burdened with known significant risks, even in the long term.In patients at high risk of SCD, either real or perceived, without a definite indication to ICD implantation, wearable cardioverter-defibrillators have been shown to offer effective temporary protection in different clinical settings, for patients with recent high-risk myocardial infarction with left ventricular dysfunction, even after myocardial revascularization procedures, heart failure with reduced ejection fraction, newly diagnosed dilated cardiomyopathy, ICD post-explant phase for infection, and bridge to cardiac transplantation.The purpose of this review is to describe the technical aspects and clinical results available in the literature on the use of wearable cardioverter-defibrillators, with particular reference to safety, efficacy, costs and patient selection, together with current and unconventional indications.The authors also report the first data related to their personal experience.

[Palliative care and heart failure: is it time to talk?] / Cure palliative e scompenso cardiaco: è ora di cominciare a parlarne?

Heart failure (HF) is one of the leading causes of hospitalization in high-income countries and has a profound negative impact on quality of life. In the United States there are more than 900,000 new cases per year and over one million hospital admissions with a primary diagnosis of HF. A prevalence of 6,500,000 cases (2.2% of the population of aged >20 years) was estimated for the US in 2014, in which there were 300,000 related deaths. Although survival has increased, thanks to the pharmacological and non pharmacological therapy, roughly 50% of HF patients die within 5 years of being diagnosed. HF is a chronic, progressive and incurable syndrome characterized by alternating periods of apparent stability and acute exacerbations, with frequent hospitalizations. Patients with HF experience a high level of symptoms and symptom burden over time, particularly at the end of life. In addition to classic symptoms such as dyspnea and edema, patients with HF frequently suffer additional symptoms such as pain, depression, gastrointestinal distress, thirst, fatigue and psychological distress. In HF patients the symptom burden is similar to cancer patients, but patients with advanced HF, in comparison to advanced cancer patients, have a greater number of physical symptoms, worse depression status and lower spiritual well-being. There is evidence that HF patients have the same palliative needs as cancer patients, roughly in 40% of cases, but only 20% actually are admitted to hospice programs in US. This situation seems to be the consequence of cultural gap between guidelines, addressing palliative care and HF, and clinical practice. Bridging this gap is a priority to implement an holistic approach to advanced HF.