[Optimizing the care management pathway of patients with ischemia and non-obstructive coronary arteries]. / Ottimizzazione del percorso clinico-gestionale del paziente con ischemia in assenza di malattia coronarica ostruttiva.

Ischemia with non-obstructive coronary arteries (INOCA) is defined by the coexistence of anginal symptoms and demonstrable ischemia, with no evidence of obstructive coronary arteries. The underlying mechanism of INOCA is coronary microvascular dysfunction with or without associated vasospasm. INOCA patients have recurrent symptoms, functional limitations, repeated access to the emergency department, impaired quality of life and a higher incidence of cardiovascular events than the general population. Although well described in chronic coronary syndrome guidelines, INOCA remains underdiagnosed in clinical practice because of insufficient awareness, lack of accurate diagnostic tools, and poorly standardized and consistent definitions to diagnose, both invasively and non-invasively, coronary microvascular dysfunction.To disseminate current scientific evidence on INOCA as a distinct clinical entity, during 2022 we conducted at 30 cardiology units all over the country a clinical practice improvement initiative, with the aim of developing uniform and shared management pathways for INOCA patients across different operational settings. The present document highlights the outcomes of this multidisciplinary initiative.

Focused ultrasound therapy in movement disorders: management roadmap toward optimal pathway organization.

MRI-guided focused ultrasound (MRgFUS) lesioning is an innovative, safe and effective treatment which provides an innovative development in the field of minimally invasive stereotactic neurosurgery. Based on the application of focused ultrasound energy under full MR planning and thermal imaging control, unilateral lesioning of the thalamus, subthalamic nucleus, and globus pallidus is indicated for the treatment of movement disorders, including essential tremor, Parkinson's disease, and dystonia. We started to apply this technique in February 2019 for the treatment of patients with movement disorders. The authors developed a diagnostic therapeutic care pathway, which is herewith proposed and applied as an explication of standard clinical practice in use. The project was the result of the application of different methods such as Health Technology Assessment (HTA), Strengths, Weaknesses, Opportunities and Threats analysis (SWOT) and Demin -Plan, Do, Check, Act (PDCA) cycle. The aim of this project was to standardize the MRgFUS diagnostic-therapeutic pathway (DTP), describe its application and the appropriateness of different phases (patient selection, intervention phase and follow-up). Here, we described in detail our experience in the DTP application from 2019 up to now in 610 patients with movement disorders.

The Optimal Targeting for Focused Ultrasound Thalamotomy Differs between Dystonic and Essential Tremor: A 12-Month Prospective Pilot Study.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is increasingly used to treat drug-resistant essential tremor (ET). Data on MRgFUS thalamotomy in dystonic tremor (DT) are anecdotal. OBJECTIVES: To investigate efficacy, safety, and differences in target coordinates of MRgFUS thalamotomy in DT versus ET. METHODS: Ten patients with DT and 35 with ET who consecutively underwent MRgFUS thalamotomy were followed for 12 months. Although in both groups the initial surgical planning coordinates corresponded to the ventralis intermediate (Vim), the final target could be modified intraoperatively based on clinical response. RESULTS: Tremor significantly improved in both groups. The thalamic lesion was significantly more anterior in DT than ET. Considering both ET and DT groups, the more anterior the lesion, the lower the odds ratio for adverse events. CONCLUSIONS: MRgFUS thalamotomy is safe and effective in DT and ET. Compared to classical Vim coordinates used for ET, more anterior targeting should be considered for DT.

Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson's disease: a multicentre, randomised, double-blind, placebo-controlled, phase II trial. The AMBITIOUS study protocol.

Background: Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme ß-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson's disease (PD). GBA-related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers. Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF). Methods and analysis: In this multicentre, double-blind, placebo-controlled, phase II clinical trial, we randomise patients with GBA-PD in a 1:1 ratio to either oral ABX 1.2 g/day or placebo. The duration of treatment is 52 weeks. Each participant is assessed at baseline and weeks 12, 26, 38, 52 and 78. Changes in the Montreal Cognitive Assessment score and the frequency of mild cognitive impairment and dementia between baseline and weeks 52 are the primary outcome measures. Secondary outcome measures include changes in validated scales/questionnaires assessing motor and non-motor symptoms. Neuroimaging features and CSF neurodegeneration markers are used as surrogate markers of disease progression. GCase activity, ABX and α-synuclein levels are also analysed in blood and CSF. A repeated-measures analysis of variance will be used for elaborating results. The primary analysis will be by intention to treat. Ethics and dissemination: The study and protocols have been approved by the ethics committee of centres. The study is conducted according to good clinical practice and the Declaration of Helsinki. The trial findings will be published in peer-reviewed journals and presented at conferences. Trial registration numbers: NCT05287503, EudraCT 2021-004565-13.

The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome.

BACKGROUND: Few observations exist with respect to the pro-coagulant profile of patients with COVID-19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce but suggestive for a clinical relevance of the problem. OBJECTIVES: Prospective observational study aimed to characterize the coagulation profile of COVID-19 ARDS patients with standard and viscoelastic coagulation tests and to evaluate their changes after establishment of an aggressive thromboprophylaxis. METHODS: Sixteen patients with COVID-19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases. RESULTS: At baseline, the patients showed a pro-coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35-63), platelet contribution to CS (PCS, 43 hPa; interquartile range 24-45), fibrinogen contribution to CS (FCS, 12 hPa; interquartile range 6-13.5) elevated D-dimer levels (5.5 µg/mL, interquartile range 2.5-6.5), and hyperfibrinogenemia (794 mg/dL, interquartile range 583-933). Fibrinogen levels were associated (R2  = .506, P = .003) with interleukin-6 values. After increasing the thromboprophylaxis, there was a significant (P = .001) time-related decrease of fibrinogen levels, D-dimers (P = .017), CS (P = .013), PCS (P = .035), and FCS (P = .038). CONCLUSION: The pro-coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.

Evaluation of ventriculo-arterial coupling in ST elevation myocardial infarction with left ventricular dysfunction treated with levosimendan.

BACKGROUND: Acute heart failure (AHF) after ST-segment elevation myocardial infarction (STEMI) is usually treated with inotropic support or vasoactive medications. In this study, we aimed at investigating the role of levosimendan on cardiovascular determinants of contractility and afterload in patients with AHF following STEMI treated with percutaneous coronary intervention (PCI). METHODS: Forty-eight consecutive STEMI patients were retrospectively enrolled. Non-invasive assessment of left ventricular elastance (Ees) and arterial elastance (Ea) and their relationship, ventriculo-arterial coupling (VAC) was performed before and after levosimendan infusion. RESULTS: After infusion of levosimendan a significant increase in SV was detected in all patients (from 48 ±â€¯17 to 60 ±â€¯21 ml, p < 0.001). VAC slightly decreased from 1.74 ±â€¯0.8 to 1.66 ±â€¯0.7 (p = NS) as a result of a profound reduction in arterial elastance (Ea 2.34 ±â€¯1.09 to 1.74 ±â€¯0.5 mm Hg/ml, p < 0.001) and in ventricular elastance (Ees 1.57 ±â€¯0.12 to 1.24 ±â€¯0.09 mm Hg/ml, p = 0.021). Ejection fraction (EF) (from 0.29 ±â€¯0.1 to 0.32 ±â€¯0.1, p < 0.01) and WMSI, (from 2.16 ±â€¯0.47 to 2.05 ±â€¯0.54, p < 0.05) also, significantly improved. Finally, baseline VAC was able to predict the use of norepinephrine (NE) and early and one-year mortality of patients treated. CONCLUSION: In STEMI patients with AHF the use of levosimendan significantly increases stroke volume after 24-hour treatment through Ea reduction. Baseline VAC seemed to predict early and late mortality and early and prolonged use of NE, however, this needs to be tested in larger series of patients and multivariate adjustments for other prognostic predictors.

Calcium priming of the central venous catheter prevents a drop in ionized calcium concentration during Regional Citrate Anticoagulation.

During citrate-based Continuous Renal Replacement Therapy (CRRT), an infusion of calcium is necessary to replace the calcium lost in the effluent. The replacement takes place through a central venous catheter (CVC) that is primed with saline solution. Thus, we hypothesized a potential systemic anticoagulation caused by the unchelated citrate reaching the patient at the start of CRRT because of 0.42 ml of line dead space. In this pilot study, two subpopulations of 7 patients who underwent Continuous Veno-Venous Hemodiafiltration (150 ml/min of blood flow, 1500 ml/h dialysate flow, 1500 ml/h of citrate predilution) were studied. One had the CVC primed with saline, the second with calcium chloride 10%. Calcium replacement rate was 6.3 ± 0.2 ml/h. Ionized calcium concentration was studied over time in the two groups and in the group with saline priming we detected a transient period of hypocalcemia (ionized calcium concentration [iCa] < 1.00 mmol/l for the first 2 hours). In the subpopulation with the calcium priming, this was not present. No significant effect on filter life emerged. Priming of the catheter with calcium seems effective in avoiding a potential issue regarding citrate accumulation at the start of CRRT. More studies are needed to assess the clinical significance of this finding.

Neutrophil gelatinase-associated lipocalin and acute kidney injury in endovascular aneurysm repair or open aortic repair: a pilot study.

INTRODUCTION: Acute kidney injury (AKI) occurs frequently after abdominal aortic surgery and there is currently no effective marker able to detect early onset. The aim of this study is to evaluate the ability of neutrophil gelatinase-associated lipocalin (NGAL) to early identify the development of acute renal damage in patients undergoing endovascular aneurysm repair (EVAR) or open aortic repair (OAR). MATERIALS AND METHODS: Serial samples of blood and urine were obtained from 25 patients undergoing both EVAR and OAR. Seven male subjects with AKI and 18 subjects with no-AKI (17 males, 1 female) were included in the study. We determined concentrations of serum creatinine (sCr) and urinary, serum and whole blood NGAL (uNGAL, sNGAL, bNGAL) collected at baseline, and after 4 and 18 hours. AKI was defined according to the RIFLE criteria (risk, injury, failure, loss of kidney function, and end-stage kidney disease): increase by 50% in sCr or reduction of at least 25% of estimated glomerular filtration rate (eGFR) from baseline. RESULTS: Seven patients developed AKI in the stage Risk. There was no significant difference in sNGAL concentrations in the AKI group as compared to no-AKI group. However, the uNGAL/uCreatinine ratio and bNGAL concentrations were significantly higher after 18 hours in the AKI group (no-AKI 1.69 (0.91 - 2.47) vs AKI 3.2 (2.08 - 5.92) ng/mg for uNGAL/uCreatinine ratio, P = 0.036; and no-AKI 83 (59 - 131) vs AKI 164 (126 - 263) ng/mL for bNGAL, P = 0.029). CONCLUSIONS: Our results suggest that uNGAL, sNGAL and bNGAL, after abdominal aortic surgery, are not suitable as early biomarkers of AKI.

Consensus Document of the Italian Association of Hospital Cardiologists (ANMCO), Italian Society of Pediatric Cardiology (SICP), and Italian Society of Gynaecologists and Obstetrics (SIGO): pregnancy and congenital heart diseases.

The success of cardiac surgery over the past 50 years has increased numbers and median age of survivors with congenital heart disease (CHD). Adults now represent two-thirds of patients with CHD; in the USA alone the number is estimated to exceed 1 million. In this population, many affected women reach reproductive age and wish to have children. While in many CHD patients pregnancy can be accomplished successfully, some special situations with complex anatomy, iatrogenic or residual pathology are associated with an increased risk of severe maternal and fetal complications. Pre-conception counselling allows women to come to truly informed choices. Risk stratification tools can also help high-risk women to eventually renounce to pregnancy and to adopt safe contraception options. Once pregnant, women identified as intermediate or high risk should receive multidisciplinary care involving a cardiologist, an obstetrician and an anesthesiologist with specific expertise in managing this peculiar medical challenge. This document is intended to provide cardiologists working in hospitals where an Obstetrics and Gynecology Department is available with a streamlined and practical tool, useful for them to select the best management strategies to deal with a woman affected by CHD who desires to plan pregnancy or is already pregnant.

[ANMCO/SICP/SIGO Consensus document: Pregnancy and congenital heart disease]. / Documento di consenso ANMCO/SICP/SIGO: Gravidanza e cardiopatie congenite.

The success of cardiac surgery over the past 50 years has increased numbers and median age of survivors with congenital heart disease (CHD). Adults now represent two-thirds of patients with CHD; in the United States alone the number is estimated to exceed 1 million.In this population many affected women reach reproductive age and wish to have children. While in many CHD patients pregnancy can be accomplished successfully, some special situations with complex anatomy, iatrogenic or residual pathology are associated with an increased risk of severe maternal and fetal complications. Pre-conception counseling allows women to come to truly informed choices. Risk stratification tools can also help high-risk women to eventually renounce to pregnancy and to adopt safe contraception options. Once pregnant, women identified as intermediate or high-risk should receive multidisciplinary care involving a cardiologist, an obstetrician and an anesthesiologist with specific expertise in managing this peculiar medical challenge.This document is intended to provide cardiologists working in hospitals where an Obstetrics and Gynecology Department is available with a streamlined and practical tool, useful for them to select the best management strategies to deal with a woman affected by CHD who desires to plan pregnancy or is already pregnant.

Foregut caustic injuries: results of the world society of emergency surgery consensus conference.

INTRODUCTION: Lesions of the upper digestive tract due to ingestion of caustic agents still represent a major medical and surgical emergency worldwide. The work-up of these patients is poorly defined and no clear therapeutic guidelines are available. PURPOSE OF THE STUDY: The aim of this study was to provide an evidence-based international consensus on primary and secondary prevention, diagnosis, staging, and treatment of this life-threatening and potentially disabling condition. METHODS: An extensive literature search was performed by an international panel of experts under the auspices of the World Society of Emergency Surgery (WSES). The level of evidence of the screened publications was graded using the Oxford 2011 criteria. The level of evidence of the literature and the main topics regarding foregut caustic injuries were discussed during a dedicated meeting in Milan, Italy (April 2015), and during the 3rd Annual Congress of the World Society of Emergency Surgery in Jerusalem, Israel (July 2015). RESULTS: One-hundred-forty-seven full papers which addressed the relevant clinical questions of the research were admitted to the consensus conference. There was an unanimous consensus on the fact that the current literature on foregut caustic injuries lacks homogeneous classification systems and prospective methodology. Moreover, the non-standardized definition of technical and clinical success precludes any accurate comparison of therapeutic modalities. Key recommendations and algorithms based on expert opinions, retrospective studies and literature reviews were proposed and approved during the final consensus conference. The clinical practice guidelines resulting from the consensus conference were approved by the WSES council. CONCLUSIONS: The recommendations emerging from this consensus conference, although based on a low level of evidence, have important clinical implications. A world registry of foregut caustic injuries could be useful to collect a homogeneous data-base for prospective clinical studies that may help improving the current clinical practice guidelines.

[Multicentre, prospective cohort study, to validate the Italian version of the Braden Q scale for the risk of the pressure sores in newborns and up to 8 years old children]. / Studio di coorte prospettico multicentrico per la validazione italiana della Braden Q per la valutazione del rischio di lesioni da decubito nei neonati e nei bambini fino ad 8 anni.

UNLABELLED: Multicenter prospective cohort study, to validate the Italian version of the Braden Q scale for the risk of pressure sores in newborns and up to 8 years old children. INTRODUCTION: Children admitted to Intensive care Units (ICU), oncology and neurology/neurosurgery wards are at risk of developing pressure sores. AIM: To validate the Italian version of the Braden Q scale for the assessment of the risk of developing pressure sores in children. METHODS: Children from 21 days to 8 years, admitted to intensive and sub intensive units were recruited. Premature babies, children admitted with a pressure sore and with a story of congenital cardiomiopathy were excluded. In this cohort, multicentre and with repeated measurements study, the first assessment was performed after 24 hours from hospital admission, using the Braden Q Scale (Suddaby's version). The pressure sores were assessed with the Skin assessment Tool and staged according to the National Pressure Ulcer Advisory Panel. RESULTS. On the 157 children 524 observation were conducted. The incidence of pressure sores was 17.2%. Only the analysis on specific subgroups of patients showed a good diagnostic accuracy: 71.4% on children 3-8 years; 85.6% in sub intensive wards. CONCLUSIONS: The Braden Q scale may be reliably used and shows a good diagnostic accuracy in children 3-8 years of age admitted to sub-intensive, neurology, oncology and heamatology wards.

Giuseppe Pasta (1742-1823): protophysician and pioneer of psychological studies in the medical field.

Giuseppe Pasta was a pioneer of psychological support in physical disease. Born in Bergamo, Italy, he was a cousin of the physician Andrea Pasta who was a pupil of Giovanni Battista Morgagni. Giuseppe's cultural and clinical resources were the teachings of Francesco Redi's medical school in Tuscany. This paper discusses the courage and philosophical tolerance of disease and the etiquette of the physician.

A new device for measuring resting energy expenditure (REE) in healthy subjects.

BACKGROUND AND AIM: Lifestyle change targeted towards increasing daily resting energy expenditure (REE) is one of the cornerstones of obesity treatment. Measurements of energy expenditure and substrate utilization are essential to understanding the metabolic basis of obesity, and the physiological responses to perturbations in habitual food intake. REE is the largest part of human energy expenditure (60-70%) and an increase or decrease in REE would have a large impact on total energy. Accurate and easy-to-use methods for measuring REE are needed, to be applied by clinicians in daily clinical settings to assess the validity of a new instrument to estimate REE in normal weight, healthy adults. METHODS: Ninety-nine subjects (52 females and 47 males) (mean+/-SD, age 38+/-14 years; body mass index (BMI) 23+/-3 kg/m(2)) were tested. REE was assessed using a Sensor Medics Vmax metabolic cart with a ventilated canopy and with the SenseWear armband. Body composition, percentage fat mass (%FM) and percentage fat free mass (%FFM) were assessed by skinfold thickness measurements (SF), bio-electrical impedance analysis (BIA) and air displacement plethysmography (BOD-POD). RESULTS: No significant difference was found among measurements of FFM using the three different techniques. Both SenseWear and Sensor Medics Vmax showed a high correlation, r=0.42 and r=0.40 (p<0.0001) respectively, with BMI. No significant difference was found in mean REE between SenseWear (1540+/-280 kcal/day) and Sensor Medics Vmax (1700+/-330 kcal/day) (p=ns) and the correlation between REE measured by SenseWear and Sensor Medics Vmax was high (r=0.86, p<0.0001). Bland-Altman plot showed no difference in REE determination between SenseWear and Sensor Medics Vmax. %FFM determined by BOD-POD correlated with SenseWear (r=0.42, p<0.0001) as well as Sensor Medics Vmax (r=0.38, p<0.001). CONCLUSION: SF, BIA and BOD-POD provide valid and reliable measurements of FFM. Our results suggest that the SenseWear armband is an acceptable device to accurately measure REE in healthy subjects. Its characteristics have the potential to reduce measurement times and make the SenseWear armband useful for epidemiological studies.

Social learning in pig-tailed macaques (Macaca nemestrina) and adult humans (Homo sapiens) on a two-action artificial fruit.

An artificial fruit (AF) was used to test for social learning in pig-tailed macaques (Macaca nemestrina) and adult humans (Homo sapiens). A monkey demonstrator opened the AF, showing alternative methods to 2 groups of cage mates. Video films of the monkey demonstrations were presented to adult humans. Compared with chimpanzees and children, the macaques watched the demonstrations significantly less and in a much more sporadic manner. They also produced only very weak and transitory evidence of social learning. In contrast, the adult humans performed as one might expect of optimum imitators, even producing evidence of components of a "ratchet effect."

Healthy status and energy balance in pediatrics.

During growth, the human body increases in size and changes proportion of various components due to hormones mediators. Nutritional status is the result of introduction, absorption and utilization of the nutrients and it has a new definition in the relationship between nutritional status and healthy status. In this view energy balance, body function and body composition are three entities correlated each other. This mini-review article examines issues and techniques specifically related to a pediatric population in the field of body composition and energy expenditure. It is broadly divided into two sections. The first section discusses body composition measurements underlying principles, advantages, disadvantages and consensus. The second section reviews energy expenditure and physical activity measurement techniques. In conclusion general clinical suggestions are offered regarding pediatric body composition, healthy status and energy balance.

Laterality of manual function in foraging and positional behavior in wild indri (Indri indri).

This research is based on the idea that some prosimian species are good models in which to test certain postulates of the "postural origins" theory proposed by MacNeilage and colleagues [Behavioral and Brain Sciences 10:247-303, 1987] to explain the evolution of hand preference within the order Primates. We investigated manual laterality in 16 wild indris (eight males and eight females, living in four social groups) in their habitat, the Madagascan tropical rain forest. Data were collected on two spontaneous behaviors: "branch-reach," an action that occurs during foraging, and "higher support," a posture typical of clingers and leapers. A total of seven subjects were significantly lateralized for branch-reach (two showed a right preference, and five showed a left preference). Four subjects were significantly lateralized for higher support, and all of them showed a right-hand preference. Most of the indris we studied showed no preference. Our research suggests that indri are at "level 1 of laterality" in the classification framework proposed by McGrew and Marchant [Yearbook of Physical Anthropology 40:201-232, 1997]. The data presented here are not discordant with the "postural origins" theory, as lateralized subjects are often in the direction predicted by MacNeilage and colleagues [Behavioral and Brain Sciences 10:247-303, 1987], but they are the minority.