Exploring Outcome Priorities and Real-Life Management of Chemotherapy-Induced Peripheral Neurotoxicity: A Survey of the Italian Association for the Study of Pain members.

Introduction: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects nearly 70% of cancer patients after chemotherapy, causing sensory, motor, autonomic dysfunction, and neuropathic pain. The Desirability of Outcome Ranking (DOOR) framework is proposed as a better way to assess preventive or therapeutic interventions for CIPN. Methods: A survey was conducted among Italian healthcare professionals and researchers affiliated to the Italian Chapter of the International Association for the Study of Pain (AISD) to identify the most important outcomes in clinical management and research. Results: Among the 73 respondents, 61 qualified for the survey, with an overall response rate of 1.2%. The vast majority were physicians (77%), most of whom were anesthesiologists (47.5%). The results showed that pain, survival, sensory impairment, motor impairment, and quality of life were consistently ranked as the most important outcomes, but there was significant disagreement in the outcomes relative ranking, making it difficult to develop a DOOR algorithm. The study also revealed that clinicians commonly use structured interviews to evaluate patients with CIPN, and the most prescribed drugs or supplements were palmitoylethanolamide, pregabalin, gabapentin and alpha lipoic acid as preventive agents and pregabalin, palmitoylethanolamide, duloxetine, gabapentin, and amitriptyline as therapeutic agents. However, many of these drugs have not been clinically proven to be effective for CIPN. Discussion: This study suggests that the implementation of a DOOR framework for CIPN using healthcare professionals is more difficult than expected, given the significant disagreement in our respondents' ranking of outcomes. Our work provides interesting topics for future research in CIPN, but its limitations include a small sample size, a low response rate, and a possible selection bias.

Pulmonary Vasodilator and Inodilator Drugs in Cardiac Surgery: A Systematic Review With Bayesian Network Meta-Analysis.

OBJECTIVE: The authors performed a systematic review to evaluate the effect of pharmacologic therapy on pulmonary hypertension in the perioperative setting of elective cardiac surgery (PROSPERO CRD42023321041). DESIGN: Systematic review of randomized controlled trials with a Bayesian network meta-analysis. SETTING: The authors searched biomedical databases for randomized controlled trials on the perioperative use of inodilators and pulmonary vasodilators in adult cardiac surgery, with in-hospital mortality as the primary outcome and duration of ventilation, length of stay in the intensive care unit, stage 3 acute kidney injury, cardiogenic shock requiring mechanical support, and change in mean pulmonary artery pressure as secondary outcomes. PARTICIPANTS: Twenty-eight studies randomizing 1,879 patients were included. INTERVENTIONS: Catecholamines and noncatecholamine inodilators, arterial pulmonary vasodilators, vasodilators, or their combination were considered eligible interventions compared with placebo or standard care. MEASUREMENTS AND MAIN RESULTS: Ten studies reported in-hospital mortality and assigned 855 patients to 12 interventions. Only inhaled prostacyclin use was supported by a statistically discernible improvement in mortality, with a number-needed-to-treat estimate of at least 3.3, but a wide credible interval (relative risk 1.26 × 10-17 - 0.7). Inhaled prostacyclin and nitric oxide were associated with a reduction in intensive care unit stay, and none of the included interventions reached a statistically evident difference compared to usual care or placebo in the other secondary clinical outcomes. CONCLUSIONS: Inhaled prostacyclin was the only pharmacologic intervention whose use is supported by a statistically discernible improvement in mortality in the perioperative cardiac surgery setting as treatment of pulmonary hypertension. However, available evidence has significant limitations, mainly the low number of events and imprecision.

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Importance: Meropenem is a widely prescribed ß-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.

Effect of a Low-Moderate Exercise Program on Dysmetabolism in Older Adults: Results of a Randomized Controlled Trial.

Physical exercise has been shown to improve dysmetabolism in older adults, reducing cardiovascular risk, while its role in preventing dysmetabolism is less known. Moreover, most of the trials use exercise programs that are difficult to put into daily practice. The purpose of this Randomized Controlled Trial (RCT) was to evaluate the effectiveness of a 3-month moderate exercise program in improving or preventing dysmetabolism in 120 older adults, randomly selected for the exercise program (experimental group) or cultural activities (control group). None of the subjects were following a hypocaloric diet, and all of them reported healthy eating habits. Anthropometric (Body Mass Index (BMI) and Waist Circumference (WC)) and metabolic variables (fasting plasma glucose (FPG), High-Density Lipoprotein Cholesterol (HDL-C), and triglycerides (TG)) were assessed at baseline (T0) and at the end of the trial (T1). Dysmetabolism was defined by the presence of an increased WC plus at least two metabolic alterations. At T0, the two groups did not differ by sex, age, education, BMI, WC, FPG, HDL-C levels, and prevalence of dysmetabolism. The mean BMI value indicated overweight, and WC values were higher than the cut-off. At T1, a slight reduction in the number of people with dysmetabolism was found only in the experimental group. However, none of the individuals without dysmetabolism at T0 in the experimental group developed it at T1, while 11.4% developed it in the control group (p = 0.032). This study highlights that a moderate exercise program, accessible in daily practice, can prevent dysmetabolism in older adults, even while being overweight, while if dysmetabolism is already present, more prolonged combined nutritional and exercise interventions will be needed.

Metabolomics and Microbiomics: New Potential Strategies in Chronic Pain Syndrome.

Chronic pain affects almost 20% of the European adult population and it significantly reduces patients' quality of life. Chronic pain is considered a multidimensional experience determined by the interaction of several genetic and environmental factors. The effect of specific genetic contributions is often unclear, and the interpretation of the results from studies focused on genetic influences on pain has been complicated by the existence of multiple pain phenotypes. A step forward from genetics could be given by the application of metabolomics and microbiomics tools. Metabolomics is a powerful approach for hypothesis generation in biology, and it aims to analyze low molecular weight compounds, either metabolic intermediates or metabolic end-products, resulting from human or microbial metabolism. Microbiomics is a fast-growing field in which all the microbes are examined together, and as a result, its perturbation may indicate the development of chronic diseases. By applying these methodologies for the study of chronic pain, several differences have been identified. The alteration of the choline-PAF pathway is an intriguing finding recognized by several groups. In our opinion, metabolomics and microbiomics techniques will allow significant progress into the medical field. Patients may benefit from the possibility of being stratified and classified based on their metabolic and microbial profile, which, in the next future, may lead to personalized therapy.

Exercise in Older Adults to Prevent Depressive Symptoms at the Time of Covid-19: Results of a Randomized Controlled Trial with Follow-Up.

Background: This study aimed to verify, through a randomized controlled trial, whether a medium-intensity mixing/aerobic/anaerobic exercise (accessible to older adults even with mild chronic diseases) can effectively counteract depressive episodes. A characteristic of the trial was that the follow-up coincided (unscheduled) with the lockdown due to Covid-19. Methods: Participants (N=120) were randomized into an intervention group, performing physical exercise, and a control group. Participants, aged 65 years and older, belonged to both genders, living at home, and cleared a medical examination, were evaluated with a screening tool to detect depressive episodes, the PHQ9, at pre-treatment, end of the trial (12-week), and follow-up (48-week). Results: A decrease in the frequency of depressive episodes after the trial (T1) was found in both groups; however, a statistically significant difference was observed only in the control group (p=0.0039). From T1 to follow-up (conducted during the lockdown), the frequency of depressive episodes increased in the control group, reaching a frequency equal to the time of study entry (p=0.788). In the experimental group, the frequency of depressive episodes did not change at the end of the trial but reached a statistically significant difference compared to the start of the study (p = 0.004) and was higher than the control group (p=0.028). Conclusion: Moderate-intensity physical exercise can be conducted safely, benefitting older adults even suffering from mild chronic disorders. Physical exercise seems to guarantee a long-term preventive effect towards depressive symptoms, especially in serious stressful situations such as the lockdown due to the Covid-19 pandemic.

Moderate Exercise Improves Cognitive Function in Healthy Elderly People: Results of a Randomized Controlled Trial.

BACKGROUND: Physical activity in the elderly is recommended by international guidelines to protect against cognitive decline and functional impairment. OBJECTIVE: This Randomized Controlled Trial (RCT) was set up to verify whether medium-intensity physical activity in elderly people living in the community is effective in improving cognitive performance. DESIGN: RCT with parallel and balanced large groups. SETTING: Academic university hospital and Olympic gyms. SUBJECTS: People aged 65 years old and older of both genders living at home holding a medical certificate for suitability in non-competitive physical activity. METHODS: Participants were randomized to a 12-week, 3 sessions per week moderate physical activity program or to a control condition focused on cultural and recreational activities in groups of the same size and timing as the active intervention group. The active phase integrated a mixture of aerobic and anaerobic exercises, including drills of "life movements", strength and balance. The primary outcome was: any change in Addenbrooke's Cognitive Examination Revised (ACE-R) and its subscales. RESULTS: At the end of the trial, 52 people completed the active intervention, and 53 people completed the control condition. People in the active intervention improved on the ACE-R (ANOVA: F(1;102)=4.32, p=0.040), and also showed better performances on the memory (F(1;102)=5.40 p=0.022) and visual-space skills subscales of the ACE-R (F(1;102)=4.09 p=0.046). CONCLUSION: A moderate-intensity exercise administered for a relatively short period of 12 weeks is capable of improving cognitive performance in a sample of elderly people who live independently in their homes.Clinical Trials Registration No: NCT03858114.

Active elderly and health-can moderate exercise improve health and wellbeing in older adults? Protocol for a randomized controlled trial.

BACKGROUND: Aging is marked by a progressive rise in chronic diseases with an impact on social and healthcare costs. Physical activity (PA) may soothe the inconveniences related to chronic diseases, has positive effects on the quality of life and biological rhythms, and can prevent the decline in motor functions and the consequent falls, which are associated with early death and disability in older adults. METHODS: We randomized 120 over-65 males and females into groups of similar size and timing and will give each either moderate physical activity or cultural and recreational activities. Being younger than 65 years, inability to participate in physical activity for any medical reason, and involvement in a massive program of physical exercise are the exclusion criteria. The primary outcome measures are: quality of life, walking speed, and postural sway. Participants are tested at baseline, post-treatment, and 6-month (24 weeks) and 12-month (48 weeks) follow-ups. DISCUSSION: This study aims at improving the quality of life, wellness, and cognitive functioning in the elderly through a low-cost affordable program of moderate physical activity. Given the growing aging of the world population and the social and economic burden of disability in the elderly, our results might have a major impact on future practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT03858114 . Registered on 28 February 2019.

The Burden of Agoraphobia in Worsening Quality of Life in a Community Survey in Italy.

OBJECTIVE: Current nosology redefined agoraphobia as an autonomous diagnosis distinct from panic disorder. We investigated the lifetime prevalence of agoraphobia, its association with other mental disorders, and its impact on the health-related quality of life (HR-QoL). METHODS: Community survey in 2,338 randomly selected adult subjects. Participants were interviewed with the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), administered by clinicians. The diagnoses were based on the ICD-10 criteria. The Short-Form Health Survey (SF-12) was used to quantify HR-QoL. RESULTS: In the sample, 35 subjects met the criteria for agoraphobia (1.5%), with greater prevalence among women (2.0%) than men (0.9%): odds ratio (OR) 2.23; 95% CI: 1.0-5-2. Agoraphobia was more often seen among those with (n=26; 1.1%) than without (n=9; 0.4%) panic disorder: OR=8.3; 2.9-24.4. Co-morbidity with other mental disorders was substantial. The mean score of SF-12 in people with agoraphobia was 35.2±7.8, with similar levels of HR-QoL in people with (35.3±7.9) or without (34.8±7.3) panic disorder: ANOVA: F(1;33)=0.0; p=1.00. CONCLUSION: One out of seventy people may suffer from agoraphobia in their lifetime. The attributable burden in terms of HR-QoL is substantial and comparable to the one observed for chronic mental disorders such as major depression, post-traumatic stress disorder, or obsessive-compulsive disorder.

Nurses' Behavior Regarding Pain Treatment in an Emergency Department: A Single-Center Observational Study.

PURPOSE: The aim of this prospective study was to assess the behavior of emergency department (ED) nurses with regard to pain and their role in pain management in a real-life clinical setting. METHODS: A total of 509 consecutive patients were enrolled during a 6-week period. A case-report form was used to collect data on nurses' approaches to pain, time to analgesia provision, and patient-perceived quality of analgesia. RESULTS: Triage nurses actively inquired about pain in almost every case, but they did not estimate pain intensity in a third of patients. In the majority of cases, triage nurses did not report pain-related findings to the physician, who was the only professional that could prescribe analgesia to patients. The assignment of the color-coding of triage by nurses appears to be related to the perceived severity of the clinical case and a more comprehensive evaluation of pain. More than half of patients were at least fairly satisfied with analgesia. CONCLUSION: Pain is increasingly screened during triage, but its comprehensive assessment and management still lack systematic application. We believe that further education and implementation of analgesia protocols may empower nurses to manage ED patients' pain more effectively and in a more timely manner.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Increasing Mortality.

OBJECTIVE: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: Two hundred fifty-one physicians from 46 countries. INTERVENTIONS: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines. MEASUREMENTS AND MAIN RESULTS: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed. CONCLUSION: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

BEEP-Bodily and Emotional Perception of Pain. A Questionnaire to Measure Reaction to Pain in Chronic Pain Disorders.

Background: The assessment of pain and its impact on quality of life is central to the evaluation of chronic pain syndromes. However, most available tools focus on the nociceptive experience of pain, and at best only consider the occurrence of anxious, depressive, or cognitive problems. Here is a new questionnaire aimed at measuring the multifaceted impact of pain in chronic pain syndromes, the Bodily and Emotional pErception of Pain (BEEP). Methods: All consecutive patients who accessed a center for the treatment of pain were invited to take part in the study. The sample included 222 participants (51 with fibromyalgia, 84 with low back pain; 87 with other chronic pain syndromes). Women were 77% of the sample, the mean age was 61 ± 15. Participants completed the BEEP, the Patient Health Questionnaire-9 (PHQ-9), and the Mood Disorder Questionnaire (MDQ). Results: Reliability was good for all questionnaires. The expected three dimensions of the BEEP were confirmed by confirmatory factor analysis, and a bifactor model with three orthogonal factors showed a good fit as well. Participants diagnosed with fibromyalgia showed higher scores on the BEEP than the participants who had been diagnosed with low back pain or other chronic pain syndromes. The prevalence of probable cases of major depression and bipolar disorder in the sample was higher than expected for non-clinical samples. Levels of depression, as measured by the PHQ-9, were associated with the three dimensions of the BEEP and with the intensity of pain. Conclusions: The BEEP is a promising measure of the impact of pain in daily life and differentiates fibromyalgia from other chronic pain syndromes. The BEEP may be helpful to evaluate the patient's response to the treatment over time and may favor the identification of unmet needs in patients' personal, social, and daily functioning.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality.

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians' opinions and routine practices to understand the clinicians' response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to "do you agree" and "do you use") showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location.

Long-term, prolonged-release oral tapentadol for the treatment of refractory chronic low back pain: a single-center, observational study.

BACKGROUND: Chronic back pain is a leading cause of disability worldwide and it is still inadequately treated. Tapentadol is a dual-acting analgesic drug µ-opioid receptor (MOR) agonist/norepinephrine reuptake inhibitor, carrying a lower risk for opioid withdrawal symptoms and opioid-related adverse effects in comparison to potent opioid drugs. This study investigates the effectiveness, safety and tolerability of the prolonged release oral formulation of tapentadol (tapentadol PR) in 27 patients affected by refractory chronic low back pain during a long-term follow-up (up to 51 months). METHODS: This is an observational study conducted at the Pain Therapy and Palliative Care Unit of University Hospital of Cagliari, Italy. We enrolled 27 patients affected by chronic low back pain refractory to other pharmacological treatments according to the inclusion criteria. We prospectively evaluated oral tapentadol PR therapy during a long-term follow-up (up to 51 months) according to the following outcomes: pain intensity during the previous 72 hours (Numeric Rating Scale 3), quality of life (Short Form-12 Health Survey), self-reported treatment effectiveness (Patient Global Impression of Change scale), physician evaluation of treatment effectiveness (Clinician Global Impression of Change scale), treatment-related adverse effects, reason for tapentadol therapy interruption and tapentadol dosage. RESULTS: All the patients reported a significant improvement of pain intensity and quality of life at the last follow-up. CONCLUSIONS: These results show the long-term effectiveness, safety and tolerability of oral tapentadol PR for the treatment of refractory chronic low back pain in a real-life clinical setting.

Healthcare-associated respiratory infections in intensive care unit can be reduced by a hand hygiene program: A multicenter study.

PURPOSE: Healthcare-associated respiratory tract infections are common and markedly affect the quality of life and mortality, as well as increasing costs for health systems due to prolonged hospitalisation. This study aimed to assess the change in both level and trend of respiratory tract infections after a specific hand hygiene program for intensive care unit (ICU) staff. MATERIALS AND METHODS: The infection data collection was carried out from January 2013 to August 2014. The hand hygiene program started in December 2013. To analyse the change in level and trend of infections after the intervention, the Interrupted Time Series method was used. Chi-square test was used to compare the incidence of respiratory tract infections before and after the intervention. RESULTS: A total of 825 patients were hospitalised in three Italian ICUs. The infection level was significantly decreased by 36.3 infections per 1000 device-days after the intervention. The infection trend was also decreased of about 1 infection per month. CONCLUSIONS: After the hand hygiene program a decreased level of infection was found. Continuous performance feedback should be provided to promote a long-term adherence to the guidelines. Organisational and individual risk factors must be individuated and correctly managed to increase quality of practice.

Prospective study on prevalence, intensity, type, and therapy of acute pain in a second-level urban emergency department.

AIM: Pain represents the most frequent cause for patient admission to emergency departments (EDs). Oligoanalgesia is a common problem in this field. The aims of this study were to assess prevalence and intensity of pain in patients who visited a second-level urban ED and to evaluate the efficacy of pharmacological treatment administered subsequent to variations in pain intensity. METHODS: A 4-week prospective observational study was carried out on 2,838 patients who visited a second-level urban ED. Pain intensity was evaluated using the Numeric Rating Scale at the moment of triage. The efficacy of prescribed analgesic therapy was evaluated at 30 and 60 minutes, and at discharge. Data concerning pain intensity were classified as absent, slight, mild, or severe. Pain was evaluated in relation to the prescribed therapy. RESULTS: Pain prevalence was 70.7%. Traumatic events were the primary cause in most cases (40.44%), followed by pain linked to urologic problems (13.52%), abdominal pain (13.39%), and nontraumatic musculoskeletal pain (7.10%). Only 32.46% of patients were given pharmacological therapy. Of these, 76% reported severe pain, 19% moderate, and 5% slight, and 66% received nonsteroidal anti-inflammatory drugs or paracetamol, 4% opioids, and 30% other therapies. A difference of at least 2 points on the Numerical Rating Scale was observed in 84% of patients on reevaluation following initial analgesic therapy. CONCLUSION: Pain represents one of the primary reasons for visits to EDs. Although a notable reduction in pain intensity has been highlighted in patients who received painkillers, results show that inadequate treatment of pain in ED continues to be a problem.

Distinctive metabolomic fingerprint in scleroderma patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) in systemic sclerosis (SS) identifies a poor prognosis subset of patients. Recent studies suggested a "metabolic theory" on the development of pulmonary arterial hypertension. On this basis we performed a metabolomic study in order to evaluate whether differences in pulmonary arterial blood metabolites were identifiable in SS patients with increased pulmonary vascular resistance (PVR). METHODS: We studied 18 SS patients (age 58.7±15.6years) free of pulmonary fibrosis who underwent a right heart catheterization (RHC). A blood sample was collected during the RHC in the distal peripheral circulation of the pulmonary arteries to perform the metabolomic analysis. RESULTS: Based on PVR we divided the population into Group A (n=8; PVR=1.16±0.23WU) and Group B (n=10; PVR=2.67±0.67WU; p<0.001 vs Group A). No significant differences were identified in terms of anthropometric, clinical, echo and therapeutic characteristics. At RHC the 2 groups showed a difference in mean pulmonary pressure values (Group A: 20±4mmHg; Group B: 27±3.4mmHg; p=0.03), with mild PAH in Group B. We applied an OSC-PLS-DA with a clear clusterization; SSc patients with PAH showed an increase in acetate, alanine, lactate, and lipoprotein levels and a decrease in γ-aminobutyrate, arginine, betaine, choline, creatine, creatinine, glucose, glutamate, glutamine, glycine, histidine, phenylalanine, and tyrosine levels CONCLUSIONS: Our results suggest that, despite similar clinical and disease-related parameters, SSc patients who develop PAH have an unfavorable metabolic profile able to cause an impaired production of metabolites with protective effects on endothelial cells.

Dabigatran overdose: a case report of acute hepatitis. Extracorporeal treatment.

Dabigatran is an oral, direct thrombin inhibitor approved by international regulatory agencies for stroke prevention in patients with paroxysmal or persistent non-rheumatic atrial fibrillation (AF). The benefits of dabigatran are widely described, but its use in the geriatric population is not without risk. Chronic kidney disease is a common comorbidity with AF, and thus frequent checks of renal function in elderly patients are recommended. We report a case of dabigatran intoxication in an elderly man affected by heart failure and worsening renal function, who developed acute hepatitis and coma, which was successfully treated with continuous veno-venous hemodiafiltration. Although extracorporeal therapy has been suggested as a strategy for clearing dabigatran during acute bleeding, this approach may be useful in other dabigatran-related, life-threatening conditions, such as that described in this report.