Sex-driven factors associated with anxiety and depression in autoimmune diabetes.

AIM: To analyze the prevalence of anxiety and depression in a large cohort of adults with autoimmune diabetes, identifying sex-driven associated factors. MATERIALS AND METHODS: In this cross-sectional study, we enrolled 553 consecutive adults with Type 1 diabetes mellitus or latent autoimmune diabetes in adults who came to the Division of Endocrinology of the S.Orsola-Malpighi Polyclinic, Bologna (Italy), to receive their second dose of SARS-CoV-2 vaccine. We administered the questionnaires: Hospital Anxiety and Depression Scale, Diabetes Distress Scale, Diabetes-related Quality of Life, Diabetes Treatment Satisfaction Questionnaire. We collected clinical and biochemical data and 14 days glucose metrics in patients with sensor use > 70% in a time span of ± 4 months from the questionnaires' administration. We excluded 119 patients from our analyses with missing data (final cohort n = 434: 79% of those enrolled). RESULTS: Anxiety and depression prevalence was respectively 30.4% and 10.8%. According to the multivariate analysis, higher diabete-related emotional burden, lower treatment satisfaction, but not physician-related distress, were risk factors for anxiety and depression; female sex was associated with anxiety (OR 0.51, 95% 0.31-0.81; p = 0.005); in women, depression was associated with increasing age (males vs. females OR 0.96 per 1 year increase, 95% CI 0.92-1.00; p = 0.036), whilst in men with HbA1c (OR 1.08 per 1 mmol/mol increase, 95% CI 1.03-1.13; p = 0.002). CONCLUSION: Nearly 1/3 of patients with autoimmune diabetes suffers from anxiety and 1/10 from depression. These conditions are associated with independent modifiable and non-modifiable characteristics. For depression, these characteristics differ between males and females.

Report from the HarmoSter study: different LC-MS/MS androstenedione, DHEAS and testosterone methods compare well; however, unifying calibration is a double-edged sword.

OBJECTIVES: Current liquid chromatography-tandem mass spectrometry (LC-MS/MS) applications for circulating androgen measurements are technically diverse. Previously, variable results have been reported for testosterone. Data are scarce for androstenedione and absent for dehydroepiandrosterone sulfate (DHEAS). We assessed the agreement of androstenedione, DHEAS and testosterone LC-MS/MS measurements among nine European centers and explored benefits of calibration system unification. METHODS: Androgens were measured twice by laboratory-specific procedures in 78 patient samples and in EQA materials. Results were obtained by in-house and external calibration. Intra- and inter-laboratory performances were valued. RESULTS: Intra-laboratory CVs ranged between 4.2-13.2 % for androstenedione, 1.6-10.8 % for DHEAS, and 4.3-8.7 % and 2.6-7.1 % for female and male testosterone, respectively. Bias and trueness in EQA materials were within ±20 %. Median inter-laboratory CV with in-house vs. external calibration were 12.0 vs. 9.6 % for androstenedione (p<0.001), 7.2 vs. 4.9 % for DHEAS (p<0.001), 6.4 vs. 7.6 % for female testosterone (p<0.001) and 6.8 and 7.4 % for male testosterone (p=0.111). Median bias vs. all laboratory median with in-house and external calibration were -13.3 to 20.5 % and -4.9 to 18.7 % for androstenedione, -10.9 to 4.8 % and -3.4 to 3.5 % for DHEAS, -2.7 to 6.5 % and -11.3 to 6.6 % for testosterone in females, and -7.0 to 8.5 % and -7.5 to 11.8 % for testosterone in males, respectively. CONCLUSIONS: Methods showed high intra-laboratory precision but variable bias and trueness. Inter-laboratory agreement was remarkably good. Calibration system unification improved agreement in androstenedione and DHEAS, but not in testosterone measurements. Multiple components, such as commutability of calibrators and EQA materials and internal standard choices, likely contribute to inter-laboratory variability.

Predictors and outcomes of pacemaker implantation in patients with cardiac amyloidosis.

OBJECTIVE: We sought to investigate prevalence, incidence and prognostic implications of permanent pacemaker (PPM) implantation in patients with cardiac amyloidosis (CA), thereby identifying the predictors of time to PPM implantation. METHODS: Seven hundred eighty-seven patients with CA (602 men, median age 74 years, 571 transthyretin amyloidosis (ATTR), 216 light-chain amyloidosis (AL)) evaluated at two European referral centres were retrospectively included. Clinical, laboratory and instrumental data were analysed. The associations between PPM implantation and mortality, heart failure (HF) or a composite endpoint of mortality, cardiac transplantation and HF were analysed. RESULTS: 81 (10.3%) patients had a PPM before initial evaluation. Over a median follow-up time of 21.7 months (IQR 9.6-45.2), 81 (10.3%) additional patients (18 with AL (22.2%) and 63 with ATTR (77.8%)) underwent PPM implantation with a median time to implantation of 15.6 months (IQR 4.2-40), complete atrioventricular block was the most common indication (49.4%). Independent predictors of PPM implantation were QRS duration (HR 1.03, 95% CI 1.02 to 1.03, p<0.001) and interventricular septum (IVS) thickness (HR 1.1, 95% CI 1.03 to 1.17, p=0.003). The model to estimate the probability of PPM at 12 months and containing both factors showed a C-statistic of 0.71 and a calibration of slope of 0.98. CONCLUSIONS: Conduction system disease requiring PPM is a common complication in CA that affects up to 20.6% of patients. QRS duration and IVS thickness are independently associated with PPM implantation. A PPM implantation at 12 months model was devised and validated to identify patients with CA at higher risk of requiring a PPM and who require closer follow-up.

Lung ultrasound in the COVID-19 era: a lesson to be learned for the future.

Lung Ultrasound (LUS) is a reliable, radiation free and bedside imaging technique to assess several pulmonary diseases. Although the diagnosis of COVID-19 is made with the nasopharyngeal swab, detection of pulmonary involvement is key for a safe patient management. LUS is a valid alternative to explore, in paucisymptomatic self-presenting patients, the presence and extension of pneumonia compared to High Resolution Computed Tomography (HRCT) that represent the gold standard. This is a single-centre prospective study with 131 patients enrolled. Twelve lung areas were explored reporting a semiquantitative assessment to obtain the LUS score. Each patient performed reverse-transcription polymerase chain reaction test (rRT-PCR), hemogasanalysis and HRCT. We observed an inverse correlation between LUSs and pO2, P/F, SpO2, AaDO2 (p value < 0.01), a direct correlation with LUSs and AaDO2 (p value < 0.01). Compared with HRCT, LUS showed sensitivity and specificity of 81.8% and 55.4%, respectively, and VPN 75%, VPP 65%. Therefore, LUS can represent an effective alternative tool to detect pulmonary involvement in COVID-19 compared to HRCT.

Predictors of bail-out stenting in patients with small vessel disease treated with drug-coated balloon percutaneous coronary intervention.

BACKGROUND: Drug-coated balloons (DCBs) have shown comparable results with drug-eluting stents in small vessel disease (SVD) percutaneous coronary intervention (PCI) in terms of target vessel revascularization and a reduced incidence of myocardial infarction. However, the relatively high rate of bail-out stenting (BOS) still represents a major drawback of DCB PCI. AIMS: The aim of the study was to investigate the clinical, anatomic, and procedural features predictive of BOS after DCB PCI in SVD. METHODS: We included all consecutive patients undergoing PCI at our institution between January 2020 and May 2022 who were treated with DCB PCI of a de novo lesion in a coronary vessel with a reference vessel diameter (RVD) between 2.0 and 2.5 mm. Angiographic success was defined as a residual stenosis <30% without flow-limiting dissection. Patients who did not meet these criteria underwent BOS. RESULTS: A total of 168 consecutive patients and 216 coronary stenoses were included. The rate of bail-out stent was 13.9%. On multivariate analysis, DCB/RVD ratio (odds ratio [OR]: 4.39, 95% confidence interval [CI]: 1.71-11.29, p < 0.01), vessel tortuosity (OR: 7.00, 95% CI: 1.66-29.62, p < 0.01), distal vessel disease (OR: 5.66, 95% CI: 2.02-15.83, p < 0.01), and high complexity (Grade C of ACC/AHA classification) coronary stenoses (OR: 6.31, 95% CI: 1.53-26.04, p = 0.01) were independent predictors of BOS. CONCLUSIONS: BOS is not an infrequent occurrence in DCB PCI of small vessels and is correlated with vessel tortuosity, distal diffuse vessel disease, higher lesion complexity, and balloon diameter oversizing.

Vascular Access in Patients With Peripheral Arterial Disease Undergoing TAVR: The Hostile Registry.

BACKGROUND: The optimal access route in patients with severe peripheral artery disease (PAD) undergoing transcatheter aortic valve replacement (TAVR) remains undetermined. OBJECTIVES: This study sought to compare clinical outcomes with transfemoral access (TFA), transthoracic access (TTA), and nonthoracic transalternative access (TAA) in TAVR patients with severe PAD. METHODS: Patients with PAD and hostile femoral access (TFA impossible, or possible only after percutaneous treatment) undergoing TAVR at 28 international centers were included in this registry. The primary endpoint was the propensity-adjusted risk of 30-day major adverse events (MAE) defined as the composite of all-cause mortality, stroke/transient ischemic attack (TIA), or main access site-related Valve Academic Research Consortium 3 major vascular complications. Outcomes were also stratified according to the severity of PAD using a novel risk score (Hostile score). RESULTS: Among the 1,707 patients included in the registry, 518 (30.3%) underwent TAVR with TFA after percutaneous treatment, 642 (37.6%) with TTA, and 547 (32.0%) with TAA (mostly transaxillary). Compared with TTA, both TFA (adjusted HR: 0.58; 95% CI: 0.45-0.75) and TAA (adjusted HR: 0.60; 95% CI: 0.47-0.78) were associated with lower 30-day rates of MAE, driven by fewer access site-related complications. Composite risks at 1 year were also lower with TFA and TAA compared with TTA. TFA compared with TAA was associated with lower 1-year risk of stroke/TIA (adjusted HR: 0.49; 95% CI: 0.24-0.98), a finding confined to patients with low Hostile scores (Pinteraction = 0.049). CONCLUSIONS: Among patients with PAD undergoing TAVR, both TFA and TAA were associated with lower 30-day and 1-year rates of MAE compared with TTA, but 1-year stroke/TIA rates were higher with TAA compared with TFA.

Coronary ectasia in different scenarios, primarily in myocardial infarction with nonobstructive coronary artery disease.

AIMS: Several causes have been reported for coronary artery ectasia (CAE), mostly atherosclerosis and tunica media abnormalities. The main aim of the present study was to investigate if CAE extension differs in distinct clinical settings. METHODS: Three hundred and forty-one patients with diagnosis of CAE were identified among 9659 coronary angiographies and divided into four groups according to the patient's admission diagnosis: stable or unstable angina (S-UA), myocardial infarction (MI), aortic disease, aortic valvular disease (AVD). S-UA and MI were subgrouped according to the presence of obstructive coronary artery disease (OCAD). Multivariable logistic regression was used to investigate the relationship between clinical diagnosis and CAE extension as expressed by Markis classification and number of coronary vessels affected by CAE. RESULTS: No significant differences in CAE extension were found among the four groups, in terms of vessels affected by CAE (P = 0.37) or Markis class (P = 0.33). CAE was not related to the extension of OCAD as assessed by the Gensini score, which was higher in MI and S-UA groups (P < 0.01). However, when ischemic patients were sub-divided on the basis of the presence of OCAD, MI without obstructive coronary artery disease (MINOCA) was associated with a higher extension of CAE in terms of Markis class 1 (OR 5.08, 95% CI 1.61-16.04; P < 0.01). CONCLUSION: The extension of CAE is comparable in patients referred to coronary angiography for different clinical scenarios, including S-UA, MI, aortic disease, and AVD; however, patients with MINOCA were associated with a higher extension of CAE.Graphical abstract: Difference in coronary artery ectasia extension in terms of Markis class severity, respectively, stratified by clinical presentation and obstructive coronary artery disease presence, http://links.lww.com/JCM/A519.

Exome sequencing in 116 patients with inherited thrombocytopenia that remained of unknown origin after systematic phenotype-driven diagnostic workup.

Inherited thrombocytopenias (IT) are genetic diseases characterized by low platelet count, sometimes associated with congenital defects or a predisposition to develop additional conditions. Next-generation sequencing has substantially improved our knowledge of IT, with more than 40 genes identified so far, but obtaining a molecular diagnosis remains a challenge especially for patients with non-syndromic forms, having no clinical or functional phenotypes that raise suspicion about specific genes. We performed exome sequencing (ES) in a cohort of 116 IT patients (89 families), still undiagnosed after a previously validated phenotype-driven diagnostic algorithm including a targeted analysis of suspected genes. ES achieved a diagnostic yield of 36%, with a gain of 16% over the diagnostic algorithm. This can be explained by genetic heterogeneity and unspecific genotype-phenotype relationships that make the simultaneous analysis of all the genes, enabled by ES, the most reasonable strategy. Furthermore, ES disentangled situations that had been puzzling because of atypical inheritance, sex-related effects or false negative laboratory results. Finally, ES-based copy number variant analysis disclosed an unexpectedly high prevalence of RUNX1 deletions, predisposing to hematologic malignancies. Our findings demonstrate that ES, including copy number variant analysis, can substantially contribute to the diagnosis of IT and can solve diagnostic problems that would otherwise remain a challenge.

Report from the HarmoSter study: inter-laboratory comparison of LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone.

OBJECTIVES: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) panels that include glucocorticoid-related steroids are increasingly used to characterize and diagnose adrenal cortical diseases. Limited information is currently available about reproducibility of these measurements among laboratories. The aim of the study was to compare LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone at eight European centers and assess the performance after unification of calibration. METHODS: Seventy-eight patient samples and commercial calibrators were measured twice by laboratory-specific procedures. Results were obtained according to in-house and external calibration. We evaluated intra-laboratory and inter-laboratory imprecision, regression and agreement against performance specifications derived from 11-deoxycortisol biological variation. RESULTS: Intra-laboratory CVs ranged between 3.3 and 7.7%, 3.3 and 11.8% and 2.7 and 12.8% for corticosterone, 11-deoxycortisol and cortisone, with 1, 4 and 3 laboratories often exceeding the maximum allowable imprecision (MAI), respectively. Median inter-laboratory CVs were 10.0, 10.7 and 6.2%, with 38.5, 50.7 and 2.6% cases exceeding the MAI for corticosterone, 11-deoxycortisol and cortisone, respectively. Median laboratory bias vs. all laboratory-medians ranged from -5.6 to 12.3% for corticosterone, -14.6 to 12.4% for 11-deoxycortisol and -4.0 to 6.5% for cortisone, with few cases exceeding the total allowable error. Modest deviations were found in regression equations among most laboratories. External calibration did not improve 11-deoxycortisol and worsened corticosterone and cortisone inter-laboratory comparability. CONCLUSIONS: Method imprecision was variable. Inter-laboratory performance was reasonably good. However, cases with imprecision and total error above the acceptable limits were apparent for corticosterone and 11-deoxycortisol. Variability did not depend on calibration but apparently on imprecision, accuracy and specificity of individual methods. Tools for improving selectivity and accuracy are required to improve harmonization.

Adequacy of Pain Management in Patients Referred for Radiation Therapy: A Subanalysis of the Multicenter ARISE-1 Study.

BACKGROUND: Pain is a prevalent symptom among cancer patients, and its management is crucial for improving their quality of life. However, pain management in cancer patients referred to radiotherapy (RT) departments is often inadequate, and limited research has been conducted on this specific population. This study aimed to assess the adequacy and effectiveness of pain management when patients are referred for RT. Moreover, we explored potential predictors of adequate pain management. METHODS: This observational, prospective, multicenter cohort study included cancer patients aged 18 years or older who were referred to RT departments. A pain management assessment was conducted using the Pain Management Index (PMI), calculated by subtracting the pain score from the analgesic score (PMI < 0 indicated inadequate pain management). Univariate and multivariate analyses were performed to identify predictors of adequate pain management. RESULTS: A total of 1042 cancer outpatients were included in the study. The analysis revealed that 42.9% of patients with pain did not receive adequate pain management based on PMI values. Among patients with pain or taking analgesics and referred to palliative or curative RT, 72% and 75% had inadequate or ineffective analgesic therapy, respectively. The odds of receiving adequate pain management (PMI ≥ 0) were higher in patients undergoing palliative RT (OR 2.52; p < 0.001), with worse ECOG-PS scores of 2, 3 and 4 (OR 1.63, 2.23, 5.31, respectively; p: 0.017, 0.002, 0.009, respectively) compared to a score of 1 for those with cancer-related pain (OR 0.38; p < 0.001), and treated in northern Italy compared to central and southern of Italy (OR 0.25, 0.42, respectively; p < 0.001). CONCLUSIONS: In this study, a substantial proportion of cancer patients referred to RT departments did not receive adequate pain management. Educational and organizational strategies are necessary to address the inadequate pain management observed in this population. Moreover, increasing the attention paid to non-cancer pain and an earlier referral of patients for palliative RT in the course of the disease may improve pain response and treatment outcomes.

Reduced Mortality With Antiplatelet Therapy Deescalation After Percutaneous Coronary Intervention in Acute Coronary Syndromes: A Meta-Analysis.

BACKGROUND: Antiplatelet therapy deescalation has been suggested as an alternative to standard treatment with potent dual antiplatelet therapy (DAPT) for 1 year in low bleeding risk patients with acute coronary syndromes undergoing percutaneous coronary intervention to mitigate the increased risk of bleeding. Whether this strategy preserves the ischemic and survival benefits of potent DAPT is uncertain. METHODS: We performed a pairwise meta-analysis in patients with acute coronary syndrome undergoing percutaneous coronary intervention treated with either 1-year standard potent DAPT versus deescalation therapy (potent DAPT for 1-3 months followed by either reduced potency DAPT or ticagrelor monotherapy for up to 1 year). Randomized trials comparing standard DAPT versus deescalation therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. The primary end point was 1-year all-cause mortality. RESULTS: The meta-analysis included 6 trials in which 20 837 patients were randomized to potent DAPT for 1 to 3 months followed by deescalation therapy for up to 1 year (n=10 392) or standard potent DAPT for 1 year (n=10 445). Deescalation therapy was associated with lower 1-year rates of all-cause mortality compared with standard therapy (odds ratio, 0.75 [95% CI, 0.59-0.95]; P=0.02). Deescalation therapy was also associated with lower rates of major bleeding (odds ratio, 0.59 [95% CI, 0.48-0.72]; P<0.0001), with no significant difference in major adverse cardiac events (major adverse cardiovascular events; odds ratio, 0.89 [95% CI, 0.77-1.04]; P=0.14). CONCLUSIONS: In low bleeding risk patients with acute coronary syndrome undergoing percutaneous coronary intervention, compared with 1-year of potent DAPT, antiplatelet therapy deescalation therapy after 1 to 3 months was associated with decreased mortality and major bleeding with similar rates of major adverse cardiovascular events.

Prognostic value of high-sensitivity cardiac troponin I early after coronary artery bypass graft surgery.

BACKGROUND: The diagnosis of periprocedural myocardial infarction (PMI) after coronary artery bypass graft (CABG) is based on biochemical markers along with clinical and instrumental findings. However, there is not a clear cutoff value of high-sensitivity cardiac troponin (hs-cTn) to identify PMI. We hypothesized that isolated hs-cTn concentrations in the first 24 h following CABG could predict cardiac adverse events (in-hospital death and PMI) and/or left ventricular ejection fraction (LVEF) decrease. METHODS: We retrospectively enrolled all consecutive adult patients undergoing CABG, alone or in association with other cardiac surgery procedures, over 1 year. Hs-cTn I concentrations (Access, Beckman Coulter) were serially measured in the post-operative period and analyzed according to post-operative outcomes. RESULTS: 300 patients were enrolled; 71.3% underwent CABG alone, 33.7% for acute coronary syndrome. Most patients showed hs-cTn I values superior to the limit required by the latest guidelines for the diagnosis of PMI. Five patients (1.7%) died, 8% developed a PMI, 10.6% showed a LVEF decrease ≥ 10%. Hs-cTn I concentrations did not significantly differ with respect to death and/or PMI whereas they were associated with LVEF decrease ≥ 10% (p value < 0.005 at any time interval), in particular hs-cTn I values at 9-12 h post-operatively. A hs-cTn I cutoff of 5556 ng/L, a value 281 (for males) and 479 (for females) times higher than the URL, at 9-12 h post-operatively was identified, representing the best balance between sensitivity (55%) and specificity (79%) in predicting LVEF decrease ≥ 10%. CONCLUSIONS: Hs-cTn I at 9-12 h post-CABG may be useful to early identify patients at risk for LVEF decrease and to guide early investigation and management of possible post-operative complications.

Adequacy of Pain Treatment in Radiotherapy Departments: Results of a Multicenter Study on 2104 Patients (Arise).

Aim: The frequent inadequacy of pain management in cancer patients is well known. Moreover, the quality of analgesic treatment in patients treated with radiotherapy (RT) has only been rarely assessed. In order to study the latter topic, we conducted a multicenter, observational and prospective study based on the Pain Management Index (PMI) in RT Italian departments. Methods: We collected data on age, gender, tumor site and stage, performance status, treatment aim, and pain (type: CP­cancer pain, NCP­non-cancer pain, MP­mixed pain; intensity: NRS: Numeric Rating Scale). Furthermore, we analyzed the impact on PMI on these parameters, and we defined a pain score with values from 0 (NRS: 0, no pain) to 3 (NRS: 7−10: intense pain) and an analgesic score from 0 (pain medication not taken) to 3 (strong opioids). By subtracting the pain score from the analgesic score, we obtained the PMI value, considering cases with values < 0 as inadequate analgesic prescriptions. The Ethics Committees of the participating centers approved the study (ARISE-1 study). Results: Two thousand one hundred four non-selected outpatients with cancer and aged 18 years or older were enrolled in 13 RT departments. RT had curative and palliative intent in 62.4% and 37.6% patients, respectively. Tumor stage was non-metastatic in 57.3% and metastatic in 42.7% of subjects, respectively. Pain affected 1417 patients (CP: 49.5%, NCP: 32.0%; MP: 18.5%). PMI was < 0 in 45.0% of patients with pain. At multivariable analysis, inadequate pain management was significantly correlated with curative RT aim, ECOG performance status = 1 (versus both ECOG-PS3 and ECOG- PS4), breast cancer, non-cancer pain, and Central and South Italy RT Departments (versus Northern Italy).Conclusions: Pain management was less adequate in patients with more favorable clinical condition and stage. Educational and organizational strategies are needed in RT departments to reduce the non-negligible percentage of patients with inadequate analgesic therapy.

Role of Quantitative Flow Ratio in Predicting Future Cardiac Allograft Vasculopathy in Heart Transplant Recipients.

BACKGROUND: Coronary angiography is the gold standard for cardiac allograft vasculopathy (CAV) diagnosis, but it usually detects the disease at an advanced stage. We investigated the role of quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, in predicting CAV development in heart transplant recipients. METHODS: Consecutive heart transplant recipients with no evidence of angiographic CAV at baseline coronary angiography were retrospectively included between January 2010 and December 2015, and QFR computation was performed. The relationship between vessel QFR and the occurrence of angiographic vessel-related CAV (≥50% stenosis) was assessed. RESULTS: One hundred forty-three patients were included and QFR computation was feasible in 241 vessels. The median value of QFR at baseline coronary angiography was 0.98 (interquartile range, 0.94-1.00). During a median follow-up of 6.0 years (interquartile range, 4.6-7.8 years), vessel-related CAV occurred in 25 (10.4%) vessels. Receiver-operating characteristic curve analysis identified a QFR best cutoff of ≤0.95 (area under the curve, 0.81 [95% CI, 0.71-0.90]; P<0.001). QFR≤0.95 was associated with an increased risk of vessel-related CAV (adjusted hazard ratio, 20.87 [95% CI, 5.35-81.43]; P<0.001). In an exploratory analysis, QFR≤0.95 in at least 2 vessels was associated with higher incidence of cardiovascular death or late graft dysfunction (71.4% in recipients with 2-3 vessels affected versus 5.1% in recipients with 0-1 vessels affected, P<0.001). CONCLUSIONS: In a cohort of heart transplant recipients, QFR computation at baseline coronary angiography may be a safe and reliable tool to predict vessel-related CAV and clinical outcomes at long-term follow-up.

Chronic Intestinal Failure in Children: An International Multicenter Cross-Sectional Survey.

Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1−4 and 14−18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores < −2. One-third had %IVSE/REE > 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children.

Report from the HarmoSter study: impact of calibration on comparability of LC-MS/MS measurement of circulating cortisol, 17OH-progesterone and aldosterone.

OBJECTIVES: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is recommended for measuring circulating steroids. However, assays display technical heterogeneity. So far, reproducibility of corticosteroid LC-MS/MS measurements has received scant attention. The aim of the study was to compare LC-MS/MS measurements of cortisol, 17OH-progesterone and aldosterone from nine European centers and assess performance according to external quality assessment (EQA) materials and calibration. METHODS: Seventy-eight patient samples, EQA materials and two commercial calibration sets were measured twice by laboratory-specific procedures. Results were obtained by in-house (CAL1) and external calibrations (CAL2 and CAL3). We evaluated intra and inter-laboratory imprecision, correlation and agreement in patient samples, and trueness, bias and commutability in EQA materials. RESULTS: Using CAL1, intra-laboratory CVs ranged between 2.8-7.4%, 4.4-18.0% and 5.2-22.2%, for cortisol, 17OH-progesterone and aldosterone, respectively. Trueness and bias in EQA materials were mostly acceptable, however, inappropriate commutability and target value assignment were highlighted in some cases. CAL2 showed suboptimal accuracy. Median inter-laboratory CVs for cortisol, 17OH-progesterone and aldosterone were 4.9, 11.8 and 13.8% with CAL1 and 3.6, 10.3 and 8.6% with CAL3 (all p<0.001), respectively. Using CAL1, median bias vs. all laboratory-medians ranged from -6.6 to 6.9%, -17.2 to 7.8% and -12.0 to 16.8% for cortisol, 17OH-progesterone and aldosterone, respectively. Regression lines significantly deviated from the best fit for most laboratories. Using CAL3 improved cortisol and 17OH-progesterone between-method bias and correlation. CONCLUSIONS: Intra-laboratory imprecision and performance with EQA materials were variable. Inter-laboratory performance was mostly within specifications. Although residual variability persists, adopting common traceable calibrators and RMP-determined EQA materials is beneficial for standardization of LC-MS/MS steroid measurements.

Female gender and mortality in ST-segment-elevation myocardial infarction treated with primary PCI.

AIMS: To investigate gender difference in mortality among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous angioplasty (PPCI). METHODS: We analyzed data from the prospective registries of two hub PPCI centres over a 10-year period to assess the role of female gender as an independent predictor of both all-cause and cardiac death at 30 days and 1 year. To account for all confounding variables, a propensity score (PS)-adjusted multivariable Cox regression model and a PS-matched comparison between the male and female were used. RESULTS: Among 4370 consecutive STEMI patients treated with PPCI at participating centres, 1188 (27.2%) were women. The survival rate at 30 days and 1 year were significantly lower in women (Log-rank P-value < 0.001). At PS-adjusted multivariable Cox regression analysis, female gender was independently associated with an increased risk of 30-day all-cause death [hazard ratio (HR) = 2.09; 95% confidence interval (CI): 1.45-3.01, P < 0.001], 30-day cardiac death (HR = 2.03;95% CI:1.41-2.93, P < 0.001), 1-year all-cause death (HR = 1.45; 95% CI:1.16-1.82, P < 0.001) and 1-year cardiac death (HR = 1.51; 95% CI:1.15-1.97, P < 0.001). For the study outcome, we found a significant interaction of gender with the multivessel disease in females who were at increased risk of mortality in comparison with men in absence of multivessel disease. After the PS matching procedure, a subset of 2074 patients were identified. Women still had a lower survival rate and survival free from cardiac death rate both at 30-day and at 1-year follow-up. CONCLUSION: As compared with men, women with STEMI treated with PPCI have higher risk of both all-cause death and cardiac mortality at 30-day and 1-year follow-up.

Standard ECG for differential diagnosis between Anderson-Fabry disease and hypertrophic cardiomyopathy.

OBJECTIVES: To evaluate the role of the ECG in the differential diagnosis between Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM). METHODS: In this multicentre retrospective study, 111 AFD patients with left ventricular hypertrophy were compared with 111 patients with HCM, matched for sex, age and maximal wall thickness by propensity score. Independent ECG predictors of AFD were identified by multivariate analysis, and a multiparametric ECG score-based algorithm for differential diagnosis was developed. RESULTS: Short PR interval, prolonged QRS duration, right bundle branch block (RBBB), R in augmented vector left (aVL) ≥1.1 mV and inferior ST depression independently predicted AFD diagnosis. A point-by-point ECG score was then derived with the following diagnostic performances: c-statistic 0.80 (95% CI 0.74 to 0.86) for discrimination, the Hosmel-Lemeshow χ2 6.14 (p=0.189) for calibration, sensitivity 69%, specificity 84%, positive predictive value 82% and negative predictive value 72%. After bootstrap resampling, the mean optimism was 0.025, and the internal validated c-statistic for the score was 0.78. CONCLUSIONS: Standard ECG can help to differentiate AFD from HCM while investigating unexplained left ventricular hypertrophy. Short PR interval, prolonged QRS duration, RBBB, R in aVL ≥1.1 mV and inferior ST depression independently predicted AFD. Their systematic evaluation and the integration in a multiparametric ECG score can support AFD diagnosis.

Clinical profile and in-hospital outcome of patients supported by intra-aortic balloon pump in the clinical setting of cardiogenic shock.

Background: Despite controversial evidences, intra-aortic balloon pump (IABP) is still the most widely used temporary mechanical support device in cardiogenic shock (CS), as a bridge to recovery or to more invasive mechanical supports/heart transplantation. Methods: We analyzed retrospectively data of all patients receiving IABP for CS from 2009 to 2018 in a referral centre for advanced heart failure and heart transplantation; we included CS following acute coronary syndrome (ACS) and other CS etiologies different from ACS. We excluded patients in which IABP was implanted as a support following cardiac surgery, non-cardiac surgery in patients with severe chronic heart failure, or in elective high risk or complicated Cath Lab procedures.We focused on in-hospital outcomes (including death, recovery, heart transplantation, LVAD) and IABP complications. Results: 403 patients received IABP, 303 (75.2%) following ACS and 100 (24.8%) in non-ACS CS. Non-ACS patients were younger (59 ± 18.3 vs 73.1 ± 12.6 years, p < 0.001), had lower median left ventricular ejection fraction (LVEF) (25% [18-35] vs 38% [25-45], p < 0.001). In patients with non-ACS etiologies IABP was more frequently a bridge to heart transplantation [20% (n = 20) vs 0.3% (n = 1), P < 0.001] or LVAD [4% (n = 4) vs 0.6% (n = 2), P = 0.055], while ACS patients were more frequently discharged without transplantation/LVAD [65.7% (n = 199) vs 33% (n = 33), P < 0.001]. Non-ACS patients showed higher in-hospital mortality [46% (n = 46) vs 33.9% (n = 103), P = 0.042]. Post-transplant/LVAD outcome in non-ACS subgroup was favorable (21 out of 24 patients were discharged). Serious IABP-related adverse events occurred in 21 patients (5.2%). Ischemic/hemorrhagic complications, infections and thrombocytopenia were more frequent with longer IABP stay. Conclusions: Despite therapy including percutaneous circulatory support, mortality in CS is still high. In our experience, in the clinical setting of refractory CS an IABP support represents a relatively safe circulatory support, associated with a low rate of serious complications in complex clinical scenarios.

Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson-Fabry disease.

Enzyme replacement therapy (ERT) is a mainstay of treatment for Anderson-Fabry disease (AFD), a pathology with negative effects on the heart and kidneys. However, no reliable biomarkers are available to monitor its efficacy. Therefore, we tested a panel of four microRNAs linked with cardiac and renal damage in order to identify a novel biomarker associated with AFD and modulated by ERT. To this end, 60 patients with a definite diagnosis of AFD and on chronic ERT, and 29 age- and sex-matched healthy individuals, were enrolled by two Italian university hospitals. Only miR-184 met both conditions: its level discriminated untreated AFD patients from healthy individuals (c-statistic = 0.7522), and it was upregulated upon ERT (P < 0.001). On multivariable analysis, miR-184 was independently and inversely associated with a higher risk of cardiac damage (odds ratio = 0.86; 95% confidence interval [CI] = 0.76-0.98; P = 0.026). Adding miR-184 to a comprehensive clinical model improved the prediction of cardiac damage in terms of global model fit, calibration, discrimination, and classification accuracy (continuous net reclassification improvement = 0.917, P < 0.001; integrated discrimination improvement [IDI] = 0.105, P = 0.017; relative IDI = 0.221, 95% CI = 0.002-0.356). Thus, miR-184 is a circulating biomarker of AFD that changes after ERT. Assessment of its level in plasma could be clinically valuable in improving the prediction of cardiac damage in AFD patients.