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Background and objectives: Endothelin-1 (ET-1) and transforming growth factor-β (TGF-β) play a pivotal role in the pathophysiology and vascular remodeling of chronic thromboembolic pulmonary hypertension (CTEPH) which is an under-diagnosed complication of acute pulmonary embolism (PE). Currently, pulmonary endarterectomy (PEA) is still the treatment of choice for selected patients suffering from CTEPH. The aim of this study was to evaluate the preoperative and postoperative circulating levels of ET-1 and TGF-β in subjects affected by CTEPH undergoing successful surgical treatment by PEA. Methods: The data from patients diagnosed with CTEPH who underwent PEA at the Foundation IRCCS Policlinico San Matteo Hospital (Pavia, Italy) were prospectively recorded in the Institutional database. Circulating ET-1 and TGF-β levels were assessed by an ELISA commercial kit before PEA, at 3 months and 1 year after PEA. The demographic data, preoperatory mean pulmonary arterial pressure (mPAP), cardiac output (CO), and pulmonary vascular resistance (PVR) were also recorded. Univariate and multivariate analyses were performed. Results: The analysis included 340 patients with complete ET-1 measurements and 206 patients with complete TGF-β measurements. ET-1 significantly decreased both at 3 months (p < 0.001) and at 1 year (p = 0.009) after PEA. On the other hand, preoperatory TGF-β levels did not significantly change after PEA. Furthermore, ET-1, but not TGF-β, was a good predictor for increased mPAP in multivariate analyses (p < 0.05). Conclusions: ET-1 but not TGF β was significantly modulated by PEA in subjects affected by CTEPH up to 1 year after surgery. The mechanisms leading to prolonged elevated circulating TGF-β levels and their clinical significance have to be further elucidated. [ABSTRACT FROM AUTHOR]

Background: Psychopathological disorders are often comorbid diagnosis in eating disorders (EDs). We aimed to assess the presence of psychopathological traits and symptoms associated with EDs in an Italian high school adolescent population. Methods: A sample of high school adolescents was enrolled, and demographic and clinical data were collected. Two self-report questionnaires, the Eating Disorder Inventory-3 (EDI-3) and the Questionnaire for the Assessment of Psychopathology in Adolescence (Q-PAD), were administered. Results: 548 adolescents (333 F/215 M; 16.89 ± 0.85 years) were included. Symptoms associated with EDs of clinical or high clinical concern were prevalent in a range of individuals, with percentages varying from 26.82% for body dissatisfaction to 51.83% for Interoceptive Deficits. The findings from the Q-PAD assessment indicated the presence of psychological distress, leading to discomfort or challenging situations requiring potential intervention in a percentage of adolescents ranging from 2.93% for psychosocial risks to 23.77% for anxiety. These percentages showed differences between genders (F > M, p < 0.001). Our study also highlighted an association between symptoms of EDs and lifestyle factors within families. We observed correlations between Q-PAD measures and EDI-3 scores, including a positive correlation between Q-PAD and EDI-3 body dissatisfaction (r = 0.7), Q-PAD interpersonal conflicts and EDI-3 interpersonal problems (r = 0.6) and a negative correlation between Q-PAD self-esteem and well-being and EDI-3 ineffectiveness Composite (r=-0.7). Conclusions: a substantial prevalence of ED symptoms and psychological distress among high school adolescents were recorded. These conditions are interrelated, suggesting the importance of addressing them comprehensively. Early detection is essential to improve treatment outcomes and to implement preventive strategies. [ABSTRACT FROM AUTHOR]

Purpose: It has been reported that the estimate of ultrasound attenuation coefficient (AC) is affected by depth of measurement, with linear decrease of values with depth. It is unknown whether backscatter coefficient (BSC) has similar behavior. Methods: This retrospective study was performed with Sequoia US system equipped with ultrasound derived fat fraction (UDFF) algorithm (Siemens Healthineers, Issaquah, WA, USA) that combines BSC with AC. UDFF was obtained positioning upper edge of the region of interest at 1.5,2,3,4,5 cm below liver capsule. BSC data were extracted from UDFF offline. A fractional polynomial regression, which selects the best model considering the polynomial development of the variables of interest, was used. Covariates included were age, sex, skin-to-liver-capsule distance, stiffness. Distance was included as linear factor or with a power ranging from − 2 to 3, and the best fitting model was chosen according to partial F test. Body mass index (BMI) was not included because of collinearity with skin-to-liver capsule distance. Results: 104 individuals (56 females; age: 57.9 ± 13.0 years; BMI: 29.0 ± 6.5 kg/m2; skin-to-liver-capsule distance: 2.3 ± 0.7 cm; liver stiffness: 7.5 ± 5.5 kiloPascal) were studied. Best fitting model for BSC included a combination of depth as linear factor and square root. BSC showed a decrease of − 13.98 dB/cm-steradian for each logarithmic increase of 1 cm depth (coefficient: − 13.98; 95% CI: − 21.016; − 5.379; p =.001). Skin-to-liver-capsule distance and stiffness also were independent predictors of BSC. Conclusions: The estimation of the BSC in the liver exhibits a depth dependence that significantly affects results. A standardized acquisition protocol is needed to compare results and reliably assess changes over time. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether meal or water intake may affect the measurement of the ultrasound (US) attenuation coefficient (AC) imaging, a parameter that is directly related to liver fat content. Methods: The study was performed in two centers (Italy and USA). AC was obtained using the ATI algorithm implemented in the Aplio i‐series US systems (Canon Medical Systems, Japan) by one operator at each center. Measurements were performed at baseline and 5, 15, 30, 45 minutes after drinking 500 mL of water (group 1), or 30, 45, 60, 90, 120 minutes after eating a meal of about 600 kcal (group 2). Multilevel generalized estimating equations for repeated measures were used for the statistical analysis to consider the clustered nature of the data. Results: Twenty‐six individuals were enrolled: 11 (10 females; age, 43.7 ± 12.5 years) in Italy and 15 (10 females; age, 60.7 ± 6.3 years) in USA. At B‐mode US, 10 (38.5%) had liver steatosis. The baseline AC values, in decibel/centimeter/megahertz, were 0.64 (0.12) in group 1 and 0.66 (0.13) in group 2. There was not any significant difference in AC values at every time‐point after water or meal intake either in group 1 or group 2. This result did not change including sex, age, and skin‐to‐liver capsule into the models. Conclusions: The measurement of the AC, which is a biomarker of liver steatosis, does not require a fasting state and drinking water does not affect the result. [ABSTRACT FROM AUTHOR]

Background and Objective: Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal. This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF). Methods: Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cleff) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days. Results: HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (β = − 8.90 (95% CI − 12.9 to − 4.87), p < 0.001) and tazobactam (β = − 8.29 (95% CI − 13.5 to − 3.08), p = 0.002) and Cleff for each antibiotic (meropenem β = − 10,206 (95% CI − 14,787 to − 5787), p = 0.001); tazobactam (β = − 4551 (95% CI − 7781 to − 1322), p = 0.012); piperacillin (β = − 3913 (95% CI − 6388 to − 1437), p = 0.002), even if the carryover effect influenced the Cleff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (β = − 38.1 (95% CI − 47.9 to − 28.3), p < 0.001) and tazobactam (β = − 4.45 (95% CI − 6.17 to − 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type. Conclusion: MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM. [ABSTRACT FROM AUTHOR]

Objectives: The main risk factor involved in CIN2+ recurrence after treatment is the HPV persistent infection. The dysregulation of the immune system permits only HR-HPVs to become persistent infections, to promote cancer development, and to increase the risk of recurrence after treatment. Therefore, there is a shift to a Th2-type cytokine pattern during the carcinogenesis pathway; for this reason, the neutrophil-lymphocytes ratio (NLR) could be a marker of this immunological change. The study aimed to analyse the predictive role of NLR in the recurrence of high-grade CIN (CIN2+) after excisional treatment in a real-world life setting of patients treated for CIN2+. Design: This study wascross-sectional study. Participants/Materials, Setting, Methods: We examined a retrospective database of 444 patients, who attended the colposcopy service of our department from 2011 to 2020 due to an abnormal screening Pap smear, and we compared the clinical characteristics to NLR performed at the time of diagnosis. All analysed patients were treated according to an established protocol (colposcopy every 6 months for the first 2 years and every year for over 3 years) and HPV-DNA test and cervical biopsy were performed at entry and the end of follow-up. All patients underwent a blood sample examination, including complete white blood cell counts and collecting neutrophil and lymphocyte values expressed as 103/mL. Results: The sensitivity (SE) and specificity (SP) of the NLR cut-off point of 1.34 for the diagnosis of CIN2+ recurrence were 0.76 and 0.67, respectively. We found that CIN2+ recurrences were significantly higher in patients with NLR <1.34 (3.7% vs. 0.6%, p = 0.033) and the 5-year recurrence-free survival was higher in patients with NLR ≥1.34 (97% vs. 93%, p = 0.030). Limitations: Firstly, the retrospective analysis and low incidence of recurrence may limit the conclusions. Second, for the retrospective design of the study, we did not take into consideration the patient's comorbidities and habits (smoking) that may influence the NLR. On the other hand, the median duration of follow-up in our study was 26 months (IQR: 22–31), which fully reflects the incidence of recurrences. Conclusions: It is well known that CIN2+ lesions are sustained by deregulation of the immune system caused by persistent HPV infection, which may lead to cervical cancer. Among the actors underlying dysregulation of immunity, lymphocytes are involved in the permission of persistent infection and for this reason, NRL could be a reliable and cost-effective biomarker in predicting the risk of recurrence, especially for high-grade cervical lesions. [ABSTRACT FROM AUTHOR]

Integrating video clips in the discharge process may enhance patients' understanding and awareness of their condition. To determine the effect of video clip-integrated discharge discussion on patient comprehension of atrial fibrillation (AF) and deep vein thrombosis (DVT), and their main complications (stroke and pulmonary embolism), we designed a multicentre, pragmatic, parallel groups, randomised clinical trial, that was conducted at two Emergency Units in Italy. A convenience sample of 144 adult patients (or their caregivers) discharged home with either AF or DVT were randomised to receive standard verbal instructions (control) or video clip-integrated doctor-patient discharge discussion. Participants were guided by the discharging physician through the clip. Mean score for primary outcome (knowledge of the diagnosis and its potential complication) (range 0–18) was 5.87 (95% CI, 5.02–6.72] in the control group and 8.28 (95% CI, 7.27–9.31) in the intervention group (mean difference, −2.41; 95% CI, −3.73 to −1.09; p < 0.001). Among secondary outcomes, mean score for knowledge of the prescribed therapy (range 0–6) was 2.98 (95% CI, 2.57–3.39) in the control group and 3.20 (95% CI, 2.73–3.67) in the study group (mean difference, −0.22; 95% CI, −0.84 to 0.39). Mean score for satisfaction (range 0–12) was 7.34 (95% CI, 6.45–8.23) in the control arm and 7.97 (95% CI, 7.15–8.78) in the intervention arm (mean difference, −0.625; 95% CI −1.82 to 0.57). Initiation rate of newly prescribed anticoagulants was 80% (36/45) in the control group and 90.2% (46/51) in the intervention group. Among 109 patients reached at a median follow up of 21 (IQR 16–28) months, 5.55% (3/54) in the control arm and 1.82% (1/55) in the intervention arm had developed stroke or pulmonary embolism. In this trial, video clip-integrated doctor-patient discharge discussion, improved participants comprehension of AF and DVT and their main complications. Physicians should consider integrating these inexpensive tools during the discharge process of patients with AF or DVT. Trial Registration: ClinicalTrials.gov Identifier "NCT03734406". [ABSTRACT FROM AUTHOR]

A connection between thyroid hormones (THs) and diverse metabolic pathways has been reported. We evaluated thyroid function and tissue sensitivity to THs in children and adolescents with T1D in comparison to euthyroid controls. Additionally, we investigate whether a relationship exists between sensitivity indices and metabolic parameters. A retrospective analysis was conducted on 80 pediatric patients diagnosed with T1D. Clinical parameters, TSH, FT3, FT4, and the presence of MS were documented. Additionally, indices of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were assessed. Thirty healthy subjects were considered as controls. The overall prevalence of MS was 7.27 %, with MS identified in 8 out of 80 (10 %) T1D subjects; none of the controls manifested MS (p<0.01). No significant differences were observed in indexes of tissue sensitivity to THs between subjects with or without MS (all p>0.05). Correlations between THs and indexes of THs tissue sensitivity and metabolic parameters in controls and T1D patients were noted. This study affirms a heightened prevalence of MS in children with T1D compared to controls and underscores the potential role of THs in maintaining metabolic equilibrium. [ABSTRACT FROM AUTHOR]

Objective: Human papillomavirus (HPV) persistence is considered the main risk factor for neoplastic progression, and evidence suggests that regulatory T cells play an important role in the failure of viral elimination. Regulatory T cells may be involved in maintaining a microenvironment favourable for viral persistence and neoplasticity, through a deregulation of the local immune response. The association between altered immune function and the development of chronic infections, cancer (solid and haematological), and autoimmune diseases is documented in the literature. The purpose of this retrospective analysis was to evaluate the possible correlation between HPV cervical infection and lymphoma incidence in women attending colposcopy due to an abnormal Pap smear during a period of 15 years. Design: This is a cross-sectional study. Participants: We investigated retrospectively the incidence of haematological diseases in women aged 21–84 with an abnormal Pap smear who referred to our centre between 2004 and 2019. Setting: This study was conducted at the university hospital. Methods: In our analysis, we included women with diagnoses of HL and NHL after the detection of abnormal Pap smears and HPV infections. We excluded patients with a diagnosis of lymphoma preceding the date of the abnormal Pap smear and HPV test. Results: We divided the patients into two groups in order to analyse the standard incidence ratio (SIR): HL patients (19/7,064, 0.26%) and NHL patients (22/7,064, 0.31%). In our sample, we reported a significant risk of developing lymphoma compared to the general population, both for HL and NHL disease, at age <45 years. Regarding HL, the SIR of disease in women 45 years was 4.886 (95% CI 2.775–9.6029) and in women between 45 and 59 years was 2.612 (95% CI 0.96–7.108804). On the other hand, for NHL in women 45 years, we reported an SIR of about 3.007 (95%, CI 1.273–7.101575), in women aged 45–59 years, the SIR was 4.291 (95% CI 2.444–7.534399), and in women aged 60–74 years, the SIR was 3.283 (95% CI 1.054–10.22303). Limitations: This retrospective analysis was conducted in a single centre in Northern Italy and did not consider all interregional differences existing in the country in terms of HPV genotypes, ethnicity, and population characteristics. Regarding the analysis of SIR for HL and NHL, we did not divide the disease into subtypes because of the small sample of cases. Finally, we considered in our analysis only women with an abnormal Pap smear and not the general population. Conclusions: Women with chronic and persistent HPV infections may have a higher relative risk of developing lymphoma. This possible association may be caused by the deregulation of the immune system response against HPV and the failure of viral clearance, especially in younger women. [ABSTRACT FROM AUTHOR]

This article presents a study that explores the use of noninvasive biomarkers for diagnosing and monitoring pediatric eosinophilic esophagitis (EoE), a chronic allergic disorder affecting the esophagus. The study identifies interleukin (IL)-17, galectin (GAL)-10, and transforming growth factor (TGF)-β as potential biomarkers for EoE. However, more research is required to validate these biomarkers and incorporate them into clinical practice. The study was conducted ethically on children and adolescents. Overall, this research suggests that these biomarkers could enhance the diagnosis and management of EoE, but further investigation is necessary. [Extracted from the article]

The magnitude of the diagnostic delay of symptomatic uncomplicated diverticular disease (SUDD) is unknown; we aimed to evaluate SUDD diagnostic delay and its risk factors. SUDD patients diagnosed at a tertiary referral centre were retrospectively enrolled (2010–2022). Demographic and clinical data were retrieved. Overall, patient-, and physician-dependant diagnostic delays were assessed. Univariate and multivariate analyses were fitted to identify risk factors for diagnostic delay. Overall, 70 SUDD patients (median age 65 years, IQR 52–74; F:M ratio = 1.6:1) were assessed. The median overall diagnostic delay was 7 months (IQR 2–24), patient-dependant delay was 3 months (IQR 0–15), and physician-dependant delay was 1 month (IQR 0–6). Further, 25% of patients were misdiagnosed with irritable bowel syndrome (IBS). At multivariate analysis, previous misdiagnosis was a significant risk factor for overall and physician-dependant diagnostic delay (OR 9.99, p = 0.01, and OR 6.46, p = 0.02, respectively). Also, a high educational level (> 13 years) was associated with a greater overall diagnostic delay (OR 8.74 p = 0.02), while previous abdominal surgery was significantly associated to reduced physician-dependant diagnostic delay (OR 0.19 p = 0.04). To conclude, SUDD may be diagnosed late, IBS being the most frequent misdiagnosis. Timely diagnosis is crucial to tackle the burden of SUDD on patients and healthcare. [ABSTRACT FROM AUTHOR]

Objectives: The primary aim was to estimate the influence of various depths on ultrasound attenuation coefficient (AC) of multiple vendors in the liver. The secondary aim was to evaluate the impact of region of interest (ROI) size on AC measurements in a subset of participants. Methods: This Institutional Review Board (IRB)‐approved Health Insurance Portability and Accountability Act (HIPAA)‐compliant retrospective study was carried out in two centers using AC‐Canon and AC‐Philips algorithms and extracting AC‐Siemens values from ultrasound‐derived fat fraction algorithm. Measurements were performed positioning ROI upper edge (3 cm size) at 2, 3, 4, 5 cm from the liver capsule with AC‐Canon and AC‐Philips and at 1.5, 2, 3 cm with Siemens algorithm. In a subset of participants, measurements were obtained with 1 and 3 cm ROI size. Univariate and multivariate linear regression models and Lin's concordance correlation coefficient (CCC) were used for statistical analysis as appropriate. Results: Three different cohorts were studied. Sixty‐three participants (34 females; mean age: 51 ± 14 years) were studied with AC‐Canon, 60 (46 females; mean age: 57 ± 11 years) with AC‐Philips, and 50 (25 females; 61 ± 13 years) with AC‐Siemens. There was a decrease in AC values per 1 cm increase in depth in all. In multivariable analysis, the coefficient was −0.049 (−0.060; −0.038 P <.001) with AC‐Canon, −0.058 (−0.066; −0.049 P <.001) with AC‐Philips and −0.081 (−0.112; −0.050 P <.001) with AC‐Siemens. AC values with 1 cm ROI were significantly higher than those obtained with 3 cm ROI at all depths (P <.001) but the agreement between AC values obtained with different ROI size was excellent (CCC 0.82 [0.77–0.88]). Conclusions: There is depth dependence in AC measurement that affects results. A standardized protocol with fixed ROI's depth and size is needed. [ABSTRACT FROM AUTHOR]

Specific learning disorders (SLDs) are the most frequently diagnosed developmental disorders in childhood. Different neurocognitive patterns have been found in patients with overweight and obesity, but no data on childhood obesity and SLDs have been reported. To increase our understanding of the relationship between neuropsychological developmental and obesity, we assessed the prevalence of SLD in a pediatric population with obesity. We retrospectively included 380 children and adolescents with obesity. For all participants, auxological, metabolic, demographic features, relationship and social skills, anamnestic data on pregnancy and the perinatal period, stages of development and family medical history were reviewed. SLD was defined according to the DSM-5 criteria. A group of 101 controls of normal weight was included. The overall prevalence of SLD was 10.8%, and SLD was more prevalent in patients with obesity (p < 0.001), with male predominance (p = 0.01). SGA was associated with SLD (p = 0.02). Speech retardation (p < 0.001), limited relationships with peers (p < 0.001) and didactic support (p < 0.001) were noted in the SLD group compared to the group without SLD. A higher prevalence of family history of neuropsychiatric disorders was observed in the SLD group (p = 0.04). A higher fasting glucose level was detected in patients with obesity and SLD compared to subjects without SLD (p = 0.01). An association between obesity and SLD could not be excluded, and an overlap of pathogenic factors for both conditions should be considered. [ABSTRACT FROM AUTHOR]

Summary: The objective of this study was to assess the role of cognitive evaluation in the prediction of phenoconversion in polysomnography‐confirmed idiopathic or isolated rapid eye movement sleep behaviour disorder, through a scoping review focussing on a longitudinal comprehensive neuropsychological assessment of patients with idiopathic REM sleep behaviour disorder. A literature search (2006–2022) yielded 1034 records, and 20 were selected for analysis. The sample included 899 patients from eight different cohorts and five countries. We extracted data on clinical evolution, mild cognitive impairment diagnosis, neuropsychological tests used, and classification of cognitive domains. Tests, cognitive domains, and mild cognitive impairment definitions were heterogeneous across the studies, precluding a meta‐analysis. Ten studies (50%) evaluated the presence of mild cognitive impairment; 14 studies (70%) grouped neuropsychological tests into between three (6 studies, 21.4%) and seven (1 study, 7.1%) cognitive domains. The most frequently used tests were semantic fluency, Stroop colour word test, trail making test A and B, digit span, Rey auditory verbal learning test, and Rey‐Osterrieth figure. All except digit span showed a role in predicting phenoconversion. The authors did not consistently assign tests to specific cognitive domains. In conclusion, we discuss methodological differences between the studies and highlight the need for a standardised framework for neuropsychological data acquisition and presentation, based on a multilevel approach covering test selection, domain assignment, and mild cognitive impairment diagnostic criteria. [ABSTRACT FROM AUTHOR]

Purpose: This study's primary aim was to assess factors affecting ultrasound attenuation coefficient (AC) measurement repeatability using the Canon ultrasound (US) system. The secondary aim was to evaluate whether similar results were obtained with other vendors' AC algorithms. Methods: This prospective study was performed at two centers from February to November 2022. AC was obtained using two US systems (Aplio i800 of Canon Medical Systems and Arietta 850 of Fujifilm). An algorithm combining AC and the backscatter coefficient was also used (Sequoia US System, Siemens Healthineers). To evaluate inter-observer concordance, AC was obtained by two expert operators using different transducer positions with regions of interest (ROIs) varying in terms of depth and size. Intra-observer concordance was evaluated on measurements performed intercostally, subcostally, and in the left liver lobe. Lin's concordance correlation coefficient was used. Results: Thirty-four participants (mean age, 49.4±15.1 years; 18 females) were studied. AC values progressively decreased with depth. The measurements in intercostal spaces on bestquality US images using a 3-cm ROI with its upper edge 2 cm below the liver capsule during breath-hold showed the highest intra-observer and inter-observer concordance (0.92 [95% confidence interval, 0.88 to 0.95] and 0.89 [0.82 to 0.96], respectively). Measurements in the left lobe showed the lowest intra-observer and inter-observer concordance (0.67 [0.43 to 0.90] and 0.58 [0.12 to 1.00], respectively). Intercostal space measurements also had the highest repeatability for the other two ultrasound systems. Conclusion: AC values obtained in intercostal spaces on best-quality images using a 3-cm ROI placed with its top 2 cm below the liver capsule were highly repeatable. [ABSTRACT FROM AUTHOR]

Recently, thanks to the greater discovery of the mechanisms of facial aging, an alternative to invasive plastic surgery has found space with less invasive aesthetic procedures, also based on an increasingly pressing request. We are specifically referring to dermal filler injection into or under the skin which leads to immediate rejuvenation and aesthetic improvements. In this study, we wanted to analyze the results obtained through the use of NEAUVIA Organic Stimulate, particularly with regard to its effectiveness, which is a cross-linked polymeric hydrogel, containing stabilized sodium hyaluronate 26 mg/mL and calcium hydroxyapatite (1%), glycine and L-proline in buffer pyrogen-free water, in its main indication, namely, the temporary correction of congenital and acquired deficiencies of the soft tissues of the face by intradermal injection. Initially, 70 patients were enrolled, but 10 did not complete the study due to non-observance of the investigation rules, so they were excluded from the protocol. The collected data demonstrate an efficient mechanical effect of the pegylated polymeric acid matrix enriched with low concertation of calcium hydroxyapatite and in accordance with other evidence in vitro and in vivo, and the mechanical support of the interstitial connective space improves the homestays of the anatomical layer rebalancing the physiological activity of the dermis cells. [ABSTRACT FROM AUTHOR]

Iron is a primary component of the human body and exerts many functions, mainly concerning red cells and the immune system. In addition, there is evidence that iron-deficiency anemia is associated with allergic diseases. Type 2 inflammation characterizes allergic diseases. Peripheral eosinophils are a reliable biomarker for type 2 inflammation. Therefore, the present study investigated the possible relationship between iron metabolism and peripheral eosinophils in a large population. Eosinophils also play important roles in immune and tissue homeostasis. A growing body of data suggests tissue eosinophils represent a plastic and heterogeneous population of functional sub-phenotypes, shaped by environmental (systemic and local) factors. The retrospective study included 2,795 subjects who were afferent to the Clinical Chemistry Analysis Laboratory during the year 2022. Men had higher peripheral eosinophil count than women (p<0.001). Furthermore, stratifications for sex, eosinophil, and hemoglobin cut-offs showed that men had more eosinophil counts than women. However, there was no correlation between iron biomarkers and peripheral eosinophils. The present study did not demonstrate a clear relationship between iron deficiency and peripheral eosinophil count. Even if this large population may include allergic subjects and patients with different diseases, it seems that iron does not directly affect eosinophil count. [ABSTRACT FROM AUTHOR]

Rare Disease patients manifested high concern regarding the possible increased risk of severe outcomes and worsening of disease-specific clinical manifestation due to the impact of COVID-19. Our aim was to assess the prevalence, outcomes, and impact of COVID-19 in patients with a rare disease such as Hereditary Hemorrhagic Telangiectasia (HHT) in Italian population. A nationwide, multicentric, cross-sectional observational study was conducted on patients with HHT from five Italian HHT centers by online survey. The association between COVID-19-related signs and symptoms and nosebleeds worsening, the impact of personal protective equipment on nosebleeds pattern, and the relationship between the presence of visceral AVMs and severe outcomes were analyzed. Out of 605 total survey responses and eligible for analysis, 107 cases of COVID-19 were reported. A mild-course COVID-19 disease, not requiring hospitalization, was observed in 90.7% of patients, while the remaining eight cases needed hospitalization, two of them requiring intensive-care access. No fatal outcome was recorded and 79.3% of patients reported a complete recovery. No difference in infection risk and outcome between HHT patients and general population was evidenced. No significative interference of COVID-19 on HHT-related bleeding was found. The majority of patients received COVID-19 vaccination, with relevant impact on symptoms and need for hospitalization in case of infection. COVID-19 in HHT patients had an infection profile similar to the general population. COVID-19 course and outcome were independent from any specific HHT-related clinical features. Moreover, COVID-19 and anti-SARS-CoV-2 measures did not seem to affect significantly HHT-related bleeding profile. [ABSTRACT FROM AUTHOR]

Background: Bone marrow lesions (BMLs) are common subchondral defects revealed by magnetic resonance imaging (MRI) in patients with osteoarthritis, often associated with pain and functional limitation. Subchondroplasty (SCP) is a relatively new technique in which bone substitute material (BSM) is injected inside BML areas to provide structural support to the subchondral bone, preventing its collapse and reducing pain. Purpose/Hypothesis: The purpose of this study was to characterize changes in pain, functional and radiological outcomes, conversion to knee replacement, and complications after SCP. We hypothesized that ≥70% of patients would achieve a reduction in pain of ≥4 points on a numeric rating scale (NRS) at a 6-month follow-up after SCP. Study Design: Case series; Level of evidence, 4. Methods: Patients with symptomatic knee BMLs who underwent SCP were prospectively evaluated preoperatively and at 1, 6, 12, and 24 months postoperatively. Functional outcomes were measured with the NRS for pain, Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) scores. Radiographs and MRI were performed preoperatively and at 6- and 12-month follow-ups to verify edema healing and changes in bone structure. Results: A total of 50 patients were included in the study. The mean follow-up was 26 months (24-30 months). Compared with preoperative values, the mean NRS score decreased at every follow-up point (P <.0001 for all) and the IKDC, WOMAC, and KSS scores improved significantly at 6- and 12-month follow-ups. At 6 months postoperatively, 27 patients (54%) registered a reduction on the NRS of ≥4 points. Postoperative MRI revealed a hypointense zone surrounded by a hyperintense signal at the injection site. Standard radiography showed osteoarthritis grade worsening in 4 (8%) patients. Knee replacement was performed in 11 patients —in 7 patients due to the worsening or persistence of disabling symptoms and in 4 patients due to the progression of osteoarthritis. The leakage of BSM occurred in 6 patients without any clinical consequences during the study period. Conclusion: About half of the study patients achieved a reduction in the NRS of 4 points at the 6-month follow-up after SCP. Registration: NCT04905394 (ClinicalTrials.gov identifier). [ABSTRACT FROM AUTHOR]

Purpose: To determine the natural history and necessity of long‐term follow‐up of renal masses that do not demonstrate enhancement on contrast‐enhanced ultrasound (CEUS). Methods: This retrospective single‐center study was approved by our local IRB and is HIPAA compliant. Exactly 405 patients with 620 non‐enhancing renal masses on CEUS from a previously reported study were followed for up to 10 years. Techniques and equipment are described in the original manuscript. Patient charts and imaging studies were reviewed for the change in features. There were 117 (18.6%) patients lost to follow‐up leading to 341 patients with 512 lesions. The lesion size, patient age, number of lesions per patient, and Bosniak class assigned at the initial examination was recorded. Results: Mean patient age was 66 ± 12.6 years (range 17–95 years). Average time of follow‐up was 58.9 ± 41.7 months (range 1–207 months). There was a mean of 1.5 ± 1.0 lesions per patient (range 1–7 lesions). Lesion size was 24.9 ± 18.2 mm (range 3–161 mm). There were 276 (53.9%) patients with >5‐year follow‐up and 78 (15.2%) patients with >10‐year follow‐up. The probability of change within 5 years was 0% (95% CI: 0–0.37 per 100PY) and 10 years 0% (95% CI: 0.0–0.18 per 100PY). Two lesions (0.4%) resolved by 60 months. Five lesions (1.0%) decreased in size. Four lesions (0.8%) increased in size >20% during the follow‐up period but remained benign on subsequent imaging. Conclusion: Any non‐enhancing renal mass on CEUS can be classified as benign. Access the CME test here and search by article title. [ABSTRACT FROM AUTHOR]

Conceiving by assisted infertility treatments may influence breastfeeding duration. In one-year time, to evaluate the goal of 6 months breastfeeding, we recruited 55 consecutive mothers who conceived using assisted treatment compared to 45 mothers conceiving naturally, all giving birth to healthy, full-term, singleton infants, sharing the double-occupancy room. At birth, maternal/neonatal characteristics were obtained by medical records and interviews. Six months after, a telephonic interview was done about the exclusivity of breastfeeding, mood instability, and breastfeeding complications. All the women were supported by the same neonatal-pediatrician team, during the study period. The number of mothers who were exclusively breastfeeding at six months was not statistically different between the two groups, as well as, breastfeeding initiation, BMI, smoking habit, mood instability, co-morbidities. In the assisted group, the women were older, had fewer previous children, upper degree of education, higher rate of cesarean sections, their neonate's birthweight was lower; they reported more breastfeeding complications, but the distribution was not different between groups. The control women had higher number of previously breastfed siblings. Our experience highlights that the mode of conception may not be the defining factor influencing the goal of 6 months lactation. The support of healthcare professional team has a crucial role in maintaining breastfeeding. [ABSTRACT FROM AUTHOR]

The emergency room (ER) is the first gateway for patients with sepsis to inpatient units, and identifying best practices and benchmarks to be applied in this setting might crucially result in better patient's outcomes. In this study, we want to evaluate the results in terms of decreased the in-hospital mortality of patients with sepsis of a Sepsis Project developed in the ER. All patients admitted to the ER of our Hospital from the 1st January, 2016 to the 31stJuly 2019 with suspect of sepsis (MEWS score ≥ of 3) and positive blood culture upon ER admission were included in this retrospective observational study. The study comprises of two periods: Period A: From the 1st Jan 2016 to the 31st Dec 2017, before the implementation of the Sepsis project. Period B: From the 1st Jan 2018 to the 31stJul 2019, after the implementation of the Sepsis project. To analyze the difference in mortality between the two periods, a univariate and multivariate logistic regression was used. The risk of in-hospital mortality was expressed as an odds ratio (OR) and a 95% confidence interval (95% CI). Overall, 722 patients admitted in ER had positive BC on admissions, 408 in period A and 314 in period B. In-hospital mortality was 18.9% in period A and 12.7% in period B (p = 0.03). At multivariable analysis, mortality was still reduced in period B compared to period A (OR 0.64, 95% CI 0.41–0.98; p = 0.045). Having an infection due to GP bacteria or polymicrobial was associated with an increased risk of death, as it was having a neoplasm or diabetes. A marked reduction in in-hospital mortality of patients with documented BSI associated with signs or symptoms of sepsis after the implementation of a sepsis project based on the application of sepsis bundles in the ER. [ABSTRACT FROM AUTHOR]

Purpose: The mode of delivery influences the genital image and perception, especially regarding the effects of delivery on sexual life and intercourse. The current literature has not adequately investigated the relationship between delivery and genital appearance. The aim of the study is to determine whether the mode of delivery changes the genital perception of the woman and, in doing so, influences their acceptance. The secondary aim is to analyze the impact of genital appearance on sexuality. Methods: A prospective survey regarding genital appearance and the impact of delivery mode on vulvar perception was conducted in patients 6 weeks after childbirth. We enrolled 365 women for evaluation, divided into three groups: spontaneous vaginal delivery (SVD 295 women 80.82%), operative vaginal delivery (OVD 36 women 9.86%) and cesarean section (CS 34 women 9.31%). Results: There was a statistically significant difference in the frequency of vulva inspection and in the perception of genital modifications among the groups (p < 0.001 and p < 0.001, respectively). The perception of overall genital modifications was significantly correlated with the frequency of inspection (p = 0.004) and the delivery mode (p = 0.0002). Conclusion: Mode of delivery may influence the genital perception and appearance of genitalia without a decrease of sexual life and daily activity in childbirth. [ABSTRACT FROM AUTHOR]

Following the innovations and new discoveries of the last 10 years in the field of lung ultrasound (LUS), a multidisciplinary panel of international LUS experts from six countries and from different fields (clinical and technical) reviewed and updated the original international consensus for point‐of‐care LUS, dated 2012. As a result, a total of 20 statements have been produced. Each statement is complemented by guidelines and future developments proposals. The statements are furthermore classified based on their nature as technical (5), clinical (11), educational (3), and safety (1) statements. [ABSTRACT FROM AUTHOR]

Eosinophilic gastrointestinal disorders (EGIDs) are chronic/remittent inflammatory diseases associated with a substantial diagnostic delay, often attributable to misdiagnosis and variable clinical presentation in adults. In the pediatric population, few studies have been conducted worldwide reporting EGID diagnostic delay and its consequences on patients. This study aims to analyze and identify potential clinical factors and complications associated with a longer diagnostic time. We performed a retrospective analysis of pediatric patients with EGIDs followed at the Center for Pediatric EGIDs in Pavia, Italy. A total of 60 patients with EGIDs were enrolled. Thirty-nine (65%) patients had EoE, and 21 (35%) non-esophageal EGIDs. EGID diagnosis was achieved about 2 years after the symptom onset, and the median diagnostic time was 12 months (IQR 12–24 months). Diagnostic time was 12 months (IQR 12–69) in non-esophageal EGIDs and 12 months (IQR 4–24 months) in EoE patients. EoE patients presenting with FTT and feeding issues experienced a longer diagnostic time (p = 0.02 and p = 0.05, respectively) than children without growth and feeding impairments. In this study, symptoms appeared about 2 years before the definitive EGID diagnosis was reached, and this diagnostic time was shorter than the delay observed in other published studies. Especially in EoE children, the diagnostic time is significantly associated with impaired child growth, highlighting the importance of an early diagnosis to prevent esophageal stenosis and failure to thrive. [ABSTRACT FROM AUTHOR]

Introduction: About 15% of people with a myeloproliferative neoplasm (MPN) are identified as MPN, unclassifiable using the 2016 WHO classification. Methods: We tested whether persons with platelet concentration ≥450 × 10E+9/L, bone marrow megakaryocyte morphology typical of prefibrotic/early myelofibrosis (pre-MF), and no minor criteria of pre-MF should be classified as a distinct MPN subtype, clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT). Results: 139 subjects meet these criteria who we compared with primary myelofibrosis (PMF) including 402 with pre-MF and 521 with overt myelofibrosis. CMD-IT subjects were more likely female and younger. They had lower frequencies of JAK2V617F compared with persons with PMF (55% vs. 70%; p < 0.001) and higher frequencies of CALR mutations (37% vs. 17%; p < 0.001). They also had lower frequency of variations associated with JAK2V617F susceptibility, JAK2 46/1 (35% vs. 47%; p = 0.021), and VEGFA rs3025039 (12% vs. 17%; p = 0.030). Subjects with CMD-IT had lower incidences of thrombotic events compared with those with pre-MF (9.7% vs. 26%; p < 0.001) and longer survival (median, not reached vs. 23 years; HR = 0.34 (0.10, 0.30); p < 0.001). Conclusion: Our data indicate CMD-IT is a distinct MPN subtype and should be included in the classification of myeloid neoplasms. [ABSTRACT FROM AUTHOR]

Identifying innovative molecules involved in the tumor immune escape process could help refine the survival stratification of colorectal cancer (CRC) patients. HLA-G, a non-classical HLA molecule, physiologically involved in tolerogenic mechanisms, has recently emerged as a relevant prognostic marker in other tumor types, but ambiguous data are reported in the CRC setting. This study aims to evaluate the HLA-G expression and prognostic potential in a series of stage II/III CRCs. HLA-G expression was evaluated in 100 pT3 CRC cases by means of immunohistochemistry using the 4H84 and MEM-G/2 monoclonal antibodies. We observed heterogeneous expression of HLA-G showing different ranges: 4H84 expression ranged from > 1 to 40%—median 7%; MEM-G/2 expression ranged from 20 to 90%—median 50%. HLA-G positivity (any intensity > 1%) varied according to the antibody employed, identifying: 8 4H84 positive, 34 MEM-G/2 positive, 6 double-positive and 52 negative cases. Correlation with clinico-pathologic data showed a significant association with a poor tumor differentiation in stage III right-sided CRC subgroup (p = 0.043), while no other pathologic variable was significantly associated. Survival analysis revealed a reduced disease-free survival rate (HR 4.304613; p = 0.031) in the subgroup of CRC-related death cases, while no correlations were observed considering the whole series and the overall survival. In conclusion, HLA-G is a promising CRC prognostic marker however much work is still required regarding technical aspects and evaluation of expression. [ABSTRACT FROM AUTHOR]

Congenital lung malformations (CLMs) involve anomalies of the lungs and respiratory tree such as congenital pulmonary airway malformation (CPAM), pulmonary sequestration (PS), bronchogenic cysts, congenital lobar emphysema, and bronchial atresia (BA). Although symptomatic lesions require surgical resection, the appropriateness of surgery for patients with asymptomatic malformations is a matter of ongoing debate. Limited data are available concerning the long-term follow-up of affected subjects. In this study, we sought to evaluate the long-term clinical and functional respiratory outcomes in children with CLMs who underwent surgical resection. We carried out a retrospective analysis of 77 children with CLMs who underwent pulmonary resection with at least one year of follow-up. The most common diagnoses were CPAM (50.65%), hybrid lesions (25.97%), lobar emphysema (11.69%), and PS (5.19%). The most common surgical approaches were lobectomy (61.3%), segmentectomy (10.7%), and pneumonectomy (5.3%). Acute post-surgery complications occurred in 31.2% of children. In addition, 73.7% experienced long-term complications, and we found no correlation between the presence of these complications and the sex of the patients, their age at time of surgery, the type of surgery undergone, the presence of symptoms prior to intervention, or acute complications after surgery. Pulmonary function tests revealed FEV1 Z-scores of <−2 SDs in 16 patients, and we found a significant correlation between pneumonectomy and the development of lung function deficit (p = 0.031). In conclusion, clinical and functional respiratory complications may occur in children with CLMs who undergo surgical resection. Long-term monitoring is needed to improve the management of asymptomatic patients. [ABSTRACT FROM AUTHOR]

Background: In end-stage chronic liver disease, transplantation represents the only curative option. However, the shortage of donors results in the death of many patients. To overcome this gap, it is mandatory to develop new therapeutic options. In the present study, we decellularised pig livers and reseeded them with allogeneic porcine mesenchymal stromal cells (pMSCs) to understand whether extracellular matrix (ECM) can influence and/or promote differentiation into hepatocyte-like cells (HLCs). Methods: After decellularisation with SDS, the integrity of ECM-scaffolds was examined by histological staining, immunofluorescence and scanning electron microscope. DNA quantification was used to assess decellularisation. pMSCs were plated on scaffolds by static seeding and maintained in in vitro culture for 21 days. At 3, 7, 14 and 21 days, seeded ECM scaffolds were evaluated for cellular adhesion and growth. Moreover, the expression of specific hepatic genes was performed by RT-PCR. Results: The applied decellularisation/recellularisation protocol was effective. The number of seeded pMSCs increased over the culture time points. Gene expression analysis of seeded pMSCs displayed a weak induction due to ECM towards HLCs. Conclusions: These results suggest that ECM may address pMSCs to differentiate in hepatocyte-like cells. However, only contact with liver-ECM is not enough to induce complete differentiation. [ABSTRACT FROM AUTHOR]

Purpose: Post-operative shoulder stiffness (SS) is a common complication after arthroscopic rotator cuff (RC) repair. The aim of this prospective study is to evaluate the role of surgical risk factors in the development of this complication, with special focus on the characteristics of the RC tears. Methods: Two-hundred and twenty patients who underwent arthroscopic RC repair for degenerative posterosuperior RC tears were included. Surgery-related risk factors for development of post-operative SS belonging to the following five categories were documented and analyzed: previous surgery, RC tear characteristics, hardware and repair type, concomitant procedures, time and duration of surgery. The incidence of post-operative SS was evaluated according to the criteria described by Brislin and colleagues. Results: The incidence of post-operative SS was 8.64%. The treatment of partial lesions by tear completion and repair technique was significantly associated with development of post-operative SS (p = 0.0083, pc = 0.04). A multivariate analysis revealed that treatment of partial lesions in patients younger than 60 years was associated to a higher risk of developing post-operative SS (p = 0.007). Previously known pre-operative risk factors such as female sex and younger age were confirmed. No other significant associations were documented. Conclusion: The treatment of partial lesions of the RC may lead to a higher risk of post-operative SS than the treatment of complete lesions, in particular in patients younger than 60 years. Possible explanations of this finding are the increased release of pro-inflammatory cytokines caused by the additional surgical trauma needed to complete the lesion and the different pain perception of the subgroup of patients who require surgical treatment already for partial tears. Evidence: A higher risk of post-operative SS should be expected after tear completion and repair of partial lesions, especially in young patients. Appropriate pre-operative counseling and post-operative rehabilitation should be considered when approaching this subgroup of RC tears. Level of evidence: Prognostic study, level II. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) patients show a higher risk of developing metabolic and cardiovascular diseases due to the presence of systemic low-grade chronic inflammation. Exercise can improve cardiovascular fitness and modulate the inflammatory processes. We evaluated the physical activity (PA) level and the fitness performance of children and adolescents with IBD. Patients and methods: We considered 54 pediatric patients with IBD (14.6 ± 2.2; 22 M), including CD (n = 27) UC (n = 24) and IBD unclassified (n = 3), and 70 healthy children. In all children, the Physical Activity Questionnaire (PAQ-C) and the International Fitness Enjoyment Scale were self-reported and recorded. Results: PAQ-C showed significant difference in PA levels in patients with IBD compared to controls (p < 0.001). A decrease in general fitness (p = 0.003), cardiorespiratory fitness (p = 0.002), strength (p = 0.01), speed agility (p = 0.003), and flexibility (p = 0.01) were also detected between patients and controls. Speed agility was related to age (p = 0.02) and BMI z-score (p = 0.01), and flexibility to BMI z-score (p = 0.05). We noted a correlation between PA levels and physician global assessment (p = 0.021) and activity disease severity (p = 0.025). Conclusions: A poorer PA level and poor physical competence were found in patients with IBD compared to healthy children and adolescents. Monitored exercise could provide multiple benefits at both physical and psychological levels. [ABSTRACT FROM AUTHOR]

Background: The primary aim of our study was to assess the correlation between an improved version of the attenuation coefficient available on the Arietta 850 ultrasound system (iATT, Fujifilm Healthcare, Tokyo, Japan) and controlled attenuation parameter (CAP). The secondary aim was to assess whether focusing only on iATT acquisition without following the strict protocol for liver stiffness measurements would affect iATT measurement. Methods: Consecutive individuals were enrolled. Pearson's r was used to test the correlation between ATT and CAP values. The concordance between iATT and CAP was tested using Lin's concordance correlation coefficient (CCC). Results: 354 individuals (203 males, 151 females) were studied. The overall Pearson correlation between CAP and iATT values obtained following or not following the liver stiffness measurement protocol, respectively, were r = 0.73 and r = 0.71. The correlation was affected by the interquartile range/median (IQR/M) of the 10 measurements: it was r = 0.75 for IQR/M ≤ 15% and r = 0.60 for IQR/M > 15%. CCC showed that there was a moderate to good concordance between iATT and CAP values. Conclusion: iATT shows a strong correlation with CAP that does not decrease when the protocol for liver stiffness acquisition is not followed. The correlation between iATT and CAP values is higher when the IQR/M ≤ 15%. [ABSTRACT FROM AUTHOR]

Objectives: To compare the estimates of attenuation coefficient (AC) for liver fat quantification between 2 Ultrasound systems and to evaluate the quality measure of a pre‐released software. Methods: AC were obtained in 30 participants in this single‐center IRB‐approved, HIPAA compliant study. Images were obtained on the Philips Epiq Elite system using experimental software and the Canon Medical Systems Aplio i800 with released software. Five AC measurements were taken and the median and IQR/M were calculated. Region of interest placement was based on a confidence map. ROI was at the same depth and size for each system. The concordance was estimated using the Lin's concordance correlation coefficient (CCC), the r Pearson's correlation coefficient, the bias‐correction factor (Cb), and the Bland–Altman method. Results: The ACs varied from 0.45 to 1.0 dB/cm/MHz for the Philips system and 0.30 to 0.96 dB/cm/MHz for the Canon system. The CCC (95% CI) was 0.792 (0.666–0.918), Pearson's r was 0.839 with Cb of 0.944, and the mean difference was 0.03 (−0.101; 0.162) suggesting the 2 methods are considered to be in agreement. Based on a Philips confidence map to determine the best location for performing the measurements, a depth of 3.5 to 4.0 cm from the liver capsule was determined, which might be significantly different than that of the Canon system. Conclusions: Estimation of the AC of the 2 systems showed a high agreement, that is, a similar trend. Assessment of the placement of the measurement box based on the quality of the measurement might be different between the 2 systems. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury (AKI) is a common complication among hospitalized patients, potentially affecting short- and long-term clinical outcomes. In this retrospective study, we evaluated renal outcomes in noncritically ill patients who required acute hemodialysis (HD) because of an AKI episode occurring during hospitalization. Methods: Sixty-three hemodynamically stable patients with AKI undergoing acute intermittent HD were included. Kidney function was evaluated at baseline control (pre-AKI), at AKI diagnosis and during the follow-up. According to serum creatinine and the estimated glomerular filtration rate (eGFR), we defined three clinical conditions: renal recovery, different stages of acute kidney disease (AKD), and chronic kidney disease (CKD). Results: Among the 63 patients evaluated, 34 patients (54%) had a history of CKD. Six patients (10%) presented early full renal recovery. HD treatment was stopped in 38 patients (60%), while 25 patients (40%) required maintenance HD. Dialysis-independent patients presented lower comorbidity and higher baseline eGFR and delta creatinine, compared to dialysis-dependent patients. Baseline CKD, previous AKI episodes, and parenchymal causes of AKI were associated with a significant risk of dialysis dependence. At 1-month control, 15 patients (39%) presented AKD stage 0, 6 patients (16%) AKD stage 1, and 17 patients (44%) AKD stage 2–3. At 3-month control, 29 out of 38 patients recovering from AKI (76%) presented CKD. AKD stage was significantly correlated with the risk of CKD development, which, resulted higher in patients with lower baseline eGFR. Conclusions: AKI might represent a risk factor for the development of chronic kidney damage, even in noncritically ill patients. [ABSTRACT FROM AUTHOR]

Background and Objective: Hydroxychloroquine was widely used during the severe acute respiratory syndrome coronavirus 2 pandemic as an antiviral drug. Most previous pharmacokinetic/pharmacodynamic studies on hydroxychloroquine were conducted on healthy volunteers or patients receiving long-term therapy. There are no studies on the elimination of hydroxychloroquine after short-term treatments. Hydroxychloroquine is known to have a pro-arrhythmic effect through QT interval prolongation, but data in this setting are not conclusive. Our aims were to estimate the time needed for hydroxychloroquine concentrations (CHCQ) to drop to a safe concentration (500 ng/mL) after a short-term therapeutic cycle and to correlate the corrected QT interval with CHCQ. Methods: We collected blood samples and electrocardiograms of patients who underwent short-term therapy with hydroxychloroquine during drug intake and after discontinuation. Hydroxychloroquine concentrations were determined by high-performance liquid chromatography–tandem mass spectrometry and analysed with a linear regression model to estimate the elimination time of the drug after its discontinuation. We conducted a multivariate analysis of the corrected QT interval correlation with CHCQ. Results: Our data suggest that short-term hydroxychloroquine courses can generate significant CHCQ persisting above 500 ng/mL up to 16 days after discontinuation of treatment. Corrected QT interval prolongation significantly correlates with CHCQ. Conclusions: The study confirms the long half-life of hydroxychloroquine and its effect on the corrected QT interval even after short-term courses of the drug. This can inform the clinician using hydroxychloroquine treatments that it would be safer to start or re-initiate treatments with corrected QT interval-prolonging potential 16 days after hydroxychloroquine discontinuation. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory disease related to SARS-CoV2 infection, with frequent cardiovascular involvement in the acute setting. The aim of the study was to evaluate the cardiac function at 6 months. Thirty-two patients diagnosed with MIS-C were enrolled and underwent advanced echocardiogram at discharge and at 6 months. According to the left ventricular ejection fraction (LVEF) at admission, the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥ 45%) and the follow-up results were compared. At discharge, all patients had normal LV and RV systolic function (LVEF 61 ± 4.4%, LV global longitudinal strain −22.1%, TAPSE 20.1mm, s' wave 0.13m/s, RV free wall longitudinal strain −27.8%) with normal LV diastolic function (E/A 1.5, E/e' 5.7, and left atrial strain 46.5%) and no significant differences at 6 months. Compared to group B, the group A patients showed a reduced, even if normal, LV global longitudinal strain at discharge (−21.1% vs. −22.6%, p-value 0.02), but the difference was no longer significant at the follow-up. Patients with MIS-C can present with depressed cardiac function, but if treated, the cardiac function recovered without late onset of cardiac disease. This favorable result was independent of the severity of acute LV dysfunction. [ABSTRACT FROM AUTHOR]

Tacrolimus (TAC) is an immunosuppressant drug approved both in the US and in the EU, widely used for the prophylaxis of organ rejection after transplantation. This is a critical dose drug: low levels in whole blood can lead to low exposure and a high risk of acute rejection, whereas overexposure puts patients at risk for toxicity and infection. Both situations can occur at whole-blood concentrations considered to be within the narrow TAC therapeutic range. We assumed a poor correlation between TAC trough concentrations in whole blood and the incidence of acute rejection; therefore, we propose to study TAC concentrations in endomyocardial biopsies (EMBs). We analyzed 70 EMBs from 18 transplant recipients at five scheduled follow-up visits during the first year post-transplant when closer TAC monitoring is mandatory. We observed five episodes of acute rejection (grade 2R) in three patients (2 episodes at 0.5 months, 2 at 3 months, and 1 at 12 months), when TAC concentrations in EMBs were low (63; 62; 59; 31; 44 pg/mg, respectively), whereas concentrations in whole blood were correct. Our results are preliminary and further studies are needed to confirm the importance of this new strategy to prevent acute rejection episodes. [ABSTRACT FROM AUTHOR]