Histogram-Based Densitometry Index to Assess the Severity of Interstitial Lung Disease in Systemic Sclerosis in Standard and Low-Dose Computed Tomography.

OBJECTIVE: Mean lung attenuation, skewness, and kurtosis are histogram-based densitometry variables that quantify systemic sclerosis-associated interstitial lung disease (SSc-ILD) and were recently merged into a computerized integrated index (CII). Our work tested the CII in low-dose 9-slice (reduced) and standard high-resolution computed tomography (CT) scans to evaluate extensive SSc-ILD and predict mortality. METHODS: CT scans from patients with SSc-ILD were assessed using the software Horos to compute standard and reduced CIIs. Extensive ILD was determined following the Goh staging system. The association between CIIs and extensive ILD was analyzed with a generalized estimating equation regression model, the predictive ability of CIIs by the area under the receiver-operation characteristic curve (AUC), and the association between CIIs and death by Kaplan-Meier analysis. RESULTS: Among 243 patients with standard and reduced CT scans available, 157 CT scans from 119 patients with SSc-ILD constituted the derivation cohort. The validation cohort included 116 standard and 175 reduced CT scans. Both CIIs from standard (odds ratio [OR] 0.53, 95% CI 0.37-0.75; AUC 0.77, 95% CI 0.68-0.87) and reduced CT scans (OR 0.54, 95% CI 0.35-0.82; AUC 0.78, 95% CI 0.70-0.87) were significantly associated with extensive ILD. A threshold of CII ≤ -0.96 for standard CT scans and CII ≤ -1.85 for reduced CT scans detected extensive ILD with high sensitivity in both derivation and validation cohorts. Extensive ILD according to Goh staging (OR 2.94, 95% CI 1.10-7.82) and standard CII ≤ -0.96 (OR 1.78, 95% CI 1.24-2.56) significantly predicted mortality; a marginal P value was observed for reduced CII ≤ -1.85 (OR 1.27, 95% CI 0.93-1.75). CONCLUSION: Thresholds for both standard and reduced CII to identify extensive ILD were developed and validated, with an additional association with mortality. CIIs might help in clinical practice when radiology expertise is missing.

The Performance of Pulmonary Function Tests in Predicting Systemic Sclerosis-Interstitial Lung Disease in the European Scleroderma Trial and Research Database.

BACKGROUND AND OBJECTIVES: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. METHODS: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. RESULTS: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. CONCLUSIONS: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.

Systemic sclerosis and primary biliary cholangitis: Longitudinal data to determine the outcomes.

Background: Several studies described the cross-sectional characteristics of systemic sclerosis patients and coexisting primary biliary cholangitis, but longitudinal prognostic data are lacking. Aims: To describe the systemic sclerosis-primary biliary cholangitis phenotype, including baseline characteristics and outcomes. Methods: We performed a multicentre the European Scleroderma Trials and Research Group study of systemic sclerosis patients with primary biliary cholangitis or with primary biliary cholangitis-specific antibodies, matched with systemic sclerosis controls free from hepatobiliary involvement matched for disease duration and cutaneous subset. Data were recorded at baseline and at the last available visit. Results: A total of 261 patients were enrolled (115 primary biliary cholangitis-systemic sclerosis, 161 systemic sclerosis). At baseline, systemic sclerosis-primary biliary cholangitis patients had a higher prevalence of anti-centromere antibodies (p = 0.0023) and a lower prevalence of complete absence of digital ulcers. The milder vascular involvement was confirmed at follow-up when crucial differences emerged in the percentage of patients experiencing digital ulcers; a significantly higher number of patients who never experienced digital ulcers were observed among primary biliary cholangitis-systemic sclerosis patients (p = 0.0015). Moreover, a greater incidence of pulmonary arterial hypertension (p < 0.001) and of conduction blocks (p = 0.0256) was observed in systemic sclerosis patients without primary biliary cholangitis. Patients with primary biliary cholangitis had higher levels of liver enzymes at baseline than systemic sclerosis patients; a significant decrease in liver enzymes was observed at follow-up. Out of 18 patients with cholangitis, one received a liver transplant at follow-up. Conclusion: Our data show that systemic sclerosis-primary biliary cholangitis exhibit a mild systemic sclerosis and primary biliary cholangitis phenotype with outcomes being in general favourable.

Universal cervical length screening for preterm birth is not useful after 24 weeks of gestation.

INTRODUCTION: Cervical length measurement using transvaginal sonography at 18+0 -24+0 weeks of gestation is used to identify women at risk of preterm delivery, who may benefit from treatment with progesterone to prevent premature birth. Few and conflicting data exist regarding the predictive value of cervical length measurement performed at later gestational ages. The primary objective of this study was to evaluate the predictive accuracy for spontaneous preterm birth of a single cervical length measurement performed between 24 and 32 weeks of gestation in asymptomatic singleton pregnancies at low risk for spontaneous preterm birth. The secondary objective was to test the predictive accuracy of different cervical length thresholds in the same population. MATERIAL AND METHODS: This was a historical cohort study conducted in a tertiary referral hospital. A total of 2728 asymptomatic women with singleton pregnancy at low risk for spontaneous preterm birth were recruited. Of these women, 1548 had cervical length measured at 24+0 -27+6 weeks of gestation and 2191 women at 28+0 -32+0 weeks. In all, 1010 women were present in both gestational age windows. Maternal demographics, medical and obstetrical history, and pregnancy outcome were reviewed. The predictive value of cervical length for spontaneous preterm birth was evaluated through logistic regression analysis. Results were adjusted for confounding factors. RESULTS: Overall, spontaneous preterm birth occurred in 53/2728 women (1.9%). In both the 24+0 -27+6 and 28+0 -32+0 weeks groups, a shorter cervical length was significantly associated with spontaneous preterm birth (p < 0.01), but it had a low predictive value, as shown by the receiver operating characteristics curve analysis (areas under the curve 0.62, 95% CI 0.50-0.74 for the 24+0 -27+6 weeks group, and 0.61, 95% CI 0.52-0.70 in the 28+0 -32+0 weeks group). When the predictive accuracy for preterm delivery of different cervical length cut-offs was evaluated, the sensitivity and positive predictive value were low in both gestational age windows, irrespective of the threshold used. CONCLUSIONS: In asymptomatic women with singleton pregnancy at low risk for spontaneous preterm birth, the predictive value of cervical length after 24+0 weeks of gestation is low. Therefore, cervical length screening in these women should be discouraged.

Long-Term Prevalence of Systolic Dysfunction in MYBPC3 Versus MYH7-Related Hypertrophic Cardiomyopathy.

BACKGROUND: The 2 sarcomere genes most commonly associated with hypertrophic cardiomyopathy (HCM), MYBPC3 (myosin-binding protein C3) and MYH7 (ß-myosin heavy chain), are indistinguishable at presentation, and genotype-phenotype correlations have been elusive. Based on molecular and pathophysiological differences, however, it is plausible to hypothesize a different behavior in myocardial performance, impacting lifetime changes in left ventricular (LV) function. METHODS: We reviewed the initial and final echocardiograms of 402 consecutive HCM patients with pathogenic or likely pathogenic MYBPC3 (n=251) or MYH7 (n=151) mutations, followed over 9±8 years. RESULTS: At presentation, MYBPC3 patients were less frequently obstructive (15% versus 26%; P=0.005) and had lower LV ejection fraction compared with MYH7 (66±8% versus 68±8%, respectively; P=0.03). Both HCM patients harboring MYBPC3 and MYH7 mutations exhibited a small but significant decline in LV systolic function during follow-up; however, new onset of severe LV systolic dysfunction (LV ejection fraction, <50%) was greater among MYBPC3 patients (15% versus 5% among MYH7; P=0.013). Prevalence of grade II/III diastolic dysfunction at final evaluation was comparable between MYBPC3 and MYH7 patients (P=0.509). In a Cox multivariable analysis, MYBPC3-positive status (hazard ratio, 2.53 [95% CI, 1.09-5.82]; P=0.029), age (hazard ratio, 1.03 [95% CI, 1.00-1.06]; P=0.027), and atrial fibrillation (hazard ratio, 2.39 [95% CI, 1.14-5.05]; P=0.020) were independent predictors of severe systolic dysfunction. No statistically significant differences occurred with regard to incidence of atrial fibrillation, heart failure, appropriate implanted cardioverter defibrillator shock, or cardiovascular death. CONCLUSIONS: MYBPC3-related HCM showed increased long-term prevalence of systolic dysfunction compared with MYH7, in spite of similar outcome. Such observations suggest different pathophysiology of clinical progression in the 2 subsets and may prove relevant for understanding of genotype-phenotype correlations in HCM.

Novel Biomarkers for Early Detection of Acute Kidney Injury and Prediction of Long-Term Kidney Function Decline after Partial Nephrectomy.

BACKGROUND: Identifying acute kidney injury (AKI) within few hours of onset is certainly helpful. However, early prediction of a long-term eGFR decline may be an even more important goal. Our aim was to identify and compare serum [creatinine, kineticGFR, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL)] and urinary (NephroCheck, NGAL, proteinuria, albuminuria, acantocytes at urinary sediment) predictors of AKI that might efficiently predict long-term GFR decline after robotic Nephron-Spearing Surgery (rNSS). METHODS: Monocentric prospective observational study. Patients scheduled for rNSS for suspected localized Renal Cell Carcinoma from May 2017 to October 2017 were enrolled. Samples were collected preoperatively and postoperatively (timepoints: 4 h, 10 h, 24 h, 48 h), while kidney function was re-assessed up to 24 months. RESULTS: 38 patients were included; 16 (42%) developed clinical AKI. The eGFR decline at 24 months was more pronounced after postoperative AKI (-20.75 vs. -7.20, p < 0.0001). KineticGFR at 4 h (p = 0.008) and NephroCheck at 10 h (p = 0.001) were, at multivariable linear regression analysis, efficient predictors of post-operative AKI and long-term eGFR decline if compared to creatinine (R2 0.33 vs. 0.04). CONCLUSIONS: NephroCheck and kineticGFR have emerged as promising noninvasive, accurate, and early biomarkers of postoperative AKI and long-term GFR decline after rNSS. Combining NephroCheck and kineticGFR in clinical practice would allow to identify high risk of postoperative AKI and long-term GFR decline as early as 10 h after surgery.

A Real-Life Study on the Use of Tildrakizumab in Psoriatic Patients.

Tildrakizumab is a humanized IgG1κ monoclonal antibody that selectively targets the p19 subunit of interleukin IL-23, thereby inhibiting the IL-23/IL-17 axis, which is primarily implicated in the immunopathogenesis of psoriasis. Tildrakizumab is approved for the treatment of moderate-to-severe plaque-type psoriasis in adults based on the evidence of two randomized and controlled phase-III clinical trials (reSURFACE 1 and reSURFACE 2). Here, we report our real-life experience treating 53 psoriatic patients (19 female and 34 male) who were administered tildrakizumab every 12 weeks and received follow-ups over 52 weeks. Descriptive and inferential statistical analyses were performed, in particular the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and, if applicable, the Nail Psoriasis Severity Index (NAPSI) and Palmoplantar Psoriasis Physician Global Assessment (PPPGA). These were assessed at baseline and after different timepoints (weeks) during the follow-up period. We described and evaluated demographical and epidemiological characteristics in our cohort group, focusing on comorbidities. In this group, 35.9% of patients were female and 64.1% were male, with 47.1% being smokers and with a mean age of 51.2 years. A total of 37.7% of these patients was affected by scalp psoriasis; regarding comorbidities, hypertension was the most frequent (32.5%), followed by psoriatic arthritis (PsA) (18.60%) and diabetes (13.9%). At week 52, 93%, 90.2% and 77% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. In addition, NAPSI, PPPGA and DLQI scores were significantly reduced by week 52. In our cohort of complex psoriasis patients, disease remission began at the end of the fourth week of treatment and remained constant from week 16 to week 52.

Guselkumab for treatment of moderate-to-severe plaque psoriasis: real-life effectiveness and drug-survival for up to 148 weeks.

BACKGROUND: Real-world data are useful to guide the management of psoriasis. Here, we present data on the effectiveness and survival of guselkumab in moderate-to-severe chronic plaque psoriasis for up to 148 weeks. RESEARCH DESIGN AND METHODS: Cross-sectional study of 122 patients receiving guselkumab (100 mg at weeks 0 and 4, and then every 8 weeks thereafter) for>12 weeks, from November 2018 to April 2022. MAIN OUTCOME MEASURES: Clinical features and drug survival were analyzed up to 148 weeks. RESULTS: Obese patients (32.8%) and those receiving prior biologics (64.8%) were included. Guselkumab treatment was associated with a rapid decrease in PASI, from 16.2 to 3.2 at week 12, and long-term improvements in all subgroups (97.6%, 82.9%, and 63.4% of patients, respectively, achieved PASI 75, 90, and 100 after 148 weeks). More non-obese than obese patients achieved PASI 100 at week 148 (86.4% vs 38.9%), as did bio-naïve vs bio-experienced patients (86.7% vs 50.0%). Previous biologic therapy was a negative prognostic factor for achieving PASI 100 over the long-term by multivariate analysis (p = 0.005). Overall, 96% of patients were on treatment after 2 years. CONCLUSIONS: Real-world data confirm the long-term effectiveness of guselkumab in patients with psoriasis.

Relationship between intensive care surge capacity and hospital factors: an extensive experience.

As a prolonged surge scenario, the COVID-19 pandemic has offered an unparalleled opportunity to improve hospital surge capacity (SC) understanding and the ability to manage it. In this study, the authors report the experience of a large hospital network and evaluate potential relationships between Intensive Care Units SC (ICU-SC) and some hospital-related variables: bed occupancy, emergency department admissions, ward admission from ED, and elective surgery procedures. Pearson's partial correlation coefficient (r) has been used to define the relationship between SC and the daily values of the above variables, collected through a dedicated digital platform that also ensured a regular quality check of the data. The observation has concerned several levels of analysis, namely two different types of SC calculation (SC base-SCb and SC actual-SCa), hospital category level and multi-hospital level, and two consecutive pandemic waves. Among the 16 hospitals observed, the correlation was shown to be moderate-positive with non-ICU bed occupancy (r/ = 0.62, r/ = 0.54), strong/moderate with ICU bed occupancy (r/ = 0.72, r/ = 0.54), and moderate with ward admissions from ED (r/ = 0.50, r/ = 0.51) On the contrary, the correlation proved to be moderate-negative with ED admissions (r/ = - 0.69, r/ = - 0.62) and low with the number of elective surgery procedures (r/ = - 0.10, r/ = - 0.16). This study identified a positive correlation between SC and three variables monitored: ICU bed occupancy, non-ICU bed occupancy, and ward admissions from ED. On the contrary, the correlation was negative for ED admission and the number of elective surgery procedures. The results have been confirmed across all levels of analysis adopted.

Combined Inhibition of Smoothened and the DNA Damage Checkpoint WEE1 Exerts Antitumor Activity in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is characterized by resistance to chemotherapy and a poor prognosis. Therefore, treatments that can effectively suppress tumor growth are urgently needed. Aberrant activation of hedgehog (HH) signaling has been implicated in several cancers, including those of the hepatobiliary tract. However, the role of HH signaling in intrahepatic CCA (iCCA) has not been completely elucidated. In this study, we addressed the function of the main transducer Smoothened (SMO) and the transcription factors (TFs) GLI1 and GLI2 in iCCA. In addition, we evaluated the potential benefits of the combined inhibition of SMO and the DNA damage kinase WEE1. Transcriptomic analysis of 152 human iCCA samples showed increased expression of GLI1, GLI2, and Patched 1 (PTCH1) in tumor tissues compared with nontumor tissues. Genetic silencing of SMO, GLI1, and GLI2 inhibited the growth, survival, invasiveness, and self-renewal of iCCA cells. Pharmacologic inhibition of SMO reduced iCCA growth and viability in vitro, by inducing double-strand break DNA damage, leading to mitotic arrest and apoptotic cell death. Importantly, SMO inhibition resulted in the activation of the G2-M checkpoint and DNA damage kinase WEE1, increasing the vulnerability to WEE1 inhibition. Hence, the combination of MRT-92 with the WEE1 inhibitor AZD-1775 showed increased antitumor activity in vitro and in iCCA xenografts compared with single treatments. These data indicate that combined inhibition of SMO and WEE1 reduces tumor burden and may represent a strategy for the clinical development of novel therapeutic approaches in iCCA.

Tryptophan degradation enzymes expression in the placenta and the Kynurenine/Tryptophan ratio in maternal plasma after elective cesarean section.

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) metabolize tryptophan in the kynurenine pathway. We evaluated these enzymes' mRNA expression in maternal and fetal sides of the placenta of uncomplicated, unlabored full-term pregnancies after elective cesarean section and compared it with that of placentas obtained from vaginal delivery. Tryptophan and kynurenine plasmatic levels after cesarean section were measured, to investigate their possible correlation with IDO1 and TDO mRNA (TDO2) expression. The results suggested that IDO1 and TDO2 expression was higher in the maternal side of the placenta and that labor significantly affects TDO2 expression and the plasma Kynurenine/Tryptophan ratio.

Ultrashort Echo-Time Magnetic Resonance Imaging Sequence in the Assessment of Systemic Sclerosis-Interstitial Lung Disease.

PURPOSE: To test respiratory-triggered ultrashort echo-time (UTE) Spiral VIBE-MRI sequence in systemic sclerosis-interstitial lung disease assessment compared with computed tomography (CT). MATERIAL AND METHODS: Fifty four SSc patients underwent chest CT and UTE (1.5 T). Two radiologists, independently and in consensus, verified ILD presence/absence and performed a semiquantitative analysis (sQA) of ILD, ground-glass opacities (GGO), reticulations and honeycombing (HC) extents on both scans. A CT software quantitative texture analysis (QA) was also performed. For ILD detection, intra-/inter-reader agreements were computed with Cohen K coefficient. UTE sensitivity and specificity were assessed. For extent assessments, intra-/inter-reader agreements and UTE performance against CT were computed by Lin's concordance coefficient (CCC). RESULTS: Three UTE were discarded for low quality, 51 subjects were included in the study. Of them, 42 QA segmentations were accepted. ILD was diagnosed in 39/51 CT. UTE intra-/inter-reader K in ILD diagnosis were 0.56 and 0.26. UTE showed 92.8% sensitivity and 75.0% specificity. ILD, GGO, and reticulation extents were 14.8%, 7.7%, and 7.1% on CT sQA and 13.0%, 11.2%, and 1.6% on CT QA. HC was <1% and not further considered. UTE intra-/inter-reader CCC were 0.92 and 0.89 for ILD extent and 0.84 and 0.79 for GGO extent. UTE RET extent intra-/inter-reader CCC were 0.22 and 0.18. UTE ILD and GGO extents CCC against CT sQA and QA were ≥0.93 and ≥0.88, respectively. RET extent CCC were 0.35 and 0.22 against sQA and QA, respectively. CONCLUSION: UTE Spiral VIBE-MRI sequence is reliable in assessing ILD and GGO extents in systemic sclerosis-interstitial lung disease patients.

Lung vascular changes as biomarkers of severity in systemic sclerosis-associated interstitial lung disease.

OBJECTIVES: It has recently become possible to assess lung vascular and parenchymal changes quantitatively in thoracic CT images using automated software tools. We investigated the vessel parameters of patients with SSc, quantified by CT imaging, and correlated them with interstitial lung disease (ILD) features. METHODS: SSc patients undergoing standard of care pulmonary function testing and CT evaluation were retrospectively evaluated. CT images were analysed for ILD patterns and total pulmonary vascular volume (PVV) extents with Imbio lung texture analysis. Vascular analysis (volumes, numbers and densities of vessels, separating arteries and veins) was performed with an in-house developed software. A threshold of 5% ILD extent was chosen to define the presence of ILD, and commonly used cut-offs of lung function were adopted. RESULTS: A total of 79 patients [52 women, 40 ILD, mean age 56.2 (s.d. 14.2) years, total ILD extent 9.5 (10.7)%, PVV/lung volume % 2.8%] were enrolled. Vascular parameters for total and separated PVV significantly correlated with functional parameters and ILD pattern extents. SSc-associated ILD (SSc-ILD) patients presented with an increased number and volume of arterial vessels, in particular those between 2 and 4 mm of diameter, and with a higher density of arteries and veins of <6 mm in diameter. Considering radiological and functional criteria concomitantly, as well as the descriptive trends from the longitudinal evaluations, the normalized PVVs, vessel numbers and densities increased progressively with the increase/worsening of ILD extent and functional impairment. CONCLUSION: In SSc patients CT vessel parameters increase in parallel with ILD extent and functional impairment, and may represent a biomarker of SSc-ILD severity.

The Role of Bronchoalveolar Lavage in Systemic Sclerosis Interstitial Lung Disease: A Systematic Literature Review.

The role of Bronchoalveolar Lavage (BAL) in the evaluation of systemic sclerosis (SSc) interstitial lung disease (ILD) is still controversial. The aim of this systematic literature review was to investigate the use of BAL in SSc-ILD, and to focus on the pros and cons of its real-life application. Methods: PubMed, Cochrane, and Embase were questioned from inception until 31 December 2021. Results: Eighteen papers were finally analyzed. A positive correlation was observed between lung function and BAL cytology; in particular, BAL neutrophilia/granulocytosis was related to lower diffusing capacity for carbon monoxide (DLCO) values and lower forced vital capacity (FVC). Moreover, a positive correlation between BAL cellularity and high-resolution computed tomography (HRCT) findings has been reported by several authors. Cytokines, chemokines, growth factors, coagulation factors, and eicosanoids have all been shown to be present, more often and in higher quantities in SSc-ILD patients than in the health control and, in some cases, they were related to more severe pulmonary disease. There was no consensus regarding the role of BAL cellularity as a predictor of mortality.

Tryptophan degradation enzymes and Angiotensin (1-7) expression in human placenta.

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are key enzymes for tryptophan degradation, regulating immune tolerance during pregnancy. The intrauterine renin-angiotensin system is also involved in the progression of a healthy pregnancy. Angiotensin(1-7) maintains the integrity of fetal membranes via counteracting the pro-inflammatory actions of Angiotensin II. No data are available on placental Angiotensin(1-7) co-expression with TDO. We aimed to characterize TDO mRNA expression and its localization in different areas of the placenta of physiological pregnancies delivered at term; its co-expression with Angiotensin(1-7) and its correlation with the plasma kynurenine/tryptophan (Kyn/Trp) ratio was investigated. This prospective observational study included a nonconsecutive series of 20 singleton uncomplicated pregnancies delivered vaginally. TDO mRNA was expressed in both maternal and fetal sides of the placentas and TDO protein also in the villi and it was co-expressed with IDO1 in almost half of the placental cells at these sites. The percentage of TDO+ and IDO1+ cells appeared to be influenced by maternal pre-gestational smoking and newborn weight. A strong correlation was found between the percentage of TDO+ and IDO1+ cells in the villi. TDO+ cells also expressed Angiotensin(1-7), with a higher percentage on the fetal side and in the villi compared to the maternal one. Kyn/Trp plasma ratio was not correlated with IDO and TDO expression nor with the patient's characteristics. Collectively, our data indicate that TDO is detectable in placental tissue and is co-expressed with IDO and with Angiotensin(1-7)+ on the fetal side and in the villi.

Lung Ultrasound B-Lines in the Evaluation of the Extent of Interstitial Lung Disease in Systemic Sclerosis.

Background: Chest computed tomography (CT) is the gold standard for the evaluation of systemic sclerosis-related interstitial lung disease (SSc-ILD). Lung ultrasound (LUS) is a radiation-free tool that identifies the B-lines as a main feature of ILD. We aimed to investigate the role of LUS in the evaluation of the extent of SSc-ILD. Methods: Adult SSc patients underwent pulmonary function tests (PFTs), LUS and CT. The CT images were qualitatively, semi-quantitatively (the Wells score on five levels and the categorical Goh et al. staging) and quantitatively (histogram-based densitometry) analysed for ILD. LUS quantified B-lines in 21 intercostal spaces on both the anterior and posterior chest wall. Results: Out of the 77 SSc patients eligible for the study, 35 presented with ILD on CT (21 limited, 14 extensive). Total B-lines significantly differentiated ILD vs. no ILD (median 24 vs. 8, p < 0.001). Posterior and total B-lines significantly differentiated limited from absent ILD, while anterior B-lines distinguished extensive from limited ILD. Total B-lines correlated with the Wells score (r = 0.446, p < 0.001) and MLA (r = −0.571, p < 0.001); similar results were confirmed when anterior and posterior B-lines were analysed separately. Conclusions: LUS is a useful tool to identify SSc-ILD and to correlate with different evaluations of ILD extent and severity.

Regional Citrate Anticoagulation and Systemic Anticoagulation during Pediatric Continuous Renal Replacement Therapy: A Systematic Literature Review.

BACKGROUND: Clotting is a major drawback of continuous renal replacement therapy (CRRT) performed on critically ill pediatric patients. Although anticoagulation is recommended to prevent clotting, limited results are available on the effect of each pharmacological strategy in reducing filter clotting in pediatric CRRT. This study defines which anticoagulation strategy, between regional citrate anticoagulation (RCA) and systemic anticoagulation with heparin, is safer and more efficient in reducing clotting, patient mortality, and treatment complications during pediatric CRRT. METHODS: A systematic literature review was run considering papers published in English until December 2021 and describing patients' and treatments' complications in CRRT performed with heparin and RCA on patients aged less than 18 years. RESULTS: Eleven studies were considered, cumulatively comprising 1.706 CRRT sessions (62% with systemic anticoagulation and 38% with RCA). Studies have consistently identified RCA's superiority over systemic anticoagulation with heparin in prolonging circuit life. The pooled estimate (95% CI) of filter clotting risk showed that RCA is a protective factor for clotting risk (RR = 0.204). CONCLUSIONS: RCA has a potential role in prolonging circuit life and seems superior to systemic anticoagulation with heparin in decreasing the risk of circuit clotting during CRRT performed in critically ill pediatric patients.

Efficacy of Tildrakizumab for the Treatment of Difficult-to-Treat Areas: Scalp, Nail, Palmoplantar and Genital Psoriasis.

Tildrakizumab, an IL-23 inhibitor, is effective and safe for the improvement of moderate-to-severe chronic plaque psoriasis. However, little evidence is available on the use of this biologic in psoriasis in difficult-to-treat locations. In this retrospective analysis, we treated patients with 100 mg tildrakizumab at Day 0, after 4 weeks and every 12 weeks thereafter. Disease severity and treatment response was assessed by the Psoriasis Area and Severity Index (PASI), the static Physician's Global Assessment of Genitalia (sPGA-G), the Psoriasis Scalp Severity Index (PSSI), Nail Psoriasis Severity Index (NAPSI) and the Palmoplantar Psoriasis Area and Severity Index (ppPASI) at baseline and after 4, 12 and 28 weeks. We followed 18 patients (mean age 49.1 ± 12.7 years, 61.1% male) with psoriasis localized to the genital region (N = 7), scalp (N = 6), nails (N = 5) and palmar/plantar areas (N = 7). PASI score decreased from 11.5 at baseline to 3.1 and 2.4 at 12 and 28 weeks. Tildrakizumab treatment decreased sPGA-G (3.3 to 0.2), PSSI (36.2 to 2.7), NAPSI (48.4 to 15.7) and ppPASI (5.3 to 0) from baseline to 28 weeks, respectively. Data from this real-life retrospective analysis shows that tildrakizumab is an effective option for the management of psoriasis in difficult-to-treat areas.