Circulating Endothelin 1 but Not Transforming Growth Factor-ß Levels Are Reduced after Pulmonary Endarterectomy in Subjects Affected by Chronic Thromboembolic Pulmonary Hypertension: A Prospective Cohort Study.

Background and objectives: Endothelin-1 (ET-1) and transforming growth factor-ß (TGF-ß) 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-ß 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-ß 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-ß 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-ß levels did not significantly change after PEA. Furthermore, ET-1, but not TGF-ß, was a good predictor for increased mPAP in multivariate analyses (p < 0.05). Conclusions: ET-1 but not TGF ß was significantly modulated by PEA in subjects affected by CTEPH up to 1 year after surgery. The mechanisms leading to prolonged elevated circulating TGF-ß levels and their clinical significance have to be further elucidated.

Clinical outcomes of diverticular disease in young adults: results from a tertiary referral center.

Introduction: Diverticular disease (DD), commonly associated with the elderly, is becoming more prevalent among younger individuals. This retrospective study aimed to evaluate the differences in the natural history and outcomes between young and old patients with DD. Methods: Adult patients with DD diagnosed between 2010 and 2022 at an Italian tertiary referral center were enrolled, and their demographic and clinical data were retrieved. The patients were categorized as young or old based on the 25th percentile of the population's age at diagnosis. Univariate and multivariate analyses were performed to assess the association between the collected variables and the age of disease presentation. Additionally, survival analyses were conducted to evaluate the association between the age of diagnosis and clinical outcomes at follow-up, including disease recurrence, hospital access, surgery, and death. Results: A total of 220 DD patients (with a median age of 66 years, IQR 55-74, and a female-to-male ratio of 1.4:1) were included in the study, comprising 54 patients receiving a diagnosis before the age of 49 years (young DD patients) and 166 patients diagnosed after the age of 49 years (old DD patients). Male sex (57 vs. 36%, p < 0.01), smoking (38 vs. 14%, p < 0.01), and alcohol consumption (54 vs. 38%) were highly prevalent in young patients. The complications at the time of diagnosis, particularly abscesses and free perforations, occurred more frequently in younger patients (p = 0.04). Moreover, young DD patients experienced a higher rate of hospitalization and surgical intervention (p = 0.01 and p = 0.04, respectively) over a median follow-up period of 5 years. Conclusion: Preventive strategies and prompt diagnosis are crucial in young patients with DD for achieving better disease outcomes and preventing complications.

The Role of Neutrophil-Lymphocytes Ratio in the Prognosis of CIN2+ Recurrence after Excisional Treatment.

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.

Sonographic detection of massive colonic pseudopolyposis in inflammatory bowel diseases.

PURPOSE: Colonic pseudopolyps are a frequent finding in inflammatory bowel disease (IBD). Yet there are no published data describing the characteristics of pseudopolyposis in intestinal ultrasound (IUS). This study aimed at identifying the key features of pseudopolyposis in IUS. METHODS: This case-control study included 12 patients with ulcerative colitis or Crohn's colitis with extensive left colon pseudopolyposis and 18 matched IBD patients without pseudopolyps at colonoscopy. Luminal (diameters, thickening, stratification, margins, and vascularity) and intraluminal (vascular signals at color Doppler), and extraluminal (mesenteric fat) parameters of the left colon were compared. Anonymized still images and videos of these patients were blindly reviewed to estimate the accuracy in detecting this condition. RESULTS: Among the IUS parameters assessed, the anteroposterior diameter ≥ 12 mm and the presence of luminal vascular signals were significantly correlated with pseudopolyposis. The detection of both these findings were able to detect extensive pseudopolyposis a sensitivity of 75% (CI 95%: 42.8-94.5%) and a specificity of 100% (CI 95%: 81.5-100%). CONCLUSION: This is the first study describing the IUS features of pseudopolyposis in IBD. The potential use of IUS to assess pseudopolyposis might have an impact on IUS monitoring and surveillance of IBD patients with condition.

Retrospective Investigation of Human Papillomavirus Cervical Infection and Lymphoma Incidence: A Clinical and Pathological Evaluation.

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.

Diagnostic delay in symptomatic uncomplicated diverticular disease: an Italian tertiary referral centre study.

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.

Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients.

RATIONALE: Whole lung lavage (WLL) is a widely accepted palliative treatment for autoimmune pulmonary alveolar proteinosis (aPAP) but does not correct myeloid cell dysfunction or reverse the pathological accumulation of surfactant. In contrast, inhaled recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a promising pharmacological approach that restores alveolar macrophage functions including surfactant clearance. Here, we evaluate WLL followed by inhaled rGM-CSF (sargramostim) as therapy of aPAP. METHODS: 18 patients with moderate-to-severe aPAP were enrolled, received baseline WLL, were randomised into either the rGM-CSF group (receiving inhaled sargramostim) or control group (no scheduled therapy) and followed for 30 months after the baseline WLL. Outcome measures included additional unscheduled "rescue" WLL for disease progression, assessment of arterial blood gases, pulmonary function, computed tomography, health status, biomarkers and adverse events. Patients requiring rescue WLL were considered to have failed their assigned intervention group. RESULTS: The primary end-point of time to first rescue WLL was longer in rGM-CSF-treated patients than controls (30 versus 18 months, n=9 per group, p=0.0078). Seven control patients (78%) and only one rGM-CSF-treated patient (11%) required rescue WLL, demonstrating a 7-fold increase in relative risk (p=0.015). Compared to controls, rGM-CSF-treated patients also had greater improvement in peripheral arterial oxygen tension, alveolar-arterial oxygen tension difference, diffusing capacity of the lungs for carbon monoxide and aPAP biomarkers. One patient from each group withdrew for personal reasons. No serious adverse events were reported. CONCLUSIONS: This long-term, prospective, randomised trial demonstrated inhaled sargramostim following WLL reduced the requirement for WLL, improved lung function and was safe in aPAP patients. WLL plus inhaled sargramostim may be useful as combined therapy for aPAP.

PEG 400 Ion Suppression in Busulfan Detection by High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Busulfan (Bu), an alkylating agent commonly used in chemotherapy and transplantation, exhibits high intraindividual pharmacokinetic variability and possible time-dependent variations in clearance, which complicate therapeutic drug monitoring. Numerous analytical methods have been developed to reduce analysis time and facilitate timely decision-making regarding treatment changes; however, the validation procedures rarely involve analysis of potentially interfering excipients. Macrogol 400 (PEG 400) should be considered as a possible interfering agent in the detection of plasma Bu levels, especially as an ionization suppressor. METHODS: Six intravenous formulations of Bu were compared with identify at least 1 common excipient (PEG 400). During the 176 therapeutic drug monitoring analyses of Bu, one of the PEG 400 specific mass-to-charge ratio transitions was determined using an instrumental method. After coelution with Bu and its internal standard (Bu-d8) was confirmed, all analyses were repeated using a different experimental setup free of ion suppression induced by PEG. The concentration-time profile of PEG 400 was also analyzed. RESULTS: The area under the curve obtained from the 2 data sets was compared and analyzed using Lin concordance correlation coefficient and Bland-Altman plot analysis. The results from the 2 analytical methods were comparable: PEG 400 negatively affected the Bu-d8 coefficient of variation but not the Bu/Bu-d8 ratio. CONCLUSIONS: The possible interference of PEG 400 should be thoroughly investigated, especially with respect to analytical methods that cannot be supported by correction of the stable isotopically labeled internal standard analog.

Quality of life analysis in bladder pain syndrome/interstitial cystitis: implications for a multimodal integrated treatment.

BACKGROUND: The aim of this study was to evaluate whether there is a higher prevalence of anxiety-depressive disorders in women with BPS/IC (bladder pain syndrome/interstitial cystitis) than in women with chronic non-neoplastic pain with or without fibromyalgia, to examine possible correlations between urological and psychiatric symptoms. METHODS: The patients included in the study were divided into two groups: 1) group 0: patients with an existing diagnosis of BPS/IC. BPS/IC was confirmed by reviewing medical record; group 1+2: patients with chronic non-neoplastic pain, suffering from fibromyalgia or other types of chronic pain (chronic arthralgia or lower back pain). Three questionnaires were administered: PHQ-9 to investigate psychological symptoms, O'Leary Saint (ICSI-ICPI) to investigate urological symptoms in women with BPS/IC and BPI to investigate specifically pain. RESULTS: The survey included 69 patients, 42 patients had a diagnosis of BPS/IC while 27 of them had chronic non-neoplastic pain. The average PHQ-9 Score was 10.3 in BPS/IC group, considered as major depression (score between 10 and 14); the average score of PHQ-9 was 6.9 in group 1+2, as in sub-threshold depression (between 5-9). CONCLUSIONS: The chronic pain of BPS/IC can affect mood more than in other painful conditions, as more than half of this population has a score that identifies depression with the PHQ-9 questionnaire, confirming the hypothesis that the syndrome is associated with a higher prevalence of an anxious-depressive condition.

Efficacy of Pegylated Hyaluronic Acid Filler Enriched with Calcium Hydroxyapatite: A 24-Week Post-Market, Observational, Prospective, Open-Label, Single-Center Study.

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.

Exclusive breastfeeding at 6 months after assisted and spontaneous conceiving: a prospective study in Northern Italy.

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.

One year of experience with combined pharmacokinetic/pharmacogenetic monitoring of anti-TNF alpha agents: a retrospective study.

Anti-tumor necrosis factor alpha (anti-TNFα) inhibitors are used extensively for the management of moderate to severe inflammatory bowel disease (IBD) in both adult and pediatric patients. Unfortunately, not all patients show an optimal response to induction therapy, while others lose their response over time for reasons yet poorly understood. We report on a pharmacokinetic/pharmacogenetic approach to monitor the therapy with anti-TNFα in a real-world cohort of seventy-nine pediatric patients affected by IBD that was analyzed retrospectively. We evaluated plasma concentrations of infliximab, adalimumab, and related anti-drug antibodies (ADAs), and single nucleotide polymorphisms (SNPs) in genes involved in immune processes and inflammation on the anti-TNFα response. We found a significant association between the SNP in TNFα promoter (-308G>A) and clinical remission without steroids in patients on infliximab therapy. Additionally, a potential connection between HLA-DQA1*05 genetic variant carriers and a higher risk of anti-TNFα immunogenicity emerged.

Ultrasonographic and Functional Features of Symptomatic Uncomplicated Diverticular Disease.

INTRODUCTION: To evaluate the ability of intestinal ultrasound (IUS) in discriminating symptomatic uncomplicated diverticular disease (SUDD) among patients with abdominal symptoms including irritable bowel syndrome (IBS). METHODS: This observational, prospective study included consecutive patients classified into the following categories: (i) SUDD; (ii) IBS; (iii) unclassifiable abdominal symptoms; and (iv) controls, including asymptomatic healthy subjects and diverticulosis. The IUS evaluation of the sigmoid: assessed the presence of diverticula, thickness of the muscularis propria, and IUS-evoked pain, namely the intensity of pain evoked by compression with the ultrasound probe on sigmoid colon compared with an area of the left lower abdominal quadrant without underlying sigmoid colon. RESULTS: We enrolled 40 patients with SUDD, 20 patients with IBS, 28 patients with unclassifiable abdominal symptoms, 10 healthy controls, and 20 patients with diverticulosis. Patients with SUDD displayed significantly ( P < 0.001) greater muscle thickness (2.25 ± 0.73 mm) compared with patients with IBS (1.66 ± 0.32 mm), patients with unclassifiable abdominal pain, and healthy subjects, but comparable with that of patients with diverticulosis (2.35 ± 0.71 mm). Patients with SUDD showed a greater (not significant) differential pain score than other patients. There was a significant correlation between the thickness of the muscularis propria and the differential pain score only for patients with SUDD ( r = 0.460; P : 0.01). Sigmoid diverticula were detected by colonoscopy in 40 patients (42.4%) and by IUS with a sensitivity of 96.0% and a specificity of 98.5%. DISCUSSION: IUS could represent a useful diagnostic tool for SUDD, potentially useful in characterizing the disease and appropriately address the therapeutic approach.

Reduction of BSI associated mortality after a sepsis project implementation in the ER of a tertiary referral hospital.

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.

Improved Breast 2D SWE Algorithm to Eliminate False-Negative Cases.

OBJECTIVES: Two-dimensional shear wave elastography (SWE) has been limited in breast lesion characterization due to false-negative results from artifacts. The aim of this study was to evaluate an updated Food and Drug Administration-approved breast 2D-SWE algorithm and compare with the standard algorithm (SA). MATERIALS AND METHODS: This prospective, single-center study was approved by our local institutional review board and Health Insurance Portability and Accountability Act compliant. From April 25, 2019 to May 2, 2022, raw shear wave data were saved on patients having screening or diagnostic breast ultrasound on a Siemens Sequoia US. After removing duplicate images and those without biopsy diagnosis or stability over 2 years, there were 298 patients with 394 lesions with biopsy-proven pathology or >2-year follow-up. Raw data were processed using the SA and a new algorithm (NA). Five-millimeter regions of interest were placed in the highest stiffness in the lesion or adjacent 3 mm on the SA. Stiffness values (shear wave speed, max) in this location from both algorithms were recorded. Statistics were calculated for comparing the 2 algorithms. RESULTS: The mean patient age was 56.3 ± 16.1 years (range, 21-93 years). The mean benign lesion size was 10.7 ± 8.0 mm (range, 2-46 mm), whereas the mean malignant lesion size was 14.9 ± 7.8 mm (range, 4-36 mm). There were 201 benign (>2-year follow-up) and 193 biopsied lesions (65 benign; 128 malignant). The mean maximum stiffness for benign lesions was 2.37 m/s (SD 1.26 m/s) for SA and 3.51 m/s (SD 2.05 m/s) for NA. For malignant lesions, the mean maximum stiffness was 4.73 m/s (SD, 1.71 m/s) for SA and 8.45 m/s (SD, 1.42 m/s) for NA. The area under the receiver operating characteristic curve was 0.87 SA and 0.95 NA when using the optimal cutoff value. Using a threshold value of 5.0 m/s for NA and comparing to SA, the sensitivity increased from 0.45 to 1.00 and the specificity decreased from 0.94 to 0.81; the positive predictive value was 0.72, the negative predictive value was 1.00, and the negative likelihood ratio was 0.00. CONCLUSIONS: Using a new breast SWE algorithm significantly improves the sensitivity of the technique with a small decrease in specificity, virtually eliminating the "soft" cancer artifact. The new 2D-SWE algorithm significantly increases the sensitivity and negative predictive value in characterizing breast lesions as benign or malignant and allows for downgrading all BI-RADS 4 lesions.

Long-Term Follow-Up of Non-Enhancing Renal Masses on CEUS.

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.

Clonal Megakaryocyte Dysplasia with Isolated Thrombocytosis Is a Distinct Myeloproliferative Neoplasm Phenotype.

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.

Congenital Lung Malformations: Clinical and Functional Respiratory Outcomes after Surgery.

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.