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Background: Thrombosis is linked to neutrophil release of neutrophil extracellular traps (NETs). NETs are proposed as a mechanism of resistance to thrombolysis. This study intends to analyze the composition of thrombi retrieved after mechanical thrombectomy, estimate the age and organization of thrombi, and evaluate associations with the use of thrombolysis, antiplatelets, and heparin., Methods: This retrospective observational study involved 72 samples (44 from cerebral and 28 coronary arteries), which were stained with hematoxylin and eosin, anti-NE (neutrophil elastase) antibody, and anti-histone H2B (histone H2B) antibody, representing different components in NET formation, all detectable during the later stages of NETosis, for histochemical and digital quantification of NET content. The histological and morphological evaluations of the specimens were correlated, through univariate and mediation analyses, with clinical information and therapy administered before intervention., Results: The results demonstrated that the composition of cerebral and coronary thrombi differs, and there were significantly more lytic cerebral thrombi than coronary thrombi (66% versus 14%; P =0.005). There was a considerably higher expression of NETs in the cerebral thrombi as testified by the higher expression of H2B ( P =0.031). Thrombolysis was remarkably associated with higher NE positivity (average marginal effect, 6.461 [95% CI, 0.7901-12.13]; P =0.02555), regardless of the origin of thrombi. There was no notable association between the administration of antiaggregant therapy/heparin and H2B/NE amount when adjusted for the thrombus location. Importantly, the age of the thrombus was the only independent predictor of NET content without any mediation of the thrombolytic treatment ( P =0.014)., Conclusions: The age of the thrombus is the driving force for NET content, which correlates with impaired clinical outcomes. The therapy that is currently administered does not modify NET content. This study supports the need to investigate new pharmacological approaches added to thrombolysis to prevent NET formation or enhance their disruption, such as recombinant human DNase I (deoxyribonuclease I)., Competing Interests: Disclosures None.

Introduction: Vitiligo is an acquired chronic pigmentation disorder of the skin. Even if the role of the immune system seems to be well established, new pathogenetic hypothesis are rising in these years. It has been recently suggested by the development of an animal model that a protein called Melanoma Inhibitory Activity (MIA) is involved in the pathogenesis of vitiligo. This protein interacts with the adhesion molecules expressed on the melanocytes causing its detachment from extracellular matrix proteins and creating the depigmented macules. A topical preparation based on oligopeptides able to inhibit the actions of the MIA protein has been introduced to the market, claiming activity on vitiligo., Patient Concerns and Diagnosis: A patient affected by non-segmental vitiligo for 10 years, recalcitrant to any treatment (such as steroids, immunomodulators, kellin, UVB-NB and UVA) came to our observation., Interventions: We used this topical preparation containing the MIA inhibitors peptides in selected areas (face and sides of the trunk) leaving untreated other areas as control (legs and arms). The patient was required to be sun exposed or to have some UVA sessions during the treatment to stimulate the melanocytes replications., Outcomes: After 9 months of treatments, he recovered from 50% to 80% of repigmentation only in the treated areas, without any side effects locally or systemically., Conclusion: Even if other studies are required to better determine the efficacy of this approach, this first observation about the use of the MIA-inhibitors peptides for the treatment of non-segmental vitiligo indicates that this topical preparation containing the MIA inhibitors peptides could be a very promising option for the cure of this disease., Competing Interests: The authors have no funding and conflicts of interest to disclose. Authors Sergi Hernandez Navarro, Jordi Segura Tejedor, Marta Bajona Roig are employers at Bella Aurora Labs; Author Matteo Bordignon is consultant for Bella Aurora Labs; Authors Roberto Luisetto, Marny Fedrigo, Chiara Castellani, Annalisa Angelini, Mauro Alaibac declare that they have no conflict of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: Objective data on epidemiology, management and outcome of patients with acute cardiac illness are still scarce, and producing evidence-based guidelines remains an issue. In order to define the clinical characteristics and the potential predictors of in-hospital and long-term mortality, we performed a retrospective, observational study, in a tertiary cardiac centre in Italy., Methods: One thousand one hundred and sixty-five consecutive patients, admitted to our intensive cardiac care unit (ICCU) during the year 2016, were included in the study. The data were collected from the hospital discharge summary and the electronic chart records., Results: Global in-hospital mortality was 7.2%. Predictors of in-hospital mortality were age [odds ratio (OR): 2.0; P = 0.011], female sex (OR: 2.18; P = 0.003), cardiac arrest (OR: 12.21; P = 0.000), heart failure/cardiogenic shock (OR: 9.99; P = 0.000), sepsis/septic shock (OR: 5.54; P = 0.000), acute kidney injury (OR: 3.25; P = 0.021) and a primary diagnosis of acute heart failure or a condition other than acute heart failure and acute coronary syndrome. During a mean follow-up period of 17.4 ± 4.8 months, 96 all-cause deaths occurred in patients who were still alive at discharge. One-year mortality rate was 8.2%. Predictors of long-term mortality were age (hazard ratio: 1.08; P = 0.000), female sex (hazard ratio: 0.59; P = 0.022), comorbidity at least 3 (hazard ratio: 1,60; P = 0.047), acute kidney injury (hazard ratio: 3.15; P = 0.001), inotropic treatment (hazard ratio: 2.54; P = 0.002) and a primary diagnosis of acute heart failure., Conclusion: In our Level-2 ICCU, predictors of in-hospital and long-term mortality are similar to those commonly found in a Level-3 ICU. These data strongly suggest that ICUs dealing with acute cardiovascular patients should be reorganized with a necessary upgrading of competences and resources for medical and nursing staff.

Background: To assess the role of the novel second-line treatments in nonsmall cell lung cancer (NSCLC)., Methods: A systematic review of the literature with meta-analysis of phase III randomized clinical trials (RCTs) was independently performed by 3 authors. All the trials comparing any novel treatment with every-3-weeks docetaxel (3WD) and designed as noninferiority trial were included in the analysis. One-year survival rate (SR) was the primary end point, and quality of life and safety represented the secondary end points., Results: Four RCTs met the selection criteria. The outcomes of 3355 patients were analyzed in the pooled analysis. No heterogeneity was documented in the primary analysis either including all the trials or analyzing separately gefitinib and the chemotherapeutic alternatives to 3WD. The cumulative odds ratio was 0.927 (P=0.313) for 1-year SR, 0.889 (P=0.323) for the chemotherapeutic alternatives to 3WD and 0.953 (P=0.616) for gefitinib. The experimental arms showed a significant advantage in quality of life in the cumulative analysis (odds ratio=1.623, P=0.01) and in the subgroup of patients treated with gefitinib (odds ratio=1.962, P<0.001); a better safety profile for the experimental arm was observed in the cumulative analysis and in the subgroups of alternative chemotherapies or gefitinib., Conclusion: All the noninferiority trials demonstrated the noninferiority of pemetrexed, oral topotecan, or gefitinib in 1-year SR (primary end point), but the improvement in overall survival remains modest. The improvement in quality of life and safety (secondary end points) represents the main value of these treatments, whose aim is mainly palliative.

Rationale: Acquisition of a procalcific phenotype by resident or circulating cells is important for calcification of atherosclerotic plaques, which is common in diabetes., Objective: We aim to identify and characterize circulating calcifying cells, and to delineate a pathophysiological role for these cells in type 2 diabetes., Methods and Results: We demonstrate for the first time that a distinct subpopulation of circulating cells expressing osteocalcin and bone alkaline phosphatase (OC(+)BAP(+)) has procalcific activity in vitro and in vivo. The study of naïve patients with chronic myeloid leukemia indicated that OC(+)BAP(+) cells have a myeloid origin. Myeloid calcifying OC(+)BAP(+) cells (MCCs) could be differentiated from peripheral blood mononuclear cells, and generation of MCCs was closely associated with expression of the osteogenic transcription factor Runx2. In gender-mismatched bone marrow-transplanted humans, circulating MCCs had a much longer half-life compared with OC(-)BAP(-) cells, suggesting they belong to a stable cell repertoire. The percentage of MCCs was higher in peripheral blood and bone marrow of type 2 diabetic patients compared with controls but was lowered toward normal levels by optimization of glycemic control. Furthermore, diabetic carotid endoarterectomy specimens showed higher degree of calcification and amounts of cells expressing OC and BAP in the α-smooth muscle actin-negative areas surrounding calcified nodules, where CD68(+) macrophages colocalize. High glucose increased calcification by MCCs in vitro, and hypoxia may regulate MCC generation in vitro and in vivo., Conclusions: These data identify a novel type of blood-derived procalcific cells potentially involved in atherosclerotic calcification of diabetic patients.

Purpose of Review: There has been a rise in the introduction of cystic fibrosis (CF) newborn screening (NBS) programs in recent years. Despite many long running and successful programs with established protocols, new strategies are being developed in an effort to improve sensitivity and specificity. In light of the emerging issues of NBS, new algorithms have been implemented and are reviewed here., Recent Findings: The increase in mixing of populations affects both immunoreactive trypsinogen values and sensitivity of genetic analysis in NBS. Adjustments to the mutation panel are not always possible. Algorithms adding nongenetic tiers may prove to be an alternative. The interpretation of the sweat test in neonates has been changing too, and there is now agreement that the upper limit of a normal sweat chloride is 29 mmol/l. Infants identified by NBS with a sweat chloride of 30-59 mmol/l and no evidence of two CF-causing mutations require further evaluation and often a long clinical follow-up before CF may be confirmed or excluded. Some NBS programs have reported a steady reduction in the incidence of CF, traceable to prenatal diagnosis on subsequent pregnancies and population-based carrier screening., Summary: Although there is not one universal CF NBS protocol that will suit the heterogeneous needs of diverse regions, many options for adjusting algorithms to local conditions are now available.

Background: Transitional fractures typically occur in patients with partially closed growth plates. In case of displacements >2 mm, osteosynthesis is recommended. Open reduction and stabilization with lag screws is the most common approach. Infection and paraesthesia are common complications of this method. This study describes an alternative approach by closed reduction and cannulated screw fixation., Methods: All patients with transitional fractures treated by closed reduction and cannulated screw fixation were identified. All patients with >1 year after implant removal were included in this investigation. Of 27 patients treated by this technique, 21 met the inclusion criteria and were sent a standardized questionnaire including the Foot Function Index (FFI). All cases with impairments in the FFI were invited for a follow-up examination., Results: Postoperative complications occurred in two patients (8.3%): one reported paraesthesia of the hallux and one showed skin irritations above the screw insertion. Average follow-up time was 3.8 years after implant removal. Of 21 patients who returned the questionnaire, three patients (14.3%) had impairment in the FFI and were invited for clinical follow-up: one patient showed mild signs of osteoarthritis without visible gaps of the joint surface, one patient had minimally restricted pronation, and one had neither clinical nor radiologic correlates for the impairment reported. Sports activity was reduced in one patient., Conclusion: If closed reduction can be achieved fixation with cannulated screws proved to be a satisfactory method with little scars and good clinical results.

Objectives: The aim of this study was to determine if nonoperative treatment of fractures of the tibial spine (intercondylar eminence) in pediatric patients is the treatment of choice for these injuries., Design/setting: Retrospective clinical analysis in a single department., Patients: All patients younger than 17 years presenting with a fracture of the intercondylar eminence between January 1, 1995 and December 31, 2004 were included in this retrospective study. Patients with ossification of the growth plate (physis) at the time of accident were excluded by protocol., Intervention: Nonoperative treatment with knee aspiration, reduction, and immobilization in a long leg cast., Main Outcome Measurements: History-taking and follow-up examinations were performed using the Cincinnati Knee Score and International Knee Documentation Committee Guidelines of 2000. In addition, a magnetic resonance imaging scan of the injured knee was offered to all patients. SPSS 12.0 and Microsoft Excel 2000 were used for data processing and statistical analysis., Results: Forty-three patients have been included in the study. Twenty-three were female and 20 male. The mean age at trauma was 11.5 years (6-16 years). Only 1 patient required a change of therapy and needed open reduction. Thirty-eight patients were available for follow-up at an interval of 1-7.5 years after trauma (mean 3.5 years). None of the patients reported pain, swelling, disability or giving-way, or was handicapped in their daily life. Of 26 magnetic resonance imaging examinations, we found a missing anterior cruciate ligament in 1 and a partial rupture in another patient., Conclusion: Based on our results, nonoperative management can still be recommended as the primary treatment for tibial spine fractures in children.

Objective: Self-measured blood pressure (BP) and 24-hour ambulatory blood pressure (ABP) monitoring are used to define the arbitrary clinical categories of masked hypertension (MH) and white-coat hypertension (WCH). Severity of target organ damage and incidence of major cardiovascular events are greater in patients with MH than in patients whose BP is normal both inside and outside the doctor's office., Methods: We reviewed studies that addressed the prognostic impact of MH and WCH., Results: Overall, WCH was associated with a better outcome and MH to a poor outcome. We, however, need the criteria to identify the clinically normotensive patients at elevated pretest probability of MH in whom a broad use of self-measured home BP and 24-hour ambulatory BP as screening tests may be appropriate and cost effective. Clinical management of patients with MH should continue to be based on current guidelines and mostly related to target organ damage and associated clinical conditions because of the normal values of clinic BP in these patients. WCH is generally defined by the coexistence of persistently high office BP with normal daytime or 24-hour ABP. Daytime ABP normalcy has been defined by values<135/85 mmHg. Data, however, suggest that incidence of cardiovascular events tends to increase consistently above the cut-off value of 130/80 mmHg for daytime BP., Conclusion: The long-term outcome of patients with WCH remains uncertain. Data suggesting an increased risk of stroke need to be confirmed in wide-scale studies.

Crossed K-wires, descending elastic stable intramedullary nailing and radial external fixator are alternatives in the operative treatment of displaced supracondylar humeral fractures. Only little knowledge of intraoperative radiation exposure exists in those procedures. We found average image intensifier times of 30.7 s for K-wires, 41.4 s for the external fixator and 80.0 s for elastic stable intramedullary nailing. Extensively increased fluoroscopy times was seen in cases switched from closed to open reduction intraoperatively. To avoid unnecessary intraoperative radiation exposure for patient, surgeon and staff, limits of radiation time are recommended as an additional indicator to change the surgical procedure to another fixation method or open reduction.