Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model.

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model. Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions. Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

Osimertinib and palbociclib in an EGFR-mutated NSCLC with primary CDK4 amplification after progression under osimertinib.

Precision cancer medicine has changed the treatment paradigm of patients with non-small cell lung cancer (NSCLC) with specific molecular aberrations. A major challenge is management of the resistance that tumor cells eventually develop against targeted therapies, either through primary or acquired resistance mechanisms. We report a 61 year-old male patient with metastatic NSCLC harboring an EGFR exon 19 deletion, a PIK3CA mutation, and CDK4 amplification. After an initial partial response to osimertinib as mono-therapy (third-generation EGFR tyrosine kinase inhibitor), the patient had progression of disease after 4 months of treatment and was referred for combined osimertinib and palbociclib (CDK4/6 inhibitor) treatment. Though complicated by transient pneumonitis, the patient has an ongoing partial response for > 10 months and has experienced clinical improvement on this treatment regimen. As amplification of CDK4 occurs in ~ 10% of treatment-naïve patients with EGFR-mutated NSCLC, the successful treatment of our patient with osimertinib and palbociclib may be highly relevant for future patients with NSCLC.

Influence of the Outflow Graft Angular Position on the Outcomes in Patients With a Left Ventricular Assist Device.

This study aimed to explore the potential impact of the angular position of the outflow graft on thromboembolic events and aortic valve regurgitation in people with a left ventricular assist device (LVAD). We analyzed contrast computed tomography (CT) data of patients with LVAD implantation between 2016 and 2021. Three-dimensional reconstructions of the outflow graft and aortic arch were performed to calculate the horizontal (azimuth) angle and vertical (polar) angle, as well as the relative distance between the outflow graft, aortic valve, and brachiocephalic artery. Among 59 patients (median age 57, 68% male), a vertical angle ≥107° correlated significantly with increased cerebrovascular accidents (hazard ratio [HR]: 5.8, 95% confidence interval [CI]: 1.3-26.3, p = 0.022) and gastrointestinal bleeding (HR: 3.4, 95% CI: 1.0-11.2, p = 0.049) during a median 25 month follow-up. No significant differences were found between the vertical angle and aortic valve regurgitation or survival. The horizontal angle and relative distance did not show differences regarding clinical adverse events. This study emphasizes the importance of the LVAD outflow graft angular position to prevent life-threatening thromboembolic events. This study suggests the need for prospective research to further validate these findings.

The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF-ß signaling.

AIM: Aortic aneurysms (AA) frequently involve dysregulation of transforming growth factor ß (TGF-ß)-signaling in the aorta. Here, FURIN was tested as aneurysm predisposition gene given its role as proprotein convertase in pro-TGF-ß maturation. METHODS AND RESULTS: Rare FURIN variants were detected by whole-exome sequencing of 781 unrelated aortic aneurysm patients and affected relatives. Thirteen rare heterozygous FURIN variants occurred in 3.7% (29) unrelated index AA patients, of which 72% had multiple aneurysms or a dissection.FURIN maturation and activity of these variants were decreased in vitro. Patient-derived fibroblasts showed decreased pro-TGF-ß processing, phosphorylation of downstream effector SMAD2 and kinases ERK1/2, and steady-state mRNA levels of the TGF-ß-responsive ACTA2 gene. In aortic tissue, collagen and fibrillin fibers were affected. One variant (R745Q), observed in 10 unrelated cases, affected TGF-ß signaling variably, indicating effect modification by individual genetic backgrounds. CONCLUSION: FURIN is a novel, frequent genetic predisposition for abdominal-, thoracic-, and multiple aortic or middle sized artery aneurysms in older patients, by affecting intracellular TGF-ß signaling, depending on individual genetic backgrounds.

De-escalation of axillary treatment in the event of a positive sentinel lymph node biopsy in cT1-2 N0 breast cancer treated with mastectomy: nationwide registry study (BOOG 2013-07).

BACKGROUND: Trials have demonstrated the safety of omitting completion axillary lymph node dissection in patients with cT1-2 N0 breast cancer operated with breast-conserving surgery who have limited metastatic burden in the sentinel lymph node. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients operated with mastectomy who have limited-volume sentinel lymph node metastasis. METHODS: Women diagnosed in 2013-2014 with unilateral cT1-2 N0 breast cancer treated with mastectomy, with one to three sentinel lymph node metastases (pN1mi-pN1a), were identified from the Netherlands Cancer Registry, and classified by axillary treatment: no completion axillary treatment, completion axillary lymph node dissection, regional radiotherapy, or completion axillary lymph node dissection followed by regional radiotherapy. The primary endpoint was 5-year regional recurrence rate. Secondary endpoints included recurrence-free interval and overall survival, among others. RESULTS: In total, 1090 patients were included (no completion axillary treatment, 219 (20.1%); completion axillary lymph node dissection, 437 (40.1%); regional radiotherapy, 327 (30.0%); completion axillary lymph node dissection and regional radiotherapy, 107 (9.8%)). Patients in the group without completion axillary treatment had more favourable tumour characteristics and were older. The overall 5-year regional recurrence rate was 1.3%, and did not differ significantly between the groups. The recurrence-free interval was also comparable among groups. The group of patients who did not undergo completion axillary treatment had statistically significantly worse 5-year overall survival, owing to a higher percentage of non-cancer deaths. CONCLUSION: In this registry study of patients with cT1-2 N0 breast cancer treated with mastectomy, with low-volume sentinel lymph node metastasis, the 5-year regional recurrence rate was low and comparable between patients with and without completion axillary treatment.

Lopesiodinia alvarengai Prado, 1973 (Odiniidae: Traginopinae) with the first description of the male and the neotype designation.

The type specimen of Lopesiodinia alvarengai Prado is lost. It is being redescribed and illustrated based on specimens from the type locality (Jacareacanga, Par, Brazil) and the neotype is here designated with the purpose of clarifying the taxonomic status and objectively securing stability of nomenclature.

Patient-reported preferences in eHealth-based cardiac rehabilitation: A qualitative investigation of behavior change techniques, barriers and facilitators.

Background: Cardiac rehabilitation (CR) reduces recurrent cardiac events and mortality in patients with cardiovascular diseases (CVD). Innovative eHealth methods can facilitate CR uptake and effectiveness by addressing barriers associated with clinic-based rehabilitation. Tailoring eHealth-based CR to patient preferences is needed to further enhance CR. Purpose: To identify preferred behavior change techniques (BCTs) as well as barriers and facilitators for the different health behaviors targeted in eHealth-based CR among patients who have been referred to CR. Methods: Thirty-nine patients were interviewed in nine focus groups in The Netherlands, Germany, and Spain. A thematic analysis, using a combined deductive and inductive approach to coding, was conducted to identify BCTs and barriers and facilitators to behavior change. Behaviors under investigation included physical activity, medication adherence, eating a cardiac healthy-diet, stress reduction and smoking cessation. Results: The perceived helpfulness of BCTs depended on the specific behavior targeted. Common barriers were negative emotional state and physical limitations. A desire to feel physically or mentally well and having experienced a cardiac life event were the most common facilitators across health behaviors. Specific BCTs, barriers and facilitators were found for each of the health behavior. Conclusions: Behavior change techniques that patients preferred for each health behavior targeted in eHealth-based CR were identified. A negative emotional state, experiencing a life event, and improving physical functioning are important barriers and facilitators in multiple behaviors targeted in eHealth-based CR programs. Additional tailoring of interventions to patient preferences for BCTs and patient-specific barriers and facilitators per health behavior could lead to further improvement of eHealth-based CR.

Mantodea (Insecta) in the Invertebrate Collection of Instituto Nacional de Pesquisas da Amaznia (INPA), Manaus, Brazil.

Increasingly, scientific collections play a fundamental role in the conservation and analysis of biodiversity as a witness and repository of ecosystem organisms at risk of losing their species. The Invertebrate Collection of the Instituto Nacional de Pesquisas da Amaznia (INPA) safeguards biological information, mainly from the Amazon biome, one of the most diverse and threatened ecosystems on the planet. Mantodea specimens deposited dry in the INPA Collection were reviewed. A total of 2,721 specimens were found deposited until the year 2019. A total of 194 species and 81 genera were found with representatives of all the neotropical and several "Old-World" families. Families such as Mantidae, Photinaidae, and Thespidae represented the highest percentages of specimens collected within the sample, with 30%, 11%, and 9%, respectively. Four genera and fourteen species are recorded for the first time for Brazil, bringing the number of species to 247. This officially makes Brazil the most diverse country in terms of Mantodea fauna on the planet. The Collection stands out for being the most diverse reported in Latin America, even with several species yet to be described. Presently it has seven primary type specimens and 26 secondary type specimens. The excellent state of conservation of the specimens, the number of specimens, and the diversity represented have made the INPA Collection an international benchmark for Amazonian and Neotropical studies on Mantodea.

The prognostic potential of mammographic growth rate of invasive breast cancer in the Nijmegen breast cancer screening cohort.

OBJECTIVES: Insight into the aggressiveness of potential breast cancers found in screening may optimize recall decisions. Specific growth rate (SGR), measured on mammograms, may provide valuable prognostic information. This study addresses the association of SGR with prognostic factors and overall survival in patients with invasive carcinoma of no special type (NST) from a screened population. METHODS: In this historic cohort study, 293 women with NST were identified from all participants in the Nijmegen screening program (2003-2007). Information on clinicopathological factors was retrieved from patient files and follow-up on vital status through municipalities. On consecutive mammograms, tumor volumes were estimated. After comparing five growth functions, SGR was calculated using the best-fitting function. Regression and multivariable survival analyses described associations between SGR and prognostic factors as well as overall survival. RESULTS: Each one standard deviation increase in SGR was associated with an increase in the Nottingham prognostic index by 0.34 [95% confidence interval (CI): 0.21-0.46]. Each one standard deviation increase in SGR increased the odds of a tumor with an unfavorable subtype (based on histologic grade and hormone receptors; odds ratio 2.14 [95% CI: 1.45-3.15]) and increased the odds of diagnosis as an interval cancer (versus screen-detected; odds ratio 1.57 [95% CI: 1.20-2.06]). After a median of 12.4 years of follow-up, 78 deaths occurred. SGR was not associated with overall survival (hazard ratio 1.12 [95% CI: 0.87-1.43]). CONCLUSIONS: SGR may indicate prognostically relevant differences in tumor aggressiveness if serial mammograms are available. A potential association with cause-specific survival could not be determined and is of interest for future research.

Effects of cylindrospermopsin, chlorpyrifos and their combination in a SH-SY5Y cell model concerning developmental neurotoxicity.

The cyanotoxin cylindrospermopsin (CYN) has been postulated to cause neurotoxicity, although the studies in this concern are very few. In addition, some studies in vitro indicate its possible effects on development. Furthermore, pesticides can be present in the same environmental samples as cyanotoxins. Therefore, chlorpyrifos (CPF) has been one of the most common pesticides used worldwide. The aim of this report was to study the effects of CYN, isolated and in combination with CPF, in a developmental neurotoxicity in vitro model. The human neuroblastoma SH-SY5Y cell line was exposed during 6 days of differentiation to both toxics to study their effects on cell viability and neurite outgrowth. To further evaluate effects of both toxicants on cholinergic signaling, their agonistic and antagonistic activities on the α7 homomeric nicotinic acetylcholine receptor (nAChR) were studied upon acute exposure. Moreover, a transcriptomic analysis by qPCR was performed after 6 days of CYN-exposure during differentiation. The results showed a concentration-dependent decrease on both cell viability and neurite outgrowth for both toxics isolated, leading to effective concentration 20 (EC20) values of 0.35 µM and 0.097 µM for CYN on cell viability and neurite outgrowth, respectively, and 100 µM and 58 µM for CPF, while the combination demonstrated no significant variations. In addition, 95 µM and 285 µM CPF demonstrated to act as an antagonist to nicotine on the nAChR, although CYN up to 2.4 µM had no effect on the efficacy of these receptors. Additionally, the EC20 for CYN (0.097 µM) on neurite outgrowth downregulated expression of the 5 genes NTNG2 (netrin G2), KCNJ11 (potassium channel), SLC18A3 (vesicular acetylcholine transporter), APOE (apolipoprotein E), and SEMA6B (semaphorin 6B), that are all important for neuronal development. Thus, this study points out the importance of studying the effects of CYN in terms of neurotoxicity and developmental neurotoxicity.

Male-Female Differences in Acute Type B Aortic Dissection.

BACKGROUND: Acute type B aortic dissection is a cardiovascular emergency with considerable mortality and morbidity risk. Male-female differences have been observed in cardiovascular disease; however, literature on type B aortic dissection is scarce. METHODS AND RESULTS: A retrospective cohort study was conducted including all consecutive patients with acute type B aortic dissection between 2007 and 2017 in 4 tertiary hospitals using patient files and questionnaires for late morbidity. In total, 384 patients were included with a follow-up of 6.1 (range, 0.02-14.8) years, of which 41% (n=156) were female. Women presented at an older age than men (67 [interquartile range (IQR), 57-73] versus 62 [IQR, 52-71]; P=0.015). Prior abdominal aortic aneurysm (6% versus 15%; P=0.009), distally extending dissections (71 versus 85%; P=0.001), and clinical malperfusion (18% versus 32%; P=0.002) were less frequently observed in women. Absolute maximal descending aortic diameters were smaller in women (36 [IQR: 33-40] mm versus 39 [IQR, 36-43] mm; P<0.001), while indexed for body surface area diameters were larger in women (20 [IQR, 18-23] mm/m2 versus 19 [IQR, 17-21] mm/m2). No male-female differences were found in treatment choice; however, indications for invasive treatment were different (P<0.001). Early mortality rate was 9.6% in women and 11.8% in men (P=0.60). The 5-year survival was 83% (95% CI, 77-89) for women and 84% (95% CI, 79-89) for men (P=0.90). No male-female differences were observed in late (re)interventions. CONCLUSIONS: No male-female differences were found in management, early or late death, and morbidity in patients presenting with acute type B aortic dissection, despite distinct clinical profiles at presentation. More details on the impact of age and type of intervention are warranted in future studies.

Aortic arch branching variations and risk of cerebrovascular accidents in patients with a left ventricular assist device.

AIMS: This retrospective study investigated the association between anatomical variations in the aortic arch branching and adverse events, including the risk of cerebrovascular accidents (CVAs), in patients with a left ventricular assist device (LVAD). METHODS: Medical charts were reviewed for all patients with HeartMate 3 LVAD support at our center from 2016 to 2021. Computed tomography scans were evaluated to categorize the variations in the aortic arch branching based on seven different types, as described in the literature. RESULTS: In total, 101 patients were included: 86 (85.1%) with a normal branching pattern and 15 (14.9%) with an anatomical variation. The following variations were observed: eight (7.9%) with a bovine arch and seven (6.9%) with a left vertebral arch. The median age was 57 years, 77.2% were men, and the median follow-up was 25 months. No difference was found in the rate of early (< 30 days) re-exploration due to bleeding after LVAD implantation. The rate of CVA and mortality did not differ significantly between patients with a normal arch or an anatomical variation during follow-up, with hazard ratios of 1.47 [95% confidence interval (CI): 0.48-4.48; P = 0.495] and 0.69 (95% CI: 0.24-1.98; P = 0.489), respectively. CONCLUSION: This preliminary study showed no differences in early and long-term adverse events, including CVA, when comparing patients with a variation in the aortic arch branching to patients with a normal aortic arch. However, knowledge of the variations in aortic arch branching could be meaningful during cardiac surgery for potential differences in surgical events in the perioperative period.

Male-female differences in contemporary elective ascending aortic surgery: insights from the Netherlands Heart Registration.

Background: Scientific research regarding male-female differences in ascending aortic surgery is scarce. The objective of this study was to identify male-female differences in presentation, treatment and peri-operative outcome in elective ascending aortic surgery. Methods: Elective ascending aortic surgery procedures that took place in the Netherlands between 01/01/2013-31/12/2017 were identified from the Netherlands Heart Registration. Male-female differences in presentation, treatment characteristics, and in-hospital mortality and morbidity were explored. Results: The study population consisted of 887 females (31%) and 1,972 males (69%). Females were older (median age 67 versus 62 years, P<0.001), more often had chronic lung disease (12.3% versus 9.1%, P=0.011), New York Heart Association (NYHA) class III-IV (21.5% versus 15.5%, P=0.003), and less often a history of percutaneous coronary intervention (PCI) (3.2% versus 5.0%, P=0.033). Isolated supracoronary aortic replacement was performed in 47.7% of females versus 30.6% of males (P<0.001), and ascending aorta with root replacement in 40.6% of females versus 56.7% of males (P<0.001). Females more often underwent concomitant interventions of the aortic arch (33.1% versus 20.2%, P<0.001) and the mitral valve (8.2% versus 5.2%, P=0.002), and less often concomitant coronary artery bypass grafting (CABG) (14.4% versus 19.1%, P=0.002). Overall, in-hospital mortality was significantly higher in females (5.1% versus 2.7%, P=0.003). In multivariable regression analysis, being female was an independent risk factor for in-hospital mortality [odds ratio (OR) 1.55, 95% confidence interval (CI): 1.02-2.37]. Conclusions: This nation-wide cohort shows clear differences between females and males in patient presentation, procedural characteristics, in-hospital outcomes, and risk factors for in-hospital mortality in elective ascending aortic surgery. Further exploration of these differences, and of modifiable within-male and within-female risk factors, may offer great opportunities in improving treatment and thereby outcomes for both males and females.

A comparison study on creating simulated patient data for individuals suffering from chronic coronary disorders.

An emerging area in data science that has lately gained attention is the virtual population (VP) and synthetic data generation. This field has the potential to significantly affect the healthcare industry by providing a means to augment clinical research databases that have a shortage of subjects. The current study provides a comparative analysis of five distinct approaches for creating virtual data populations from real patient data. The data set utilized for the current analyses involved clinical data collected among patients scheduled for elective coronary artery bypass graft surgery (CABG). To that end, the five computational techniques employed to augment the given dataset were: (i) Tabular Preset, (ii) Gaussian Copula Model (iii) Generative Adversarial Network based (GAN) Deep Learning data synthesizer (CTGAN), (iv) a variation of the CTGAN Model (Copula GAN), and (v) VAE-based Deep Learning data synthesizer (TVAE). The performance of these techniques was assessed against their effectiveness in producing high-quality virtual data. For this purpose, dataset correlation matrices, cosine similarity distance, density histograms, and kernel density estimation are employed to perform a comparative analysis of each attribute and the respective synthetic equivalent. Our findings demonstrate that Gaussian Copula Model prevails in creating virtual data with consistent distributions (Kolmogorov-Smirnov (KS) and Chi-Squared (CS) tests equal to 0.9 and 0.98, respectively) and correlation patterns (average cosine similarity equals to 0.95).Clinical Relevance- It has been shown that the use of a VP can increase the predictive performance of a ML model, i.e., above using a smaller non-augmented population.

Pilot Study: Short Term Impact of Radiation Therapy on Bone Mineral Density and Bone Metabolism.

Despite the risk of complications, high dose radiation therapy is increasingly utilized in the management of selected bone malignancies. In this study, we investigate the impact of moderate to high dose radiation (over 50 Gy) on bone metabolism and structure. Between 2015 and 2018, patients with a primary malignant bone tumor of the sacrum that were either treated with high dose definitive radiation only or a combination of moderate to high dose radiation and surgery were prospectively enrolled at a single institution. Quantitative CTs were performed before and after radiation to determine changes in volumetric bone mineral density (BMD) of the irradiated and non-irradiated spine. Bone histomorphometry was performed on biopsies of the irradiated sacrum and the non-irradiated iliac crest of surgical patients using a quadruple tetracycline labeling protocol. In total, 9 patients were enrolled. Two patients received radiation only (median dose 78.3 Gy) and 7 patients received a combination of preoperative radiation (median dose 50.4 Gy), followed by surgery. Volumetric BMD of the non-irradiated lumbar spine did not change significantly after radiation, while the BMD of the irradiated sacrum did (pre-radiation median: 108.0 mg/cm3 (IQR 91.8-167.1); post-radiation median: 75.3 mg/cm3 (IQR 57.1-110.2); p = 0.010). The cancellous bone of the non-irradiated iliac crest had a stable bone formation rate, while the irradiated sacrum showed a significant decrease in bone formation rate [pre-radiation median: 0.005 mm3/mm2/year (IQR 0.003-0.009), post-radiation median: 0.001 mm3/mm2/year (IQR 0.001-0.001); p = 0.043]. Similar effects were seen in the cancellous and endocortical envelopes. This pilot study shows a decrease of volumetric BMD and bone formation rate after high-dose radiation therapy. Further studies with larger cohorts and other endpoints are needed to get more insight into the effect of radiation on bone. Level of evidence: IV.

Bone biopsy devices - a patent review.

INTRODUCTION: Bone biopsies have great value for the diagnosis of, amongst others, hematologic diseases. Although the bone biopsy procedure is mostly performed minimally invasive with the use of a slender cannula, the patient may still experience discomfort, especially when the procedure has to be repeated due to an unsuccessful biopsy. AREAS COVERED: This review presents a comprehensive overview of bone biopsy devices presented in the patent literature. The patents were obtained using a classification search combined with keywords in the Espacenet patent database and were subsequently verified using pre-set eligibility criteria. This resulted in 62 unique patents included in this review. EXPERT OPINION: The included patents were categorized based on the used strategies for the three steps that can be identified during a bone biopsy (1) biopsy sampling, (2) biopsy severing and (3) biopsy harvesting. Most patents described strategies for multiple steps. Insight into the used strategies and the comprehensive overview may serve as a source of inspiration for the design of novel bone biopsy devices.

Isolation and functional analysis of phage-displayed antibody fragments targeting the staphylococcal superantigen-like proteins.

Staphylococcus aureus produces numerous virulence factors that manipulate the immune system, helping the bacteria avoid phagocytosis. In this study, we are investigating three immune evasion molecules called the staphylococcal superantigen-like proteins 1, 5, and 10 (SSL1, SSL5, and SSL10). All three SSLs inhibit vital host immune processes and contribute to S. aureus immune evasion. This study aimed to identify single-chain variable fragment (scFvs) antibodies from synthetic antibody phage libraries, which can recognize either of the three SSLs and could block the interaction between the SSLs and their respective human targets. The antibodies were isolated after three rounds of panning against SSL1, SSL5, and SSL10, and their ability to bind to the SSLs was studied using a time-resolved fluorescence-based immunoassay. We successfully obtained altogether 44 unique clones displaying binding activity to either SSL1, SSL5, or SSL10. The capability of the SSL-recognizing scFvs to inhibit the SSLs' function was tested in an MMP9 enzymatic activity assay, a P-selectin glycoprotein ligand 1 competitive binding assay, and an IgG1-mediated phagocytosis assay. We could show that one scFv was able to inhibit SSL1 and maintain MMP9 activity in a concentration-dependent manner. Finally, the structure of this inhibiting scFv was modeled and used to create putative scFv-SSL1-complex models by protein-protein docking. The complex models were subjected to a 100-ns molecular dynamics simulation to assess the possible binding mode of the antibody.

BRAF V600E is associated with higher incidence of second cancers in adults with Langerhans cell histiocytosis.

In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.

The determination of pleurodesis using sonography after surgical pleurectomy for pneumothorax: a pilot study.

The aim of this study is to evaluate feasibility of monitoring the process of pleurodesis after surgical pleurectomy with thoracic ultrasound. Repetitive measurements with thoracic ultrasound after surgical pleurectomy could provide information on the extent and development speed of pleurodesis. We conducted a prospective single-center cohort study. Adult patients who required surgical pleurectomy after pneumothorax were eligible. Participants had daily thoracic ultrasound examination until discharge to determine lung sliding [present (0 point), questionable (1 point), or absent (2 points)], and pleural thickening [normal (0 point), questionable (1 point), or present (2 points)]. Thoracic ultrasound was performed in six regions, the sum of all scores was divided by the number of regions. Fourteen patients were enrolled. Thoracic ultrasound on day 1-4 was 0.25±0.26, 0.39±0.48, 0.84±0.49, 1.12±0.56 for mean lung sliding, and 1.0±0.56, 1.17±0.48, 1.44±0.44, 1.54±0.34 for mean pleural thickening. Lung sliding and pleural thickening increased significantly between day 1 and day 4 (P=0.002 and P=0.023, respectively). One (7%) and 3 (21%) patients reached the maximum achievable grade for lung sliding and pleural thickening, respectively. Thoracic ultrasound grades tended to be lower in three patients with recurrent pneumothorax, although this was not statistically significant. This study shows a significant increase in thoracic ultrasound grading for pleurodesis lung sliding and pleural thickening during the first postoperative days after surgical pleurectomy, probably attributable to progressing pleurodesis. Only a minority of patients reached complete pleurodesis before discharge despite complete surgical pleurodesis (SP). The results of this study may guide future research regarding optimal timing of chest tube removal.