EuroGuiderm guideline on lichen sclerosus-introduction into lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

Revised contraindications for the use of non-medical WB-electromyostimulation. Evidence-based German consensus recommendations.

Whole-body electromyostimulation has proven to be a highly effective alternative to conventional resistance-type exercise training. However, due to adverse effects in the past, very extensive contraindications have been put in place for the commercial, non-medical WB-EMS market. Considering recent positive innovations e.g., federal regulation, mandatory trainer education, revised guidelines, and new scientific studies on WB-EMS application, we believe that a careful revision of the very restrictive contraindications on WB-EMS is needed. This applies all the more because many cohorts with limited options for conventional exercise have so far been excluded. During a first meeting of an evidence-based consensus process, stakeholders from various backgrounds (e.g., research, education, application) set the priorities for revising the contraindications. We decided to focus on four categories of absolute contraindications: "Arteriosclerosis, arterial circulation disorders", "Diabetes mellitus" (DM), "Tumor and cancer" (TC), "Neurologic diseases, neuronal disorders, epilepsy". Based on scientific studies, quality criteria, safety aspects and benefit/risk assessment of the category, DM and TC were moved to the relative contraindication catalogue, while arteriosclerosis/arterial circulation disorders and neurologic diseases/neuronal disorders/epilepsy were still considered as absolute contraindications. While missing evidence suggests maintaining the status of neurologic diseases/neuronal disorders as an absolute contraindication, the risk/benefit-ratio does not support the application of WB-EMS in people with arteriosclerosis/arterial circulation diseases. Despite these very cautious modifications, countries with less restrictive structures for non-medical WB-EMS should consider our approach critically before implementing the present revisions. Considering further the largely increased amount of WB-EMS trials we advice regular updates of the present contraindication list.

Palliative care outpatients in a German comprehensive cancer center-identifying indicators for early and late referral.

PURPOSE: Despite that early integration of palliative care is recommended in advanced cancer patients, referrals to outpatient specialised palliative care (SPC) frequently occur late. Well-defined referral criteria are still missing. We analysed indicators associated with early (ER) and late referral (LR) to SPC of an high volume outpatient unit of a comprehensive cancer center. METHODS: Characteristics, laboratory parameters and symptom burden of 281 patients at first SPC referral were analysed. Timing of referral was categorized as early, intermediate and late (> 12, 3-12 and < 3 months before death). Ordinal logistic regression analysis was used to identify factors related to referral timing. Kruskal-Wallis test was used to determine symptom severity and laboratory parameter in each referral category. RESULTS: LRs (50.7%) had worse scores of weakness, loss of appetite, drowsiness, assistance of daily living (all p < 0.001) and organisation of care (p < 0.01) in contrast to ERs. The mean symptom sum score was significantly higher in LRs than ERs (13.03 vs. 16.08; p < 0.01). Parameters indicative of poor prognosis, such as elevated LDH, CRP and neutrophil-to-lymphocyte ratio (NLR) (p < 0.01) as well as the presence of ascites (p < 0.05), were significantly higher (all p < 0.001) in LRs. In univariable analyses, psychological distress (p < 0.05) and female gender (p < 0.05) were independently associated with an ER. CONCLUSION: A symptom sum score and parameters of poor prognosis like NLR or LDH might be useful to integrate into palliative care screening tools.

Prevalence of anxiety and depression in people with different types of cancer or haematologic malignancies: a cross-sectional study.

AIMS: Cancer patients often present with psychological symptoms that affect their quality of life, physical health outcomes and survival. Two of the most frequent psychiatric comorbidities are anxiety and depression. However, the prevalence of these disorders among cancer patients remains unclear, as studies frequently report varying rates. In the present study, we aimed to provide robust point estimates for the prevalence of anxiety and depression for both a mixed cancer sample and for 13 cancer types separately, considering confounding variables. METHODS: In a sample of 7509 cancer outpatients (51.4% female), we used the Hospital Anxiety and Depression Scale to assess rates of anxiety and depression. Applying ordinal logistic regression models, we compared the prevalence of anxiety and depression between different cancer types, controlling for age and gender. RESULTS: About one third of our sample showed symptoms of anxiety (35.2%) or depression (27.9%), and every sixth patient had a very likely psychiatric condition, with women being more frequently affected. Elderly patients more often showed signs of depression. The prevalence of anxiety and depression was significantly higher in lung and brain cancer patients, than in other cancer patients. Lowest depression rates were found in breast cancer patients. CONCLUSIONS: The prevalence of anxiety and depression is high in cancer patients. Type of cancer is an important predictor for anxiety and depressive symptoms, with lung and brain cancer patients being highly burdened. Considering a personalised medicine approach, physicians should take into account the high prevalence of psychiatric comorbidities and include psychiatric consultations in the treatment plan.

Estudio retrospectivo en pacientes con Cáncer de Colon etapa III. ¿El tratamiento adyuvante es iniciado de forma oportuna?

Introducción: En Chile, el Cáncer colorrectal (CC) abarca el 11,5% de todas las neoplasias malignas. La cirugía es la piedra angular del tratamiento del cáncer de colon, y en pacientes en etapa III, la quimioterapia adyuvante forma parte del tratamiento estándar. Materiales y Métodos: Estudio descriptivo retrospectivo transversal, de centro único, de pacientes con cáncer de colon en estadio III patológico. Objetivo principal de este estudio es conocer si, en pacientes con cáncer de colon etapa III, la quimioterapia adyuvante se entrega de manera oportuna. Resultados: En el período comprendido entre abril de 2016 y abril de 2021 se operaron 35 pacientes con cáncer de colon en estadio III patológico. Se realizó quimioterapia adyuvante en un 80%, y en siete pacientes durante las primeras ocho semanas poscirugía. La dehiscencia de anastomosis ocurrió en un 11,4%, aumentando la mediana de hospitalización en 2,2 veces. Discusión: En nuestro estudio, la adyuvancia en cáncer de colon etapa III se administró a un alto porcentaje de los pacientes (80%), pero observamos un retraso importante, ya que sólo en un 25% se inició el tratamiento durante las primeras 8 semanas poscirugía, lo cual puede ser explicado por múltiples factores, siendo la dehiscencia de anastomosis un punto importante a considerar. Conclusión: En estadio III de CC la adyuvancia puede verse retrasada por múltiples factores, lo que puede repercutir en la sobrevida de los pacientes, por lo tanto, conocer las causas de este retraso podría ayudar a instaurar nuevas estrategias, como la neoadyuvancia, para mejorar los resultados oncológicos.

Introduction: In Chile, colorectal cancer covers 11.5% of all malignant neoplasms. Surgery is the cor- nerstone of colon cancer treatment and in stage III patients adjuvant chemotherapy is part of standard treatment. Materials and Methods: A descriptive, retrospective, cross-sectional study, single center, of patients with pathological stage III colon cancer. Main objective of this study is to know if in patients with stage III colon cancer adjuvant chemotherapy is delivered in a timely manner. Results: Between April 2016 and April 2021, 35 patients with pathological stage III colon cancer were operated on. Adjuvant chemotherapy was performed in 80%, and in seven patient during the first eight weeks after surgery. Anastomotic dehiscence occurred in 11.4%, the median hospitalization increased by 2.2 times. Discussion: In this study, adjuvant stage III colon cancer was administered to a high percentage of patients (80%), but we observed a significant delay, since only 25% began treatment during the first 8 weeks post-surgery, which can be explained by multiple factors, with anastomotic dehiscence being an important point to consider. Conclusion: In stage III CC, adjuvant treatment can be delayed by multiple factors, which may affect patient survival; therefore, knowing the causes of this delay could help to establish new strategies, such as neoadjuvant therapy, to improve oncological results.

F18-FDG PET/CT imaging early predicts pathologic complete response to induction chemoimmunotherapy of locally advanced head and neck cancer: preliminary single-center analysis of the checkrad-cd8 trial.

AIM: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy. METHODS: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3-14 days before (pre-ICIT) and 21-28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu). RESULTS: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value. CONCLUSION: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value. TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT03426657.

Is extracapsular dissection for pleomorphic adenoma rather a euphemism for enucleation that jeopardises the intactness of the capsule?

The aim of this study was to compare several surgical modalities with respect to the incidence of positive margins and focal capsular exposure of pleomorphic adenoma of the parotid gland. The clinical records and histopathological findings of all patients who underwent parotidectomy for pleomorphic adenoma between 2006 and 2020 were retrospectively evaluated (n = 845). The lesion was removed by extracapsular dissection in 577 cases (68%) and facial nerve dissection in 268 (32%). Our analysis did not reveal a statistically significant difference between the examined modalities regarding positive margins (p=0.648) or capsular exposure (p=0.112). Recurrences were detected in 7/845 cases (0.82%) with a mean (range) follow-up time of 82.3 (6-183) months. The choice of surgical method does not seem to have a significant effect on the incidence of positive margins, or on the capsular exposure of a pleomorphic adenoma.

Optimal timing and criteria of interim PET in DLBCL: a comparative study of 1692 patients.

Interim 18F-fluorodeoxyglucose positron emission tomography (Interim-18F-FDG-PET, hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-cell lymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determine the optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL. Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects of timing and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using ΔSUVmax, respectively. ΔSUVmax identified a larger proportion of poor responders than DS5 did. For all criteria, the negative predictive value was >80%, and positive predictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3 discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs, 2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOP therapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Good response at I-PET2 is suggested for de-escalation trials, and poor response using ΔSUVmax at I-PET4 is suggested for randomized trials that are evaluating new therapies.

Interleukin 13 (IL-13)-regulated expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging cartilage.

OBJECTIVE: The adamalysin metalloproteinase 15 (ADAM15) has been shown to protect against development of osteoarthritis in mice. Here, we have investigated factors that control ADAM15 levels in cartilage. DESIGN: Secretomes from wild-type and Adam15 -/- chondrocytes were compared by label-free quantitative mass spectrometry. mRNA was isolated from murine knee joints, either with or without surgical induction of osteoarthritis on male C57BL/6 mice, and the expression of Adam15 and other related genes quantified by RT-qPCR. ADAM15 in human normal and osteoarthritic cartilage was investigated similarly and by fluorescent immunohistochemistry. Cultured HTB94 chondrosarcoma cells were treated with various anabolic and catabolic stimuli, and ADAM15 mRNA and protein levels evaluated. RESULTS: There were no significant differences in the secretomes of chondrocytes from WT and Adam15 -/- cartilage. Expression of ADAM15 was not altered in either human or murine osteoarthritic cartilage relative to disease-free controls. However, expression of ADAM15 was markedly reduced upon aging in both species, to the extent that expression in joints of 18-month-old mice was 45-fold lower than in that 4.5-month-old animals. IL-13 increased expression of ADAM15 in HTB94 â€‹cells by 2.5-fold, while modulators of senescence and autophagy pathways had no effect. Expression of Il13 in the joint was reduced with aging, suggesting this cytokine may control ADAM15 levels in the joint. CONCLUSION: Expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging human and murine joints, possibly due to a concomitant reduction in IL-13 expression. We thus propose IL-13 as a novel factor contributing to increased osteoarthritis risk upon aging.

Effects of FK506 on the healing of diaphyseal, critical size defects in the rat femur.

There is much interest in understanding the influence of the immune system on bone healing, including a number of reports suggesting a beneficial effect of FK506 (tacrolimus) in this regard. The influence of FK506 in a rat, femoral, critical size defect was examined using locally implanted, recombinant, human (rh) BMP-2 and adenovirally-transduced, autologous, adipose-derived mesenchymal stromal cells (AD-MSCs) expressing BMP-2. FK506 was delivered systemically using an implanted osmotic pump. Empty defects and those implanted with unmodified AD-MSCs did not heal in the presence or absence of FK506. Defects treated with rhBMP-2 healed with a large callus containing thin cortices and wispy trabeculae; this, too, was unaffected by FK506. A third of defects implanted with adenovirally-transduced AD-MSCs healed, but this improved to 100 % in the presence of FK506. New bone formed in response to BMP-2 synthesised endogenously by the genetically modified cells had a slimmer callus than those healed by rhBMP-2, with improved cortication and advanced reconstitution of marrow. These results suggest that FK506 may have had little effect on the intrinsic biology of bone healing, but improved healing in response to adenovirally-transduced cells by inhibiting immune responses to the first-generation adenovirus used here. Because the genetically modified cells produced bone of higher quality at far lower doses of BMP-2, this approach should be explored in subsequent research.

Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells.

Cytotoxic T lymphocytes (CTLs) kill infected and cancerous cells. We detected transfer of cytotoxic multiprotein complexes, called supramolecular attack particles (SMAPs), from CTLs to target cells. SMAPs were rapidly released from CTLs and were autonomously cytotoxic. Mass spectrometry, immunochemical analysis, and CRISPR editing identified a carboxyl-terminal fragment of thrombospondin-1 as an unexpected SMAP component that contributed to target killing. Direct stochastic optical reconstruction microscopy resolved a cytotoxic core surrounded by a thrombospondin-1 shell of ~120 nanometer diameter. Cryo-soft x-ray tomography analysis revealed that SMAPs had a carbon-dense shell and were stored in multicore granules. We propose that SMAPs are autonomous extracellular killing entities that deliver cytotoxic cargo targeted by the specificity of shell components.

Effects of epigenetic pathway inhibitors on corticotroph tumour AtT20 cells.

Medical treatments for corticotrophinomas are limited, and we therefore investigated the effects of epigenetic modulators, a new class of anti-tumour drugs, on the murine adrenocorticotropic hormone (ACTH)-secreting corticotrophinoma cell line AtT20. We found that AtT20 cells express members of the bromo and extra-terminal (BET) protein family, which bind acetylated histones, and therefore, studied the anti-proliferative and pro-apoptotic effects of two BET inhibitors, referred to as (+)-JQ1 (JQ1) and PFI-1, using CellTiter Blue and Caspase Glo assays, respectively. JQ1 and PFI-1 significantly decreased proliferation by 95% (P < 0.0005) and 43% (P < 0.0005), respectively, but only JQ1 significantly increased apoptosis by >50-fold (P < 0.0005), when compared to untreated control cells. The anti-proliferative effects of JQ1 and PFI-1 remained for 96 h after removal of the respective compound. JQ1, but not PFI-1, affected the cell cycle, as assessed by propidium iodide staining and flow cytometry, and resulted in a higher number of AtT20 cells in the sub G1 phase. RNA-sequence analysis, which was confirmed by qRT-PCR and Western blot analyses, revealed that JQ1 treatment significantly altered expression of genes involved in apoptosis, such as NFκB, and the somatostatin receptor 2 (SSTR2) anti-proliferative signalling pathway, including SSTR2. JQ1 treatment also significantly reduced transcription and protein expression of the ACTH precursor pro-opiomelanocortin (POMC) and ACTH secretion by AtT20 cells. Thus, JQ1 treatment has anti-proliferative and pro-apoptotic effects on AtT20 cells and reduces ACTH secretion, thereby indicating that BET inhibition may provide a novel approach for treatment of corticotrophinomas.

[ANDROMEDA-an investigation of factors influencing the adherence of patients with neovascular age-related macular degeneration using the newly developed patient questionnaire LAF-IVT]. / ANDROMEDA ­ Eine Untersuchung von Einflussfaktoren auf die Adhärenz von Patienten mit neovaskulärer altersabhängiger Makuladegeneration mithilfe des neu konzipierten Patientenfragebogens LAF-IVT.

BACKGROUND: Lack of adherence to treatment is a widespread problem in the anti-VEGF (Vascular Endothelial Growth Factor) treatment of patients with neovascular age-related macular degeneration (nAMD). In contrast to the extent of the lack of treatment adherence, there is so far insufficient evidence for elucidating the causes of nonadherence. The ANDROMEDA study was initiated to investigate the influencing factors on the adherence of nAMD patients to treatment. The focus of the study was on patient reported endpoints, as the perceptions and experiences of the patients are of enormous importance for the investigation of the various aspects of adherence to treatment. OBJECTIVE: This publication presents the design of the ANDROMEDA study as well as the development of a new patient questionnaire for the assessment of barriers to treatment within the design of the study. MATERIAL AND METHODS: This prospective noninterventional observational study to assess the compliance of patients with nAMD and anti-VEGF treatment was started at the end of January 2019. It is planned to include 1000 patients in 120 study centers throughout Germany with an observational period of 24 months. Patient interviews on general and vision-related quality of life, treatment satisfaction and possible barriers to treatment will be conducted at the beginning and after 4, 12 and 24 months. All patient visits will be documented by the study centers as part of the clinical routine. To date, there has been no suitable instrument for recording patient-related circumstances and potential barriers to anti-VEGF treatment. Therefore, a specific patient questionnaire for longitudinal assessment of adherence factors to intravitreal (anti-VEGF) therapy (LAF-IVT) was developed as part of the study concept. The questionnaire, developed by an expert panel, was tested via qualitative interviews for its cognitive characteristics ahead of its use. RESULTS: The results of the study are expected in early 2023. The cognitive examination of the LAF-IVT confirmed the feasibility of the new questionnaire. The practicability and significance of the new instrument can be assessed after completion of the quantitative data collection. CONCLUSION: The symptoms, barriers, burdens and quality of life effects experienced by patients influence the adherence to treatment and thus the outcome. A better understanding of the patient's views and experiences is the basis for long-term optimization of care.

Prediction of response to anti-PD-1 therapy in patients with non-small-cell lung cancer by electronic nose analysis of exhaled breath.

BACKGROUND: Immune checkpoint inhibitors have improved survival outcome of advanced non-small-cell lung cancer (NSCLC). However, most patients do not benefit. Therefore, biomarkers are needed that accurately predict response. We hypothesized that molecular profiling of exhaled air may capture the inflammatory milieu related to the individual responsiveness to anti-programmed death ligand 1 (PD-1) therapy. This study aimed to determine the accuracy of exhaled breath analysis at baseline for assessing nonresponders versus responders to anti-PD-1 therapy in NSCLC patients. METHODS: This was a prospective observational study in patients receiving checkpoint inhibitor therapy using both a training and validation set of NSCLC patients. At baseline, breath profiles were collected in duplicate by a metal oxide semiconductor electronic nose (eNose) positioned at the rear end of a pneumotachograph. Patients received nivolumab or pembrolizumab of which the efficacy was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at 3-month follow-up. Data analysis involved advanced signal-processing and statistics based on independent t-tests followed by linear discriminant and receiver operating characteristic (ROC) analysis. RESULTS: Exhaled breath data of 143 NSCLC patients (training: 92, validation: 51) were available at baseline. ENose sensors contributed significantly (P < 0.05) at baseline in differentiating between patients with different responses at 3 months of anti-PD-1 treatment. The eNose sensors were combined into a single biomarker with an ROC-area under the curve (AUC) of 0.89 [confidence interval (CI) 0.82-0.96]. This AUC was confirmed in the validation set: 0.85 (CI 0.75-0.96). CONCLUSION: ENose assessment was effective in the noninvasive prediction of individual patient responses to immunotherapy. The predictive accuracy and efficacy of the eNose for discrimination of immunotherapy responder types were replicated in an independent validation set op patients. This finding can potentially avoid application of ineffective treatment in identified probable nonresponders.

Bronquiectasias no fibrosis quística: desde la infancia a la adultez: enfoque diagnostico y terapéutico / Bronchiectasis no cystic fibrosis: from childhood to adult: diagnostic and therapeutic approach

Bronchiectasis is a suppurative lung disease with heterogeneous phenotypic characteristics. It is defined as abnormal dilation of the bronchi, losing the existing relationship between bronchial sizes and accompanying artery. According to their form, they can be cylindrical, varicose, saccular or cystic. According to its location, they could be diffuse or localized. The diagnosis of bronchiectasis is usually suspected in patients with chronic cough, mucopurulent bronchorrea, and recurrent respiratory infections. The etiology can be varied, being able to classify in cystic fibrosis bronchiectasis, when there is cystic fibrosis transmembrane regulator (CFTR) gene mutation and not cystic fibrosis, being post infectious the most frequent. Its relationship with childhood is unknown. Severe respiratory infections can predispose in a susceptible subject the so-called theory of the "vicious circle" and the development of these. Persistent bacterial bronchitis in children has been described as a probable cause of not cystic fibrosis bronchiectasis in adults. The treatment is based on the management of symptoms and the prevention of exacerbations. The evidence is poor and many treatments are extrapolated from cystic fibrosis bronchiectasis. We are going to describe the diagnostic and therapeutic approach of non-cystic fibrosis bronchiectasis in adults.

La bronquiectasia es una enfermedad pulmonar supurativa con características fenotípicas heterogéneas. Se define como la dilatación anormal de los bronquios, perdiendo la relación existente entre tamaño bronquial y arteria que acompaña. Según su forma, pueden ser clasificadas en cilíndricas, varicosas, saculares o quísticas y según su etiología presentarse de forma difusa o localizada. El diagnóstico de bronquiectasias se sospecha generalmente en pacientes con tos crónica, broncorrea mucosa, mucupurulenta e infecciones respiratorias recurrentes. La etiología es variada, pudiendo clasificarse en bronquiectasias fibrosis quística, aquellas que se encuentran en el contexto de la mutación del gen regulador transmembrana de fibrosis quística (CFTR) y no fibrosis quística, de etiologías diversas, siendo post infecciosas la gran mayoría. No se conoce con certeza su relación con la infancia, es sabido que infecciones respiratorias severas pueden predisponer en un sujeto susceptible, a la llamada teoría del "circulo vicioso" y el desarrollo de estas. La bronquitis bacteriana persistente en niños se ha descrito como una causa probable del desarrollo de bronquiectasias no fibrosis quística en adultos. El tratamiento se basa en el manejo de los síntomas y la prevención de las exacerbaciones. La evidencia es escasa y la mayoría de las terapias se han investigado en las bronquiectasias tipo fibrosis quística. En este trabajo se explicará el enfrentamiento diagnóstico y terapéutico de los adultos portadores de bronquiectasias no fibrosis quística.

Surgical removal of the index node marked using magnetic seed localization to assess response to neoadjuvant immunotherapy in patients with stage III melanoma.

This pilot study explored the value of localized index node removal after neoadjuvant immunotherapy in patients with stage III melanoma, for use as a response indicator to guide the extent of completion lymph node dissection. Promising technology.

[Pathophysiology of aseptic femoral head necrosis: Pathogenesis and histopathological differential diagnosis]. / Pathophysiologie der aseptischen Hüftkopfnekrose: Pathogenese und histopathologische Differenzialdiagnostik.

BACKGROUND: Aseptic osteonecrosis is characterized by a complete death of the tissue (necrosis), more specifically, an ischemic necrosis of the lamellar bone tissue. The denotation aseptic refers to causal pathogenesis; therefore, it is not a matter of an infectious, septic-induced bone necrosis as in the case of acute infectious osteomyelitis. Formal pathogenesis leads to either (1) a hypoperfusion of the lamellar bone in the sense of an ischemic necrosis or (2) to directly induced damage of osteocytes and osteoblasts, which causes aseptic osteonecrosis. CAUSE: The causes of hypoperfusion/ischemia are manifold and entail vascular malformations, coagulopathies, haemoglobinopathies, thrombotic embolisms, myeloproliferative illnesses, air embolisms, decompression-caused illnesses, macro as well as micro traumata and, finally, vasculitis with necrosis, which complete the vascular-induced spectrum. Direct toxic damage to the osteocytes and osteoblasts is primarily caused by alcohol abuse, medical drug therapies (i. e. chemotherapeutic substances or cortisone) and disorders of the lipid embolism. Contemporary molecular and cellular models of pathogenesis assume a so-called dysbalance of the catabolic and anabolic osseous metabolism in osteocytes and osteoblasts. The RANKL-RANK system, the ROS system and PPAR-gamma signal transduction are involved in the molecular pathogenesis. DIFFERENTIAL DIAGNOSIS: The most relevant histopathologic differential diagnosis entails the complete spectrum of focal osseous changes among which osteonecrosis can occur to a diverse extent: infectious osteomyelitis, chronic immunologic induced osteomyelitis, pseudoarthrosis, infected pseudoarthrosis, bone fractures and malignant metastatic intraosseous diseases and non-metastatic intraosseous malignant diseases.

The real evidence for polymyalgia rheumatic as a paraneoplastic syndrome.

Not available.