Clinical Validation of Artificial Intelligence-Powered PD-L1 Tumor Proportion Score Interpretation for Immune Checkpoint Inhibitor Response Prediction in Non-Small Cell Lung Cancer.

PURPOSE: Evaluation of PD-L1 tumor proportion score (TPS) by pathologists has been very impactful but is limited by factors such as intraobserver/interobserver bias and intratumor heterogeneity. We developed an artificial intelligence (AI)-powered analyzer to assess TPS for the prediction of immune checkpoint inhibitor (ICI) response in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The AI analyzer was trained with 393,565 tumor cells annotated by board-certified pathologists for PD-L1 expression in 802 whole-slide images (WSIs) stained by 22C3 pharmDx immunohistochemistry. The clinical performance of the analyzer was validated in an external cohort of 430 WSIs from patients with NSCLC. Three pathologists performed annotations of this external cohort, and their consensus TPS was compared with AI-based TPS. RESULTS: In comparing PD-L1 TPS assessed by AI analyzer and by pathologists, a significant positive correlation was observed (Spearman coefficient = 0.925; P < .001). The concordance of TPS between AI analyzer and pathologists according to TPS ≥50%, 1%-49%, and <1% was 85.7%, 89.3%, and 52.4%, respectively. In median progression-free survival (PFS), AI-based TPS predicted prognosis in the TPS 1%-49% or TPS <1% group better than the pathologist's reading, with the TPS ≥50% group as a reference (hazard ratio [HR], 1.49 [95% CI, 1.19 to 1.86] v HR, 1.36 [95% CI, 1.08 to 1.71] for TPS 1%-49% group, and HR, 2.38 [95% CI, 1.69 to 3.35] v HR, 1.62 [95% CI, 1.23 to 2.13] for TPS <1% group). CONCLUSION: PD-L1 TPS assessed by AI analyzer correlates with that of pathologists, with clinical performance also being comparable when referenced to PFS. The AI model can accurately predict tumor response and PFS of ICI in advanced NSCLC via assessment of PD-L1 TPS.

Perioperative Methadone for Spine Surgery: A Scoping Review.

Complex spine surgery is associated with significant acute postoperative pain. Methadone possesses pharmacological properties that make it an attractive analgesic modality for major surgeries. This scoping review aimed to summarize the evidence for the perioperative use of methadone in adults undergoing complex spine surgery. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A search was performed using MEDLINE, CINAHL, Cochrane Library, Scopus, Embase, and Joanna Briggs between January 1946 and April 2023. The initial search identified 317 citations, of which 12 met the criteria for inclusion in the review. There was significant heterogeneity in the doses, routes of administration, and timing of perioperative methadone administration in the included studies. On the basis of the available literature, methadone has been associated with reduced postoperative pain scores and reduced postoperative opioid consumption. Though safety concerns have been raised by observational studies, these have not been confirmed by prospective randomized studies. Further research is required to explore optimal methadone dosing regimens, the potential synergistic relationships between methadone and other pharmacological adjuncts, as well as the potential long-term antinociceptive benefits of perioperative methadone administration.

Augmented interpretation of HER2, ER, and PR in breast cancer by artificial intelligence analyzer: enhancing interobserver agreement through a reader study of 201 cases.

BACKGROUND: Accurate classification of breast cancer molecular subtypes is crucial in determining treatment strategies and predicting clinical outcomes. This classification largely depends on the assessment of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) status. However, variability in interpretation among pathologists pose challenges to the accuracy of this classification. This study evaluates the role of artificial intelligence (AI) in enhancing the consistency of these evaluations. METHODS: AI-powered HER2 and ER/PR analyzers, consisting of cell and tissue models, were developed using 1,259 HER2, 744 ER, and 466 PR-stained immunohistochemistry (IHC) whole-slide images of breast cancer. External validation cohort comprising HER2, ER, and PR IHCs of 201 breast cancer cases were analyzed with these AI-powered analyzers. Three board-certified pathologists independently assessed these cases without AI annotation. Then, cases with differing interpretations between pathologists and the AI analyzer were revisited with AI assistance, focusing on evaluating the influence of AI assistance on the concordance among pathologists during the revised evaluation compared to the initial assessment. RESULTS: Reevaluation was required in 61 (30.3%), 42 (20.9%), and 80 (39.8%) of HER2, in 15 (7.5%), 17 (8.5%), and 11 (5.5%) of ER, and in 26 (12.9%), 24 (11.9%), and 28 (13.9%) of PR evaluations by the pathologists, respectively. Compared to initial interpretations, the assistance of AI led to a notable increase in the agreement among three pathologists on the status of HER2 (from 49.3 to 74.1%, p < 0.001), ER (from 93.0 to 96.5%, p = 0.096), and PR (from 84.6 to 91.5%, p = 0.006). This improvement was especially evident in cases of HER2 2+ and 1+, where the concordance significantly increased from 46.2 to 68.4% and from 26.5 to 70.7%, respectively. Consequently, a refinement in the classification of breast cancer molecular subtypes (from 58.2 to 78.6%, p < 0.001) was achieved with AI assistance. CONCLUSIONS: This study underscores the significant role of AI analyzers in improving pathologists' concordance in the classification of breast cancer molecular subtypes.

Inflamed immune phenotype predicts favorable clinical outcomes of immune checkpoint inhibitor therapy across multiple cancer types.

BACKGROUND: The inflamed immune phenotype (IIP), defined by enrichment of tumor-infiltrating lymphocytes (TILs) within intratumoral areas, is a promising tumor-agnostic biomarker of response to immune checkpoint inhibitor (ICI) therapy. However, it is challenging to define the IIP in an objective and reproducible manner during manual histopathologic examination. Here, we investigate artificial intelligence (AI)-based immune phenotypes capable of predicting ICI clinical outcomes in multiple solid tumor types. METHODS: Lunit SCOPE IO is a deep learning model which determines the immune phenotype of the tumor microenvironment based on TIL analysis. We evaluated the correlation between the IIP and ICI treatment outcomes in terms of objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) in a cohort of 1,806 ICI-treated patients representing over 27 solid tumor types retrospectively collected from multiple institutions. RESULTS: We observed an overall IIP prevalence of 35.2% and significantly more favorable ORRs (26.3% vs 15.8%), PFS (median 5.3 vs 3.1 months, HR 0.68, 95% CI 0.61 to 0.76), and OS (median 25.3 vs 13.6 months, HR 0.66, 95% CI 0.57 to 0.75) after ICI therapy in IIP compared with non-IIP patients, respectively (p<0.001 for all comparisons). On subgroup analysis, the IIP was generally prognostic of favorable PFS across major patient subgroups, with the exception of the microsatellite unstable/mismatch repair deficient subgroup. CONCLUSION: The AI-based IIP may represent a practical, affordable, clinically actionable, and tumor-agnostic biomarker prognostic of ICI therapy response across diverse tumor types.

In vitro anticancer and antifungal properties of the essential oil from the leaves of Lippia origanoides kunth.

The essential oil from Lippia origanoides (EOLO) is employed in traditional medicine as it has both antimicrobial and anti-inflammatory properties. The current investigation first evaluated the EOLO's cytotoxic activity in tumour (SiHa and HT-29) and non-tumour (human lymphocyte) cells by MTT. The effect on ROS production was further evaluated in cancer cells by fluorimetry. The oil's mutagenic and antifungal activities were also evaluated using, respectively, the in vitro micronucleus test and the broth microdilution method. The EOLO displayed significant cytotoxicity in both cancer cell lines, with IC50 values of 20.2 µg/mL and 24.3 µg/mL for HT-29 and for SiHa cell lines, respectively. EOLO increased ROS production, was unable to raise the micronucleus frequencies and significantly reduced the cytokinesis block proliferation indices, revealing its anti-proliferative action. The results demonstrate that EOLO is devoid of mutagenic activity but possesses significant activity against tumour and non-tumour human cells, reinforcing its biological potential.

Experts' recommendations in laser use for the treatment of urolithiasis: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training-Research in Urological Surgery and Technology (T.R.U.S.T.)-Group.

PURPOSE: To identify laser lithotripsy settings used by experts for specific clinical scenarios and to identify preventive measures to reduce complications. METHODS: After literature research to identify relevant questions, a survey was conducted and sent to laser experts. Participants were asked for preferred laser settings during specific clinical lithotripsy scenarios. Different settings were compared for the reported laser types, and common settings and preventive measures were identified. RESULTS: Twenty-six laser experts fully returned the survey. Holmium-yttrium-aluminum-garnet (Ho:YAG) was the primary laser used (88%), followed by thulium fiber laser (TFL) (42%) and pulsed thulium-yttrium-aluminum-garnet (Tm:YAG) (23%). For most scenarios, we could not identify relevant differences among laser settings. However, the laser power was significantly different for middle-ureteral (p = 0.027), pelvic (p = 0.047), and lower pole stone (p = 0.018) lithotripsy. Fragmentation or a combined fragmentation with dusting was more common for Ho:YAG and pulsed Tm:YAG lasers, whereas dusting or a combination of dusting and fragmentation was more common for TFL lasers. Experts prefer long pulse modes for Ho:YAG lasers to short pulse modes for TFL lasers. Thermal injury due to temperature development during lithotripsy is seriously considered by experts, with preventive measures applied routinely. CONCLUSIONS: Laser settings do not vary significantly between commonly used lasers for lithotripsy. Lithotripsy techniques and settings mainly depend on the generated laser pulse's and generator settings' physical characteristics. Preventive measures such as maximum power limits, intermittent laser activation, and ureteral access sheaths are commonly used by experts to decrease thermal injury-caused complications.

Deep learning model improves tumor-infiltrating lymphocyte evaluation and therapeutic response prediction in breast cancer.

Tumor-infiltrating lymphocytes (TILs) have been recognized as key players in the tumor microenvironment of breast cancer, but substantial interobserver variability among pathologists has impeded its utility as a biomarker. We developed a deep learning (DL)-based TIL analyzer to evaluate stromal TILs (sTILs) in breast cancer. Three pathologists evaluated 402 whole slide images of breast cancer and interpreted the sTIL scores. A standalone performance of the DL model was evaluated in the 210 cases (52.2%) exhibiting sTIL score differences of less than 10 percentage points, yielding a concordance correlation coefficient of 0.755 (95% confidence interval [CI], 0.693-0.805) in comparison to the pathologists' scores. For the 226 slides (56.2%) showing a 10 percentage points or greater variance between pathologists and the DL model, revisions were made. The number of discordant cases was reduced to 116 (28.9%) with the DL assistance (p < 0.001). The DL assistance also increased the concordance correlation coefficient of the sTIL score among every two pathologists. In triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients who underwent the neoadjuvant chemotherapy, the DL-assisted revision notably accentuated higher sTIL scores in responders (26.8 ± 19.6 vs. 19.0 ± 16.4, p = 0.003). Furthermore, the DL-assistant revision disclosed the correlation of sTIL-high tumors (sTIL ≥ 50) with the chemotherapeutic response (odd ratio 1.28 [95% confidence interval, 1.01-1.63], p = 0.039). Through enhancing inter-pathologist concordance in sTIL interpretation and predicting neoadjuvant chemotherapy response, here we report the utility of the DL-based tool as a reference for sTIL scoring in breast cancer assessment.

Exposure to Dichlorvos pesticide alters the morphology of and lipid metabolism in the ventral prostate of rats.

Organophosphate pesticides are widely used in agriculture, leading to soil, water, and food contamination. Among these compounds is Dichlorvos [O,O-dimethyl O-(2,2-dichlorovinyl)phosphate, DDVP], which is listed as a highly toxic compound by the Environmental Protection Agency and World Health Organization. Exposure to DDVP can result in nervous, respiratory, hepatic, and reproductive abnormalities, in addition to endocrine disrupting, mutagenic, and carcinogenic effects. Little is known about the impacts of DDVP on the reprogramming of lipid metabolism, which is also associated with the development and progression of cancer, since the tumor cells need to recruit, capture, and use fatty acids to compose their building membranes. This study aimed to evaluate the influence of the pesticide DDVP on lipid metabolism in the prostate, after chemical induction by the carcinogen N-methyl-N-nitrosourea (MNU). For this, 32 Fischer rats aged 90 days were randomly divided into four experimental groups: Control, DDVP, MNU, and MNU + DDVP. The MNU and MNU + DDVP groups underwent chemical induction with MNU (15 mg/kg) and the DDVP and MNU + DDVP groups received a diet supplemented with DDVP (10 mg/kg). Histopathological analyses of the rat ventral prostate showed 100% incidence of epithelial hyperplasia in the MNU and MNU + DDVP groups. This finding was accompanied by an increase of the epithelial compartment in the MNU + DDVP group. Immunolocalization of important proteins linked to lipid metabolism has been established. In the MNU + DDVP group, Western blotting analyses pointed out an increased expression of the protein LIMP II (Lysosomal Integral Membrane Protein-II), which is correlated with the capture and distribution of lipids in tumor cells. Together, these results indicate that the association of a low dose of DDVP with MNU was able to promote alterations in the morphology and lipid metabolism of the rat ventral prostate, which may be related to tumor progression in this organ.

Organizing Pneumonia and Ulcerative Colitis: A Relationship To Remember.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterised by relapsing and remitting mucosal inflammation of the colon. Despite primarily affecting the gastrointestinal tract, UC has various extraintestinal manifestations that often affect other organs and systems. Although pulmonary involvement is uncommon, organising pneumonia (OP), which affects the lung parenchyma, is one of the potential extraintestinal manifestations of UC. We report a case of OP in a 35-year-old male with a longstanding history of UC, well-medicated with sulfasalazine (SSZ). He presented to the emergency department (ED) with complaints of fatigue, coughing, myalgia, thoracalgia and dyspnoea. A chest X-ray showed parenchymal infiltrates and computed tomography revealed bilateral consolidation. Under a preliminary diagnosis of atypical pneumonia, he was treated with an empirical broad-spectrum antimicrobial agent, which did not lead to any clinical, laboratory or imaging improvement. Furthermore, the diagnostic work-up excluded any malignancy or infectious cause. A probable diagnostic hypothesis was OP as an extraintestinal manifestation of UC or as an adverse effect of SSZ therapy. Hence, SSZ was discontinued, and he was successfully treated with corticosteroids, exhibiting significant improvements and recovering completely during the follow-up period. Despite lung involvement in UC being rare, we present this case to emphasise the importance of a thorough differential diagnosis when treating acute respiratory illness in patients with UC, including extraintestinal manifestations of UC, especially OP, even during a period of remission. We also emphasise the importance of early initiation of corticosteroid therapy to prevent major complications and promote recovery.

Potential Role of Fourier Transform Infrared Spectroscopy as a Screening Approach for Breast Cancer.

Breast cancer is a heterogeneous disease, and its spread involves a succession of clinical and pathological stages. Screening is predominantly based on mammography, which has critical limitations related to the effectiveness and production of false-positive or false-negative results, generating discomfort and low adherence. In this context, infrared with attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy emerges as a non-destructive sample tool, which is non-invasive, label-free, has a low operating-cost, and requires only a small amount of sample, including liquid plasma samples. We sought to evaluate the clinical applicability of ATR FT-IR in breast cancer screening. ATR FT-IR spectroscopy through its highest potential spectral biomarker could distinguish, by liquid plasma biopsy, breast cancer patients and healthy controls, obtaining a sensitivity of 97%, specificity of 93%, a receiver operating characteristic ROC curve of 97%, and a prediction accuracy of 94%. The main variance between the groups was mainly in the band 1511 cm-1 of the control group, 1502 and 1515 cm-1 of the cancer group, which are the peaks of the bands referring to proteins and amide II. ATR FT-IR spectroscopy has demonstrated to be a promising tool for breast cancer screening, given its time efficiency, cost of approach, and its high ability to distinguish between the liquid plasma samples of breast cancer patients and healthy controls.

Artificial Intelligence-Powered Whole-Slide Image Analyzer Reveals a Distinctive Distribution of Tumor-Infiltrating Lymphocytes in Neuroendocrine Neoplasms.

Despite the importance of tumor-infiltrating lymphocytes (TIL) and PD-L1 expression to the immune checkpoint inhibitor (ICI) response, a comprehensive assessment of these biomarkers has not yet been conducted in neuroendocrine neoplasm (NEN). We collected 218 NENs from multiple organs, including 190 low/intermediate-grade NENs and 28 high-grade NENs. TIL distribution was derived from Lunit SCOPE IO, an artificial intelligence (AI)-powered hematoxylin and eosin (H&E) analyzer, as developed from 17,849 whole slide images. The proportion of intra-tumoral TIL-high cases was significantly higher in high-grade NEN (75.0% vs. 46.3%, p = 0.008). The proportion of PD-L1 combined positive score (CPS) ≥ 1 case was higher in high-grade NEN (85.7% vs. 33.2%, p < 0.001). The PD-L1 CPS ≥ 1 group showed higher intra-tumoral, stromal, and combined TIL densities, compared to the CPS < 1 group (7.13 vs. 2.95, p < 0.001; 200.9 vs. 120.5, p < 0.001; 86.7 vs. 56.1, p = 0.004). A significant correlation was observed between TIL density and PD-L1 CPS (r = 0.37, p < 0.001 for intra-tumoral TIL; r = 0.24, p = 0.002 for stromal TIL and combined TIL). AI-powered TIL analysis reveals that intra-tumoral TIL density is significantly higher in high-grade NEN, and PD-L1 CPS has a positive correlation with TIL densities, thus showing its value as predictive biomarkers for ICI response in NEN.

A Phase II Study of Nivolumab plus Gemcitabine in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (KCSG HN17-11).

PURPOSE: Although programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors are promising agents for recurrent or metastatic nasopharyngeal carcinoma (NPC), PD-1/PD-L1 inhibitor monotherapy has shown modest efficacy. This study evaluated the efficacy and safety of nivolumab plus gemcitabine in patients with NPC who failed prior platinum-based chemotherapy. PATIENTS AND METHODS: This is a phase II, multicenter, open-label, single-arm study. Patients with recurrent or metastatic NPC received nivolumab 3 mg/kg and gemcitabine 1,250 mg/m2 every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. To identify potential biomarkers, whole-exome sequencing, whole-transcriptome sequencing, and immune phenotype analysis based on Lunit SCOPE IO, an artificial intelligence-powered spatial tumor-infiltrating lymphocyte analyzer, were performed. RESULTS: Thirty-six patients were enrolled between June 2018 and June 2019. The ORR was 36.1% and disease control rate was 97.2%. With median follow-up of 22.0 months, median PFS was 13.8 months [95% confidence interval (CI), 8.6-16.8 months]. Median OS was not reached, and OS rate at 6 months was 97.0% (95% CI, 80.4%-99.6%). The grade ≥3 treatment-related adverse events were hypertension (2.8%) and anemia (2.8%). In multivariate analysis of mutation of chromatin modifier gene, tumor mutational burden (≥ 2.1 mut/Mb), and somatic copy-number alteration (SCNA) level, the group with high SCNA (> 3 points; HR, 7.0; 95% CI, 1.3-37.9; P = 0.02) had independently associated with poor PFS. Immune phenotype analysis showed that tumors with high proportion of immune-excluded immune phenotype was significantly correlated with poor PFS (HR, 4.4; 95% CI, 1.2-16.2; P = 0.018). CONCLUSIONS: Nivolumab plus gemcitabine showed promising efficacy with favorable toxicity profiles in patients with advanced NPC in whom platinum-based combination chemotherapy failed.

Artificial intelligence-powered programmed death ligand 1 analyser reduces interobserver variation in tumour proportion score for non-small cell lung cancer with better prediction of immunotherapy response.

BACKGROUND: Manual evaluation of programmed death ligand 1 (PD-L1) tumour proportion score (TPS) by pathologists is associated with interobserver bias. OBJECTIVE: This study explored the role of artificial intelligence (AI)-powered TPS analyser in minimisation of interobserver variation and enhancement of therapeutic response prediction. METHODS: A prototype model of an AI-powered TPS analyser was developed with a total of 802 non-small cell lung cancer (NSCLC) whole-slide images. Three independent board-certified pathologists labelled PD-L1 TPS in an external cohort of 479 NSCLC slides. For cases of disagreement between each pathologist and the AI model, the pathologists were asked to revise the TPS grade (<1%, 1%-49% and ≥50%) with AI assistance. The concordance rates among the pathologists with or without AI assistance and the effect of the AI-assisted revision on clinical outcome upon immune checkpoint inhibitor (ICI) treatment were evaluated. RESULTS: Without AI assistance, pathologists concordantly classified TPS in 81.4% of the cases. They revised their initial interpretation by using the AI model for the disagreement cases between the pathologist and the AI model (N = 91, 93 and 107 for each pathologist). The overall concordance rate among the pathologists was increased to 90.2% after the AI assistance (P < 0.001). A reduction in hazard ratio for overall survival and progression-free survival upon ICI treatment was identified in the TPS subgroups after the AI-assisted TPS revision. CONCLUSION: The AI-powered TPS analyser assistance improves the pathologists' consensus of reading and prediction of the therapeutic response, raising a possibility of standardised approach for the accurate interpretation.

Artificial Intelligence-Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as Complementary Biomarker for Immune Checkpoint Inhibition in Non-Small-Cell Lung Cancer.

PURPOSE: Biomarkers on the basis of tumor-infiltrating lymphocytes (TIL) are potentially valuable in predicting the effectiveness of immune checkpoint inhibitors (ICI). However, clinical application remains challenging because of methodologic limitations and laborious process involved in spatial analysis of TIL distribution in whole-slide images (WSI). METHODS: We have developed an artificial intelligence (AI)-powered WSI analyzer of TIL in the tumor microenvironment that can define three immune phenotypes (IPs): inflamed, immune-excluded, and immune-desert. These IPs were correlated with tumor response to ICI and survival in two independent cohorts of patients with advanced non-small-cell lung cancer (NSCLC). RESULTS: Inflamed IP correlated with enrichment in local immune cytolytic activity, higher response rate, and prolonged progression-free survival compared with patients with immune-excluded or immune-desert phenotypes. At the WSI level, there was significant positive correlation between tumor proportion score (TPS) as determined by the AI model and control TPS analyzed by pathologists (P < .001). Overall, 44.0% of tumors were inflamed, 37.1% were immune-excluded, and 18.9% were immune-desert. Incidence of inflamed IP in patients with programmed death ligand-1 TPS at < 1%, 1%-49%, and ≥ 50% was 31.7%, 42.5%, and 56.8%, respectively. Median progression-free survival and overall survival were, respectively, 4.1 months and 24.8 months with inflamed IP, 2.2 months and 14.0 months with immune-excluded IP, and 2.4 months and 10.6 months with immune-desert IP. CONCLUSION: The AI-powered spatial analysis of TIL correlated with tumor response and progression-free survival of ICI in advanced NSCLC. This is potentially a supplementary biomarker to TPS as determined by a pathologist.

Dermatomyositis: A Cancer Red Flag.

Dermatomyositis is an inflammatory disease that affects muscle strength and causes skin manifestations. There is an increased incidence of cancer in patients with this diagnosis although the pathophysiology of this association is still not completely understood. We report a case of a 65-year-old man who presented to the emergency department with proximal muscle weakness, weight loss, dysphagia, enlarged supraclavicular lymph nodes, an erythematous rash in the malar and supraciliary regions, and papules in the extensor metacarpophalangeal and interphalangeal joints. He had elevated creatine kinase and positive anti-nuclear matrix protein-2 autoantibodies. The skin and muscle biopsies performed confirmed the diagnosis of dermatomyositis. A thorough investigation seeking an associated condition was conducted and a prostate adenocarcinoma was diagnosed. The patient was treated with glucocorticoids and intravenous immune globulin with dysphagia and muscle weakness improvement and therefore allowing hospital discharge. He is currently undergoing oncologic treatment. Myositis-specific antibodies have proved to be extremely useful in the diagnosis, prognosis, and management of patients with dermatomyositis. Various phenotypes of the disease can associate differently with a systemic condition (namely a malignant disease). This case illustrates a rare form of cancer presentation that every clinician, especially those who work in the emergency room or in primary care and therefore have immediate contact with many patients, must be able to recognize.

Detection of Myxoma Virus DNA in Ticks from Lagomorph Species in Spain Suggests Their Possible Role as Competent Vector in Viral Transmission.

Myxoma virus (MYXV) causes morbidity and mortality in European wild rabbits (Oryctolagus cuniculus) worldwide, and recently in Iberian hares (Lepus granatensis) in Spain. We aimed to assess the presence of MYXV-specific DNA in ixodid ticks collected from both hosts. A total of 417 ticks harvested from 30 wild lagomorphs, including wild rabbits and Iberian hares were collected from southern Spain. Enzyme-linked immunosorbent assay and PCR-sequencing were used to detect virus exposure and presence, respectively. Antibodies to MYXV were detected in 68% (17/25) of wild rabbits and in 67% (2/3) of Iberian hares. We detected MYXV DNA in 50.7% of pools of two different tick species (nymphs and adults of Rhipicephalus pusillus, and nymphs of Hyalomma lusitanicum) parasitizing rabbits and hares. The obtained partial sequence of the viral major envelope protein gene showed a mutation (G383A) within the MYXV_gp026 locus between the rabbit strain and Iberian hare strain (recently isolated in tissues of infected hares from Spain). However, in our study, the viral DNA presence was detected for the first time using tick DNA as the PCR-template, but the possible role of ticks as vectors of MYXV still needs to be elucidated.

Intraoperative pulmonary hyperdistention estimated by transthoracic lung ultrasound: A pilot study.

INTRODUCTION: Transthoracic lung ultrasound can assess atelectasis reversal and is considered as unable to detect associated hyperdistention. In this study, we describe an ultrasound pattern highly suggestive of pulmonary hyperdistention. METHODS: Eighteen patients with normal lungs undergoing lower abdominal surgery were studied. Electrical impedance tomography was calibrated, followed by anaesthetic induction, intubation and mechanical ventilation. To reverse posterior atelectasis, a recruitment manoeuvre was performed. Positive-end expiratory pressure (PEEP) titration was then obtained during a descending trial - 20, 18, 16, 14, 12, 10, 8, 6 and 4cmH2O. Ultrasound and electrical impedance tomography data were collected at each PEEP level and interpreted by two independent observers. Spearman correlation test and receiving operating characteristic curve were used to compare lung ultrasound and electrical impedance tomography data. RESULTS: The number of horizontal A lines increased linearly with PEEP: from 3 (0, 5) at PEEP 4cmH2O to 10 (8, 13) at PEEP 20cmH2O. The increase number of A lines was associated with a parallel and significant decrease in intercostal space thickness (p=0.001). The lung ultrasound threshold for detecting pulmonary hyperdistention was defined as the number of A lines counted at the PEEP preceding the PEEP providing the best respiratory compliance. Six A lines was the median threshold for detecting pulmonary hyperdistention. The area under the receiving operating characteristic curve was 0.947. CONCLUSIONS: Intraoperative transthoracic lung ultrasound can detect lung hyperdistention during a PEEP descending trial. Six or more A lines detected in normally aerated regions can be considered as indicating lung hyperdistention. TRIAL REGISTRATION: NCT02314845 Registered on ClinicalTrials.gov.

A prospective controlled randomized multicenter study to evaluate the severity of compensatory sweating after one-stage bilateral thoracic sympathectomy versus unilateral thoracic sympathectomy in the dominant side.

OBJECTIVE: To evaluate the contribution that unilateral thoracic sympathectomy in dominant side or two-stage bilateral thoracic sympathectomy can have as strategies to reduce the incidence of compensatory sweating after sympathectomy for palmar hyperhidrosis. METHODS: This is a prospective, controlled, randomized multicenter trial of 200 participants with palmar hyperhidrosis, which will be randomized into two arms: (a) one-stage bilateral thoracic sympathectomy (control arm); or (b) unilateral thoracic sympathectomy in dominant side (intervention arm). At six months the participants submitted to unilateral procedure can make the contralateral surgery if they wanted it, creating a third group called two-stage bilateral sympathectomy. Participants will be evaluated for the degree of sweating by the Hyperhidrosis Disease Severity Scale (HDSS) and of quality of life questionnaires. RESULTS: 96 participants out of the 200 proposed have been included so far, with 48 participants randomized to each arm. From the sample 61 (63.5%) are female, with a mean age of 24 (20-32) years. There were exclusive palmar hiperhydrosis in 14 cases (14.5%), palmar and plantar hyperhidrosis in 36 (37.5%) cases, palmar and axillar hyperhidrosis in 12 (12,5%) cases and palmar-axillary-plantar hyperhidrosis in 34 (35,4%) cases. The age at the beginning of the disease was childhood (78%), with mean of time of disease 15 (11-22) years. CONCLUSIONS: If one or both hypothesis: (a) unilateral sympathectomy in dominant hand is a satisfactory treatment; b) two-stage bilateral sympathectomy causes less compensatory sweating than in one stage are confirmed there is a chance that surgical therapy for palmar hyperhidrosis can be changed for better.

Odor characterization of post-consumer and recycled automotive polypropylene by different sensory evaluation methods and instrumental analysis.

Despite the growing interest of the automotive industry in using recycled polymers, their undesired odor is limiting their application in vehicles' interior components. To get deeper insights into its causes, this study aimed at characterizing the odor of post-consumer and recycled automotive polypropylene with different contents of talc and an anti-fogging additive. Samples were evaluated by different sensory methods currently applied by the automotive industry (GMW 3205 and VDA 270), which confirmed, that they are not feasible for reuse in interior automotive applications. As these odor evaluations are usually performed by non-trained panelists and do not allow a detailed description of the samples' single odor qualities, sensory evaluation according to ISO 13299 was performed by trained panelists. Samples showed medium-high odor intensities rated from 5.1 to 5.6, and a general dislike of the odor with hedonic ratings from 1.8 to 2.6 (scale 0-10). Their odor profiles correlated well with the odorants identified by chemo-analytical characterization using gas chromatography-olfactometry (GC-O) and two-dimensional GC-O coupled with mass spectrometry (2D-GC-MS/O). An array of odorants with benzene and phenolic structures were identified as potential contributors to the samples' overall smell and are likely to originate from degradation of additives commonly used in automotive components. While the addition of talc or anti-fogging additive did not significantly improve the odor of the samples, the description of the samples' smell and the identification of odor-active compounds related to it allow the development of avoidance strategies for the manufacturing of neutral smelling products intended for vehicles' interior applications.