Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tertiary lymphoid structures improve immunotherapy and survival in melanoma.

Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.

Accuracy of linear measurements for implant planning based on low-dose cone beam CT protocols: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review was to verify the accuracy of linear measurements performed on low-dose CBCT protocols for implant planning, in comparison with those performed on standard and high-resolution CBCT protocols. METHODS: The literature search included four databases (Pubmed, Web of Science, Embase, and Scopus). Two reviewers independently screened titles/abstracts and full texts according to eligibility criteria, extracted the data, and examined the methodological quality. Risk of bias assessment was performed using the Quality Assessment Tool For In Vitro Studies. Random-effects meta-analysis was used for pooling measurement error data. RESULTS: The initial search yielded 4684 titles. In total, 13 studies were included in the systematic review, representing a total of 81 samples, while 9 studies were included in the meta-analysis. The risk of bias ranged from medium to low. The main results across the studies indicate a strong consistency in linear measurements performed on low-dose images in relation to the reference methods. The overall pooled planning measurement error from low-dose CBCT protocols was -0.24 mm (95% CI, -0.52 to 0.04) with a high level of heterogeneity, showing a tendency for underestimation of real values. Various studies found no significant differences in measurements across different protocols (eg, voxel sizes, mA settings, or dose levels), regions (incisor, premolar, molar) and types (height vs. width). Some studies, however, noted exceptions in measurements performed on the posterior mandible. CONCLUSION: Low-dose CBCT protocols offer adequate precision and accuracy of linear measurements for implant planning. Nevertheless, diagnostic image quality needs must be taken into consideration when choosing a low-dose CBCT protocol.

Neoadjuvant carboplatin in triple-negative breast cancer: results from NACATRINE, a randomized phase II clinical trial.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is the mainstay of treatment of stages II and III triple-negative breast cancer (TNBC). This study aims to evaluate if the addition of carboplatin to NACT is associated with an increase in the pathological complete response (pCR) rates in TNBC. METHODS: We conducted an open-label phase II randomized clinical trial in a single center in Brazil. Patients with stage II and III TNBC were randomized to receive standard NACT with or without carboplatin. All the patients received doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) both intravenously (i.v.) q21 days for four cycles. Patients were then randomized for additional treatment with weekly (wk) paclitaxel (80 mg/m2 i.v., for 12 cycles) plus wk carboplatin AUC 1.5 (experimental arm) or without wk carboplatin (control arm). Randomization was stratified according to gBRCA status, age, and AJCC 8th edition clinical stage (II vs. III). The primary endpoint was the pathologic complete response (pCR) rate. Secondary endpoints included recurrence-free survival and overall survival. RESULTS: Between 2017 and 2021, 146 patients were randomized, 73 on each arm. The median age was 45 years. Most patients (66.4%) had locally advanced stage III disease, 67.1% had T3/T4 tumors, and 56.2% had clinically positive axillary lymph nodes. Germline BRCA status was available for all patients, and 19.9% had pathogenic BRCA1/2 variants. The pCR rate (ypT0ypN0) was numerically increased by 13.7%, being 43.8% (31 of 73 patients) in the experimental and 30.1% (22 of 73 patients) in the control arm, not meeting the prespecified goal of increasing the pCR in 15% (p-value = 0.08). Survival outcomes are immature. CONCLUSION: The addition of carboplatin to standard NACT in stages II and III TNBC was associated with a non-statistically significant numerical increase in the pCR rate. Follow-up for survival outcomes and translational research initiatives are ongoing.

Immune-cell infiltration in high-grade soft tissue sarcomas; prognostic implications of tumor-associated macrophages and B-cells.

BACKGROUND: Soft tissue sarcomas are rare, morphologically, and genetically heterogenous. Though the tumors display abundant tumor stroma with infiltrating immune cells, the prognostic impact of various immunologic markers in sarcoma remains poorly defined. We aimed to characterize the immune landscape of a treatment-naïve cohort of soft tissue sarcoma of the extremities and the trunk wall with correlations to metastasis-free survival. MATERIALS AND METHODS: We surveyed immunohistochemical expression patterns for CD163, CD20, CD3, CD8, and FOXP3 in 134 adult high-grade leiomyosarcomas, liposarcomas, and synovial sarcomas. RESULTS: Macrophages outnumbered tumor-infiltrating lymphocytes. High CD163 infiltration was identified in 49% of the tumors and was overrepresented (66%) in leiomyosarcoma compared to liposarcoma (46%) and synovial sarcoma (9%). Tumor-grade also correlated with CD163 positivity with high expression in 53% of the high-grade lesions and 28% in low-grade tumors. Infiltrating CD3, CD8 and FOXP3-positive T-cells were significantly more prevalent in leiomyosarcomas than in liposarcomas/synovial sarcomas. CD20+ B-cells were identified only in 14% of the STS. Correlation to established prognostic factors revealed a correlation between CD163+ macrophages and necrosis and predicted an increased risk of metastases. No correlation between CD20+ B-cells and known prognostic factors could be established, though CD20+ B-cells infiltration predicted improved overall survival. CONCLUSION: We confirm that tumor-infiltrating macrophages outnumber tumor-infiltrating lymphocytes in soft tissue sarcoma and signify an increased risk of metastasis. CD20+ B-cells are scarce in STS and correlate to improved survival. To date, immunotherapeutic strategies directed against T-cells have shown limited effect in soft tissue sarcoma. Our observations suggest that immunomodulatory agents focusing on macrophages may be worthwhile for further investigations in this tumor type. Further studies exploring the prognostic and predictive significance of CD20+ B cells are warranted.

Transformative dimensions of resilience and brittleness during health systems' collapse: a case study in Brazil using the Functional Resonance Analysis Method.

BACKGROUND: As health systems struggle to tackle the spread of Covid-19, resilience becomes an especially relevant attribute and research topic. More than strength or preparedness, to perform resiliently to emerging shocks, health systems must develop specific abilities that aim to increase their potential to adapt to extraordinary situations while maintaining their regular functioning. Brazil has been one of the most affected countries during the pandemic. In January 2021, the Amazonas state's health system collapsed, especially in the city of Manaus, where acute Covid-19 patients died due to scarcity of medical supplies for respiratory therapy. METHODS: This paper explores the case of the health system's collapse in Manaus to uncover the elements that prevented the system from performing resiliently to the pandemic, by carrying out a grounded-based systems analysis of the performance of health authorities in Brazil using the Functional Resonance Analysis Method. The major source of information for this study was the reports from the congressional investigation carried out to unveil the Brazilian response to the pandemic. RESULTS: Poor cohesion between the different levels of government disrupted essential functions for managing the pandemic. Moreover, the political agenda interfered in the abilities of the system to monitor, respond, anticipate, and learn, essential aspects of resilient performance. CONCLUSIONS: Through a systems analysis approach, this study describes the implicit strategy of "living with Covid-19", and an in-depth view of the measures that hampered the resilience of the Brazilian health system to the spread of Covid-19.

Intestinal parasite infections associated with sociodemographic and seasonal factors in the Western Amazon.

Intestinal parasites are a constant public health problem in the Amazon region, with a high prevalence of cases related to poor sanitary conditions. We investigated the sociodemographic and seasonal factors associated with human intestinal parasite infections in an area of the Western Amazon, Brazil, from September 2017 to August 2019. Data were collected using a database available at the Diagnostic Support Centre (Centro de Apoio ao Diagnóstico, CAD) of the Municipality of Rio Branco, on positive diagnoses for intestinal parasites. Among the 53,200 samples analysed, 18.3% (n = 9712) were positive. Of these, 96.4% (n = 9363) and 3.6% (n = 349) were protozoan and helminthic infections, respectively. Males showed higher odds ratio (OR) for Enterobius vermicularis infection (OR: 2.3) and giardiasis (OR: 1.9) and lower OR for Endolimax nana (OR: 0.9) and Entamoeba coli (OR: 0.9) infections. Individuals aged ≥ 15 presented higher OR for Strongyloides stercoralis (OR: 3.4), hookworms (OR: 2.3), and almost all protozoan infections than younger individuals. In the dry season, the OR for hookworms (OR: 1.5), Iodamoeba butschlii (OR: 1.4), and Endolimax nana (OR: 1.3) infections was higher than that in the rainy season, including a high chance of polyparasitism (OR: 1.6). We concluded that there was a significant difference between the different types of intestinal parasites, particularly protozoa, with high OR in the dry season and for certain groups.

In vitro manipulation of the bacterial community to improve the performance of bioflocs in aquaculture systems.

Although biofloc technology is already recognized as advantageous and practical for aquaculture for the effects of maintaining water quality and improving the health status and resistance of cultivated animals against pathogens, little is known about the way of action involved. This study aimed to evaluate the performance of bacterial groups as inducers in the formation of flocs compared to a system with spontaneous formation. Therefore, three microsystems were built in 3L tanks with constant aeration to induce the biofloc aggregation with addition of bacterial consortiuns with differentiated functions. It was used a control, without addition of bacterial consortium; B1 with addition of probiotic bacteria consortium; and B2, with adding nitrifying bacteria consortium. During the experimental period were evaluated physicochemical variables and quantifications of bacterial cultivable groups: Heterotrophic Bacteria and Vibrio. Also was the microscopic characterization of the flakes and tests of antimicrobial activity against pathogenic bacteria. Systems B1 and B2 showed promising results in relation to control (spontaneous bioflocs), showing more homogeneous flake formation, antimicrobial activity against the tested pathogens and greater biological diversity in the systems. The bacteria used in these tests were able to optimize the formation of microbial aggregates, showing potential for application in cultivation systems, in order to obtain improvements in productivity.

Volume-based tomography for the diagnosis of incipient silicosis in former gold miners.

OBJECTIVE: To evaluate silicosis diagnosed through CT, with integration of clinical-occupational data, in silica-exposed workers presenting chest X-rays within International Labor Organization (ILO) category 0. METHODS: Cross-sectional study with 339 former gold miners, with comparable exposures and X-rays classified as ILO subcategory 0/0 (n=285) and 0/1 (n=54) were submitted to volume-based CT. The findings were classified according to the International Classification of HRCT CT for Occupational and Environmental Respiratory Diseases. RESULTS: A profusion degree of round opacities (RO)>1 was found in 22.4% (76/339) of the CT exams. After integrating the CT findings with clinical and occupational data, silicosis was diagnosed as follows: 43/285 (15.1%) and 14/54 (25.9%) in workers whose X-rays had been classified as 0/0 and 0/1, respectively. There was an upward trend towards longer exposures, reaching 38.9% when working more than 10 years underground and classified as 0/1 (p=0019). Those with presence of RO whose final diagnosis was not silicosis were mainly cases of tuberculosis or 'indeterminate nodules'. Emphysema was found in 65/339 (19.1%), only 5 being detected in the X-ray. CONCLUSION: Volume-based CT proved to be useful in the investigation of silicosis among individuals with a relevant exposure to silica, capturing diagnoses that had not been identified on X-rays. A response gradient of silicosis was showed by CT even in this population with ILO category 0 radiographs. It can be indicated based on quantitative and/or qualitative criteria of occupational exposure, especially considering the possibilities of low CT dosage.

Long-term impact of congenital toxoplasmosis on phenotypic and functional features of circulating leukocytes from infants one year after treatment onset.

Changes in immune response of children with congenital toxoplasmosis (CT) regarding infection evolution and therapeutic intervention was addressed. Infants with CT presented increased counts of monocytes, CD3-CD16-CD56High, CD3+CD56+ and CD4+ T-cells 1-year after treatment onset (TOXO1-yearAT). Smaller numbers of CD3-CD16-CD56+ and TCRγδ+ T-cells were specifically observed in infants with retinochoroidal lesions (L(+)). When infants were classified based on the baseline status, expansion of CD3-CD16-CD56High and CD4+ T-cells were observed in L(+) who had active, active/cicatricial or cicatricial lesions. Infants who had active or active/cicatricial lesions display augmented numbers of monocytes, CD3-CD16+CD56+, CD3+CD56+, CD8+DR+ and TCRγδ+ T-cells and those with active/cicatricial or cicatricial at baseline displayed increase in CD14+CD64+ monocytes. Moreover, all L(+) had increased IFN-γ+ and IL-10+ CD4+ T-cells, while L(-) had increased ratios of TNF+, IFN-γ+ and IL-4+ NK-cells upon antigen-specific stimulation. Persistent alterations in leukocytes in TOXO1-yearAT suggest long-term sequels in the immune system of infants with CT.

Intercontinental trials reveal stable QTL for Northern corn leaf blight resistance in Europe and in Brazil.

KEY MESSAGE: NCLB is the most devastating leaf disease in European maize, and the introduction of Brazilian resistance donors can efficiently increase the resistance levels of European maize germplasm. Northern corn leaf blight (NCLB) is one of the most devastating leaf pathogens in maize (Zea mays L.). Maize cultivars need to be equipped with broad and stable NCLB resistance to cope with production intensification and climate change. Brazilian germplasm is a great source to increase low NCLB resistance levels in European materials, but little is known about their effect in European environments. To investigate the usefulness of Brazilian germplasm as NCLB resistance donors, we conducted multi-parent QTL mapping, evaluated the potential of marker-assisted selection as well as genome-wide selection of 742 F1-derived DH lines. The line per se performance was evaluated in one location in Brazil and six location-by-year combinations (= environments) in Europe, while testcrosses were assessed in two locations in Brazil and further 10 environments in Europe. Jointly, we identified 17 QTL for NCLB resistance explaining 3.57-30.98% of the genotypic variance each. Two of these QTL were detected in both Brazilian and European environments indicating the stability of these QTL in contrasting ecosystems. We observed moderate to high genomic prediction accuracies between 0.58 and 0.83 depending on population and continent. Collectively, our study illustrates the potential use of tropical resistance sources to increase NCLB resistance level in applied European maize breeding programs.

Exploiting genetic diversity in two European maize landraces for improving Gibberella ear rot resistance using genomic tools.

KEY MESSAGE: High genetic variation in two European maize landraces can be harnessed to improve Gibberella ear rot resistance by integrated genomic tools. Fusarium graminearum (Fg) causes Gibberella ear rot (GER) in maize leading to yield reduction and contamination of grains with several mycotoxins. This study aimed to elucidate the molecular basis of GER resistance among 500 doubled haploid lines derived from two European maize landraces, "Kemater Landmais Gelb" (KE) and "Petkuser Ferdinand Rot" (PE). The two landraces were analyzed individually using genome-wide association studies and genomic selection (GS). The lines were genotyped with a 600-k maize array and phenotyped for GER severity, days to silking, plant height, and seed-set in four environments using artificial infection with a highly aggressive Fg isolate. High genotypic variances and broad-sense heritabilities were found for all traits. Genotype-environment interaction was important throughout. The phenotypic (r) and genotypic ([Formula: see text]) correlations between GER severity and three agronomic traits were low (r = - 0.27 to 0.20; [Formula: see text]= - 0.32 to 0.22). For GER severity, eight QTLs were detected in KE jointly explaining 34% of the genetic variance. In PE, no significant QTLs for GER severity were detected. No common QTLs were found between GER severity and the three agronomic traits. The mean prediction accuracies ([Formula: see text]) of weighted GS (wRR-BLUP) were higher than [Formula: see text] of marker-assisted selection (MAS) and unweighted GS (RR-BLUP) for GER severity. Using KE as the training set and PE as the validation set resulted in very low [Formula: see text] that could be improved by using fixed marker effects in the GS model.

Minocycline alleviates depression-like symptoms by rescuing decrease in neurogenesis in dorsal hippocampus via blocking microglia activation/phagocytosis.

Clinical studies examining the potential of anti-inflammatory agents, specifically of minocycline, as a treatment for depression has shown promising results. However, mechanistic insights into the neuroprotective and anti-inflammatory actions of minocycline need to be provided. We evaluated the effect of minocycline on chronic mild stress (CMS) induced depressive-like behavior, and behavioral assays revealed minocycline ameliorate depressive behaviors. Multiple studies suggest a role of microglia in depression, revealing that microglia activation correlates with a decrease in neurogenesis and increased depressive-like behavior. The effect of minocycline on microglia activation in different areas of the dorsal or ventral hippocampus in stressed mice was examined by immunohistochemistry. We observed the increase in the number of activated microglia expressing CD68 after exposure to three weeks of chronic stress, whereas no changes in total microglia number were observed. These changes were observed throughout the DG, CA1 and CA2 regions in dorsal hippocampus but restricted to the DG of the ventral hippocampus. In vitro experiments including western blotting and phagocytosis assay were used to investigate the effect of minocycline on microglia activation. Activation of primary microglia by LPS in vitro causes and ERK1/2 activation, enhancement of iNOS expression and phagocytic activity, and alterations in cellular morphology that are reversed by minocycline exposure, suggesting that minocycline directly acts on microglia to reduce phagocytic potential. Our results suggest the most probable mechanism by which minocycline reverses the pathogenic phagocytic potential of neurotoxic M1 microglia, and reduces the negative phenotypes associated with reduced neurogenesis caused by exposure to chronic stress.

Mortality from silicosis in Brazil: Temporal trends in the period 1980-2017.

BACKGROUND: Silicosis is the most prevalent pneumoconiosis in Brazil. We aimed to estimate mortality rates and temporal trends for silicosis, and to identify areas of highest mortality. METHODS: Records of silicosis as the underlying (1980-2017) or contributory (2000-2017) cause of death in adults aged 20 years and older were retrieved from the Brazilian Mortality Database. Age-standardized mortality rates (ASMR) were calculated. The annual trend in ASMR was analyzed by joinpoint regression. Mortality rates per 100,000 person-years were calculated for each municipality. We analyzed temporal trends in municipalities where similar activities with exposure to silica were performed. RESULTS: There were 3164 death records (96.6% men) distributed over 14% of the municipalities. Mean age of death was 59.2 (SD 15.1) and mean ASMR was 0.085/100,000 (confidence interval 0.080-0.091). Joinpoint regression showed a significant increase in ASMR from 1980 to 2006 and a significant decrease after 2006 driven by a decline in deaths of individuals younger than 70 years. The highest mortality rate was 21.83/100,000 person-years, in a municipality with small mining operations for gems. Gold mining municipalities showed the highest composite death rate, 4.0/100,000 person-years. Tuberculosis was the main cause of death when silicosis was a contributing cause. CONCLUSIONS: In contrast with developed countries, silicosis mortality in Brazil increased to 2006 and subsequently started to drop, mostly from a plateau or decrease in deaths occurring in municipalities which regulated economic activities. However, this decrease did not occur in the older age group nor in the unregulated sector, the latter being the main challenge for exposure control and surveillance.

COVID-19 Remote Consultation Services and Population in Health Inequity-Concentrating Territories: A Scoping Review.

Background: This review aimed to map initiatives for measuring the satisfaction of vulnerable populations with teleconsultation services offered by public and private health care providers in their territories, during the coronavirus disease (COVID-19) pandemic. Systematic studies on the opinions of people most affected by health inequities are limited. Therefore, we included evaluations of teleconsultation-based services offered to socioeconomically disadvantaged and clinically vulnerable populations globally, with a focus on surveillance, treatment, and prevention of COVID-19. Materials and Methods: This review includes analytical and descriptive observational studies primarily from MEDLINE, EMBASE, SCOPUS, and Web of Science databases, published after the World Health Organization received the first warnings about COVID-19 from Chinese authorities in December, 2019, until December 2020. The search strategy combined aspects of COVID-19, telemedicine, patient satisfaction, and key concepts of vulnerable populations. Results: We selected 33 studies for full-text reading and 10 for critical appraisal. Two categories emerged from the qualitative analysis: telehealth evaluation and services during COVID-19, and opinions of vulnerable populations. Television and social networks play a crucial role in providing information. Although teleconsultations are practical and cost effective for patients, the majority preferred receiving in-person treatment in primary care clinics. Conclusions: Listening to the opinions of vulnerable groups and their caregivers is critical both before and during adoption of COVID-19 control measures. Health managers need to monitor the health of and delivery of services to socioeconomically and clinically vulnerable people closely, to improve services, and provide care from a human rights perspective.

Inflammatory and oxidative stress biomarkers induced by silica exposure in crystal craftsmen.

BACKGROUND: Identification of biomarkers associated with the diagnosis and prognosis of silicosis would be highly advantageous in the clinical setting. The aim of this study is to evaluate inflammatory and oxidative stress biomarkers in subjects exposed to silica. METHODS: A cross-sectional study of crystal craftsmen currently (n = 34) or formerly (n = 35) exposed and a group of nonexposed subjects (n = 12) was performed. Personal respirable dust samples were collected. Plasma inflammatory mediators (bone morphogenetic protein- BMP2 and chemokines CXCL16, and CCL5), oxidative stress enzymes (thiobarbituric acid reactive substances [TBARs] and superoxide dismutase [SOD]), and nitrite (NO2- ) were analyzed in parallel with nitric oxide in exhaled breath (FeNO). RESULTS: Being currently or formerly exposed to silica was related to increased levels of CXCL16 and TBARs. Currently, exposed subjects showed decreased levels of SOD. Thirty-seven craftsmen with silicosis (26 formerly and 11 currently exposed) showed higher levels of CXCL16, which was positively associated with the radiological severity of silicosis. Compared with the nonexposed, subjects with silicosis had higher levels of TBARs and those with complicated silicosis had lower levels of SOD. In multivariate analysis, higher levels of CXCL16 were associated with exposure status and radiological severity of silicosis. Smoking was not a confounder. FeNO did not distinguish between the exposure status and the presence of silicosis. CONCLUSION: CXCL16 emerged as a potential biomarker that could distinguish both silica exposure and silicosis. TBARs were elevated in exposed individuals. However, their clinical applications demand further investigation in follow-up studies of representative samples.

Diagnostic accuracy of imaging studies for diagnosing root avulsions in post-traumatic upper brachial plexus traction injuries in adults.

BACKGROUND: There is no consensus about which type of imaging study, computed tomography myelography (CTM) or magnetic resonance imaging (MRI), provides better information concerning root avulsion in adult brachial plexus injuries. METHODS: Patients with upper brachial plexus traumatic injuries underwent both CTM and MRI and surgical exploration. The imaging studies were analyzed by two independent radiologists and the data were compared with the intraoperative findings. The statistical analysis was based on dichotomous classification of the nerve roots (normal or altered). The interobserver agreement was assessed using Cohen's Kappa. The accuracy of CTM and MRI in comparison with the intraoperative findings was evaluated using the same methodology. RESULTS: Fifty-two adult patients were included. CTM tended to yield slightly higher percentages of alterations than MRI The interobserver agreement was better on CTM than on MRI for all nerve roots: C5, 0.9960 (strong) vs. 0.145 (poor); C6, 0.970 (strong) vs. 0.788 (substantial); C7, 0.969 (strong) vs. 0.848 (strong). The accuracy regarding the intraoperative findings was also higher on CTM (moderate, kappa 0.40-0.59) than on MRI (minimal, kappa 0.20-0.39) for all nerve roots. Accordingly, the overall percentage concordance (both normal or both altered) was superior in the CTM evaluation (approx. 70-75% vs. 60-65%). CTM was superior for both sensitivity and specificity at all nerve roots. CONCLUSION: CTM had greater interobserver agreement and higher diagnostic accuracy than MRI in adult patients with root avulsions due to brachial plexus injury.

Lingual Lateral Canal Mimicking Mandible Fracture.

Lingual lateral canal is a rare variation in the trajectory of the mandibular canal, and is usually detected as an incidental finding on radiographic exams, especially on cone-beam computed tomography. Due to its radiographic characteristics, this anatomical variation might be confused with a mandible fracture. Therefore, the knowledge of its presence is essential not only to differentiate it from a fracture, but also for the success of surgical procedures performed in the mandible, making it easier to avoid clinical complications such as swelling, bruising, bleeding, and neurovascular disorders. This report shows the case of a lingual lateral canal mimicking a fracture on the mandibular body.

A Population-Based Comparison of the AJCC 7th and AJCC 8th Editions for Patients Diagnosed with Stage III Cutaneous Malignant Melanoma in Sweden.

BACKGROUND: Cutaneous melanoma is steadily increasing worldwide. The new AJCC 8th edition was recently launched and introduced several changes in melanoma staging, particularly for stage III. We conducted a population-based registry study with the purpose to evaluate the impact and prognostic accuracy of the new classification in Sweden. METHODS: Consecutive patients diagnosed with stage III melanoma between January 2005 and September 2017 were identified by the Swedish Melanoma Registry (SMR) and included for analyses. Patients with multiple primary melanomas were excluded. Patients were classified according to the AJCC 7th as well as the 8th edition. Melanoma-specific survival (MSS) was retrieved from the Swedish Cause of Death Registry. RESULTS: A total of 2067 eligible patients were identified from the SMR; 1150 patients (57%) changed stage III subgroup when reclassified according to the AJCC 8th edition. The median 5- and 10-year MSS for the whole cohort of stage III melanoma patients was 59% and 51% respectively. The MSS for substage IIIA, B, and C were all improved when patients were reclassified by using to the AJCC 8th edition. The newly defined substage IIID had the worst prognosis with a 10-year MSS of 16%. CONCLUSIONS: A high proportion of patients diagnosed with stage III melanoma in Sweden between 2005 and 2017 was restaged to another subgroup, when they were reclassified according to the AJCC 8th of staging manual. We established an improved MSS for all substages compared with the former AJCC 7th edition. This may have implications on decisions about adjuvant treatment.

Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study.

BACKGROUND: While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in metastatic uveal melanoma. Thus, metastatic uveal melanoma remains a disease with an urgent unmet medical need. Reports of treatment with immune checkpoint inhibitors have thus far been disappointing. Based on animal experiments, it is reasonable to hypothesize that the effect of immunotherapy may be augmented by epigenetic therapy. Proposed mechanisms include enhanced expression of HLA class I and cancer antigens on cancer cells, as well as suppression of myeloid suppressor cells. METHODS: The PEMDAC study is a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD1 inhibitor pembrolizumab and the class I HDAC inhibitor entinostat in adult patients with metastatic uveal melanoma. Primary endpoint is objective response rate. Eligible patients have histologically confirmed metastatic uveal melanoma, ECOG performance status 0-1, measurable disease as per RECIST 1.1 and may have received any number of prior therapies, with the exception of anticancer immunotherapy. Twenty nine patients will be enrolled. Patients receive pembrolizumab 200 mg intravenously every third week in combination with entinostat 5 mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24 months. DISCUSSION: The PEMDAC study is the first trial to assess whether the addition of an HDAC inhibitor to anti-PD1 therapy can yield objective anti-tumoral responses in metastatic UM. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT02697630 . (Registered 3 March 2016). EudraCT registration number: 2016-002114-50.