BACKGROUND AND PURPOSE:

Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors.

BACKGROUND AND PURPOSE:

There has been a distinction made in the 2001 Canadian C-Spine Rule regarding patients 65 and older and younger than 65 years of age as far as indications for cervical spine CT scanning. We sought to determine if there are differences in the symptoms, mechanisms of injury, fracture locations, and types that are still relevant in 2024.

BACKGROUND AND PURPOSE:

Periprocedural intracranial hemorrhage is one of common complications after stent placement for symptomatic intracranial atherosclerotic stenosis. This study was conducted to demonstrate predictors and long-term outcomes of periprocedural intracranial hemorrhage after stent placement for symptomatic intracranial atherosclerotic stenosis.

BACKGROUND AND PURPOSE:

Reocclusion after treatment is a concern in endovascular therapy for isolated intracranial atherothrombotic stroke-related large-vessel occlusion (AT-LVO). However, the optimal endovascular therapy technique for AT-LVO has not yet been investigated. This study evaluated the optimal endovascular therapy technique for AT-LVO in a real-world setting.

BACKGROUND AND PURPOSE:

Intracranial vessel wall imaging is technically challenging to implement, given the simultaneous requirements of high spatial resolution, excellent blood and CSF signal suppression, and clinically acceptable gradient times. Herein, we present our preliminary findings on the evaluation of a deep learning–optimized sequence using T1-weighted imaging.

BACKGROUND AND PURPOSE:

Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees.

SUMMARY:

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.

Spinal CSF leak care has evolved during the past several years due to pivotal advances in its diagnosis and treatment. To the reader of the American Journal of Neuroradiology (AJNR), it has been impossible to miss the exponential increase in groundbreaking research on spinal CSF leaks and spontaneous intracranial hypotension (SIH). While many clinical specialties have contributed to these successes, the neuroradiologist has been instrumental in driving this transformation due to innovations in noninvasive imaging, novel myelographic techniques, and image-guided therapies. In this editorial, we will delve into the exciting advancements in spinal CSF leak diagnosis and treatment and celebrate the vital role of the neuroradiologist at the forefront of this revolution, with particular attention paid to CSF leak–related work published in the AJNR.

We present a unique case of a single patient presenting with two mutationally distinct, PD-L1⁺ diffuse large B-cell lymphomas (DLBCLs). One of these DLBCLs demonstrated exceptionally high mutational burden (eight disease-associated variants and 41 variants of undetermined significance) with microsatellite instability (MSI) and an acquired PMS2 mutation with loss of PMS2 protein expression, detected postchemotherapy. This report, while highlighting the extent of possible tumor heterogeneity across separate clonal expansions as well as possible syndromic B-cell neoplasia, supports the notion that, although rare, PD-L1 expression and associated states permissive of high mutational burden (such as mismatch repair gene loss of function/MSI) should be more routinely considered in DLBCLs. Appropriate testing may be predictive of outcome and inform the utility of targeted therapy in these genetically diverse and historically treatment-refractory malignancies.

The diagnosis of maturity-onset diabetes of the young (MODY), a monogenic form of diabetes mellitus caused by a mutation in a single gene, is often uncertain until genetic testing is performed. We report a 13-yr-old Korean boy who was initially diagnosed with type 2 diabetes (T2DM). MODY was suspected because of his nonobese body habitus and family history of multiple affected members. Targeted panel sequencing of all MODY-related genes was performed using the NextSeq 550Dx platform (Illumina). Sanger sequencing was performed using blood samples from the parents, siblings, and other relatives. A frameshift variant in the 3' region of the last exon of PDX1 was detected in the patient and his family members with diabetes. PP1_Moderate criterion was applied and this variant was confirmed to be the genetic cause of diabetes in the family and classified as likely pathogenic. The study highlights the importance of genetic testing for nonobese, early-onset diabetic patients with multiple affected family members. Increased awareness and aggressive genetic testing for MODY are needed.

Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum–bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement—an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome.

Electron transport chain (ETC) disorders are a group of rare, multisystem diseases caused by impaired oxidative phosphorylation and energy production. Deficiencies in complex III (CIII), also known as ubiquinol–cytochrome c reductase, are particularly rare in humans. Ubiquinol–cytochrome c reductase core protein 2 (UQCRC2) encodes a subunit of CIII that plays a crucial role in dimerization. Several pathogenic UQCRC2 variants have been identified in patients presenting with metabolic abnormalities that include lactic acidosis, hyperammonemia, hypoglycemia, and organic aciduria. Almost all previously reported UQCRC2-deficient patients exhibited neurodevelopmental involvement, including developmental delays and structural brain anomalies. Here, we describe a girl who presented at 3 yr of age with lactic acidosis, hyperammonemia, and hypoglycemia but has not shown any evidence of neurodevelopmental dysfunction by age 15. Whole-exome sequencing revealed compound heterozygosity for two novel variants in UQCRC2: c.1189G>A; p.Gly397Arg and c.437T>C; p.Phe146Ser. Here, we discuss the patient's clinical presentation and the likely pathogenicity of these two missense variants.

Anorectal malformations (ARMs) constitute a group of congenital defects of the gastrointestinal and urogenital systems. They affect males and females, with an estimated worldwide prevalence of 1 in 5000 live births. These malformations are clinically heterogeneous and can be part of a syndromic presentation (syndromic ARM) or as a nonsyndromic entity (nonsyndromic ARM). Despite the well-recognized heritability of nonsyndromic ARM, the genetic etiology in most patients is unknown. In this study, we describe three siblings with diverse congenital anomalies of the genitourinary system, anemia, delayed milestones, and skeletal anomalies. Genome sequencing identified a novel, paternally inherited heterozygous Caudal type Homeobox 2 (CDX2) variant (c.722A > G (p.Glu241Gly)), that was present in all three affected siblings. The variant identified in this family is absent from population databases and predicted to be damaging by most in silico pathogenicity tools. So far, only two other reports implicate variants in CDX2 with ARMs. Remarkably, the individuals described in these studies had similar clinical phenotypes and genetic alterations in CDX2. CDX2 encodes a transcription factor and is considered the master regulator of gastrointestinal development. This variant maps to the homeobox domain of the encoded protein, which is critical for interaction with DNA targets. Our finding provides a potential molecular diagnosis for this family's condition and supports the role of CDX2 in anorectal anomalies. It also highlights the clinical heterogeneity and variable penetrance of ARM predisposition variants, another well-documented phenomenon. Finally, it underscores the diagnostic utility of genomic profiling of ARMs to identify the genetic etiology of these defects.

Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions.

TP53 plays a critical role as a tumor suppressor by controlling cell cycle progression, DNA repair, and apoptosis. Post-translational modifications such as acetylation of specific lysine residues in the DNA binding and carboxy-terminus regulatory domains modulate its tumor suppressor activities. In this study, we addressed the functional consequences of the germline TP53 p.K164E (NM_000546.5: c.490A>G) variant identified in a patient with early-onset breast cancer and a significant family history of cancer. K164 is a conserved residue located in the L2 loop of the p53 DNA binding domain that is post-translationally modified by acetylation. In silico, in vitro, and in vivo analyses demonstrated that the glutamate substitution at K164 marginally destabilizes the p53 protein structure but significantly impairs sequence-specific DNA binding, transactivation, and tumor cell growth inhibition. Although p.K164E is currently considered a variant of unknown significance by different clinical genetic testing laboratories, the clinical and laboratory-based findings presented here provide strong evidence to reclassify TP53 p.K164E as a likely pathogenic variant.

T-lymphoblastic lymphoma (T-LLy) is the most common lymphoblastic lymphoma in children and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here, we discuss the case of a previously healthy 3-yr-old male who presented with mediastinal T-LLy with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4 c.1420-1G > T p.? and EZH2 c.1943G > C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in Chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age, warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumor DNA can fulfill that purpose, particularly when standard first-line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes.

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B, MyD88, TP53, TBL1XR1, and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance.

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library. This is then followed by amplification of the library, which can then be used for biopanning using multiple methods. This protocol describes amplification of affibody libraries, followed by biopanning using phage display and analysis of the selection output. The general procedure is mainly for selection of first-generation affibody molecules from large naive (unbiased) libraries, typically yielding affibody hits with affinities in the low nanomolar range. For selection from affinity maturation libraries with the aim of isolating variants of even higher affinities, the procedure is similar, but parameters such as target concentration and washing are adjusted to achieve the proper stringency.

BackgroundDuring the COVID-19 pandemic, global trends of reduced healthcare-seeking behaviour were observed. This raises concerns about the consequences of healthcare avoidance for population health.AimTo determine the association between healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality.Design and settingThis was a 32-month follow-up within the population-based Rotterdam Study, after sending a COVID-19 questionnaire at the onset of the pandemic in April 2020 to all communty dwelling participants (n = 6241/8732, response rate 71.5%).MethodCox proportional hazards models assessed the risk of all-cause mortality among respondents who avoided health care because of the COVID-19 pandemic. Mortality status was collected through municipality registries and medical records.ResultsOf 5656 respondents, one-fifth avoided health care because of the COVID-19 pandemic (n = 1143). Compared with non-avoiders, those who avoided health care more often reported symptoms of depression (n = 357, 31.2% versus n = 554, 12.3%) and anxiety (n = 340, 29.7% versus n = 549, 12.2%), and more often rated their health as poor to fair (n = 336, 29.4% versus n = 457, 10.1%) . Those who avoided health care had an increased adjusted risk of all-cause mortality (hazard ratio [HR] 1.30, 95% confidence interval [CI] = 1.01 to 1.67), which remained nearly identical after adjustment for history of any non-communicable disease (HR 1.20, 95% CI = 0.93 to 1.54). However, this association attenuated after additional adjustment for mental and physical self-perceived health factors (HR 0.93, 95% CI = 0.71 to 1.20).ConclusionThis study found an increased risk of all-cause mortality among individuals who avoided health care during COVID-19. These individuals were characterised by poor mental and physical self-perceived health. Therefore, interventions should be targeted to these vulnerable individuals to safeguard their access to primary and specialist care to limit health disparities, inside and beyond healthcare crises.

BackgroundLong-term health conditions are major challenges for care systems. Social prescribing link workers have been introduced via primary care networks (PCNs) across England since 2019 to address the wider determinants of health by connecting individuals to activities, groups, or services within their local community.AimTo assess whether the rollout of social prescribing link workers was in areas with the highest need.Design and settingA retrospective study of social prescribing link workers in England from 2019 to 2023.MethodWorkforce, population, survey, and area-level data at the PCN-level from April 2020 to October 2023 were combined. Population need before the rollout of link workers was measured using reported lack of support from local services in the 2019 General Practice Patient Survey. To assess if rollout reflected need, linear regression was used to relate provision of link workers (measured by full-time equivalent [FTE] per 10 000 patients) in each quarter to population need for support.ResultsPopulations in urban, more deprived areas and with higher proportions of people from minority ethnic groups had the highest reported lack of support. Geographically these were in the North West and London. Initially, there was no association between need and provision; then from July 2022, this became negative and significant. By October 2023, a 10-percentage point higher need for support was associated with a 0.035 (95% confidence interval = −0.634 to −0.066) lower FTE per 10 000 patients.ConclusionRollout of link workers has not been sufficiently targeted at areas with the highest need. Future deployments should be targeted at those areas.

BackgroundOrlistat is recommended as an adjunct to diet and exercise for weight loss in the treatment of type 2 diabetes mellitus (T2DM).AimTo explore associations between patient characteristics and orlistat prescribing, and to determine associations of orlistat with weight loss in T2DM and prediabetes.Design and settingCohort study using anonymised health records from a UK database of general practice.MethodThe UK Clinical Practice Research Datalink (CPRD) Aurum database was searched to compile a cohort of patients aged ≥18 years, first diagnosed with T2DM or prediabetes in 2016 or 2017. Once the data had been collated, multivariable logistic regression models were used to determine associations with starting orlistat and stopping it early (<12 weeks of prescriptions) and orlistat’s associations with weight loss in those who had not been prescribed second-line antidiabetic medications.ResultsOut of 100 552 patients with incident T2DM or prediabetes, 655 (0.8%) patients with T2DM and 128 (0.7%) patients with prediabetes were prescribed orlistat. Younger people, females, those in areas of deprivation, current smokers, those coprescribed metformin, and those recorded as having hypertension were statistically significantly more likely to be prescribed orlistat; higher baseline glycated haemoglobin levels were associated with early stopping. In comparison with patients not on orlistat, those who continued using it for ≥12 weeks were more likely to lose ≥5% weight (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI] = 1.07 to 2.67) but those who stopped orlistat early were less likely to lose ≥5% weight (AOR 0.56, 95% CI = 0.29 to 1.09).ConclusionOrlistat was significantly associated with weight loss in patients with T2DM and prediabetes when taken for at least 12 weeks; however, it was infrequently prescribed and often taken for <12 weeks. Orlistat may be a useful adjunct to lifestyle modifications for patients with T2DM and prediabetes, but barriers to continued use means it may not be effective for everyone in managing weight loss.

We primary care clinicians, scholars, and leaders ascribe value to Barbara Starfield’s core tenets of primary care—the 4 Cs: first contact, comprehensiveness, coordination, and continuity. In today’s era of rapid technological advancements and dwindling resources, what are the implications for face-to-face interactions of patient-clinician relationships? We propose adding a 5th C: "Contiguity." Contiguity—or physical proximity and presence—is a key dimension that not only enables the necessary technical aspects of a physical exam but also authenticates the most human aspects of a relationship and occurs specifically when we are physically vulnerable and responsible for the other before us. This, in turn, may best enable us to bridge difference and nurture trust with our patients. We measure what we value and, thus, naming Contiguity as a core tenet assures that we will not lose sight of this keystone in a patient’s relationship with their personal physician.

Patient expectations of receiving antibiotics for common symptoms can trigger unnecessary use. We conducted a survey (n = 564) between January 2020 to June 2021 in public and private primary care clinics in Texas to study the prevalence and predictors of patients’ antibiotic expectations for common symptoms/illnesses. We surveyed Black patients (33%) and Hispanic/Latine patients (47%), and over 93% expected to receive an antibiotic for at least 1 of the 5 pre-defined symptoms/illnesses. Public clinic patients were nearly twice as likely to expect antibiotics for sore throat, diarrhea, and cold/flu than private clinic patients. Lack of knowledge of potential risks of antibiotic use was associated with increased antibiotic expectations for diarrhea (odds ratio [OR] = 1.6; 95% CI, 1.1-2.4) and cold/flu symptoms (OR = 2.9; 95% CI, 2.0-4.4). Lower education and inadequate health literacy were predictors of antibiotic expectations for diarrhea. Future antibiotic stewardship interventions should tailor patient education materials to include information on antibiotic risks and guidance on appropriate antibiotic indications.

PURPOSE

We undertook a trial to test the efficacy of a technology-assisted health coaching intervention for weight management, called Goals for Eating and Moving (GEM), within primary care.

BACKGROUND

For many patients with post–COVID-19 condition (long COVID), primary care is the first point of interaction with the health care system. In principle, primary care is well situated to manage long COVID. Beyond expressions of disempowerment, however, the patient’s perspective regarding the quality of long COVID care is lacking. Therefore, this study aimed to analyze the expectations and experiences of primary care patients seeking treatment for long COVID.

Mammalian astrocytes have regional roles within the brain parenchyma. Indeed, the notion that astrocytes are molecularly heterogeneous could help explain how the central nervous system (CNS) retains embryonic positional information through development into specialized regions into adulthood. A growing body of evidence supports the concept of morphological and molecular differences between astrocytes in different brain regions, which might relate to their derivation from regionally patterned radial glia and/or local neuron inductive cues. Here, we review evidence for regionally encoded functions of astrocytes to provide an integrated concept on lineage origins and heterogeneity to understand regional brain organization, as well as emerging technologies to identify and further investigate novel roles for astrocytes.

Approximately 8.5%–16.2% of childhood cancers are associated with a pathogenic/likely pathogenic germline variant—a prevalence that is likely to rise with improvements in phenotype recognition, sequencing, and variant validation. One highly informative, classical hereditary cancer predisposition syndrome is Li–Fraumeni syndrome (LFS), associated with germline variants in the TP53 tumor suppressor gene, and a >90% cumulative lifetime cancer risk. In seeking to improve outcomes for young LFS patients, we must improve the specificity and sensitivity of existing cancer surveillance programs and explore how to complement early detection strategies with pharmacology-based risk-reduction interventions. Here, we describe novel precision screening technologies and clinical strategies for cancer risk reduction. In particular, we summarize the biomarkers for early diagnosis and risk stratification of LFS patients from birth, noninvasive and machine learning–based cancer screening, and drugs that have shown the potential to be repurposed for cancer prevention.

Background

In an evolving landscape of practices and policies, reviewing and incorporating the latest scientific evidence is necessary to ensure optimal clinical management for people with opioid use disorder. We provide a synopsis of the 2024 update of the 2018 National Guideline for the Clinical Management of Opioid Use Disorder, from the Canadian Research Initiative in Substance Matters.

Stage III nonsmall cell lung cancer (NSCLC) represents a wide range of tumour (T1 to T4) and nodal (N0 to N3) components, requiring variable management and a multidisciplinary approach. Recent advancements in minimally invasive techniques, molecular biology and novel drug discoveries have accelerated the refinement of stage III NSCLC management. The latest developments in staging include the forthcoming update of the nodal component in the 9th TNM (tumour–node–metastasis) edition, which emphasises the critical role for endobronchial ultrasonography in mediastinal staging. Recent treatment developments include the use of immunotherapy and targeted molecular therapy in both the neoadjuvant and adjuvant setting, either in combination with other modalities or used alone as consolidation. Surgical and radiotherapy advancements have further enhanced patient outcomes. These developments have significantly improved the prognosis for patients with stage III NSCLC. Fast-changing recommendations have also brought about a challenge, with clinicians facing a number of options to choose from. Therefore, a multimodal approach by a multidisciplinary team has become even more crucial in managing stage III NSCLC.

Central sleep apnoea (CSA) is characterised by recurrent episodes of airway cessation or reduction in the absence of respiratory effort. Although CSA is less common than obstructive sleep apnoea, it shares similar symptoms. CSA can be secondary to various medical conditions, high altitude and medication exposure. CSA can also emerge during obstructive sleep apnoea therapy. There are a range of treatment options and selecting the right therapy requires an understanding of the pathophysiology of CSA. This review explores the aetiology, pathophysiology and clinical management of non-hypercapnic CSA.

Chronic pulmonary aspergillosis has a range of manifestations from indolent nodules to semi-invasive infection. Patients may be asymptomatic or have chronic symptoms such as cough and weight loss or present with life-threatening haemoptysis. The physician can choose from a range of available therapies including medical therapy with antifungals, minimally invasive therapy with intracavitary antifungal therapy and surgery involving open thoracotomy or video-assisted thoracoscopic surgery. The patients with the most severe forms of pulmonary infection may not be surgical candidates due to their underlying pulmonary condition. The management of haemoptysis can include tranexamic acid, bronchial artery embolisation, antifungals or surgery. There are few controlled studies to inform clinicians managing complex cases, so a multidisciplinary approach may be helpful.

The respiratory literature, both written and in online formats, is growing exponentially. Capturing quality content, to meet the learning needs of those working in all fields of respiratory medicine and delivering it in a palatable, accessible format is challenging but paramount. In this article we discuss ways to determine the information content and review different methods of delivering this content to those who need it.

Palliative care pertains to the holistic multidimensional concept of "patient-centred" care. It is an interprofessional specialty, primarily aiming to improve quality of care for cancer patients and their families, from the time of diagnosis of malignant disease, over the continuum of cancer care, and extending after the patient's death to the period of bereavement to support the patient's family. There are various complex and frequently unmet needs of lung cancer patients and their families/caregivers, not only physical but also psychological, social, spiritual and cultural. Systematic monitoring of patients’ symptoms using validated questionnaires and patient-reported outcomes (PROs), on a regular basis, is highly encouraged and recommended in recent guidelines on the role of PRO measures in the continuum of cancer clinical care. It improves patient–physician communication, physician awareness of symptoms, symptom control, patient satisfaction, health-related quality of life and cost-effectiveness. This implies that all treating physicians should improve their skills in communication with lung cancer patients/relatives and become more familiar with this multidimensional assessment, repeatedly screening patients for palliative care needs. Therefore, they should receive education and training to develop palliative care knowledge, skills and attitudes. This review is dedicated to lung cancer palliative care essentials that should be within the competences of treating physicians, i.e. pneumologists/thoracic oncologists.

The driverless vehicles still can't take L.A.'s notorious highways.

HBO's Casey Bloys was asked about the Game of Thrones author's spicy take on House of the Dragon season two.

Jade Ho explains what is possible for university students when they are given opportunities to learn about –and get involved with– social justice and labour issues in their own communities.

The post Students can be agents of change: Talking about activism in universities with Jade Ho appeared first on rabble.ca.

A new report by the global union Education International shows that AI can degrade the quality of education, worsen working conditions for teachers and provide inferior schooling for students.

The post Artificial Intelligence can cause fake education appeared first on rabble.ca.

Deepfakes can be close to indistinguishable from authentic video, and are now being used to perpetrate gender based abuse.

The post Deepfakes and gender based violence appeared first on rabble.ca.

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The United Nations says South Sudan’s four-year-old civil war has left half of the nation’s population — 6 million people — in need of humanitarian aid. The conflict began when South Sudan’s army split between factions loyal to President Salva Kiir and former Vice President Riek Machar. The two men mobilized their respective tribes, the Dinka and the Nuer. The war has caused what is now one of the world’s worst refugee crises.

SIMONA FOLTYN: Civil war is emptying huge swaths of South Sudan. The violence has uprooted four million people, including two million who’ve fled to neighboring countries. In the last year, more than a million South Sudanese have poured into northern Uganda alone, crossing makeshift bridges like this one to flee fighting, hunger, and brutal attacks on civilians.

SEME LUPAI, REFUGEE: They started fighting very, very severely. So that made us to escape with our properties to this side.

SIMONA FOLTYN: When Seme Lupai’s family went to one of the refugee camps, initially, he stayed behind to look after the family’s most precious commodity — their cattle. He hid for a year to escape the violence. The refugees carry whatever they can salvage — mattresses, pots, clothes, notebooks — remnants of once peaceful lives turned upside down. At checkpoints, Ugandan soldiers search their belongings for weapons, before the refugees proceed to reception centers. After entering Uganda, the refugees sign in at small waystations. For many, it’s the first night spent in safety after walking for days to escape fighting. Levi Arike fled with his wife and four children.

LEVI ARIKE, REFUGEE: When the gunshots started, we laid under a tree with the whole family, because there was nowhere else to hide. We waited for the fighting to stop, and then we got up and started walking to Uganda.

SIMONA FOLTYN: Uganda now shoulders most of the burden of Africa’s biggest refugee crisis, managing a constellation of camps which require food, water, healthcare, and policing. At Imvepi Camp, now home to more than 120,000 South Sudanese, new arrivals receive vaccinations, hot meals, and basic items such as soap and plastic tarps to build a house. The government also gives each refugee family a small plot of land, about a twentieth of an acre, where they can build a tent shelter and grow crops to eat or sell. But the land often proves too rocky for farming.

SIMONA FOLTYN, IMVEPI REFUGEE CAMP, NORTHERN UGANDA: After completing the registration process, the new arrivals will receive their plot, to start a new life as refugees in Uganda. While they are safe here, there are many challenges ahead, not least processing the trauma of what they experienced back home.

This woman, who we’ll call “Agnes,” agreed to tell us about her harrowing experience. She says four government soldiers from President Salva Kiir’s Dinka tribe stopped her as she was fleeing South Sudan and raped her right in front of her family.

AGNES (translated to English): When they started raping me, they told me not to raise alarm, otherwise they would shoot me. Still when I’m sleeping, I’m dreaming of the Dinka, that they are coming to rape me again.

SIMONA FOLTYN: How often do you have those dreams?

AGNES: Daily, every time I lie down, those dreams come.

SIMONA FOLTYN: A recent Human Rights Watch report on South Sudan found “…a clear pattern of government forces unlawfully targeting civilians for killings, rapes, torture…and destruction of property..” The victims are from ethnic groups suspected to support the rebels.

AGNES: They are doing it, because they know very well that those soldiers are our brothers. So they do it to punish them..

SIMONA FOLTYN: Although the rebels, known as the Sudan People’s Liberation Army In Opposition, purport to protect local communities, there are also reports of their fighters assaulting civilians near the Ugandan border. Josephine Yanya told us she didn’t feel safe in the presence of either side’s soldiers. Her family and neighbors fled their village after government soldiers killed her uncle.

They hid in the mountains only to find themselves under attack again, this time by opposition fighters from the Nuer tribe loyal to former vice president Riek Machar. Yanya says ethnic Nuer soldiers from the SPLA-IO rebel group raped a member of her group and stole her father’s’ cattle.

JOSEPHINE YANYA (translated to English): Before we were thinking that the rebels would protect us, but if they are lacking food, they just come and take things by force.

SIMONA FOLTYN: With nowhere left to hide, Yanya fled to Uganda with her son.
But instead of finding a place to rebuild their lives, they are in limbo. And aid groups don’t have enough food to distribute.

JOSEPHINE YANYA (translated to English):We are getting small food rations. I know it won’t be enough even for one month.

SIMONA FOLTYN: According to the United Nations, the international community has given less than a-third of the $1.4 billion dollars needed for the refugee response in South Sudan’s neighboring countries. These refugees foresee more hardship and have no idea when they might return home.

JOSEPHINE YANYA (translated to English): I’m always praying for peace in South Sudan, and until then, I’ll just stay here.

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JUDY WOODRUFF: But first: Sunday’s elections Austria were the latest ample of a shift to the right Europe’s politics, as 31-year-old Christian Kurz was elected chancellor on an anti-immigration platform.

He may now form a government with a far-right party founded in the 1950s by former Nazis.

That follows recent elections in Germany, where a far-right party roiled the race and dealt a blow to returning leader Angela Merkel.

In Sweden, too, there is a strong challenge from the right and a neo-Nazi group that looks stand in elections next year.

Special correspondent Malcolm Brabant ha been surveying the political landscape in Germany and Sweden, and he begins his report in Scandinavia.

MALCOLM BRABANT, Special Correspondent: In a Gothenburg parking lot, supporters of the Nordic Resistance Movement form up for what they hope will be their biggest-ever march, to propagate an ideology espoused by mother of eight Paulina Forslund.

PAULINA FORSLUND, Nordic Resistance Movement: When white becomes the minority, they will be destroyed. I want my children to have a secure future. I want them not only for them to have a secure Sweden. I want them to have a secure world. And I want other people to fight for the same thing.

MALCOLM BRABANT: When addressing her fellow neo-Nazis, Forslund’s rhetoric sharpens.

PAULINA FORSLUND (through interpreter): I’m the welder’s daughter, the forester’s grandchild. My line consists of hardworking men and women. It’s people like them we can thank for the welfare system that our lying politicians are now giving away to imported scum.

MALCOLM BRABANT: Clearly expecting trouble, the movement’s leaders have a muscular protection detail, marching past a silent protest. The sign reads “No Nazis on our streets.”

This protester would only give her name as Johanna.

JOHANNA, Anti-Nazi Protester: They are racist people. They are people who think that certain people are better than others, and I will not stand for that. It’s not something I think has a place in a modern society.

MALCOLM BRABANT: Experts say the resistance movement is recruiting aggressively, and believe this demonstration is emblematic of the rise of the far right.

It took place on Yom Kippur, the Jewish day of atonement.

Allan Stutzinky is leader of Gothenburg’s Jewish community.

ALLAN STUTZINKY, Jewish Community Leader (through interpreter): Nazism has returned. The descendants of the murderers are organizing the same marches today, waving the same flags, shouting the same slogans, and have the same racist agenda.

MALCOLM BRABANT: Anna Johansson is a member of the governing Social Democrat Party. It’s considering outlawing the Nordic Resistance Movement.

ANNA JOHANSSON, Swedish Social Democratic Party: In Sweden and in Denmark, and in other countries, extreme parties are growing, and the hatred is spreading around.

MALCOLM BRABANT: “Go home to mama,” he shouts. “Nazi pigs,” chant the anti- fascist protesters, as a bottle flies through the air.

DAMON, Nordic Resistance Movement: If someone calls themselves a Nazi, most of us would dissociate with that person. That’s nothing we stand for ourselves. I never call myself a Nazi. I’m a national socialist.

MALCOLM BRABANT: Hitler’s party was also called National Socialist, but Damon, a 40-year-old welder, insists he’s a nonviolent family man.

DAMON: The demographic landscape of our — of the whole of Europe is changing, so, basically, it’s a concern on preserving my heritage for my family and our kin.

MALCOLM BRABANT: This demonstration has been stopped short of its destination. The Nordic Resistance Movement is currently trapped between a line of police and anti-fascist protesters. And it looks as though this demonstration isn’t going any further.

Violence briefly erupts as the resistance movement tries to break through police lines, and several marchers are arrested.

PAULINA FORSLUND: We are not your enemy. We are the government’s enemy.

They say we live in a democracy, but we have never had an election about if we want to take all these people in.

MALCOLM BRABANT: When Europe’s refugee crisis began in 2015, Sweden copied Germany’s open-door policy, and 160,000 migrants entered the country. Two years on, Sweden has tighter borders and has begun deporting some of the newcomers.

The new atmosphere alarms Floid Gumbo, entertaining an anti-Nazi rally.

FLOID GUMBO, Singer Originally from Zimbabwe: I came to Sweden over 20 years ago. The climate in Sweden, the people were so friendly, and things were completely different, more welcoming. And I feel like things have sort of gradually changed.

I’m very concerned, because I have children, because I’m thinking what I experienced here is not the same kind of climate, atmosphere that they are going to experience here.

ANNA JOHANSSON: It’s not so long ago that the Nazis ruined Europe. And that makes me very worried. The German elections were terrifying, I think.

MALCOLM BRABANT: Johansson is referring to last month’s success of the right-wing Alternative For Germany Party, or AFD, when it entered Parliament for the first time with 13 percent of the vote.

HUGH BRONSON, Alternative For Germany Party: The AFD only came into existence because Merkel deserted the traditional conservative Christian voters. They were looking for a home, and the AFD has offered them a safe place.

MALCOLM BRABANT: Hugh Bronson is deputy leader of the AFD in Berlin.

Now his party, the third largest in Parliament, is demanding that Angela Merkel imposes tougher immigration rules.

Your opponents claim that you are a party of hate. What’s your response to that?

HUGH BRONSON: We embrace foreigners who respect our laws, pay their taxes, send their children to school, and go about their normal life. The problem is with people who abuse the system to have a better life, or let others pay for their better lives, or who are criminals.

MALCOLM BRABANT: Outside the opera house in Dresden, former East Germany, singer Luca Bergelt is dismayed by the political landscape shifting to the right.

LUCA BERGELT, Singer: My fear is that they will tear Europe apart. They are going to raise up the walls again. They’re going to build new walls between the countries, and that Europe will get more close into itself.

MALCOLM BRABANT: Anti-immigrant sentiment is strong in Dresden. The city was the birthplace of a pan-European anti-Islamic movement, and it delivered the largest number of votes for the right-wing party.

On a holiday to celebrate German unification after the fall of communism, retired engineer Wilfried Schmidt explained why he sent a message to Angela Merkel.

WILFRIED SCHMIDT, Retired Engineer (through interpretor): Let’s put it this way. We all need to recognize that Germany is undergoing social changes that are becoming harder to control. For one, there is mass immigration from difficult regions that is increasingly uncontrollable, of people with entirely different concepts of life, from fundamental differently structured societies that are problematic.

MALCOLM BRABANT: About one million migrants poured into Germany in 2015. Chancellor Merkel consistently defended her pro-refugee policies, but now she has been punished by voters who believe she ignored their concerns.

Chancellor Merkel has promised to listen to the people who voted for the AFD, and she says she’s going to try to win them over with what she calls good politics. But she will not countenance having the party in her coalition.

But the chancellor needs to find new partners who are prepared to be tough on immigration.

As she tries to forge a coalition, the chancellor has agreed to put an annual cap of 200,000 on the number of immigrants, something she previously refused to do. But will it be enough to woo back people who deserted her at the election?

A question for Werner Patzelt, a political scientist at Dresden University.

WERNER PATZELT, Dresden University: Since Chancellor Merkel has made so many U-turns in German domestic politics, it wouldn’t be a surprise if she would try to do a U-turn, also winning back AFD voters.

But this is a really hard political task, because so many of them are so much disappointed by the Christian Democratic Union in general, and by Chancellor Merkel in particular, that they will do anything to avoid going back.

MALCOLM BRABANT: Back in Sweden, the governing party is horrified at the concept of conceding ground to right-wingers, and is trying to isolate them.

ANNA JOHANSSON: Experience shows that, when you adopt the ideas from these right-wing parties, they spread. These parties have their agenda implemented by other parties. And I wouldn’t want to see that happen in Sweden.

FLOID GUMBO: We’re all human beings. We share this world. We’re all here. There’s enough space for us all.

MALCOLM BRABANT: But that’s an appeal that an increasing number of Swedes are rejecting, as the country and much of Europe go through a crisis of identity.

For the PBS NewsHour, I’m Malcolm Brabant in Gothenburg.

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More than 500,000 Rohingya Muslims have fled their homes since August to escape systematic violence at the hands of government soldiers in Myanmar. The U.N. has called the actions taken by Myanmar forces against the group “a textbook example of ethnic cleansing.”

A report released by Amnesty International on Wednesday documents widespread rape, killings and burnings of Rohingya across the Rakhine State in Myanmar. The report includes extensive interviews of Rohingya refugees who tell stories of live burnings, sexual violence and mass shootings at the hands of soldiers.

To escape persecution, Rohingya refugees are fleeing in droves to neighboring Bangladesh, a country described by some as a reluctant host for the thousands of refugees behind its borders. Conditions within Bangladesh show refugee camps beyond capacity, as organizations struggle to keep up with humanitarian aid.

Find out more: Rohingya Muslims have been denied citizenship in Myanmar since 1982, though they’ve lived in the area since the 12th century. They are not considered one of the country’s official ethnic groups. As such, their lack of official identity bars them from government services and travel.

Officials from Myanmar, a majority Buddhist state, claim Rohingya are actually immigrants from Bangladesh to justify their exclusion of the group. This most recent burst of violence comes from Myanmar’s crackdown following clashes with the Arakan Rohingya Salvation Army (ARSA). After the government declared ARSA a terrorist organization, the retaliation escalated into hundreds of Rohingya villages.

Where to give: BRAC, a top-ranked NGO based out of Bangladesh, is scaling up humanitarian efforts for clean water, health, sanitation and child care for refugees from Myanmar. You can learn more about their efforts here.

An emergency appeal was made by the Disasters Emergency Committee for immediate crisis relief funds. DEC distributes funds to 13 member aid organizations.
UNHCR, UNICEF and Save the Children have donation pages dedicated to the crisis, as does the International Rescue Committee. CNN’s Public Good page provides a user-friendly resource to find NGOs that match your giving goals.

To give to starvation relief, try Action Against Hunger or the World Food Programme.

Be sure to research organizations receiving your financial contributions, not only to find the best organization aligned with your goals, but also to avoid potential scams. For the latest information on aid organizations and charities, visit GuideStar or Charity Navigator to ensure your donations are going in the right direction.

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HARI SREENIVASAN: But first: The de facto capital of the Islamic State, Raqqa, in Syria fell yesterday to U.S.-backed forces.

However, the largest city the militants once held was Mosul in Iraq. They were ousted from it in July after a brutal 10-month-long fight that killed thousands.

Now a new major task: finding and destroying the ISIS mines, booby-traps and bombs that litter the city.

Special correspondent Marcia Biggs reports from Iraq.

MARCIA BIGGS, Special Correspondent: It was once a center of learning for over 6,000 students of technology, agriculture, and medicine.

Today, Mosul Technical Institute’s classrooms are burnt to the ground, laboratories reduced to rubble, and books charred and shredded. It’s one of the city’s five universities ravaged by the Islamic State and the battle to oust it.

Now that the battle is over, a new danger looms, the trail of land mines and booby-traps left by ISIS.

So this is the wire, and this is where it was buried.

CHRISTIAN, Team Leader, Janus Global Operations: Yes, they would cut the asphalt, and then they lay the wire in and put the main charge here.

MARCIA BIGGS: We spent the day with Christian, a team leader from Janus Global, a security and risk management firm hired by the U.S. government to sweep and clear major areas of unexploded ordnance and mines.

He’s not allowed to show his face or use his last name, for security reasons.

CHRISTIAN: There’s actually two more on that road before we get to the target building that have to be excavated and/or rendered safe.

MARCIA BIGGS: So, the first building you have to clear, you have got to get rid of the IEDs on the road to that building?

CHRISTIAN: Yes.

MARCIA BIGGS: It’s a long process.

CHRISTIAN: It is, but that’s what makes it interesting.

MARCIA BIGGS: The United States has sunk $30 million this year into clearing former ISIS territories all over Northern Iraq. Under this program, Janus has already cleared 727 buildings, removing 3,000 IEDs, which they say ISIS was producing on assembly lines at an industrial scale.

But State Department officials and experts say the number of unexploded ordnance in Mosul itself is unprecedented.

What’s your first line of attack, in terms of trying to clear Mosul?

CHRISTIAN: Our priority is more the community, rather than the individual, you know, infrastructure. You have got schools, power, sewer, water, so that the area can accept people back into it. And then, once this stabilization phase is over, we can move into the individual homes, so that they can be safer.

MARCIA BIGGS: Clearing Mosul is a process that they say could take years, even decades. So Janus is training local Iraqis to do the job, sending them out as a front-line search team, then investigating and removing any suspicious items themselves.

CHRISTIAN: We’re not going to be here the whole time, so when we — it’s our time to leave, they will have the capacity built from us, and the mentoring we have done, so that they can do it on their own.

MARCIA BIGGS: How are they doing?

CHRISTIAN: They’re — a lot of them are very apt to learn. They’re quick. They’re smart.

MARCIA BIGGS: Fawzi al Nabdi is the team leader for the Iraqi local partner. He’s cleared mines all over Iraq for the last six years.

CHRISTIAN: What you got?

FAWZI AL NABDI, Team Leader, Al Fahad Company (through interpreter): We are ready for this, because it’s my job and I love it. The Americans are here to complete our work and to help us. They have greater experience than we do. If we find any mines, we have to stop and they will investigate it and make a plan to remove it.

MARCIA BIGGS: But he says Mosul is the biggest project he has ever seen, and we’re told it could take at least a month to just get the campus cleared of mines. Only then can they start cleaning it up, so that students can resume classes, this itself a huge task.

ISIS fighters closed the university back in 2014, and used it as a military base. As coalition forces pounded ISIS targets, this seat of higher learning became a battleground.

Ghassan Alubaidy is the institute’s dean.

GHASSAN ALUBAIDY, Dean, Mosul Technical Institute (through interpreter): ISIS used our university to manufacture mines and bombs. For this reason, it was the target of airstrikes in the beginning. They struck the institute nine times, and they struck our workshops, too. Now we can’t use them.

MARCIA BIGGS: The former commander of coalition forces in Iraq, Lieutenant General Stephen Townsend, recently listed 81 locations where bombs were dropped, but had not yet exploded.

Facilities used to make weapons were often on the list of high-value targets for the coalition. So now those places are twice as likely to contain dangerous items.

So, this was once a workshop for electrical engineering students. You can still see the lab tables here. It was hit by an airstrike in 2015. Afterwards, members of the university staff found bomb-making instructions among the rubble. This was likely an ISIS bomb-making factory, and judging by the crater, a high-value target.

Despite the damage, Dean Alubaidy says he will hold classes this fall in alternate buildings, until the campus is ready. He’s expecting registration to be in the thousands, students who lost three years of education during the fighting and don’t want to lose another one.

GHASSAN ALUBAIDY (through interpreter): On our Facebook pages, we found a great number of students posting that they were full of encouragement to come back. For us, it was unbelievable. We couldn’t imagine it, to see how many students wanted to start again, how they were dreaming of the first day of classes, when they could sit in front of teachers again and start to live their lives again.

MARCIA BIGGS: Next door, Mosul University has already started classes. Students even volunteered to help in the cleanup.

But across the river, West Mosul was the site of ISIS’ last stand and bore the brunt of the battle. It’s densely packed Old City, with its flattened buildings, is a challenge for mine-sweeping.

FAWZI AL-NABDI (through interpreter): Most of the homes here were full of mines. And just here in front of us, a man with two kids came back to his home, and when he opened the door, the bomb killed him and his kids.

MARCIA BIGGS: Ahmed Younes fled back in early July with only the clothes on his back. Residents have been virtually banned from returning to his neighborhood on the outskirts of the Old City, but Ahmed said he got special permission, in order to retrieve some personal items.

AHMED YOUNES, Local Resident (through interpreter): We came on our own. We got permission to come, but they are not responsible if anything happens to us.

MARCIA BIGGS: Right now, there is no plan to begin clearing the Old City or even to determine how many mines there are. It is still out of bounds to anyone but the Iraqi security forces.

So the Janus team is focusing on progress in the rest of the city, building by building, bomb by bomb.

CHRISTIAN: Whoever made this device had a set goal. And to allow him to win, people get hurt. So you kind of compete against him to be better than him to take it out before it can do any harm.

MARCIA BIGGS: So, you feel like you’re winning the battle against ISIS?

CHRISTIAN: Yes, one IED at a time.

MARCIA BIGGS: For the PBS NewsHour, I’m Marcia Biggs in Mosul, Iraq.

HARI SREENIVASAN: Tune in later.

Frontline’s latest film, “Mosul,” was on the ground filming the fight as it unfolded street by street and house by house. That’s tonight on PBS.

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HUNDREDS of travellers’ holiday plans are in disarray after all Tigerair flights in and out of Bali were cancelled again today and early tomorrow.