Inherent mosaicism and extensive mutation of human placentas.

Placentas can exhibit chromosomal aberrations that are absent from the fetus1. The basis of this genetic segregation, which is known as confined placental mosaicism, remains unknown. Here we investigated the phylogeny of human placental cells as reconstructed from somatic mutations, using whole-genome sequencing of 86 bulk placental samples (with a median weight of 28 mg) and of 106 microdissections of placental tissue. We found that every bulk placental sample represents a clonal expansion that is genetically distinct, and exhibits a genomic landscape akin to that of childhood cancer in terms of mutation burden and mutational imprints. To our knowledge, unlike any other healthy human tissue studied so far, the placental genomes often contained changes in copy number. We reconstructed phylogenetic relationships between tissues from the same pregnancy, which revealed that developmental bottlenecks genetically isolate placental tissues by separating trophectodermal lineages from lineages derived from the inner cell mass. Notably, there were some cases with full segregation-within a few cell divisions of the zygote-of placental lineages and lineages derived from the inner cell mass. Such early embryonic bottlenecks may enable the normalization of zygotic aneuploidy. We observed direct evidence for this in a case of mosaic trisomic rescue. Our findings reveal extensive mutagenesis in placental tissues and suggest that mosaicism is a typical feature of placental development.

Spatial and molecular profiling of the mononuclear phagocyte network in classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate, which is an intrinsic component of the neoplastic process. Malignant Hodgkin Reed-Sternberg cells (HRSCs) create an immunosuppressive microenvironment by the expression of regulatory molecules, preventing T-cell activation. It has also been demonstrated that mononuclear phagocytes (MNPs) in the vicinity of HRSCs express similar regulatory mechanisms in parallel, and their presence in tissue is associated with inferior patient outcomes. MNPs in cHL have hitherto been identified by a small number of canonical markers and are usually described as tumor-associated macrophages. The organization of MNP networks and interactions with HRSCs remains unexplored at high resolution. Here, we defined the global immune-cell composition of cHL and nonlymphoma lymph nodes, integrating data across single-cell RNA sequencing, spatial transcriptomics, and multiplexed immunofluorescence. We observed that MNPs comprise multiple subsets of monocytes, macrophages, and dendritic cells (DCs). Classical monocytes, macrophages and conventional DC2s were enriched in the vicinity of HRSCs, but plasmacytoid DCs and activated DCs were excluded. Unexpectedly, cDCs and monocytes expressed immunoregulatory checkpoints PD-L1, TIM-3, and the tryptophan-catabolizing protein IDO, at the same level as macrophages. Expression of these molecules increased with age. We also found that classical monocytes are important signaling hubs, potentially controlling the retention of cDC2 and ThExh via CCR1-, CCR4-, CCR5-, and CXCR3-dependent signaling. Enrichment of the cDC2-monocyte-macrophage network in diagnostic biopsies is associated with early treatment failure. These results reveal unanticipated complexity and spatial polarization within the MNP compartment, further demonstrating their potential roles in immune evasion by cHL.

Decoding human fetal liver haematopoiesis.

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.

Nunavimmi puvakkut kaggutimik aanniaqarniq: Qanuilirqitaa? Lung cancer in Nunavik: How are we doing? A retrospective matched cohort study.

BACKGROUND: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively. METHODS: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik (n = 71) and 720 (95% CI 536-1208) days for Montréal residents (n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik (n = 24) and 270 (95% CI 194-766) days for Montréal residents (n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41). INTERPRETATION: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents.

Intra-tumour diversification in colorectal cancer at the single-cell level.

Every cancer originates from a single cell. During expansion of the neoplastic cell population, individual cells acquire genetic and phenotypic differences from each other. Here, to investigate the nature and extent of intra-tumour diversification, we characterized organoids derived from multiple single cells from three colorectal cancers as well as from adjacent normal intestinal crypts. Colorectal cancer cells showed extensive mutational diversification and carried several times more somatic mutations than normal colorectal cells. Most mutations were acquired during the final dominant clonal expansion of the cancer and resulted from mutational processes that are absent from normal colorectal cells. Intra-tumour diversification of DNA methylation and transcriptome states also occurred; these alterations were cell-autonomous, stable, and followed the phylogenetic tree of each cancer. There were marked differences in responses to anticancer drugs between even closely related cells of the same tumour. The results indicate that colorectal cancer cells experience substantial increases in somatic mutation rate compared to normal colorectal cells, and that genetic diversification of each cancer is accompanied by pervasive, stable and inherited differences in the biological states of individual cancer cells.

A Longitudinal Investigation of Lower-Risk Gambling Limits in the Canadian National Study.

Recent years have seen increased attention given to identifying and describing the levels of gambling participation that confer a risk of harm in order to generate public health advice regarding lower-risk gambling. However, most of the existing literature has failed to explicitly assess these limits in a prospective manner. The purpose of this study is to employ a methodology consistent with prior investigations to evaluate the level of gambling participation associated with an increased risk of future gambling-related harm. Using data from the Alberta Gambling Research Institute's National Project Online Panel Survey, risk ratios and Receiver Operating Characteristic (ROC) analyses were used to determine the relative risk of gambling-related harm associated with participating in a greater number of gambling formats, gambling more days per month, and spending a greater proportion of income gambling. Prospective lower-risk limits were largely consistent with those identified in previous cross-sectional analyses (e.g., no more than two gambling formats, no more than once a week), with the exception that higher limits were found for the percent of household income spent gambling (3.4-6.4% vs. 1%). We advise that future research on lower-risk gambling limits consider the use of more granular assessment instruments and prospective methods to more closely evaluate the association between gambling participation and gambling harm.

Heterozygous p.Y955C mutation in DNA polymerase γ leads to alterations in bioenergetics, complex I subunit expression, and mtDNA replication.

In human cells, ATP is generated using oxidative phosphorylation machinery, which is inoperable without proteins encoded by mitochondrial DNA (mtDNA). The DNA polymerase gamma (Polγ) repairs and replicates the multicopy mtDNA genome in concert with additional factors. The Polγ catalytic subunit is encoded by the POLG gene, and mutations in this gene cause mtDNA genome instability and disease. Barriers to studying the molecular effects of disease mutations include scarcity of patient samples and a lack of available mutant models; therefore, we developed a human SJCRH30 myoblast cell line model with the most common autosomal dominant POLG mutation, c.2864A>G/p.Y955C, as individuals with this mutation can present with progressive skeletal muscle weakness. Using on-target sequencing, we detected a 50% conversion frequency of the mutation, confirming heterozygous Y955C substitution. We found mutated cells grew slowly in a glucose-containing medium and had reduced mitochondrial bioenergetics compared with the parental cell line. Furthermore, growing Y955C cells in a galactose-containing medium to obligate mitochondrial function enhanced these bioenergetic deficits. Also, we show complex I NDUFB8 and ND3 protein levels were decreased in the mutant cell line, and the maintenance of mtDNA was severely impaired (i.e., lower copy number, fewer nucleoids, and an accumulation of Y955C-specific replication intermediates). Finally, we show the mutant cells have increased sensitivity to the mitochondrial toxicant 2'-3'-dideoxycytidine. We expect this POLG Y955C cell line to be a robust system to identify new mitochondrial toxicants and therapeutics to treat mitochondrial dysfunction.

Top advances of the year: Genitourinary cancer.

There have been significant advances in the treatment of urology cancers, with a number of practice-changing treatments. There is now greater clarity on the role of the use of immunotherapies in renal cell carcinoma. The use of triplet combinations with immune checkpoint inhibition with anti-vascular endothelial growth factor tyrosine kinase inhibitors in the front-line setting for metastatic disease (COSMIC313) has been explored. The use of adjuvant therapy has been complicated by a series of negative immune therapy trials. Promising results with the HIF-2α transcription factor inhibitor, belzutifan, alone or in combination with other agents, have been reported. Antibody drug conjugates, including enfortumab vedotin and sacituzumab govitecan, have continued to show activity in urothelial cancer with promising clinical outcomes. This has led to further exploration of the combination of these novel agents with immunotherapy and accelerated Food and Drug Administration approvals. Data are also discussed regarding intensification for front-line therapy of metastatic castrate sensitive prostate cancer. The combination of androgen-signaling inhibitors, docetaxel, and androgen deprivation therapy (PEACE-1, ARASENS), as well as the use of abiraterone acetate for adjuvant therapy in high-risk disease (STAMPEDE), is included. There is also growing evidence for the use of the radioligand therapy 177 Lu-PSMA-617 in metastatic castrate resistant disease, with an established overall survival benefit in this patient population (VISION, TheraP). PLAIN LANGUAGE SUMMARY: There have been many advancements in the treatment of cancers of the kidney, bladder, and prostate in the past year. Several studies using new therapies or new combinations of therapies have improved the chances of patients living longer with these cancers, especially those with advanced disease. Here, we discuss a selection of the most compelling recently published data that have changed the way these cancers are treated, as well as those that are expected to change treatment in the near future.

Poleward shifts and altered periodicity in boreal bird irruptions over six decades.

Range boundaries are long-term biogeographic features of species distributions and abundance. However, many species demonstrate dynamic range boundaries, reflecting strong seasonal and annual variability in migratory behaviour. As a form of facultative migration, irruptions involve the movement of many individuals outside of their resident range in response to climate variability, resource availability, and demographic processes. Many species have experienced range shifts and altered phenology in response to modern climate change, but spatiotemporal changes in irruption dynamics are less well known. We quantified changes in the geography and periodicity of boreal bird irruptions across eastern North America from 1960 to 2021. Using data from Audubon's Christmas Bird Count for nine finch species, including several exhibiting recent population declines, we evaluated latitudinal trends in southern range and irruption boundaries and characterized irruption periodicity using spectral wavelet analysis. Six boreal birds exhibited significant northward shifts in their southern range boundaries and three species displayed shifts in their southern irruption boundaries. Irruption periodicity across multiple species was consistent across the 1960s and 1970s, culminating in frequent and synchronized irruptions of multiple species (superflights) during earlier decades. Coherence between species dampened beginning in the early 1980s as superflight periodicity became increasingly unstructured, finally reforming in recent decades, after 2000. Boreal birds are considered important sentinels of the boreal forests, and northward shifts and altered periodicity of irruptions may indicate broad-scale changes in climate- and resource-associated drivers operating across the boreal forests.

The pathophysiology of bilateral and multifocal Wilms tumors: What we can learn from the study of predisposition syndromes.

Approximately 5% of patients with Wilms tumor present with synchronous bilateral disease. The development of synchronous bilateral Wilms tumor (BWT) is highly suggestive of a genetic or epigenetic predisposition. Patients with known germline predisposition to Wilms tumor (WT1 variants, Beckwith Wiedemann spectrum, TRIM28 variants) have a higher incidence of BWT. This Children's Oncology Group (COG)-International Society for Pediatric Oncology (SIOP-) HARMONICA initiative review for pediatric renal tumors details germline genetic and epigenetic predisposition to BWT development, with an emphasis on alterations in 11p15.5 (ICR1 gain of methylation, paternal uniparental disomy, and postzygotic somatic mosaicism), WT1, TRIM28, and REST. Molecular mechanisms that result in BWT are often also present in multifocal Wilms tumor (multiple separate tumors in one or both kidneys). We identify priority areas for international collaborative research to better understand how predisposing genetic or epigenetic factors associate with response to neoadjuvant chemotherapy, oncologic outcomes, and long-term renal function outcomes.

Occipital Nocardia Abscess Presenting With Positive Visual Phenomenon and Quadrantanopsia.

ABSTRACT: A 74-year-old man with chronic obstructive pulmonary disease, glaucoma, and Stage IIIB squamous cell lung cancer experienced several minutes of flashing lights in his right visual hemifield, followed by onset of a right visual field defect. On examination, the patient had a right homonymous hemianopsia that was most dense inferiorly by confrontation testing. Emergent CT scan of the head revealed a 2.5 × 3 cm hypodensity in the left occipital lobe, which was interpreted as an acute stroke. Continuous EEG monitoring captured left posterior quadrant seizures that were temporally correlated to the positive visual phenomena. Subsequent MRI of the brain with and without contrast revealed a conglomerate of centrally necrotic and peripherally enhancing mass lesions. On biopsy, a thick purulent material was drained and Gram stain of the sample revealed gram-positive beaded rods, which speciated to Nocardia farcinica . The patient was treated with a six-week course of intravenous meropenem and a one-year course of oral trimethroprim-sulfamethoxazole. On follow-up, the patient experienced resolution of the right visual field deficit.

A systematic review of anterior lumbar interbody fusion (ALIF) versus posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), posterolateral lumbar fusion (PLF).

PURPOSE: The rate of elective lumbar fusion has continued to increase over the past two decades. However, there remains to be a consensus on the optimal fusion technique. This study aims to compare stand-alone anterior lumbar interbody fusion (ALIF) with posterior fusion techniques in patients with spondylolisthesis and degenerative disc disease through a systematic review and meta-analysis of the available literature. METHODS: A systematic review was performed by searching the Cochrane Register of Trials, MEDLINE, and EMBASE from inception to 2022. In the two-stage screening process, three reviewers independently reviewed titles and abstracts. The full-text reports of the remaining studies were then inspected for eligibility. Conflicts were resolved through consensus discussion. Two reviewers then extracted study data, assessed it for quality, and analysed it. RESULTS: After the initial search and removal of duplicate records, 16,435 studies were screened. Twenty-one eligible studies (3686 patients) were ultimately included, which compared stand-alone ALIF with posterior approaches such as posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), and posterolateral lumbar fusion (PLF). A meta-analysis showed surgical time and blood loss was significantly lower in ALIF than in TLIF/PLIF, but not in those who underwent PLF (p = 0.08). The length of hospital stay was significantly shorter in ALIF than in TLIF, but not in PLIF or PLF. Fusion rates were similar between the ALIF and posterior approaches. The Visual Analogue Scale (VAS) scores for back and leg pain were not significantly different between the ALIF and PLIF/TLIF groups. However, VAS back pain favoured ALIF over PLF at one year (n = 21, MD - 1.00, CI - 1.47, - 0.53), and at two years (2 studies, n = 67, MD - 1.39, CI - 1.67, - 1.11). The VAS leg pain scores (n = 46, MD 0.50, CI 0.12 to 0.88) at two years significantly favoured PLF. The Oswestry Disability Index (ODI) scores at one year were not significantly different between ALIF and the posterior approaches. At two years, ODI scores were also similar between the ALIF and the TLIF/PLIF. However, the ODI scores at two years (2 studies, n = 67, MD - 7.59, CI - 13.33, - 1.85) significantly favoured ALIF over PLF (I2 = 70%). The Japanese Orthopaedic Association Score (JOAS) for low back pain at one year (n = 21, MD - 0.50, CI - 0.78) and two years (two studies, n = 67, MD - 0.36, CI - 0.65, - 0.07) significantly favoured ALIF over PLF. No significant differences were found in leg pain at the 2-year follow-up. Adverse events displayed no significant differences between the ALIF and posterior approaches. CONCLUSIONS: Stand-alone-ALIF demonstrated a shorter operative time and less blood loss than the PLIF/TLIF approach. Hospitalisation time is reduced with ALIF compared with TLIF. Patient-reported outcome measures were equivocal with PLIF or TLIF. VAS and JOAS, back pain, and ODI scores mainly favoured ALIF over PLF. Adverse events were equivocal between the ALIF and posterior fusion approaches.

Automating Detection of Drug-Related Harms on Social Media: Machine Learning Framework.

BACKGROUND: A hallmark of unregulated drug markets is their unpredictability and constant evolution with newly introduced substances. People who use drugs and the public health workforce are often unaware of the appearance of new drugs on the unregulated market and their type, safe dosage, and potential adverse effects. This increases risks to people who use drugs, including the risk of unknown consumption and unintentional drug poisoning. Early warning systems (EWSs) can help monitor the landscape of emerging drugs in a given community by collecting and tracking up-to-date information and determining trends. However, there are currently few ways to systematically monitor the appearance and harms of new drugs on the unregulated market in Canada. OBJECTIVE: The goal of this work is to examine how artificial intelligence can assist in identifying patterns of drug-related risks and harms, by monitoring the social media activity of public health and law enforcement groups. This information is beneficial in the form of an EWS as it can be used to identify new and emerging drug trends in various communities. METHODS: To collect data for this study, 145 relevant Twitter accounts throughout Quebec (n=33), Ontario (n=78), and British Columbia (n=34) were manually identified. Tweets posted between August 23 and December 21, 2021, were collected via the application programming interface developed by Twitter for a total of 40,393 tweets. Next, subject matter experts (1) developed keyword filters that reduced the data set to 3746 tweets and (2) manually identified relevant tweets for monitoring and early warning efforts for a total of 464 tweets. Using this information, a zero-shot classifier was applied to tweets from step 1 with a set of keep (drug arrest, drug discovery, and drug report) and not-keep (drug addiction support, public safety report, and others) labels to see how accurately it could extract the tweets identified in step 2. RESULTS: When looking at the accuracy in identifying relevant posts, the system extracted a total of 584 tweets and had an overlap of 392 out of 477 (specificity of ~84.5%) with the subject matter experts. Conversely, the system identified a total of 3162 irrelevant tweets and had an overlap of 3090 (sensitivity of ~94.1%) with the subject matter experts. CONCLUSIONS: This study demonstrates the benefits of using artificial intelligence to assist in finding relevant tweets for an EWS. The results showed that it can be quite accurate in filtering out irrelevant information, which greatly reduces the amount of manual work required. Although the accuracy in retaining relevant information was observed to be lower, an analysis showed that the label definitions can impact the results significantly and would therefore be suitable for future work to refine. Nonetheless, the performance is promising and demonstrates the usefulness of artificial intelligence in this domain.

The antiretroviral 2',3'-dideoxycytidine causes mitochondrial dysfunction in proliferating and differentiated HepaRG human cell cultures.

Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs used to treat human immunodeficiency virus infection, and their use can cause mitochondrial toxicity, including mitochondrial DNA (mtDNA) depletion in several cases. The first-generation NRTIs, including 2',3'-dideoxycytidine (ddC), were originally and are still pursued as anticancer agents. NRTI-sensitive DNA polymerases localizing to mitochondria allow for the opportunity to poison proliferating cancer cell mtDNA replication as certain cancers rely heavily on mitochondrial functions. However, mtDNA replication is independent of the cell cycle creating a significant concern that toxicants such as ddC impair mtDNA maintenance in both proliferating and nonproliferating cells. To examine this possibility, we tested the utility of the HepaRG cell line to study ddC-induced toxicity in isogenic proliferating (undifferentiated) and nonproliferating (differentiated) cells. Following ddC exposures, we measured cell viability, mtDNA copy number, and mitochondrial bioenergetics utilizing trypan blue, Southern blotting, and extracellular flux analysis, respectively. After 13 days of 1 µM ddC exposure, proliferating and differentiated HepaRG harbored mtDNA levels of 0.9% and 17.9% compared with control cells, respectively. Cells exposed to 12 µM ddC contained even less mtDNA. By day 13, differentiated cell viability was maintained but declined for proliferating cells. Proliferating HepaRG bioenergetic parameters were severely impaired by day 8, with 1 and 12 µM ddC, whereas differentiated cells displayed defects of spare and maximal respiratory capacities (day 8) and proton-leak linked respiration (day 14) with 12 µM ddC. These results indicate HepaRG is a useful model to study proliferating and differentiated cell mitochondrial toxicant exposures.

Case 299: Sellar Spine.

History Part one of this case appeared 4 months previously and may contain larger images. A 32-year-old woman presented to an ophthalmologist for bilateral blurry vision. She underwent MRI of the brain and orbits, which showed a focal abnormality within the pituitary gland. The patient was referred to an endocrinologist for further evaluation. Review of systems and physical examination by the endocrinologist revealed no symptoms or signs of endocrine dysfunction. Anterior pituitary hormone levels, including growth hormone, prolactin, thyroid stimulating hormone, follicular-stimulating hormone, luteinizing hormone, and adrenocorticotropic hormone, were normal. Dynamic contrast-enhanced MRI of the sella and pituitary gland and subsequent CT of the anterior skull base were performed.

Central Retinal Artery Visualization with Cone-Beam CT Angiography.

Background There are multiple tools available to visualize the retinal and choroidal vasculature of the posterior globe. However, there are currently no reliable in vivo imaging techniques that can visualize the entire retrobulbar course of the retinal and ciliary vessels. Purpose To identify and characterize the central retinal artery (CRA) using cone-beam CT (CBCT) images obtained as part of diagnostic cerebral angiography. Materials and Methods In this retrospective study, patients with catheter DSA performed between October 2019 and October 2020 were included if CBCT angiography included the orbit in the field of view. The CBCT angiography data sets were postprocessed with a small field-of-view volume centered in the posterior globe to a maximum resolution of 0.2 mm. The following were evaluated: CRA origin, CRA course, CRA point of penetration into the optic nerve sheath, bifurcation of the CRA at the papilla, visualization of anatomic variants, and visualization of the central retinal vein. Descriptive statistical analysis was performed. Results Twenty-one patients with 24 visualized orbits were included in the analysis (mean age, 55 years ± 15; 14 women). Indications for angiography were as follows: diagnostic angiography (n = 8), aneurysm treatment (n = 6), or other (n = 7). The CRA was identified in all orbits; the origin, course, point of penetration of the CRA into the optic nerve sheath, and termination in the papilla were visualized in all orbits. The average length of the intraneural segment was 10.6 mm (range, 7-18 mm). The central retinal vein was identified in six of 24 orbits. Conclusion Cone-beam CT, performed during diagnostic angiography, consistently demonstrated the in vivo central retinal artery, demonstrating excellent potential for multiple diagnostic and therapeutic applications. © RSNA, 2021 Online supplemental material is available for this article.

Acute extracorporeal shockwave lithotripsy for ureteric stones - 7-years' experience from a busy district general hospital.

OBJECTIVES: To demonstrate the efficacy and cost-effectiveness of acute extracorporeal shockwave lithotripsy (ESWL) for ureteric stones we present our experience of ESWL in 530 ureteric stone cases, in the largest UK series we are aware of to date. ESWL is underutilised in ureteric stone management. The Getting It Right First Time (GIRFT) report showed just four units nationally treated >10% of acute ureteric stones with ESWL. Despite guideline recommendations as a first-line treatment option, few large volume studies have been published. PATIENTS AND METHODS: Retrospective review of prospectively collected data between December 2012 and February 2020 was performed. Data relating to patient demographics, stone characteristics, skin-to-stone distance, and treatment failure were collected. Cost analysis was conducted by the Trust's surgical financial manager. Multivariable analyses were performed to assess for predictors of ESWL success. RESULTS: A success rate of 68% (95% confidence interval 64%-72%) at 6 weeks was observed (n = 530). The median (interquartile range) number of treatment sessions was 2 (1, 2). Stone diameter was observed to be a predictor of ESWL success. The small number of stones treated of >13 mm or >1250 HU had an ~50% chance of successful treatment. Acute ureteric ESWL was less costly than acute ureterorenoscopy, consistent with findings from previous NHS studies. CONCLUSION: Acute ESWL is a safe, reliable, and financially viable treatment option for a wider spectrum of patients than reflected in international guidelines based on our large, heterogenous series. In the coronavirus disease 2019 (COVID-19) era, with theatre access reduced and concerns over aerosol generating procedures, acute ESWL remains an attractive first-line treatment option.

Exploring associations between social determinants of health and mental health outcomes in families from socioeconomically and racially and ethnically diverse households.

This cross-sectional study investigated the associations between Social Determinants of Health (SDOH) and mental health outcomes of parents and children (n = 1307) from the Latinx, Native American, Somali/Ethiopian, White, Hmong, and African American communities. Logistic regression models were used to estimate the adjusted associations between five parent and child mental health measures and 25 measures of SDOH. False discovery rate q-values were computed to account for multiple comparisons. Families of color reported 5.3-7.8 SDOH barriers while White families reported 1.7 SDOH barriers on average. Adjusted analyses indicated that low family functioning and high perceived discrimination were associated with low resiliency among parents and increased behavioral difficulties among children. Other SDOH that were adversely associated with parent or child mental health included lack of social support, recent stressful life events, and adverse childhood experiences among parents. SDOH in the social and community context were most likely to be associated with mental health problems. Community-engaged evidence-based interventions are needed to improve population mental health.

Video Radiology Reports: A Valuable Tool to Improve Patient-Centered Radiology.

BACKGROUND. Improved communication between radiologists and patients is a key component of patient-centered radiology. OBJECTIVE. The purpose of this study was to create patient-centered video radiology reports using simple-to-understand language and annotated images and to assess the effect of these reports on patients' experience and understanding of their imaging results. METHODS. During a 4-month study period, faculty radiologists created video radiology reports using a tool integrated within the diagnostic viewer that allows both image and voice capture. To aid patients' understanding of cross-sectional images, cinematically rendered images were automatically created and made immediately available to radiologists at the workstation, allowing their incorporation into video radiology reports. Video radiology reports were made available to patients via the institutional health portal along with the written radiology report and the examination images. Patient views of the video report were recorded, and descriptive analyses were performed on radiologist and examination characteristics as well as patient demographics. A survey was sent to patients to obtain feedback on their experience. RESULTS. During the study period, 105 of 227 faculty radiologists created 3763 video radiology reports (mean number of reports per radiologist, 36 ± 27 [SD] reports). Mean time to create a video report was 238 ± 141 seconds. Patients viewed 864 unique video reports. The mean overall video radiology report experience rating based on 101 patient surveys was 4.7 of 5. The mean rating for how well the video report helped patients understand their findings was also 4.7 of 5. Of the patients who responded to the survey, 91% preferred having both written and video reports together over having written reports alone. CONCLUSION. Patient-centered video radiology reports are a useful tool to help improve patient understanding of imaging results. The mechanism of creating the video reports and delivering them to patients can be integrated into existing informatics infrastructure. CLINICAL IMPACT. Video radiology reports can play an important role in patient-centered radiology, increasing patient understanding of imaging results, and they may improve the visibility of radiologists to patients and highlight the radiologist's important role in patient care.