Epithelial Nlrp10 inflammasome mediates protection against intestinal autoinflammation.

Unlike other nucleotide oligomerization domain-like receptors, Nlrp10 lacks a canonical leucine-rich repeat domain, suggesting that it is incapable of signal sensing and inflammasome formation. Here we show that mouse Nlrp10 is expressed in distal colonic intestinal epithelial cells (IECs) and modulated by the intestinal microbiome. In vitro, Nlrp10 forms an Apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)-dependent, m-3M3FBS-activated, polyinosinic:polycytidylic acid-modulated inflammasome driving interleukin-1ß and interleukin-18 secretion. In vivo, Nlrp10 signaling is dispensable during steady state but becomes functional during autoinflammation in antagonizing mucosal damage. Importantly, whole-body or conditional IEC Nlrp10 depletion leads to reduced IEC caspase-1 activation, coupled with enhanced susceptibility to dextran sodium sulfate-induced colitis, mediated by altered inflammatory and healing programs. Collectively, understanding Nlrp10 inflammasome-dependent and independent activity, regulation and possible human relevance might facilitate the development of new innate immune anti-inflammatory interventions.

Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes.

People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. 1), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.

Hepatocellular carcinoma after direct-acting antivirals for hepatitis C is associated with KIR-HLA types predicting weak NK cell-mediated immunity.

BACKGROUND AND AIMS: Second-generation direct-acting antivirals (2G DAA) to cure HCV have led to dramatic clinical improvements. HCV-associated hepatocellular carcinoma (HCC), however, remains common. Impaired immune tumor surveillance may play a role in HCC development. Our cohort evaluated the effects of innate immune types and clinical variables on outcomes including HCC. METHODS: Participants underwent full HLA class I/KIR typing and long-term HCV follow-up. RESULTS: A total of 353 HCV+ participants were followed for a mean of 7 years. Cirrhosis: 25% at baseline, developed in 12% during follow-up. 158 participants received 2G DAA therapy. HCC developed without HCV therapy in 20 subjects, 24 HCC after HCV therapy, and 10 of these after 2G DAA. Two predictors of HCC among 2G DAA-treated patients: cirrhosis (OR, 10.0, p = 0.002) and HLA/KIR profiles predicting weak natural killer (NK) cell-mediated immunity (NK cell complementation groups 6, 9, 11, 12, OR of 5.1, p = 0.02). Without 2G DAA therapy: cirrhosis was the main clinical predictor of HCC (OR, 30.8, p < 0.0001), and weak NK-cell-mediated immunity did not predict HCC. CONCLUSION: Cirrhosis is the main risk state predisposing to HCC, but weak NK-cell-mediated immunity may predispose to post-2G DAA HCC more than intermediate or strong NK-cell-mediated immunity.

Artificial Intelligence for Real-Time Prediction of the Histology of Colorectal Polyps by General Endoscopists.

BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.

The role of urology and radiology in prostate biopsy: current trends and future perspectives.

PURPOSE: Prostate biopsy is central to the accurate histological diagnosis of prostate cancer. In current practice, the biopsy procedure can be performed using a transrectal or transperineal route with different technologies available for targeting of lesions within the prostate. Historically, the biopsy procedure was performed solely by urologists, but with the advent of image-guided techniques, the involvement of radiologists in prostate biopsy has become more common. Herein, we discuss the pros, cons and future considerations regarding their ongoing role. METHODS: A narrative review regarding the current evidence was completed. PubMed and Cochrane central register of controlled trials were search until January 2024. All study types were of consideration if published after 2000 and an English language translation was available. RESULTS: There are no published studies that directly compare outcomes of prostate biopsy when performed by a urologist or radiologist. In all published studies regarding the learning curve for prostate biopsy, the procedure was performed by urologists. These studies suggest that the learning curve for prostate biopsy is between 10 and 50 cases to reach proficiency in terms of prostate cancer detection and complications. It is recognised that many urologists are poorly able to accurately interpret multi parametric (mp)-MRI of the prostate. Collaboration between the specialities is of importance with urology offering the advantage of being involved in prior and future care of the patient while radiology has the advantage of being able to expertly interpret preprocedure MRI. CONCLUSION: There is no evidence to suggest that prostate biopsy should be solely performed by a specific specialty. The most important factor remains knowledge of the relevant anatomy and sufficient volume of cases to develop and maintain skills.

The Impact of Additive Population(s), Intervention, Comparator(s), and Outcomes in a European Joint Clinical Health Technology Assessment.

OBJECTIVES: To assess the potential number of European Union (EU) population(s), intervention, comparator(s), and outcomes (PICOs) based on European Network for Health Technology Assessment 21 (EUnetHTA 21) guidance and to explore further evidence-based opportunities to produce more predictable and workable EU PICOs. METHODS: The consolidated EU PICOs of 2 future hypothetical medicines in first-line non-small cell lung cancer (1L NSCLC) and third line multiple myeloma (3L MM) were derived using published health technology assessment reports of 2 recent medicines in similar indications based on EUnetHTA 21 proposed guidance. Sensitivity analysis assessed the impact of additional PICO requests. The number of analyses requested was estimated. RESULTS: In 1L NSCLC and 3L MM, 6 and 9 EU Member States (MS), respectively, had published health technology assessment reports. PICO consolidation resulted in 10 PICOs for 1L NSCLC and 16 PICOs for 3L MM, increasing to 14 and 18 PICOs, respectively, when England's National Institute for Health and Care Excellence scope was included to proxy remaining MS. A minimum of 280 and 720 analyses would be requested, exponentially increasing as additional outcome measures and subgroups are requested. CONCLUSIONS: The PICO approach outlined by EUnetHTA 21 results in a significant number of analysis requests and substantial resources. Use of complementary analyses alongside evidence-based methods to derive PICOs and engaging with the health technology developer throughout the process would create a workable EU PICO that is predictable and most impactful for the EU, resulting in a timely and high-quality assessment report that is more usable at a MS level.

Evaluation of the EMA log kow trigger for fish BCF testing based on data for several human pharmaceuticals.

In the European Medicines Agency (EMA) "Guideline for Environmental Risk Assessment of Medicinal Products for Human Use," a fish bioconcentration factor (BCF) study is triggered in Phase I for pharmaceuticals having log Kow >4.5, to support Persistence, Bioaccumulation and Toxicity (PBT) screening, and in Phase II to assess secondary poisoning and bioaccumulation ('B') potential when log Kow ≥3. The standard sampling schedule outlined in OECD Test Guideline 305 (TG305) may require assessment of approximately 200 fish following exposure to low- and high-test concentrations and a negative control. We report experimental log Kow and BCF values for 64 human pharmaceuticals that were used to evaluate the current BCF testing trigger of log Kow ≥3, and whether a single BCF exposure concentration allows accurate classification of bioaccumulation potential. Our data support raising the BCF testing trigger to log Kow ≥4, and use of a single test concentration. The resulting reduction in the use of fish is consistent with the 3 R s principle and did not adversely affect classification accuracy. An assessment of potential risk of secondary poisoning was also conducted for three drugs classified as either B or vB, and no risks were identified.

Including isolated aphasia improves sensitivity and negative predicative value for large vessel occlusion screening.

BACKGROUND: Large Vessel Occlusion (LVO) screening tools provide objective assessments to guide diagnostic decisions during acute stroke activations. The Stroke VAN screening tool includes weakness, vision, aphasia, and neglect; however, only screens positive if weakness is present regardless of presence of other symptoms including isolated aphasia. The purpose of this project was to evaluate wAve, a modified Stroke VAN screening tool. WAve includes components of VAN with emphasis on isolated aphasia. METHODS: We conducted a retrospective cohort study on 376 persons who presented with stroke symptoms within 24 h of last known well (LKW) to the Emergency Department of an urban comprehensive stroke center in north central Texas between July 2019 and January 2020. Comparison of VAN and wAve predictive values was calculated using Chi square analysis. Sensitivity and specificity was checked by using MedCalc software. Data from the electronic medical record was obtained for analysis including a documented wAve score and a calculated VAN score. Results of CT angiogram diagnostic testing was used to determine congruence of screening results with evidence of LVO. Power analysis described by Hajian- Tilaki was used to estimate study size. RESULTS: Results included 192 positive wAve screens and 184 negative wAve screens compared to 152 positive VAN screens and 224 negative VAN screens. The sensitivities for wAve and VAN were 89 % and 80 % respectively. Negative predictive values for wAve and VAN were 97 % and 95 % respectively. In isolated aphasic person, one of eight presented with a LVO and received intervention. CONCLUSION: The team discovered more LVOs were identified with wAve than VAN in persons exhibiting isolated aphasia symptoms. Larger studies are needed to understand the role isolated aphasia plays in LVO detection.

A Prospective Multi-institutional Study Using a Novel Safety Valve for the Prevention of Catheter Balloon Inflation Injury of the Urethra.

PURPOSE: We prospectively assessed the ability of a novel transurethral catheterization safety valve to prevent urethral catheter balloon injury in a multi-institutional clinical setting. MATERIALS AND METHODS: A prospective, multi-institution study was conducted. The safety valve was introduced for urinary catheterization in 6 hospital groups (4 in Ireland; 2 in the UK). The safety valve allows fluid in the catheter system to vent through a pressure relief valve if attempted intraurethral inflation of the catheter's anchoring balloon occurs. Device usage was studied over a 12-month period, with data recorded using a 7-item data sticker containing a scannable QR code. "Venting" through the safety valve during catheterization was indicative of prevention of a urethral injury. An embedded 3-month study was conducted in 3 centers, with any catheter balloon injuries occurring during catheterization without safety valve use referred to the on-call urology team recorded. Health economic analyses were also performed. RESULTS: During the overall 12-month device study phase, 994 urethral catheterizations were performed across study sites. Twenty-two (2.2%) episodes of safety valve venting were recorded. No urethral injuries occurred in these patients. In the embedded 3-month study, 18 catheter balloon injuries were recorded in association with catheterizations performed without the safety valve. Based on confirmed and device-prevented urethral injuries, the injury rate for urethral catheterization without safety valve use was calculated to be 5.5/1,000 catheterizations. CONCLUSIONS: The safety valve has the potential to eliminate catheter balloon injury if widely adopted. It represents a simple, effective, and innovative solution to this recurring problem applicable to all patient cohorts.

Coral adaptive capacity insufficient to halt global transition of coral reefs into net erosion under climate change.

Projecting the effects of climate change on net reef calcium carbonate production is critical to understanding the future impacts on ecosystem function, but prior estimates have not included corals' natural adaptive capacity to such change. Here we estimate how the ability of symbionts to evolve tolerance to heat stress, or for coral hosts to shuffle to favourable symbionts, and their combination, may influence responses to the combined impacts of ocean warming and acidification under three representative concentration pathway (RCP) emissions scenarios (RCP2.6, RCP4.5 and RCP8.5). We show that symbiont evolution and shuffling, both individually and when combined, favours persistent positive net reef calcium carbonate production. However, our projections of future net calcium carbonate production (NCCP) under climate change vary both spatially and by RCP. For example, 19%-35% of modelled coral reefs are still projected to have net positive NCCP by 2050 if symbionts can evolve increased thermal tolerance, depending on the RCP. Without symbiont adaptive capacity, the number of coral reefs with positive NCCP drops to 9%-13% by 2050. Accounting for both symbiont evolution and shuffling, we project median positive NCPP of coral reefs will still occur under low greenhouse emissions (RCP2.6) in the Indian Ocean, and even under moderate emissions (RCP4.5) in the Pacific Ocean. However, adaptive capacity will be insufficient to halt the transition of coral reefs globally into erosion by 2050 under severe emissions scenarios (RCP8.5).

Inequity in smoking cessation clinical trials testing pharmacotherapies: exclusion of smokers with mental health disorders.

OBJECTIVES: People suffering from mental health disorder (MHDs) are often under-represented in clinical research though the reasons for their exclusion are rarely recorded. As they have higher rates of smoking and nicotine dependence, it is crucial that they are adequately represented in clinical trials of established pharmacotherapy interventions for smoking cessation. This review aims to examine the practice of excluding smokers with MHDs and reasons for such exclusion in clinical trials evaluating pharmacotherapy treatments for smoking cessation. DATA SOURCE: The Cochrane database of systematic reviews was searched until September 2020 for reviews on smoking cessation using pharmacotherapies. STUDY SELECTION: Randomised controlled trials (RCTs) within the selected Cochrane reviews were included. DATA EXTRACTION: Conducted by one author and independently verified by three authors. DATA SYNTHESIS: We included 279 RCTs from 13 Cochrane reviews. Of all studies, 51 (18.3%) explicitly excluded participants with any MHDs, 152 (54.5%) conditionally excluded based on certain MHD criteria and 76 (27.2%) provided insufficient information to ascertain either inclusion or exclusion. Studies of antidepressant medications used for smoking cessation were found to be 3.33 times more likely (95% CI 1.38 to 8.01, p=0.007) to conditionally exclude smokers with MHDs than explicitly exclude compared with studies of nicotine replacement therapy. CONCLUSION: Smokers with MHDs are not sufficiently represented in RCTs examining the safety and effectiveness of smoking cessation medications. Greater access to clinical trial participation needs to be facilitated for this group to better address access to appropriate pharmacotherapeutic interventions in this vulnerable population.

Growth Rates of Pulmonary Carcinoid Tumors and Hamartomas.

BACKGROUND: Pulmonary nodule growth is often measured by volume doubling time (VDT), which may guide management. Most malignant nodules have a VDT of 20 to 400 days, with longer VDTs typically observed in indolent nodules. We assessed the utility of VDT in differentiating pulmonary carcinoids and hamartomas. METHODS: A review was performed from January 2012 to October 2021 to identify patients with pathologic diagnoses and at least 2 chest computed tomography scans obtained 6 or more months apart. Visualization software was used to segment nodules and calculate diameter and volume. Volume doubling time was calculated for scans with 1-mm slices. For the remainder, estimated nodule volume doubling time (eVDT) was calculated using nodule diameter. Volume doubling times/eVDTs were placed into growth categories: less than 400 days; 400-600 days; and more than 600 days. RESULTS: Sixty nodules were identified, 35 carcinoids and 25 hamartomas. Carcinoids were larger than hamartomas (median diameter, 13.5 vs 11.5 mm; P = 0.05). For carcinoid tumors, median VDT (n = 15) was 1485 days, and median eVDT (n = 32) was 1309 days; for hamartomas, median VDT (n = 8) was 2040 days and median eVDT (n = 25) was 2253 days. Carcinoid tumor eVDT was significantly shorter than hamartomas ( P = 0.03). By growth category, 1 of 25 hamartomas and 5 of 35 carcinoids had eVDT less than 400 days and 24 of 25 hamartomas and 27 of 35 carcinoids had eVDT more than 600 days. Of 4 carcinoid tumors with metastases, 2 had eVDT less than 400 days and 2 had eVDT more than 600 days. CONCLUSIONS: Growth rate was not a reliable differentiator of pulmonary hamartomas and carcinoids. Slow growing carcinoids can metastasize. Radiologists should be cautious when discontinuing computed tomography follow-up based on growth rates alone.

Measuring the predictability of life outcomes with a scientific mass collaboration.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences.

Macrophage metabolism in the intestine is compartment specific and regulated by the microbiota.

Intestinal macrophages play a vital role in the maintenance of gut homeostasis through signals derived from the microbiota. We previously demonstrated that microbial-derived metabolites can shape the metabolic functions of macrophages. Here, we show that antibiotic-induced disruption of the intestinal microbiota dramatically alters both the local metabolite environment and the metabolic functions of macrophages in the colon. Broad-spectrum antibiotic administration in mice increased the expression of the large neutral amino acid transporter LAT1 and accordingly, amino acid uptake. Subsequently, antibiotic administration enhanced the metabolic functions of colonic macrophages, increasing phosphorylation of components of mammalian/mechanistic target of rapamycin signalling pathways, with increased expression of genes involved in glycolysis and oxidative phosphorylation (OXPHOS), increased mitochondrial function, increased rate of extracellular acidification (ECAR; measure of glycolysis) and increased rate of oxygen consumption (OCR; measure of OXPHOS). Small bowel macrophages were less metabolically active than their colonic counterparts, with macrophage metabolism in the small intestine being independent of the microbiota. Finally, we reveal tissue-resident Tim4+  CD4+ macrophages exhibit enhanced fatty acid uptake alongside reduced fatty acid synthesis compared to recruited macrophages. Thus, the microbiota shapes gut macrophage metabolism in a compartment-specific manner, with important implications for monocyte recruitment and macrophage differentiation.

Ureteroscopy with thulium fiber laser lithotripsy results in shorter operating times and large cost savings.

PURPOSE: Prolonged ureteroscopy (URS) is associated with complications including ureteral perforation, stricture, and urosepsis. As laser lithotripsy is one of the most common urologic procedures, small cost savings per case can have a large financial impact. This retrospective study was designed to determine if Thulium fiber laser (TFL) lithotripsy decreases operative time and costs compared to standard Holmium:YAG (Ho:YAG) lithotripsy without pulse modulation. METHODS: A retrospective review of URS with laser lithotripsy was conducted for 152 cases performed from August 2020 to January 2021. Variables including cumulative stone size, location, chemical composition, prior ureteral stenting, and ureteral access sheath use were recorded for each case. A cost benefit analysis was performed to show projected cost savings due to potentially decreased operative times. RESULTS: Compared to Ho:YAG, use of TFL resulted in an average decrease of 12.9 min per case (p = .021, 95% CI [2.03-23.85]). In subgroup analysis of cases with cumulative stone diameter less than 15 mm, the difference was 14.0 min (p = .007, CI [3.95-23.95]). For cases less than 10 mm, the mean difference was 17.3 min in favor of TFL (p = .002, 95% CI [6.89-27.62]). This ~ 13 min reduction in operative time resulted in saving $440/case in direct operating room costs giving our institution a range of $294,000 to $381,900 savings per year. CONCLUSIONS: TFL has a significantly shorter operative time and decreased cost when compared to the standard Ho:YAG for equivalent kidney stone and patient characteristics. Longer term follow up is needed to see if recurrence rates are affected.

Toward Realigning Automatic Speaker Verification in the Era of COVID-19.

The use of face masks has increased dramatically since the COVID-19 pandemic started in order to to curb the spread of the disease. Additionally, breakthrough infections caused by the Delta and Omicron variants have further increased the importance of wearing a face mask, even for vaccinated individuals. However, the use of face masks also induces attenuation in speech signals, and this change may impact speech processing technologies, e.g., automated speaker verification (ASV) and speech to text conversion. In this paper we examine Automatic Speaker Verification (ASV) systems against the speech samples in the presence of three different types of face mask: surgical, cloth, and filtered N95, and analyze the impact on acoustics and other factors. In addition, we explore the effect of different microphones, and distance from the microphone, and the impact of face masks when speakers use ASV systems in real-world scenarios. Our analysis shows a significant deterioration in performance when an ASV system encounters different face masks, microphones, and variable distance between the subject and microphone. To address this problem, this paper proposes a novel framework to overcome performance degradation in these scenarios by realigning the ASV system. The novelty of the proposed ASV framework is as follows: first, we propose a fused feature descriptor by concatenating the novel Ternary Deviated overlapping Patterns (TDoP), Mel Frequency Cepstral Coefficients (MFCC), and Gammatone Cepstral Coefficients (GTCC), which are used by both the ensemble learning-based ASV and anomaly detection system in the proposed ASV architecture. Second, this paper proposes an anomaly detection model for identifying vocal samples produced in the presence of face masks. Next, it presents a Peak Norm (PN) filter to approximate the signal of the speaker without a face mask in order to boost the accuracy of ASV systems. Finally, the features of filtered samples utilizing the PN filter and samples without face masks are passed to the proposed ASV to test for improved accuracy. The proposed ASV system achieved an accuracy of 0.99 and 0.92, respectively, on samples recorded without a face mask and with different face masks. Although the use of face masks affects the ASV system, the PN filtering solution overcomes this deficiency up to 4%. Similarly, when exposed to different microphones and distances, the PN approach enhanced system accuracy by up to 7% and 9%, respectively. The results demonstrate the effectiveness of the presented framework against an in-house prepared, diverse Multi Speaker Face Masks (MSFM) dataset, (IRB No. FY2021-83), consisting of samples of subjects taken with a variety of face masks and microphones, and from different distances.

Cost and healthcare utilization analysis of culturally sensitive, shared medical appointment model for Latino children with type 1 diabetes.

OBJECTIVE: This study evaluated costs and healthcare utilization associated with a culturally-sensitive, medical and education program for pediatric Latino patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Program participants included Latino children ages 1-20 years old diagnosed with type 1 diabetes (n = 57). Control subjects with type 1 diabetes were matched by age, sex, and zip code to intervention participants from the Colorado All Payer Claims Database. Data included emergency department (ED) visits, hospitalizations, demographic information, and health insurance claims data 180 days prior to program start/index date through 1 year after program start/index date. We tracked program staff time and estimated costs for healthcare utilization using data from the scientific literature. Generalized Estimating Equation (GEE) models with logit link were used to estimate group differences in probabilities of ED visits and hospitalizations over 6-month periods pre/post-study, accounting for correlation of within-subject data across time points. Sensitivity analyses modeled longer-term cost differences under different assumptions. RESULTS: The intervention group had fewer hospitalizations, 2% versus 12% of controls (p = 0.047,OR = 0.13;95%CI: 0.02-0.97) for 6 months following start date. The intervention group had fewer ED visits, 19% versus 32% in controls (n.s.; p = 0.079,OR = 0.52;95%CI:0.25-1.08) and significantly fewer hospitalizations, 4% versus 15% of controls (p = 0.039,OR = 0.21;95%CI: 0.05-0.93) 6-12 months post-start date. One-year per-patient program costs of $633 and healthcare cost savings of $2710 yielded total per-patient savings of $2077, or a 5-year cost savings of $14,106. CONCLUSION: This unique type 1 diabetes management program altered health service utilization of program participants, reducing major healthcare cost drivers, ED visits, and hospitalizations.

Natural growth pattern of sporadic renal angiomyolipoma.

BACKGROUND: Surveillance of sporadic renal angiomyolipomas is a growing issue for physicians and radiologists. Current treatment recommendations favor active surveillance. However, the evidence underlying these is based on small case series, which also typically include angiomyolipomas associated with tuberous sclerosis. PURPOSE: To evaluate the natural growth pattern of sporadic renal angiomyolipomas in patients without tuberous sclerosis. MATERIAL AND METHODS: A retrospective review was performed in three separate tertiary referral centers. A keyword search of each institutions PACS history was performed. Inclusion criteria were angiomyolipomas > 1 cm in size, three years of follow-up, and lesions requiring treatment before reaching three years of follow-up. Exclusion criteria included a diagnosis of tuberous sclerosis, pregnancy, prior treatment with embolization without any prior imaging, and lesions which were treated on presentation. Growth of the angiomyolipomas was evaluated on the basis of maximum dimension on initial and follow-up images. RESULTS: Sixty-three patients were identified in total, with 64 lesions eligible for inclusion. The majority of patients were women (55/63). The mean age at which the angiomyolipomas discovered was 56.4 years. Mean total growth was 0.085 mm and mean follow-up was 65.5 months. At initial measurement, the mean maximum dimension of the lesions in our cohort was 2.08 cm. After follow-up, this was 2.16 cm. The average rate of growth was 0.015 cm per year. CONCLUSION: Sporadic angiomyolipomas exhibit minimal, if any, natural growth. Current surveillance strategies could be relaxed.

Complications in image-guided musculoskeletal injections.

OBJECTIVE: To establish the incidence and define the nature of complications occurring following image-guided musculoskeletal injections at our institution. MATERIALS AND METHODS: All patients undergoing image-guided musculoskeletal injection during the study period (16/3/2016 to 24/01/2020) were included. Departmental records were reviewed to identify all patients describing possible complications following injection, what therapy was required (if any) and what the outcome was. No patients were excluded. Complications were classified as minor or major. Injections were categorised as follows: cervical spine, lumbar facet joint, lumbar nerve root, caudal epidural and 'other'. The complication rate for each individual category of procedure was compared with the combined complication rate for all other categories by constructing contingency tables and using Fisher's exact test. RESULTS: A total of 8226 patients underwent image-guided musculoskeletal injections within the study period. Exactly 100 patients were identified as having reported a complication, producing an overall complication rate of 1.2%. One complication was categorised as 'major', with the patient requiring expedited surgery. The remainder (99 patients) were categorised as having experienced minor complications. The incidence of complications after 'other' injections was significantly greater than for other categories of injection (1.86%, p = 0.028). There was no significant difference in the complication rate for cervical spine (0.93%, p = 0.257), lumbar nerve root (0.85%, p = 0.401), lumbar facet joint (0.67%, p = 0.326) or caudal epidural (1.29%, p = 0.687) injections. 'Other' injections were subsequently further sub-categorised by anatomical site and imaging modality used. Glenohumeral (2.97%, p = 0.0361) and sacro-iliac (3.51%, p = 0.0498) joint injections were associated with a significantly increased risk of complications. There was no difference in the incidence of complications with fluoroscopic or ultrasound guidance. CONCLUSION: In conclusion, image-guided musculoskeletal injections are safe and well-tolerated procedures. Complications are rare, occurring in just 1.2% of patients. 99% of complications are minor, either not requiring intervention or resolving with simple supportive treatment.

Precision Assessment of COVID-19 Phenotypes Using Large-Scale Clinic Visit Audio Recordings: Harnessing the Power of Patient Voice.

COVID-19 cases are exponentially increasing worldwide; however, its clinical phenotype remains unclear. Natural language processing (NLP) and machine learning approaches may yield key methods to rapidly identify individuals at a high risk of COVID-19 and to understand key symptoms upon clinical manifestation and presentation. Data on such symptoms may not be accurately synthesized into patient records owing to the pressing need to treat patients in overburdened health care settings. In this scenario, clinicians may focus on documenting widely reported symptoms that indicate a confirmed diagnosis of COVID-19, albeit at the expense of infrequently reported symptoms. While NLP solutions can play a key role in generating clinical phenotypes of COVID-19, they are limited by the resulting limitations in data from electronic health records (EHRs). A comprehensive record of clinic visits is required-audio recordings may be the answer. A recording of clinic visits represents a more comprehensive record of patient-reported symptoms. If done at scale, a combination of data from the EHR and recordings of clinic visits can be used to power NLP and machine learning models, thus rapidly generating a clinical phenotype of COVID-19. We propose the generation of a pipeline extending from audio or video recordings of clinic visits to establish a model that factors in clinical symptoms and predict COVID-19 incidence. With vast amounts of available data, we believe that a prediction model can be rapidly developed to promote the accurate screening of individuals at a high risk of COVID-19 and to identify patient characteristics that predict a greater risk of a more severe infection. If clinical encounters are recorded and our NLP model is adequately refined, benchtop virologic findings would be better informed. While clinic visit recordings are not the panacea for this pandemic, they are a low-cost option with many potential benefits, which have recently begun to be explored.