Parameters Predictive of Propofol-Associated Acute Pancreatitis in Critically Ill Patients with COVID-19 Pneumonia: A Retrospective Cohort Study.

BACKGROUND: Propofol, a commonly used agent for short- and long-term sedation, is associated with acute pancreatitis. The main indirect mechanism of propofol-associated acute pancreatitis is by inducing hypertriglyceridemia. Patients with severe coronavirus disease 2019 (COVID-19) pneumonia often require prolonged mechanical ventilation and sedation. We examined the incidence rate of acute pancreatitis among critically ill adults with COVID-19 pneumonia on mechanical ventilation receiving propofol. In addition, we attempted to determine cutoff levels of serum triglycerides and doses of propofol that are predictive of propofol-associated acute pancreatitis. METHODS: This was a multicenter retrospective cohort study using a large dataset of hospitalized patients with COVID-19. The collected data included the number of days on propofol, cumulative doses of propofol, peak levels of serum triglycerides, serum lipase levels, and abdominal imaging findings. We used receiver-operating characteristic analysis in conjunction with Youden's index to identify the optimal thresholds for propofol administration parameters and levels of triglycerides that would provide maximal sensitivity and specificity for predicting acute pancreatitis. RESULTS: Out of 499 critically ill patients with COVID-19 pneumonia, 154 met the inclusion criteria. Six (4%) patients had suspected acute pancreatitis based on elevated serum lipase levels. Cutoff values greater than 688 mg/dL for peak level of triglycerides, 4.5 days on propofol, 3007 mg/day for average daily propofol dose, and 24 113 mg for cumulative propofol dose were associated with high risk of suspected acute pancreatitis. The negative predictive values for suspected acute pancreatitis using these cutoffs ranged from 98% to 100%. CONCLUSIONS: Propofol use in critically ill COVID-19 patients is associated with a low incidence rate of acute pancreatitis. We identified cutoff values for serum triglycerides and cumulative propofol dose that are linked to higher risk of propofol-associated pancreatitis. More research is needed to examine the true incidence of propofol-associated pancreatitis and help develop optimal cutoff values for certain parameters to help guide safe propofol administration.

Hemorrhagic transformation in acute ischemic stroke: hemorrhagic subtypes and symptomatic intracranial hemorrhage.

BACKGROUND: Few clinical studies perform detailed analyses of subtypes of intracranial hemorrhage (ICH) after mechanical thrombectomy (MT) used to treat acute ischemic stroke. Symptomatic intracranial hemorrhage (sICH) is a formidable complication of MT and is widely used in clinical trials as a safety outcome. However, variable definitions of sICH are used across clinical studies. OBJECTIVE: To radiographically subcategorize post-MT ICH development within this large cohort and examine overlap with sICH. Second, to examine the agreement of this definition of sICH with local site-reported occurrences of sICH to see how sICH rates change with modifications of the definitions used. METHODS: A large cohort of patients treated with MT for acute ischemic stroke (n=1395) was analyzed to (1) radiographically characterize hemorrhagic subtypes of intracranial hemorrhage (ICH) occurring after MT; (2) examine associations of hemorrhagic subtypes with sICH; and (3) compare core laboratory-adjudicated occurrences of sICH with site-reported sICH. RESULTS: The overall rate of ICH was 552/1395 patients (39.6%), and the overall rate of sICH was 47/1395 (3.4%). The most common type of ICH was hemorrhagic infarction type 1 (HI1), which represented 45.3% of all ICH cases- followed by HI2 (31.5%) and subarachnoid hemorrhage (SAH, 29.2%). Parenchymal hematoma 2 (PH2) represented only 3.3% of all ICH cases. Of the PH2 hemorrhages, only 33.3% were determined to be symptomatic. Of sICH cases, the most common ICH subtypes were HI2 (48.9%) and SAH (38.3%). Comparison of sICH rates as determined by core laboratory adjudication versus local site-reported results showed that only 14 patients were identified as having sICH with both definitions, with 47 patients total with sICH according to one definition, but not the other. CONCLUSIONS: Results of this analysis demonstrate the radiographic subtypes of ICH and also highlight the limitations of variable criteria used to define sICH, suggesting that it might be appropriate to revisit how sICH is defined post-MT. TRIAL REGISTRATION NUMBER: Clinical trial NCT03845491.

Placing the balloon-guide catheter in the high cervical segment of the internal carotid artery is associated with improved recanalization.

BACKGROUND: Mechanical thrombectomy (MT) is part of the standard of care for stroke treatment, and improving its efficacy is one of the main objectives of clinical investigation. Of importance is placement of the distal end of balloon-guided catheters (BGC). We aim to determine if this influences outcomes. METHODS: We analyzed data from the ASSIST Registry, an international, multicenter prospective study of 1492 patients. We divided patients treated with BGC according to the placement of the BGC: low cervical (LCG (the lower 2/3 of cervical internal carotid artery (ICA)) or high cervical (HCG (upper 1/3 of cervical ICA, petro-lacerum or higher)). We analyzed characteristics and outcomes overall and stratified on the primary MT technique: Stent-Retriever only (SR Classic), Combined use of aspiration catheter and SR (Combined), and Direct Aspiration (ADAPT). RESULTS: Our study included 704 subjects -323 in the low cervical and 381 in the high cervical groups. Statistical differences were seen in the proportion of females and tandem lesions (both higher for LCG). Placing the BGC in the high cervical segment is associated with better recanalization rates (expanded treatment in cerebral infarction (eTICI) score of 2c-3) at the end of the procedure (P<0.0001) and shorter procedures (P=0.0005). After stratifying on the three primary techniques (SR Classic, Combined, and ADAPT), placing the BGC in the high segment is associated with a better first-pass effect (FPE), less distal emboli, and better clinical outcomes in the SR Classic technique. CONCLUSIONS: Placing the distal end of the BGC at the high cervical segment or higher is associated with better recanalization.

Predictors of Corporal Punishment during the COVID-19 Pandemic.

Although current policies discourage the use of corporal punishment (CP), its use is still widespread in the US. The objective of this study was to assess the proportion of parents who used CP during the pandemic and identify related risk and protective factors. We analyzed results of a nationwide cross-sectional internet panel survey of 9000 US caregivers who responded in three waves from November 2020 to July 2021. One in six respondents reported having spanked their child in the past week. Spanking was associated with intimate partner violence and the use of multiple discipline strategies and not significantly associated with region or racial self-identification. Parents who spanked sought out more kinds of support, suggesting an opportunity to reduce spanking through more effective parenting resources. Additionally, these results suggest that parents who report using CP may be at risk for concurrent domestic violence.

Technique and impact on first pass effect primary results of the ASSIST global registry.

BACKGROUND: Patients treated with mechanical thrombectomy (MT) for acute ischemic strokes from large vessel occlusion (LVO) have better outcomes with effective reperfusion. However, it is unknown which technique leads to better technical and clinical success. We aimed to determine which technique yields the most effective first pass reperfusion during MT. METHODS: In a prospective, multicenter global registry we enrolled patients treated with operator preferred MT technique at 71 hospitals from January 2019 to January 2022. Three techniques were assessed: SR Classic with stent retriever (SR) and balloon guide catheter (BGC); SR Combination which employed SR with contact aspiration with or without BGC; and direct aspiration (DA) with or without BGC. The primary outcome was achieving an expanded Thrombolysis In Cerebral Infarction (eTICI) score of 2c or 3 on the first pass, with the primary technique as adjudicated by core lab. The primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2. RESULTS: A total of 1492 patients were enrolled. Patients treated with SR Classic or SR Combination were more likely to achieve first pass eTICI 2c or 3 reperfusion (P=0.01). There was no significant difference in mRS 0-2 (P=0.46) or safety endpoints. CONCLUSIONS: The use of SR Classic or SR Combination was more likely to achieve first pass eTICI 2c or 3 reperfusion. There were no significant differences in clinical outcomes and safety endpoints.

Strength Training Is Associated With Less Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: We aimed to evaluate the relationship of a history of strength training with symptomatic and structural outcomes of knee osteoarthritis (OA). METHODS: This study was a retrospective, cross-sectional study within the Osteoarthritis Initiative (OAI), a multicenter prospective longitudinal observational study. Data were collected at four OAI clinical sites: Memorial Hospital of Rhode Island, the Ohio State University, the University of Pittsburgh, and the University of Maryland/Johns Hopkins. The study included 2,607 participants with complete data on strength training, knee pain, and radiographic evidence of knee OA (male, 44.2%; mean ± SD age 64.3 ± 9.0 years; mean ± SD body mass index 28.5 ± 4.9 kg/m2 ). We used a self-administered questionnaire at the 96-month OAI visit to evaluate the exposure of strength training participation during four time periods throughout a participant's lifetime (ages 12-18, 19-34, 35-49, and ≥50 years old). The outcomes (dependent variables) were radiographic OA (ROA), symptomatic radiographic OA (SOA), and frequent knee pain. RESULTS: The fully adjusted odds ratios (95% confidence interval) for frequent knee pain, ROA, and SOA among those who participated in strength training any time in their lives were 0.82 (0.68-0.97), 0.83 (0.70-0.99), and 0.77 (0.63-0.94), respectively. Findings were similar when looking at the specific age ranges. CONCLUSION: Strength training is beneficial for future knee health, counteracting long-held assumptions that strength training has adverse effects.

Knee cartilage change on magnetic resonance imaging: Should we lump or split topographical regions? A 2-year study of data from the osteoarthritis initiative.

OBJECTIVE: We challenge the paradigm that a simplistic approach evaluating anatomic regions (e.g., medial femur or tibia) is ideal for assessing articular cartilage loss on magnetic resonance (MR) imaging. We used a data-driven approach to explore whether specific topographical locations of knee cartilage loss may identify novel patterns of cartilage loss over time that current assessment strategies miss. DESIGN: We assessed 60 location-specific measures of articular cartilage on a sample of 99 knees with baseline and 24-month MR images from the Osteoarthritis Initiative, selected as a group with a high likelihood to change. We performed factor analyses of the change in these measures in two ways: (1) summing the measures to create one measure for each of the six anatomically regional-based summary (anatomic regions; e.g., medial tibia) and (2) treating each location separately for a total of 60 measures (location-specific measures). RESULTS: The first analysis produced three factors accounting for 66% of the variation in the articular cartilage changes that occur over 24 months of follow-up: (1) medial tibiofemoral, (2) medial and lateral patellar, and (3) lateral tibiofemoral. The second produced 20 factors accounting for 75% of the variance in cartilage changes. Twelve factors only involved one anatomic region. Five factors included locations from adjoining regions (defined by the first analysis; e.g., medial tibiofemoral). Three factors included articular cartilage loss from disparate locations. CONCLUSIONS: Novel patterns of cartilage loss occur within each anatomic region and across these regions, including in disparate regions. The traditional anatomic regional approach is simpler to implement and interpret but may obscure meaningful patterns of change.

Anterior circulation location-specific results for stent-assisted coiling - carotid versus distal aneurysms: 1-year outcomes from the Neuroform Atlas Stent Pivotal Trial.

BACKGROUND: The Neuroform Atlas Stent System is an established treatment modality for unruptured anterior and posterior circulation intracranial aneurysms. Location-specific results are needed to guide treatment decision-making. However, it is unclear whether there are differences in safety and efficacy outcomes between carotid and more distal anterior circulation aneurysms. METHODS: The ATLAS IDE trial was a prospective, multicenter, single-arm, open-label interventional study that evaluated the safety and efficacy of the Neuroform Atlas Stent System. We compared differences in efficacy and safety outcomes of proximal internal carotid artery (ICA) versus distal and bifurcation anterior circulation aneurysms. RESULTS: Of 182 cases, there were 70 aneurysms in the ICA and 112 in the distal anterior circulation (including ICA terminus/bifurcation). There were no significant differences in the primary efficacy endpoint (85.5% vs 83.9%, p=0.78) and complete aneurysm occlusion rates (88.7% vs 87.9%, p=0.78) between proximal ICA aneurysms and distal aneurysms, respectively. Complications were more often encountered in distal and bifurcation aneurysms, but the overall rate of major safety events was low and comparable between the two groups (1.4% vs 6.3%, p=0.14). Recanalization and retreatment rates were also similar between the groups. CONCLUSION: The results of this study suggest that the Neuroform Atlas Stent System is a safe and efficacious treatment modality for unruptured anterior circulation intracranial aneurysms, regardless of aneurysm location. TRIAL REGISTRATION NUMBER: NCT02340585.

Clinical Manifestations of Subjects With the Non-Specific Pulmonary Function Test Pattern.

Introduction: Non-specific pattern (NSP) is a subgroup of preserved ratio impaired spirometry (PRISm) that requires a normal total lung capacity measurement. NSP has been historically classified as being an obstructive lung disease pattern. There has been heightened interest and investigation into PRISm recently as it has been associated with an increased likelihood of developing chronic obstructive pulmonary disease (COPD). Given the inherent challenges of understanding the clinical significance of the NSP, the aim of this study was to further explore the clinical characteristics of patients with this pulmonary function test pattern. Material and methods: We identified 111 and 79 subjects using pre-bronchodilator (pre-BD) and post-bronchodilator (post-BD) values, respectively, that met criteria for NSP. The outpatient medical records were retrospectively reviewed for associated diagnoses that were then clustered into 'obstructive' or 'non-obstructive' groups based on the treating physician's primary pulmonary clinical diagnosis. Results: Within this NSP cohort, cough, wheezing and sputum production were documented more frequently in those with an obstructive lung disease diagnosis. Whether identified using pre-BD or post-BD spirometric values, those with NSP and a positive BD response were more likely to carry an obstructive lung disease diagnosis. Conclusion: Approximately one third of patients with NSP in this study were not given an obstructive lung disease diagnosis by their clinician, which supports the classification of NSP as not an exclusively obstructive lung disease pattern. However, the presence of supporting clinical symptoms, such as cough with sputum production and wheeze, and/or a positive BD response on PFT, support a diagnosis of obstruction in patients with NSP.

Introducción: El patrón inespecífico constituye un subgrupo de alteraciones de la espirometría con conservación de la relación (PRISm, siglas en inglés) que precisa de una medición de la capacidad pulmonar total normal; históricamente se ha clasificado como un patrón de neumopatía obstructiva. En épocas recientes se ha intensificado el interés en las PRISm y su investigación, ya que se ha asociado a un aumento de la probabilidad de aparición de una enfermedad pulmonar obstructiva crónica (EPOC). Dadas las dificultades inherentes que conlleva interpretar la importancia clínica del patrón inespecífico, el objetivo de este estudio consistió en explorar con más detalle las características clínicas de los pacientes con dicho patrón en las pruebas de la función pulmonar. Material y métodos: Se identificaron 111 y 79 sujetos empleando valores prebroncodilatador y posbroncodilatador, respectivamente, que cumplieron los criterios de patrón inespecífico. Se revisaron retrospectivamente las historias clínicas ambulatorias para detectar diagnósticos asociados que después se agregaron en grupos «obstructivos¼ o «no obstructivos¼ en función del diagnóstico clínico pulmonar primario del médico. Resultados: En esta cohorte de pacientes con patrones inespecíficos, se documentó una mayor incidencia de tos, sibilancias y producción de esputo entre los que tenían un diagnóstico de neumopatía obstructiva. Los pacientes con patrón inespecífico y una respuesta positiva al broncodilatador, que hubiesen sido identificados con valores pre o posbroncodilatador, tenían más probabilidades de haber recibido un diagnóstico de neumopatía obstructiva. Conclusión: Aproximadamente un tercio de los pacientes con patrón inespecífico de este estudio no habían recibido un diagnóstico de neumopatía obstructiva, dato que avala no clasificar los patrones inespecíficos exclusivamente en las neumopatías obstructivas. Sin embargo, la presencia de síntomas clínicos indicativos, como tos productiva y sibilancias, o una respuesta positiva al broncodilatador en las pruebas de la función pulmonar, sustenta un diagnóstico de obstrucción en los pacientes con patrón inespecífico.

Comparative analysis of long term effectiveness of Neuroform Atlas stent versus low profile visualized intraluminal stent/Woven EndoBridge devices in treatment of wide necked intracranial aneurysms.

BACKGROUND: We compared the outcomes of wide necked aneurysms (WNA) treated with the Neuroform Atlas with those treated with the low profile visualized intraluminal stent (LVIS) or the Woven EndoBridge (WEB). METHODS: Objective, prospectively collected, core laboratory adjudicated data from published trials for the Neuroform Atlas, LVIS, and WEB devices were reviewed. ATLAS (Safety and Effectiveness of the Treatment of Wide Neck, Saccular Intracranial Aneurysms With the Neuroform Atlas Stent System) study patients were included if they met other studies' inclusion criteria. Outcomes included (1) primary effectiveness (complete aneurysmal occlusion without retreatment/>50% parent vessel stenosis), (2) primary safety, (3) complete aneurysmal occlusion, and (4) retreatment rates (outcomes evaluated at the 12 month follow-up). Matching adjusted indirect comparison analysis was used to compare outcomes. RESULTS: Analytical samples included 141 ATLAS subjects meeting WEB-IT (Woven EndoBridge Intrasaccular Therapy Study) criteria (ATLAS/WEB-IT) and 241 meeting LVIS (Pivotal Study of the Low Profile Visualized Intraluminal Support) criteria (ATLAS/LVIS). ATLAS/WEB-IT exhibited significantly higher rates of primary effectiveness and complete occlusion versus WEB (86.6% vs 53.9 %, P<0.0001, and 90.3% vs 53.9%, P<0.0001, respectively). For LVIS, there was no significant differences in primary effectiveness rates between ATLAS and LVIS (84.2% vs 77.7%, respectively, P=0.12). However, ATLAS/LVIS had a significantly higher proportion of patients achieving complete occlusion than LVIS (88.1 vs 79.1, P=0.03). Retreatment rates and primary safety outcomes were not significantly different (P>0.05) for the Atlas versus other devices except for a lower retreatment rate for ATLAS/WEB-IT versus WEB-IT (2.4% vs 9.8%, P=0.01). CONCLUSION: The Neuroform Atlas provided higher occlusion rates and similar retreatment rates in comparable datasets compared with LVIS and WEB devices when treating WNA.

Cardiac Cachexia in Left Ventricular Assist Device Recipients and the Implications of Weight Gain Early After Implantation.

Background Severe cardiac cachexia or malnutrition are commonly considered relative contraindications to left ventricular assist device (LVAD) implantation, but post-LVAD prognosis for patients with cachexia is uncertain. Methods and Results Intermacs (Interagency Registry for Mechanically Assisted Circulatory Support) 2006 to 2017 was queried for the preimplantation variable cachexia/malnutrition. Cox proportional hazards modeling examined the relationship between cachexia and LVAD outcomes. Of 20 332 primary LVAD recipients with available data, 516 (2.54%) were reported to have baseline cachexia and had higher risk baseline characteristics. Cachexia was associated with higher mortality during LVAD support (unadjusted hazard ratio [HR], 1.36 [95% CI, 1.18-1.56]; P<0.0001), persisting after adjustment for baseline characteristics (adjusted HR, 1.23 [95% CI, 1.0-1.42]; P=0.005). Mean weight change at 12 months was +3.9±9.4 kg. Across the cohort, weight gain ≥5% during the first 3 months of LVAD support was associated with lower mortality (unadjusted HR, 0.90 [95% CI, 0.84-0.98]; P=0.012; adjusted HR, 0.89 [95% CI, 0.82-0.97]; P=0.006). Conclusions The proportion of LVAD recipients recognized to have cachexia preimplantation was low at 2.5%. Recognized cachexia was independently associated with higher mortality during LVAD support. Early weight gain ≥5% was independently associated with lower mortality during subsequent LVAD support.

"They Can't Believe They're a Tiger": Insights from pediatric speech-language pathologist mobile app users and app designers.

BACKGROUND: Children with communication disorders experience difficulty in one or more areas of articulation and speech, language, fluency, voice and social communication, and they work with speech-language pathologists (SLPs) to improve their communication. With the rise of adoption and use for mobile applications among special education and healthcare service providers, SLPs also have implemented, and for some, contributed to the design of, mobile applications (apps) during clinical practice. However, how these mobile apps are designed and implemented for clinicians to facilitate their clients' communication and learning experiences during therapy remains underinvestigated. AIMS: This qualitative research study investigated how mobile apps were designed for clinicians to target assessment and intervention goals. Additionally, it focused on how clinicians adopted these apps while integrating therapy techniques to facilitate their clients' learning. METHODS AND PROCEDURES: Informed by the Research, Practice, and Design for iPad Apps (iRPD) framework and the Consolidated Framework for Implementation Research (CFIR), semi-structured interviews were conducted with 37 licensed pediatric SLPs, including 23 SLPs who have used apps and 14 SLPs who have contributed to the design of their own mobile apps. Two rounds of qualitative coding via template analysis and thematic analysis were then used to analyse client and clinician characteristics, clinical practice, therapy tools, app characteristics, influential factors and app design and use recommendations. OUTCOMES AND RESULTS: Results showed SLPs utilise different genres of assistive, educational and recreational game apps to support children's communication development when working with children who have diverse disorders and therapy needs across different age groups. SLPs who have designed their own apps emphasised the importance of following evidence-based practice, well-researched teaching methods and learning theories. Additionally, multiple financial, sociocultural, political and ethical factors contributed to the design, adoption and implementation of mobile apps during services. CONCLUSIONS AND IMPLICATIONS: By understanding the clinician's app use practices situated in various therapy activities and techniques, we specified a list of design recommendations for app designers who are interested in creating mobile apps for supporting children's speech and language development. By bringing insights from both clinical practitioners as well as those with additional technical design backgrounds, this study contributes to the understanding of clinical practice needs and strategies and will lead to the most optimal app design and adoption practice to support the well-being of children with communication disorders. WHAT THIS PAPER ADDS: What is already known on the subject Speech language pathologist (SLPs) implement mobile apps for clients with diverse therapy needs, and their app adoption and use are influenced by multifaceted factors. Although prior studies have reported SLPs' mobile app use, additional information is still needed. For example, the research literature does not include how specific technology is used during therapy practice, or specific details about challenges and needs in implementing and utilising the technology. Additional research also needs to include influential factors (e.g., financial, sociocultural, political, ethical) that are considered when selecting, implementing, assessing and designing an app. The lack of research in these areas directly affects the understanding of clinical mobile technology practices and further hinders clinicians' abilities to advocate for better clinical and design decisions towards identifying and implementing effective mobile apps that facilitate children's communication. What this study adds to existing knowledge This qualitative study is the first known empirical research that interviewed pediatric speech-language pathologists who have used and designed mobile apps for children who receive speech-language therapy across different clinical settings. By investigating experiences from clinician stakeholders to illustrate a holistic overview of app design and development to deployment, this study reported finding on (1) how clinicians use mobile apps to help children to participate in different therapy activities, and (2) a list of recommended design and development guidelines that informs the design and use of mobile apps that best support and motivate children to engage in therapy. What are the potential or actual clinical implications of this work? This study disseminates clinician-reported practices of app design and use with pediatric clients across different speech-language disorders, and identifies gaps and needs for clinicians and researchers who are interested in understanding the role of mobile technology in relationship to human communication and interaction. Additionally, the paper demonstrates that SLPs have instrumental roles rather than passive users in influencing the design and implementation of different genres of mobile apps through evidence-based clinical practice, and call for partnerships across clinicians, special educators and technologists to support children's communication development.

Passive Surveillance of Human-Biting Ixodes scapularis Ticks in Massachusetts from 2015-2019.

This study aimed to analyze human-biting Ixodes scapularis ticks submitted to TickReport tick testing service from 2015-2019 in Massachusetts to (1) examine possible patterns of pathogen-positive adult and nymphal ticks over time and (2) explore how socioeconomic factors can influence tick submissions. A passive surveillance data set of ticks and tick-borne pathogens was conducted over 5 years (2015-2019) in Massachusetts. The percentages of four tick-borne pathogens: Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, and Borrelia miyamotoi were determined by Massachusetts county and by month and year. Regression models were used to examine the association between zip-code-level socioeconomic factors and submissions. A total of 13,598 I. scapularis ticks were submitted to TickReport from Massachusetts residents. The infection rate of B. burgdorferi, A. phagocytophilum, and B. microti was 39%, 8%, and 7% in adult ticks; 23%, 6%, and 5% in nymphal ticks, respectively. A relatively higher level of education was associated with high tick submission. Passive surveillance of human-biting ticks and associated pathogens is important for monitoring tick-borne diseases, detecting areas with potentially high risks, and providing public information. Socioeconomic factors should be considered to produce more generalizable passive surveillance data and to target potentially underserved areas.

Interstitial lung abnormalities in a large clinical lung cancer screening cohort: association with mortality and ILD diagnosis.

BACKGROUND: Interstitial lung abnormalities (ILA) are CT findings suggestive of interstitial lung disease in individuals without a prior diagnosis or suspicion of ILD. Previous studies have demonstrated that ILA are associated with clinically significant outcomes including mortality. The aim of this study was to determine the prevalence of ILA in a large CT lung cancer screening program and the association with clinically significant outcomes including mortality, hospitalizations, cancer and ILD diagnosis. METHODS: This was a retrospective study of individuals enrolled in a CT lung cancer screening program from 2012 to 2014. Baseline and longitudinal CT scans were scored for ILA per Fleischner Society guidelines. The primary analyses examined the association between baseline ILA and mortality, all-cause hospitalization, and incidence of lung cancer. Kaplan-Meier plots were generated to visualize the associations between ILA and lung cancer and all-cause mortality. Cox regression proportional hazards models were used to test for this association in both univariate and multivariable models. RESULTS: 1699 subjects met inclusion criteria. 41 (2.4%) had ILA and 101 (5.9%) had indeterminate ILA on baseline CTs. ILD was diagnosed in 10 (24.4%) of 41 with ILA on baseline CT with a mean time from baseline CT to diagnosis of 4.47 ± 2.72 years. On multivariable modeling, the presence of ILA remained a significant predictor of death, HR 3.87 (2.07, 7.21; p < 0.001) when adjusted for age, sex, BMI, pack years and active smoking, but not of lung cancer and all-cause hospital admission. Approximately 50% with baseline ILA had progression on the longitudinal scan. CONCLUSIONS: ILA identified on baseline lung cancer screening exams are associated with all-cause mortality. In addition, a significant proportion of patients with ILA are subsequently diagnosed with ILD and have CT progression on longitudinal scans. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov; No.: NCT04503044.

The natural history of end-stage knee osteoarthritis: Data from the osteoarthritis initiative.

OBJECTIVE: We aimed to describe the natural history leading to end-stage knee osteoarthritis (esKOA), focusing on knee symptoms, radiographic severity, and the presence of limited mobility or instability. METHODS: We performed knee-based analyses of Osteoarthritis Initiative data from 7691 knees (4165 participants). We used a validated definition of esKOA that relied on meeting one of two criteria: (1) severe radiographic knee osteoarthritis (Kellgren-Lawrence [KL] grade=4) with moderate-to-intense pain (Likert WOMAC pain+function>11/88) or (2) KL grade<4 with intense or severe pain (WOMAC pain+function>22) and limited mobility (flexion contracture≥5°) or instability (based on a varus and valgus stress test). We also introduced an alternate definition of esKOA that relied on meeting one of two criteria that omitted physical exam findings:(1) severe radiographic knee osteoarthritis (KL grade=4) with at least moderate symptoms or (2) KL grade=2 or 3 with intense or severe symptoms and persistent knee pain (frequent knee pain during three or more months in the past year). We used descriptive statistics to explore the frequency of components of esKOA at the index visit when they had incident esKOA, at the annual visit before developing esKOA, and the interval change between those visits. RESULTS: Our analytic sample was mostly female (58%), without radiographic knee osteoarthritis (KL grade=0 or 1; 60%), without stability or mobility concerns (91%), and without persistent knee pain (77%). At the visit before incident esKOA, most knees already had moderate-to-severe radiographic osteoarthritis using the original (62%) or alternate (50%) definition (versus <15% for either definition of no esKOA). Over 80% of knees that reached the criteria for esKOA achieved this based on increased knee symptom severity - typically without worsening radiographic severity (80%). CONCLUSION: Radiographic severity predisposed a knee to esKOA. However, worsening knee symptoms led to the development of incident esKOA. If investigators want to increase the chance of identifying incident esKOA as an outcome, they should enrich their study samples with people with moderate-to-severe radiographic osteoarthritis. Our findings also highlight the potential reversibility of esKOA (a knee that is classified with esKOA but later is not classified with esKOA). Reversibility is not a flaw of an outcome defining esKOA but rather a desirable clinical outcome to demonstrate a therapeutic intervention can help people with esKOA improve their knee symptoms and delay a knee replacement.

Improving Health Behaviors and Weight Parameters With Motivational Interviewing and the TEEEN Program in an Ethnically and Socioeconomically Diverse Pediatric Population.

Objective: Obesity affects 14.7 million children and adolescents in the United States. Children's health behaviors are affected by parental health practices. Therefore, pediatric obesity interventions should include parents. The objective of this study was to assess the changes in self-reported health behaviors in a diverse population attending the TEEEN program, with motivational interviewing of child-parent dyads as a key component, for 1 year. Methods: Here we assessed the changes in Family and Nutrition and Physical Activity (FNPA) screening tool scores, a tool that assesses obesogenic behaviors, in the context of MI of child-parent dyads in a racially, ethnically, and socioeconomically diverse population who attended the TEEEN (Teens, Empowerment, Education, Exercise, Nutrition) program, a nonclinic and family-based behavior program in Massachusetts, for 1 year. Results: Participation in the TEEEN program, which includes MI of child-parent dyads, was associated with a significant increase in the overall FNPA score (median change= 4 points, P = .007). We observed that 76.5% of children experienced a decrease in BMI% and BMI z-score. The change in BMI% (median= -0.9, P = .006) and change in BMI z-score (median= -0.2, P = .008) were statistically significant. Conclusion: Participation in the TEEEN program seemed to be beneficial based on aspects of the FNPA screening tool and changes in weight parameters. The FNPA screening tool enhanced-motivational interviewing of child-parent dyads shows promise as an approach to address obesogenic behaviors. This study provides a detailed framework for medical providers to address pediatric obesity in a nonclinic setting with less time constraints.

Female sex and advanced age are associated with invasive cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: Limited data exist to describe sex-based differences in the severity of cytomegalovirus (CMV) infection after solid organ transplant (SOT). We sought to identify if a difference exists in likelihood of tissue-invasive disease between male and female SOT recipients and to understand how age affects this relationship. METHODS: A retrospective cohort of 180 heart, liver, and kidney recipients treated for CMV was examined. A logistic regression model was developed to assess the relationship between female sex and CMV type (noninvasive vs. invasive). A secondary regression analysis looked at the relationship of invasive CMV with a variable combining sex with age above or below 50. RESULTS: There were 37 cases of proven or probable invasive CMV, occurring in 30% of females versus 16% of males. After adjustment for potential confounders, females with CMV infection were significantly more likely to have invasive disease (odds ratio (OR) 2.69, 95% confidence interval (CI) 1.25-5.90, p = .01). Females 50 years or older were at particular risk compared with males under 50 years (adjusted OR 4.54, 95% CI 1.33-18.83, p = .02). CONCLUSION: Female SOT recipients with CMV in our cohort were more likely than males to have tissue-invasive disease, with the highest risk among older females. Further prospective studies are warranted to explore underlying immunologic mechanisms.

Outcome and Prognostic Factors in Cats Undergoing Resection of Intestinal Adenocarcinomas: 58 Cases (2008-2020).

The purpose of this multi-institutional retrospective study was to expand the available data pertaining to pre-operative clinical findings, progression-free and overall survival times, and potential prognostic factors for cats undergoing surgery for intestinal adenocarcinomas. Fifty-eight cats treated over a 12-year period were included in the study. Progression-free and overall survival times were estimated using Kaplan-Meier analyses. Potential prognostic variables were evaluated for associations with progression-free and overall survival using univariate Cox proportional hazards regression analyses. Prior to surgery, the intestinal mass was identified using ultrasonography in 89% of cats in which it was applied; however, imaging findings suggestive of intrathoracic metastases were observed in only 9% of cats. Among 22 cats undergoing ultrasound-guided fine needle aspiration cytology, the results agreed with the results of histopathology in only 10 cats. Discordant results were most commonly related to the presence of marked inflammation in cytology samples, which may have obscured the presence of neoplastic cells. Diffuse intestinal small cell lymphoma was identified as a comorbidity in 5 cats. Resection of the tumor with the objective of obtaining wide surgical margins was performed in each cat. On histopathology, 20 tumors were classified as mucinous adenocarcinoma and 28 were adenocarcinoma not otherwise specified. Intestinal transection site margins were complete in 94% of cats; however, complete mural margins were present in only 15% of cats. Local lymph node metastases were identified in 52% of cats and carcinomatosis was diagnosed in 81% of cats. Disease progression was documented in 32 of the 58 cats (55%). Of these 32 cats, 14 (43%) had local recurrence of the primary intestinal tumor. Median progression-free survival was 203 days (95% CI 130-299 days), and median overall survival time was 284 days (95% CI 200-363 days). Mitotic count was inversely associated with progression-free survival (HR 1.04; 95% CI 1.01-1.07, P = 0.005); however, none of the remaining potential prognostic factors, including administration of adjuvant chemotherapy, were significantly associated with progression-free or overall survival. Feline intestinal adenocarcinoma remains an aggressive and highly fatal disease. Large, randomized controlled clinical trials will be needed to improve the survival prospects for affected cats.

Maternal Lipid Metabolism Is Associated With Neonatal Adiposity: A Longitudinal Study.

CONTEXT: Pregnancy is characterized by progressive decreases in glucose insulin sensitivity. Low insulin sensitivity resulting in hyperglycemia is associated with higher neonatal adiposity. However, less is known regarding lipid metabolism, particularly lipid insulin sensitivity in pregnancy and neonatal adiposity. OBJECTIVE: Because higher maternal prepregnancy body mass index is strongly associated with both hyperlipidemia and neonatal adiposity, we aimed to examine the longitudinal changes in basal and clamp maternal lipid metabolism as contributors to neonatal adiposity. METHODS: Twelve women planning a pregnancy were evaluated before pregnancy, in early (12-14 weeks), and late (34-36 weeks) gestation. Body composition was estimated using hydrodensitometry. Basal and hyperinsulinemic-euglycemic clamp glucose and glycerol turnover (GLYTO) were measured using 2H2-glucose and 2H5-glycerol and substrate oxidative/nonoxidative metabolism with indirect calorimetry. Total body electrical conductivity was used to estimate neonatal body composition. RESULTS: Basal free-fatty acids decreased with advancing gestation (P = 0.0210); however, basal GLYTO and nonoxidative lipid metabolism increased over time (P = 0.0046 and P = 0.0052, respectively). Further, clamp GLYTO and lipid oxidation increased longitudinally over time (P = 0.0004 and P = 0.0238, respectively). There was a median 50% increase and significant positive correlation during both basal and clamp GLYTO from prepregnancy through late gestation. Neonatal adiposity correlated with late pregnancy basal and clamp GLYTO (r = 0.6515, P = 0.0217; and r = 0.6051, P = 0.0371). CONCLUSIONS: Maternal prepregnancy and late pregnancy measures of basal and clamp lipid metabolism are highly correlated. Late pregnancy basal and clamp GLYTO are significantly associated with neonatal adiposity and account for ~40% of the variance in neonatal adiposity. These data emphasize the importance of maternal lipid metabolism relating to fetal fat accrual.

Specialized Pro-Resolving Mediators Reduce Scarring After Cleft Lip Repair.

Objective: Residual scarring after cleft lip repair surgery remains a challenge for both surgeons and patients and novel therapeutics are critically needed. The objective of this preclinical experimental study was to evaluate the impact of the methyl-ester of pro-resolving lipid mediator lipoxin A4 (LXA4-ME) on scarring in a novel rabbit model of cleft lip repair. Methods: A defect of the lip was surgically created and repaired in eight six-week old New Zealand white rabbits to simulate human cleft lip scars. Rabbits were randomly assigned to topical application of PBS (control) or 1 ug of LXA4-ME (treatment). 42 days post surgery all animals were euthanized. Photographs of the cleft lip area defect and histologic specimens were evaluated. Multiple scar assessment scales were used to compare scarring. Results: Animals treated with LXA4-ME exhibited lower Visual Scar Assessment scores compared to animals treated with PBS. Treatment with LXA4-ME resulted in a significant reduction of inflammatory cell infiltrate and density of collagen fibers. Control animals showed reduced 2D directional variance (orientation) of collagen fibers compared to animals treated with LXA4-ME demonstrating thicker and more parallel collagen fibers, consistent with scar tissue. Conclusions: These data suggest that LXA4-ME limits scarring after cleft lip repair and improves wound healing outcomes in rabbits favoring the resolution of inflammation. Further studies are needed to explore the mechanisms that underlie the positive therapeutic impact of LXA4-ME on scarring to set the stage for future human clinical trials of LXA4-ME for scar prevention or treatment after cleft lip repair.