Feasibility assessment of catheter-free water vapor thermal therapy for treatment of benign prostatic hyperplasia.

PURPOSE: To investigate safety and feasibility of performing water vapor thermal therapy (WVTT; Rezum, Boston Scientific, Marlborough, MA, USA) without postoperative catheterization among men with benign prostatic hyperplasia. METHODS: This is a prospective, single arm, unblinded pilot study of 20 consecutive male patients ages 40-80 who underwent WVTT at a single academic institution. All patients underwent 1 injection per lobe at the point of maximal obstruction based on visualization. Primary outcome was evaluation of voiding parameters, symptom scores, and need for catheterization at 3 day, 1, 3, and 6 month follow up compared to baseline visit 30 days prior to surgery. RESULTS: Mean age was 65 years (range 55-75). Mean prostate volume and PVR were 43 cc (range 30-68) and 89 cc, with 30% (n = 6) having median lobes. Patients received 2-3 treatments based on presence of bilobar versus trilobar hyperplasia. One patient (55 cc prostate, no median lobe) required catheterization for acute urinary retention on postoperative day 2. No patients required antibiotics for urinary tract infection or inpatient readmission within 30 days. Qmax significantly increased from 6 mL/s to 8, 13, 12, and 14 at 3 days, 1, 3, and 6 months (p < 0.05). IPSS decreased from 17 preoperatively to 10, 6, 7, and 8 (p < 0.05). No significant differences were noted in PVR, IIEF, MSHQ-EjD, or SF-12. CONCLUSIONS: In well-selected men, catheter-free WVTT is feasible and improved voiding parameters and symptom scores. No changes in sexual function, infectious complications, or readmission were noted. Only 1 patient (5%) required postoperative catheterization within 30 days.

Current clinical evidence is insufficient to support HMME-PDT as the first choice of treatment for young children with port wine birthmarks.

BACKGROUND: Port wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the "gold standard" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades. AIM: To evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities. METHOD: PubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C0), with data weighted by cohort size, was used to evaluate the final efficacy for each modality. RESULT: A total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME-PDT in cohorts with patients of all ages (C0, 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C0, 0.54 vs. 0.46, p = 0.714), and young children (C0, 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long-term data on follow-up evaluations for efficacy and impact of HMME-PDT on young children in general, and central nervous system development in particular, because their blood-brain barriers have a greater permeability as compared to adults. CONCLUSION: PDL shows overall albeit insignificantly higher clearance rates than HMME-PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME-PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off-target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; -and (4) lack of long-term data on the potential impact of HMME on central nervous system development in young children.

Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline.

Trigonelline (TRG) is a natural polar hydrophilic alkaloid that is found in many plants such as green coffee beans and fenugreek seeds. TRG potentially acts on multiple molecular targets, including nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor γ, glycogen synthase kinase, tyrosinase, nerve growth factor, estrogen receptor, amyloid-ß peptide, and several neurotransmitter receptors. In this review, we systematically summarize the pharmacological activities, medicinal properties, and mechanistic actions of TRG as a potential therapeutic agent. Mechanistically, TRG can facilitate the maintenance and restoration of the metabolic homeostasis of glucose and lipids. It can counteract inflammatory constituents at multiple levels by hampering pro-inflammatory factor release, alleviating inflammatory propagation, and attenuating tissue injury. It concurrently modulates oxidative stress by the blockage of the detrimental Nrf2 pathway when autophagy is impaired. Therefore, it exerts diverse therapeutic effects on a variety of pathological conditions associated with chronic metabolic diseases and age-related disorders. It shows multidimensional effects, including neuroprotection from neurodegenerative disorders and diabetic peripheral neuropathy, neuromodulation, mitigation of cardiovascular disorders, skin diseases, diabetic mellitus, liver and kidney injuries, and anti-pathogen and anti-tumor activities. Further validations are required to define its specific targeting molecules, dissect the underlying mechanistic networks, and corroborate its efficacy in clinical trials.

A multi-site, international laboratory study to assess the performance of penicillin susceptibility testing of Staphylococcus aureus.

OBJECTIVES: There is clinical uncertainty over the optimal treatment for penicillin-susceptible Staphylococcus aureus (PSSA) infections. Furthermore, there is concern that phenotypic penicillin susceptibility testing methods are not reliably able to detect some blaZ-positive S. aureus. METHODS: Nine S. aureus isolates, including six genetically diverse strains harbouring blaZ, were sent in triplicate to 34 participating laboratories from Australia (n = 14), New Zealand (n = 6), Canada (n = 12), Singapore (n = 1) and Israel (n = 1). We used blaZ PCR as the gold standard to assess susceptibility testing performance of CLSI (P10 disc) and EUCAST (P1 disc) methods. Very major errors (VMEs), major error (MEs) and categorical agreement were calculated. RESULTS: Twenty-two laboratories reported 593 results according to CLSI methodology (P10 disc). Nineteen laboratories reported 513 results according to the EUCAST (P1 disc) method. For CLSI laboratories, the categorical agreement and calculated VME and ME rates were 85% (508/593), 21% (84/396) and 1.5% (3/198), respectively. For EUCAST laboratories, the categorical agreement and calculated VME and ME rates were 93% (475/513), 11% (84/396) and 1% (3/198), respectively. Seven laboratories reported results for both methods, with VME rates of 24% for CLSI and 12% for EUCAST. CONCLUSIONS: The EUCAST method with a P1 disc resulted in a lower VME rate compared with the CLSI methods with a P10 disc. These results should be considered in the context that among collections of PSSA isolates, as determined by automated MIC testing, less than 10% harbour blaZ. Furthermore, the clinical relevance of phenotypically susceptible, but blaZ-positive S. aureus, remains unclear.

Predicting hepatitis B e Antigen seroconversion after pregnancy-The SydPregScore.

BACKGROUND AND AIMS: Achieving Hepatitis B e antigen seroconversion (HBeAg SC) at an earlier age confers a better prognosis. We examined baseline and post-partum factors associated with HBeAg SC after pregnancy. We developed a tool, the SydPregScore, to estimate the likelihood of HBeAg SC in the years after pregnancy. METHODS: A retrospective analysis of an HBeAg-positive pregnant cohort was conducted. Variables including baseline age, parity, alanine aminotransferase level, HBV viral load, quantitative HBsAg, use of antiviral therapy and post-partum flare were collected. Univariate and multivariate Cox regression analyses to determine predictors of HBeAg SC and develop a predictor score were performed. RESULTS: We analysed HBeAg SC rates in 220 pregnancies to 149 HBeAg-positive women from 2006 to 2019. At baseline, their median age was 33 (IQR 29-37), ALT 23 U/L (IQR 17-33) and viral load 8 log10 IU/mL (IQR 6.3-8.2 log10 IU/mL). The majority (133/198, 67.2%) received short-course antiviral therapy to prevent mother-to-child transmission, and 109/192 (56.8%) had a post-partum flare. HBeAg SC occurred in 74/220 (33.6%) after pregnancy (median follow-up 814 days, IQR 405-1531). Multivariate analysis identified baseline viral load <8 log10 IU/mL (HR 2.426 [1.224-4.809], p = .011), baseline ALT ≥2 ULN (HR 2.726 [1.299-5.721], p = .008) and age <35 (HR 2.859 [1.255-6.513], p = .012) to be positive predictors of HBeAg SC. The 'SydPreg Score' estimated the probability of HBeAg SC at 2000 days as 10%, 30%, 70% and 80% for 0, 1, 2, and 3 predictors respectively. CONCLUSION: The SydPreg Score allows the prediction of HBeAg SC in the years after pregnancy. Even in those without elevated ALT, age <35 and viral load <8 log10 IU/mL can identify women with a good chance of subsequent HBeAg SC. Those without a chance may benefit from viral suppression.

Microfabricated disk technology: Rapid scale up in midbrain organoid generation.

By providing a three-dimensional in vitro culture system with key features of the substantia nigra region in the brain, 3D neuronal organoids derived from human induced pluripotent stem cells (iPSCs) provide living neuronal tissue resembling the midbrain region of the brain. However, a major limitation of conventional brain organoid culture is that it is often labor-intensive, requiring highly specialized personnel for moderate throughput. Additionally, the methods published for long-term cultures require time-consuming maintenance to generate brain organoids in large numbers. With the increasing need for human midbrain organoids (hMOs) to better understand and model Parkinson's disease (PD) in a dish, there is a need to implement new workflows and methods to both generate and maintain hMOs, while minimizing batch to batch variation. In this study, we developed a method with microfabricated disks to scale up the generation of hMOs. This opens up the possibility to generate larger numbers of hMOs, in a manner that minimizes the amount of labor required, while decreasing variability and maintaining the viability of these hMOs over time. Taken together, producing hMOs in this manner opens up the potential for these to be used to further PD studies.

An approach to measuring protein turnover in human induced pluripotent stem cell organoids by mass spectrometry.

Patient-derived organoids from induced pluripotent stem cells have emerged as a model for studying human diseases beyond conventional two-dimensional (2D) cell culture. Briefly, these three-dimensional organoids are highly complex, capable of self-organizing, recapitulate cellular architecture, and have the potential to model diseases in complex organs, such as the brain. For example, the hallmark of Parkinson's disease (PD) - proteostatic dysfunction leading to the selective death of neurons in the substantia nigra - present a subtle distinction in cell type specificity that is lost in 2D cell culture models. As such, the development of robust methods to study global proteostasis and protein turnover in organoids will remain essential as organoid models evolve. To solve this problem, we have designed a workflow to reproducibly extract proteins from brain organoids, measure global turnover using mass spectrometry, and statistically investigate turnover differences between genotypes. We also provide robust methodology for data filtering and statistical treatment of turnover data. Using human midbrain organoids (hMO) as a model system, our method accurately characterized the half-lives of 773 midbrain proteins. We compared these half-lives both to Parkin knockout hMOs and to previously reported data from primary cell cultures and in vivo models. Overall, this method will facilitate the study of proteostasis in organoid models of human disease and will provide an analytical and statistical framework to measure protein turnover in organoids of all cell types.

A deep learning approach for transgender and gender diverse patient identification in electronic health records.

BACKGROUND: Although accurate identification of gender identity in the electronic health record (EHR) is crucial for providing equitable health care, particularly for transgender and gender diverse (TGD) populations, it remains a challenging task due to incomplete gender information in structured EHR fields. OBJECTIVE: Using TGD identification as a case study, this research uses NLP and deep learning to build an accurate patient gender identity predictive model, aiming to tackle the challenges of identifying relevant patient-level information from EHR data and reducing annotation work. METHODS: This study included adult patients in a large healthcare system in Boston, MA, between 4/1/2017 to 4/1/2022. To identify relevant information from massive clinical notes, we compiled a list of gender-related keywords through expert curation, literature review, and expansion via a fine-tuned BioWordVec model. This keyword list was used to pre-screen potential TGD individuals and create two datasets for model training, testing, and validation. Dataset I was a balanced dataset that contained clinician-confirmed TGD patients and cases without keywords. Dataset II contained cases with keywords. The performance of the deep learning model was compared to traditional machine learning and rule-based algorithms. RESULTS: The final keyword list consists of 109 keywords, of which 58 (53.2%) were expanded by the BioWordVec model. Dataset I contained 3,150 patients (50% TGD) while Dataset II contained 200 patients (90% TGD). On Dataset I the deep learning model achieved a F1 score of 0.917, sensitivity of 0.854, and a precision of 0.980; and on Dataset II a F1 score of 0.969, sensitivity of 0.967, and precision of 0.972. The deep learning model significantly outperformed rule-based algorithms. CONCLUSION: This is the first study to show that deep learning-integrated NLP algorithms can accurately identify gender identity using EHR data. Future work should leverage and evaluate additional diverse data sources to generate more generalizable algorithms.

The Role of Physician Advocacy in Supporting Policy Change That Reduces Leaded Aviation Gasoline Emissions.

BACKGROUND: Leaded aviation gasoline (AvGas) accounts for 70%, or 935,082 pounds, of total lead emissions in the United States and has been repeatedly linked to elevated blood lead levels (BLLs) in those living in the vicinity of airports using AvGas. The well-established link between lead exposure and adverse health outcomes provided a platform ripe for environmental health advocates and pediatric health experts to assist a local environmental health organization in addressing lead waste from a local airport, Montgomery-Gibbs Executive Airport (MYF). METHOD: We detail the steps we took, as a physician clean-air advocacy group. We provide a qualitative analysis of our efforts in addressing leaded air pollution through targeted and creative environmental health advocacy through three main avenues: government, public awareness, and academia. OBJECTIVES: Our actions were taken to ensure the City of San Diego installed an unleaded fuel tank at MYF to reduce leaded aviation gasoline usage and subsequently lead air pollution in the surrounding area. DISCUSSION: Ultimately, the identified objective of an unleaded fuel tank was added to the San Diego City budget and scheduled for construction. We hope our actions can serve as a framework to provide concrete steps for clinicians and other advocates to enact change in their communities.

Climate Change Imperils Pediatric Health: Child Advocacy Through Fossil Fuel Divestment.

Climate change poses an existential threat to children's health. Divestment of ownership stakes in fossil fuel companies is one tool available to pediatricians to address climate change. Pediatricians are trusted messengers regarding children's health and therefore bear a unique responsibility to advocate for climate and health policies that affect children. Among the impacts of climate change on pediatric patients are allergic rhinitis and asthma; heat-related illnesses; premature birth; injuries from severe storms and fires; vector-borne diseases; and mental illnesses. Children are disproportionately affected as well by climate-related displacement of populations, drought, water shortages, and famine. The human-generated burning of fossil fuels emits greenhouse gases (GHG) such as carbon dioxide, which trap heat in the atmosphere and cause global warming. The US healthcare industry is responsible for 8.5% of the nation's entire greenhouse gases and toxic air pollutants. In this perspectives piece we review the principle of divestment as a strategy for improving childhood health. Healthcare professionals can help combat climate change by embracing divestment in their personal investment portfolios and by their universities, healthcare systems, and professional organizations. We encourage this collaborative organizational effort to reduce greenhouse gas emissions.

Genome-wide occupancy of Arabidopsis SWI/SNF chromatin remodeler SPLAYED provides insights into its interplay with its close homolog BRAHMA and Polycomb proteins.

SPLAYED (SYD) is a SWItch/Sucrose Non-Fermentable (SWI/SNF)-type chromatin remodeler identified in Arabidopsis thaliana (Arabidopsis). It is believed to play both redundant and differential roles with its closest homolog BRAHMA (BRM) in diverse plant growth and development processes. To better understand how SYD functions, we profiled the genome-wide occupancy of SYD and its impact on the global transcriptome and trimethylation of histone H3 on lysine 27 (H3K27me3). To map the global occupancy of SYD, we generated a GFP-tagged transgenic line and used it for chromatin immunoprecipitation experiments followed by next-generation sequencing, by which more than 6000 SYD target genes were identified. Through integrating SYD occupancy and transcriptome profiles, we found that SYD preferentially targets to nucleosome-free regions of expressed genes. Further analysis revealed that SYD occupancy peaks exhibit five distinct patterns, which were also shared by BRM and BAF60, a conserved SWI/SNF complex component, indicating the common target sites of these SWI/SNF chromatin remodelers and the functional relevance of such distinct patterns. To investigate the interplay between SYD and Polycomb-group (PcG) proteins, we performed a genome-wide analysis of H3K27me3 in syd-5. We observed both increases and decreases in H3K27me3 levels at a few hundred genes in syd-5 compared to wild type. Our results imply that SYD can act antagonistically or synergistically with PcG at specific genes. Together, our SYD genome-wide occupancy data and the transcriptome and H3K27me3 profiles provide a much-needed resource for dissecting SYD's crucial roles in the regulation of plant growth and development.

Health Within Reach-a Patient-Centered Intervention to Increase Hepatitis B Screening Among Asian Americans: a Randomized Clinical Trial.

BACKGROUND: There are few studies to date of interventions to increase viral hepatitis screening among Asian Americans, who have high rates of chronic hepatitis B (HBV) infection. OBJECTIVE: To develop, implement, and test the efficacy of a mobile application (Hepatitis App) delivered in four languages to increase HBV screening among Asian Americans. DESIGN: Cluster-randomized clinical trial. PARTICIPANTS: Four hundred fifty-two Asian American patients ≥ 18 years of age, who had no prior HBV testing, and received primary care within two healthcare systems in San Francisco, CA. INTERVENTIONS: The intervention group received the Hepatitis App, delivering interactive video education on viral hepatitis in English, Cantonese, Mandarin, or Vietnamese and a provider printout (Provider Alert) and Provider Panel Notification. The comparison group received a mobile application delivering nutrition and physical activity education and Provider Panel Notification. MAIN MEASURES: Primary outcomes were patient-provider discussion about HBV and documentation of a HBV screening test within 3 months post-intervention. Secondary outcome was documentation of an order for a HBV screening test. KEY RESULTS: Participants had a mean age of 57 years and were 64% female, 80% foreign-born, and 44% with limited English fluency. At post-visit, over 80% of intervention participants reported they liked using the Hepatitis App. At 3-month follow-up, the intervention group was more likely than the comparison group (all P < 0.001) to have discussed HBV with their provider (70% vs.16%), have a HBV test ordered (44% vs.10%), and receive a HBV test (38% vs.8%). In multivariable analyses, the intervention odds ratio for HBV test ordering was 7.6 (95% CI: 3.9, 14.8) and test receipt was 7.5 (95% CI: 3.6, 15.5). CONCLUSIONS: A multi-lingual educational intervention using a mobile application in primary care clinics was well received by Asian American patients, enhanced patient-provider communication about HBV, and increased HBV screening. Technology can improve healthcare quality among Asian Americans. TRIAL REGISTRATION: ClinicalTrials.gov NCT02139722 ( https://clinicaltrials.gov/ct2/show/NCT02139722 ).

Spike protein of SARS-CoV-2 activates macrophages and contributes to induction of acute lung inflammation in male mice.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a crucial role in mediating viral entry into host cells. However, whether it contributes to pulmonary hyperinflammation in patients with coronavirus disease 2019 is not well known. In this study, we developed a spike protein-pseudotyped (Spp) lentivirus with the proper tropism of the SARS-CoV-2 spike protein on the surface and determined the distribution of the Spp lentivirus in wild-type C57BL/6J male mice that received an intravenous injection of the virus. Lentiviruses with vesicular stomatitis virus glycoprotein (VSV-G) or with a deletion of the receptor-binding domain (RBD) in the spike protein [Spp (∆RBD)] were used as controls. Two hours postinfection (hpi), there were 27-75 times more viral burden from Spp lentivirus in the lungs than in other organs; there were also about 3-5 times more viral burden from Spp lentivirus than from VSV-G lentivirus in the lungs, liver, kidney, and spleen. Deletion of RBD diminished viral loads in the lungs but not in the heart. Acute pneumonia was observed in animals 24 hpi. Spp lentivirus was mainly found in SPC+ and LDLR+ pneumocytes and macrophages in the lungs. IL6, IL10, CD80, and PPAR-γ were quickly upregulated in response to infection in the lungs as well as in macrophage-like RAW264.7 cells. Furthermore, forced expression of the spike protein in RAW264.7 cells significantly increased the mRNA levels of the same panel of inflammatory factors. Our results demonstrated that the spike protein of SARS-CoV-2 confers the main point of viral entry into the lungs and can induce cellular pathology. Our data also indicate that an alternative ACE2-independent viral entry pathway may be recruited in the heart and aorta.

Selective internal radiation therapy for hepatocellular carcinoma: A 15-year multicenter Australian cohort study.

BACKGROUND AND AIM: The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS: We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION: We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.

Single-Amplicon Multiplex Real-Time Reverse Transcription-PCR with Tiled Probes To Detect SARS-CoV-2 spike Mutations Associated with Variants of Concern.

To provide an accessible and inexpensive method to surveil for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations, we developed a multiplex real-time reverse transcription-PCR (rRT-PCR) assay, the Spike single-nucleotide polymorphism (SNP) assay, to detect specific mutations in the spike receptor binding domain. A single primer pair was designed to amplify a 348-bp region of spike, and probes were initially designed to detect K417, E484K, and N501Y. The assay was evaluated using characterized variant sample pools and residual nasopharyngeal samples. Variant calls were confirmed by SARS-CoV-2 genome sequencing in a subset of samples. Subsequently, a fourth probe was designed to detect L452R. The lower limit of 95% detection was 2.46 to 2.48 log10 genome equivalents (GE)/ml for the three initial targets (∼1 to 2 GE/reaction). Among 253 residual nasopharyngeal swabs with detectable SARS-CoV-2 RNA, the Spike SNP assay was positive in 238 (94.1%) samples. All 220 samples with threshold cycle (CT) values of <30 for the SARS-CoV-2 N2 target were detected, whereas 18/33 samples with N2 CT values of ≥30 were detected. Spike SNP results were confirmed by sequencing in 50/50 samples (100%). Addition of the 452R probe did not affect performance for the original targets. The Spike SNP assay accurately identifies SARS-CoV-2 mutations in the receptor binding domain, and it can be quickly modified to detect new mutations that emerge.

Opiates prescribed for acute renal colic are associated with prolonged use.

PURPOSE: Patients presenting with acute renal colic may be at risk of opiate abuse. We sought to analyze prescribing patterns and identify risk factors associated with prolonged opiate use during episodes of acute renal colic. METHODS: Retrospective study of patients presenting with both a stone confirmed on imaging and an acute pain episode from 6/2017-2/2020. Opiate prescription data was obtained from a statewide prescribing database. Primary outcome was an opiate refill or new opiate prescription prior to resolution of the stone episode (either passage or surgery). Univariate and multivariate linear regression analysis was performed. RESULTS: A total of 271 patients met inclusion criteria. Mean age was 52 years and 48% had a history of nephrolithiasis. 180 (66%) patients filled a new opiate prescription during their acute stone episode. Thirty-eight (14%) patients had an existing opiate prescription within 3 months of their stone episode. Seventy-four (27%) patients refilled an opiate prescription prior to stone passage or surgery. Larger stone size, need for surgery, prolonged time to treatment, existing opiate prescription, new opiate prescription at presentation, and greater initial number of pills prescribed were associated with increased risk of requiring a refill prior to stone resolution. CONCLUSIONS: Patients prescribed new opiates for acute nephrolithiasis and those with an existing opioid prescription are likely to require refills before resolution of the stone episode. Larger stones that require surgery (not spontaneous passage) also increase the risk. Timely treatment of these patients and initial treatment with non-narcotics may reduce the risk of prolonged opiate use.

Mtor inhibitors associated with higher cardiovascular adverse events-A large population database analysis.

There are limited real-world data available regarding adverse events (AEs) of immunosuppressants. We utilized the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2018 to perform a retrospective database analysis. We analyzed AE reports due to the individual agents tacrolimus, sirolimus, or everolimus and compared reporting odds ratios of the mTOR inhibitors to tacrolimus. The mTOR inhibitors arm had 1282 reports with 4176 AEs, while the tacrolimus arm had a total of 7587 reports with 20 940 individual AEs. mTOR inhibitors had significantly higher incidences of cardiovascular (ROR 1.95, 95% CI 1.70, 2.23), dermatologic (ROR 1.34, 95% CI 1.04, 1.73), endocrine (ROR 1.52, 95% CI 1.26, 1.82), gastrointestinal (ROR 1.15, 95% CI 1.01, 1.30), infectious disease (ROR 1.35, 95% 1.20, 1.52), musculoskeletal (ROR 1.39, 95% CI 1.13, 1.70), pulmonary (ROR 3.46, 95% 2.97, 4.03), renal (ROR 1.27, 95% CI 1.10, 1.46), and vascular AEs (ROR 3.10, 95% CI 2.14, 4.49). Across every organ type, mTOR inhibitors had greater cardiovascular AEs compared to tacrolimus, specifically in arteriosclerosis, heart failure, hypotension, tachycardia, chest pain, edema, and pericardial disorders. mTOR inhibitors may be associated with higher cardiovascular AEs. Further investigation is required to determine the potential mechanism of this effect.

A Solution to Academic Radiology's Experience With Solicitation E-mails From Predatory Journals.

OBJECTIVE. The objective of our study was to help academic researchers avoid predatory publishers by characterizing the problem with respect to radiology and medical imaging and to test an intervention to address aggressive e-mail solicitation. MATERIALS AND METHODS. In total, 803 faculty from 10 U.S. academic radiology departments and 193 faculty in the senior author's department were surveyed about their experiences with soliciting journals. To document the characteristics of these journals and their publishers, we retrospectively reviewed the academic institutional e-mail box of one radiologist over 51 days. Journals' bibliometric parameters were compared with those of established medical imaging journals offering open access publishing. We tested filters for selected syntax to identify spam e-mails during two time periods. RESULTS. Of 996 faculty, 206 responded (16% nationally, 42% locally). Most (98%) received e-mails from soliciting publishers. Only 7% published articles with these publishers. Submission reasons were invitations, fee waivers, and difficulty publishing elsewhere. Overall, 94 publishers sent 257 e-mails in 51 days, 50 of which offered publishing opportunities in 76 imaging journals. Six journals were indexed in PubMed, and two had verifiable impact factors. The six PubMed-indexed journals had a lower mean publication fee ($824) than top medical imaging journals ($3034) (p < 0.001) and had a shorter mean duration of existence (9.5 vs 49.0 years, respectively; p = 0.005). The e-mail filters captured 71% of soliciting e-mails during the initial 51-day period and 85% during the same period 1 year later. CONCLUSION. Soliciting publishers have little impact on scientific literature. Academicians can avoid soliciting e-mails with customized e-mail filters.

Follow-up study on serum cholesterol profiles and potential sequelae in recovered COVID-19 patients.

BACKGROUND: COVID-19 patients develop hypolipidemia. However, it is unknown whether lipid levels have improved and there are potential sequlae in recovered patients. OBJECTIVE: In this follow-up study, we evaluated serum lipidemia and various physiopathological laboratory values in recovered patients. METHODS: A 3-6 month follow-up study was performed between June 15 and September 3, 2020, to examine serum levels of laboratory values in 107 discharged COVID-19 patients (mild = 59; severe/critical = 48; diagnoses on admission). Sixty-one patients had a revisit chest CT scan. A Wilcoxon signed-rank test was used to analyze changes in laboratory values at admission and follow-up. RESULTS: LDL-c and HDL-c levels were significantly higher at follow-up than at admission in severe/critical cases (p <  0.05). LDL-c levels were significantly higher at follow-up than at admission in mild cases (p <  0.05). Coagulation and liver functional values were significantly improved at follow-up than at admission for patients (p <  0.05). Increases in HDL-c significantly correlated with increases in numbers of white blood cells (p <  0.001) during patients' recovery. With exclusion of the subjects taking traditional Chinese medicines or cholesterol-lowering drugs, LDL-c and HDL-c levels were significantly increased at follow-up than at admission in severe/critical cases (p <  0.05). Residue lesions were observed in CT images in 72% (44 of 61) of follow-up patients. CONCLUSIONS: Improvements of LDL-c, HDL-c, liver functions, and incomplete resolution of lung lesions were observed at 3-6 month follow-up for recovered patients, indicating that a long-term recovery process could be required and the development of sequelae such as pulmonary fibrosis could be expected in some patients.

Novel mRNA-Based Therapy Reduces Toxic Galactose Metabolites and Overcomes Galactose Sensitivity in a Mouse Model of Classic Galactosemia.

Classic galactosemia (CG) is a potentially lethal inborn error of galactose metabolism that results from deleterious mutations in the human galactose-1 phosphate uridylyltransferase (GALT) gene. Previously, we constructed a GalT-/- (GalT-deficient) mouse model that exhibits galactose sensitivity in the newborn mutant pups, reduced fertility in adult females, impaired motor functions, and growth restriction in both sexes. In this study, we tested whether restoration of hepatic GALT activity alone could decrease galactose-1 phosphate (gal-1P) and plasma galactose in the mouse model. The administration of different doses of mouse GalT (mGalT) mRNA resulted in a dose-dependent increase in mGalT protein expression and enzyme activity in the liver of GalT-deficient mice. Single intravenous (i.v.) dose of human GALT (hGALT) mRNA decreased gal-1P in mutant mouse liver and red blood cells (RBCs) within 24 h with low levels maintained for over a week. Repeated i.v. injections increased hepatic GalT expression, nearly normalized gal-1P levels in liver, and decreased gal-1P levels in RBCs and peripheral tissues throughout all doses. Moreover, repeated dosing reduced plasma galactose by 60% or more throughout all four doses. Additionally, a single intraperitoneal dose of hGALT mRNA overcame the galactose sensitivity and promoted the growth in a GalT-/- newborn pup.