Injectable Fluocinolone Implant for the Management of Cystoid Macular Edema in Coats' Disease.

A six-year-old boy with history of Coats' disease and cystoid macular edema (CME) was treated with a combination of peripheral retinal laser, anti-vascular endothelial grown factor injections, and short-acting injectable steroids to control his disease process. Given the excellent response to shorter acting steroids and the need for general anesthesia for each procedure, the patient underwent placement of the injectable fluocinolone acetonide implant 0.18 mg (YUTIQ) with control of his CME at 30 months of follow-up. The authors conclude that a long-acting steroid implant may be beneficial in select patients with Coats' disease. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Cochrane systematic reviews in orthodontics: trends across updates.

BACKGROUND: Systematic reviews (SR) are regularly updated to reflect new evidence. However, updates are time-consuming and costly, and therefore should ideally be informed by new high-quality research. The purpose of this study is to assess trends in the quantity, quality, and recency of evidence intervening updates of orthodontic SR. METHODS: SR relevant to orthodontics with at least two versions were identified from the Cochrane Database. The number, risk of bias, and year of publication of included trials were recorded for each update. Multivariate regression was conducted to assess factors affecting the risk of bias in trials, and the proportions within SR. RESULTS: Forty-five SR inclusive of updates were included. The median number of trials was three per review and this increased across subsequent versions. Seven reviews (15.6%) included no evidence, and 40.74% of updates included no new evidence. Most of the primary research was considered high risk of bias (57.3%), although this was reduced marginally across updates. The proportion of studies considered low risk did not improve significantly between updates. There was no impact of publication year of clinical trials on the risk of bias (P = 0.349). However, average age of trials included in a systematic review significantly affected the proportion of low risk-of-bias studies (P = 0.039). CONCLUSIONS: SR are frequently updated without including new evidence. New evidence that is included is commonly deemed to be at high risk of bias. Targeted strategies to improve the efficient use of resources and improve research quality should be considered.

Zinner Syndrome: The Diagnosis and Management of a Rare Urogenital Malformation.

This case highlights an atypical but important consideration in young males presenting with persistent gastrointestinal and/or genitourinary symptoms. Zinner syndrome (ZS) develops from embryologic maldevelopment of the distal mesonephric duct, resulting in ejaculatory duct atresia with consequent obstruction of the seminal vesicle and concomitant ureteral bud malformation, leading to renal agenesis/dysplasia. The lack of distinct clinical symptoms makes ZS a difficult diagnosis to reach: Abdominal pain and dysuria are often mistaken for prostatitis or cystitis. However, the use of modern imaging modalities aids in establishing the diagnosis. Early identification of ZS may delay progression to infertility as the duct obstruction may not be as extensive, though further research is needed to establish this connection.

FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55α/PP2A through helical motifs.

The Ser/Thr protein phosphatase 2 A (PP2A) regulates the dephosphorylation of many phosphoproteins. Substrate recognition are mediated by B regulatory subunits. Here, we report the identification of a substrate conserved motif [RK]-V-x-x-[VI]-R in FAM122A, an inhibitor of B55α/PP2A. This motif is necessary for FAM122A binding to B55α, and computational structure prediction suggests the motif, which is helical, blocks substrate docking to the same site. In this model, FAM122A also spatially constrains substrate access by occluding the catalytic subunit. Consistently, FAM122A functions as a competitive inhibitor as it prevents substrate binding and dephosphorylation of CDK substrates by B55α/PP2A in cell lysates. FAM122A deficiency in human cell lines reduces the proliferation rate, cell cycle progression, and hinders G1/S and intra-S phase cell cycle checkpoints. FAM122A-KO in HEK293 cells attenuates CHK1 and CHK2 activation in response to replication stress. Overall, these data strongly suggest that FAM122A is a short helical motif (SHeM)-dependent, substrate-competitive inhibitor of B55α/PP2A that suppresses multiple functions of B55α in the DNA damage response and in timely progression through the cell cycle interphase.

Essential Tremors: A Literature Review of Current Therapeutics.

Essential tremors (ETs) commonly manifest as involuntary shaking of the hands that disrupt daily activities. These tremors involve the central motor network of the cerebellum, thalamus, and cortical networks, leading to different clinical phenotypes. The goal of this review was to establish evidence-based recommendations for effective care and simplify decisions for those dealing with ET. For this narrative literature review, we conducted a thorough search using core keywords such as "essential tremor" and "therapy." From the 27 selected articles, relevant data were presented regarding pathophysiology, medications, and other treatment options, with necessary supplemental data such as side effects and use cases. This paper examines treatments for ET, including commonly prescribed medications such as propranolol and primidone; invasive treatments such as deep brain stimulation, focused ultrasound thalamotomy, transcranial magnetic stimulation, and some surgical methods; and non-invasive methods such as the neuromodulation technique of transcutaneous afferent patterned stimulation. Overall, this study presents a synthesized understanding of the currently available modalities for managing ETs. It is intended to guide care providers in choosing the best possible method to contain symptoms.

Patient-Reported Outcomes in Phase 3 Clinical Trials for Blood Cancers: A Systematic Review.

Importance: Published research suggests that patient-reported outcomes (PROs) are neither commonly collected nor reported in randomized clinical trials (RCTs) for solid tumors. Little is known about these practices in RCTs for hematological malignant neoplasms. Objective: To evaluate the prevalence of PROs as prespecified end points in RCTs of hematological malignant neoplasms, and to assess reporting of PROs in associated trial publications. Evidence Review: All issues of 8 journals known for publishing high-impact RCTs (NEJM, Lancet, Lancet Hematology, Lancet Oncology, Journal of Clinical Oncology, Blood, JAMA, and JAMA Oncology) between January 1, 2018, and December 13, 2022, were searched for primary publications of therapeutic phase 3 trials for adults with hematological malignant neoplasms. Studies that evaluated pretransplant conditioning regimens, graft-vs-host disease treatment, or radiotherapy as experimental treatment were excluded. Data regarding trial characteristics and PROs were extracted from manuscripts and trial protocols. Univariable analyses assessed associations between trial characteristics and PRO collection or reporting. Findings: Ninety RCTs were eligible for analysis. PROs were an end point in 66 (73%) trials: in 1 trial (1%) as a primary end point, in 50 (56%) as a secondary end point, and in 15 (17%) as an exploratory end point. PRO data were reported in 26 of 66 primary publications (39%): outcomes were unchanged in 18 and improved in 8, with none reporting worse PROs with experimental treatment. Trials sponsored by for-profit entities were more likely to include PROs as an end point (49 of 55 [89%] vs 17 of 35 [49%]; P < .001) but were not significantly more likely to report PRO data (20 of 49 [41%] vs 6 of 17 [35%]; P = .69). Compared with trials involving lymphoma (18 of 29 [62%]) or leukemia or myelodysplastic syndrome (18 of 28 [64%]), those involving plasma cell disorders or multiple myeloma (27 of 30 [90%]) or myeloproliferative neoplasms (3 of 3 [100%]) were more likely to include PROs as an end point (P = .03). Similarly, compared with trials involving lymphoma (3 of 18 [17%]) or leukemia or myelodysplastic syndrome (5 of 18 [28%]), those involving plasma cell disorders or multiple myeloma (16 of 27 [59%]) or myeloproliferative neoplasms (2 of 3 [67%]) were more likely to report PROs in the primary publication (P = .01). Conclusions and Relevance: In this systematic review, almost 3 of every 4 therapeutic RCTs for blood cancers collected PRO data; however, only 1 RCT included PROs as a primary end point. Moreover, most did not report resulting PRO data in the primary publication and when reported, PROs were either better or unchanged, raising concern for publication bias. This analysis suggests a critical gap in dissemination of data on the lived experiences of patients enrolled in RCTs for hematological malignant neoplasms.

Derivation of human primary prostate epithelial cell lines by differentially targeting the CDKN2A locus along with expression of hTERT.

Prostate cancer (PCa) is the most common cancer diagnosed in men worldwide and the second leading cause of cancer-related deaths in US males in 2022. Prostate cancer also represents the second highest cancer mortality disparity between non-Hispanic blacks and whites. However, there is a relatively small number of prostate normal and cancer cell lines compared to other cancers. To identify the molecular basis of PCa progression, it is important to have prostate epithelial cell (PrEC) lines as karyotypically normal as possible. Our lab recently developed a novel methodology for the rapid and efficient immortalization of normal human PrEC that combines simultaneous CRISPR-directed inactivation of CDKN2A exon 2 (which directs expression of p16INK4A and p14ARF) and ectopic expression of an hTERT transgene. To optimize this methodology to generate immortalized lines with minimal genetic alterations, we sought to target exon 1α of the CDKN2A locus so that p16INK4A expression is ablated while p14ARF expression remains unaltered. Here we describe the establishment of two cell lines: one with the above-mentioned p16INK4A only loss, and a second line targeting both products in the CDKN2A locus. We characterize the potential lineage origin of these new cell lines along with our previously obtained clones, revealing distinct gene expression signatures. Based on the analyses of protein markers and RNA expression signatures, these cell lines are most closely related to a subpopulation of basal prostatic cells. Given the simplicity of this one-step methodology and the fact that it uses only the minimal genetic alterations necessary for immortalization, it should also be suitable for the establishment of cell lines from primary prostate tumor samples, an urgent need given the limited number of available prostate cancer cell lines.

Optimising referral letters for the dental practitioner.

Referrals are defined as 'a process in which a health worker at one level of the health system, having insufficient resources (drugs, equipment, skills) to manage a clinical condition, seeks the help of a better or differently resourced facility at the same or higher level to assist in patient management'. Within the UK, the NHS dental service is divided into nationally defined levels of care, which provide treatment based upon complexity and patient modifying factors. Having a sound knowledge of these levels will help general dental practitioners (GDPs) make appropriate and efficient onward referrals to the correct service.This article aims to outline the key information required for all strong GDP referrals, as well as highlighting information that may be specific to each speciality. This is with the hope of creating a key list for GDPs to use on clinic when writing referrals to reduce the incidence of missed information and subsequent rejection. The article also aims to outline the levels of NHS dental care and what factors and treatments are suitable for each to aid GDPs during their referral decision-making process.

Outcomes and factors associated with cryptococcal disease among cirrhotics: A study of the national inpatient sample 2005 to 2014.

BACKGROUND: Cryptococcal disease (CD) confers a higher mortality in cirrhotic patients compared to non-cirrhotic patients. Factor association for CD in cirrhotic patients is poorly understood. Our aim was to determine the incidence, demographic, and comorbidities associated with CD among cirrhotic patients in the United States (US). METHOD: Retrospective analysis of admissions of cirrhotic patients, with or without CD, using the National Inpatient Sample (NIS) database from 2005 to 2014. The number of admissions were reported in raw and weighted frequencies. The trends of CD among cirrhotic patients and overall CD were evaluated. Rao-Scott chi-square, t-tests, and multivariate logistic regressions were performed to evaluate variables and CD among cirrhotic patients. RESULTS: There were 886,962 admissions for cirrhosis, and 164 of these with CD. By adjusted odds ratio (AOR), CD was more often associated with cirrhosis in Southern (2.95; 95 % CI 1.24, 7.02) and Western regions (4.45; 95 % CI 1.91, 10.37), Hispanic patients (1.80; 95 % CI 1.01, 3.20), and patients with chronic kidney disease (CKD) (3.13; 95 % CI 2.09, 4.69). Of note, CD in cirrhotic patients was associated with higher inpatient mortality (AOR of 3.89, 95 % CI 2.53, 5.99), longer length of stay (9.87 vs. 4.88 days), and a higher total charge ($76,880 vs. $ 37,227) when compared to cirrhotic patients without CD. DISCUSSION: Patients with cirrhosis admitted with CD have a high inpatient mortality. The geographical location and CKD were important factors associated with CD among cirrhotic patients. Autoimmune liver diseases and immunosuppression did not appear to increase the risk of CD.

Evaluating Large Language Models for Drafting Emergency Department Discharge Summaries.

Importance: Large language models (LLMs) possess a range of capabilities which may be applied to the clinical domain, including text summarization. As ambient artificial intelligence scribes and other LLM-based tools begin to be deployed within healthcare settings, rigorous evaluations of the accuracy of these technologies are urgently needed. Objective: To investigate the performance of GPT-4 and GPT-3.5-turbo in generating Emergency Department (ED) discharge summaries and evaluate the prevalence and type of errors across each section of the discharge summary. Design: Cross-sectional study. Setting: University of California, San Francisco ED. Participants: We identified all adult ED visits from 2012 to 2023 with an ED clinician note. We randomly selected a sample of 100 ED visits for GPT-summarization. Exposure: We investigate the potential of two state-of-the-art LLMs, GPT-4 and GPT-3.5-turbo, to summarize the full ED clinician note into a discharge summary. Main Outcomes and Measures: GPT-3.5-turbo and GPT-4-generated discharge summaries were evaluated by two independent Emergency Medicine physician reviewers across three evaluation criteria: 1) Inaccuracy of GPT-summarized information; 2) Hallucination of information; 3) Omission of relevant clinical information. On identifying each error, reviewers were additionally asked to provide a brief explanation for their reasoning, which was manually classified into subgroups of errors. Results: From 202,059 eligible ED visits, we randomly sampled 100 for GPT-generated summarization and then expert-driven evaluation. In total, 33% of summaries generated by GPT-4 and 10% of those generated by GPT-3.5-turbo were entirely error-free across all evaluated domains. Summaries generated by GPT-4 were mostly accurate, with inaccuracies found in only 10% of cases, however, 42% of the summaries exhibited hallucinations and 47% omitted clinically relevant information. Inaccuracies and hallucinations were most commonly found in the Plan sections of GPT-generated summaries, while clinical omissions were concentrated in text describing patients' Physical Examination findings or History of Presenting Complaint. Conclusions and Relevance: In this cross-sectional study of 100 ED encounters, we found that LLMs could generate accurate discharge summaries, but were liable to hallucination and omission of clinically relevant information. A comprehensive understanding of the location and type of errors found in GPT-generated clinical text is important to facilitate clinician review of such content and prevent patient harm.

Cost-effectiveness of adding quizartinib to induction chemotherapy for patients with FLT3-mutant acute myeloid leukemia.

The FLT3 inhibitor quizartinib has been shown to improve overall survival when added to intensive induction chemotherapy ("7 + 3") in patients 18-75 years old with newly diagnosed AML harboring a FLT3-ITD mutation. However, the health economic implications of this approval are unknown. We evaluated the cost-effectiveness of quizartinib using a partitioned survival analysis model. One-way and probabilistic sensitivity analyses were conducted. In the base case scenario, the addition of quizartinib to 7 + 3 resulted in incremental costs of $289,932 compared with 7 + 3 alone. With an incremental gain of 0.84 quality-adjusted life years (QALYs) with quizartinib + 7 + 3 induction vs. 7 + 3 alone, the incremental cost-effectiveness ratio for the addition of quizartinib to standard 7 + 3 was $344,039/QALY. Only an 87% reduction in the average wholesale price of quizartinib or omitting quizartinib continuation therapy after completion of consolidation therapy and allogeneic hematopoietic cell transplant would make quizartinib a cost-effective option.

Severe Spontaneous Tilt of Scleral-Fixated Intraocular Lenses.

PURPOSE: To report and evaluate a multicenter series of 18 cases of severe, spontaneous IOL tilt involving the flanged intrascleral haptic fixation technique (FISHF). DESIGN: Clinical study with historical controls. METHODS: We report a cross-sectional study of 46 FISHF cases using the CT Lucia 602 IOL at a single academic center over a period of 24 weeks to determine the incidence of severe rotisserie-style rotational tilt. These rates were then compared with the same time-frame the prior year to help determine if this is a new phenomenon. Additional cases of severe tilt were solicited from another 4 academic centers. RESULTS: Among 46 FISHF cases at a single center, 5 developed severe tilt. No clear pattern in surgical technique, ocular history, or ocular anatomy was evident in these cases compared with controls, although the involved IOLs clustered within a narrow diopter range, indicative of a batch effect. In the same 24-week interval the year before, 33 FISHF cases were performed, none of which exhibited severe rotational tilt. In our multicenter dataset, 18 cases of tilt were identified. Surgeons included fellow and early-career physicians as well as surgeons with multiple years of experience with the Yamane technique. A variety of surgical approaches for FISHF were represented. In at least 8 of the cases, haptic rotation and/or dehiscence at the optic-haptic junction were documented. CONCLUSIONS: The identification of haptic rotation and dehiscence intraoperatively in several cases may reflect a new stability issue involving the optic-haptic junction.

Examining the Interrelationships Between Social Isolation and Loneliness and Their Correlates Among Older British Adults Before and During the COVID-19 Lockdown: Evidence From Four British Longitudinal Studies.

Background and Objectives: Unprecedented social restrictions during the coronavirus disease 2019 (COVID-19) pandemic have provided a new lens for considering the interrelationship between social isolation and loneliness in later life. We present these interrelationships before and during the COVID-19 restrictions and investigate to what extent demographic, socioeconomic, and health factors associated with such experiences differed during the pandemic. Research Design and Methods: We used data from four British longitudinal population-based studies (1946 NSHD, 1958 NCDS, 1970 BCS, and ELSA, N = 12,129). Rates, co-occurrences, and correlates of social isolation and loneliness are presented prior to and during the early stage of the COVID-19 pandemic and the interrelationships between these experiences are elucidated in both periods. Results: Across the Four studies, prepandemic proportions reporting social isolation ranged from 15% to 54%, with higher rates in older ages (e.g., 32% of individuals aged 70-79 years and 54% of those more than 80). During the pandemic, the percentage of older people reporting both social isolation and loneliness and isolation only slightly increased. The interrelationship between social isolation and loneliness did not change. Associations between sociodemographic and health characteristics and social isolation and loneliness also remained consistent, with greater burden among those with higher economic precarity (females, nonhomeowners, unemployed, illness, and greater financial stress). Discussion and Implications: There were already large inequalities in experiences of social isolation and loneliness and the pandemic had a small impact on worsening extent and inequalities in these. The concepts of loneliness and social isolation are not interchangeable, and clarity is needed in how they are conceptualized, operationalized, and interpreted. Given many older adults experience high levels of social isolation, there should be greater emphasis on reducing social isolation and the inequalities observed in who experiences greater isolation and loneliness.

Electrochemistry at the Edge of a van der Waals Heterostructure.

Artificial van der Waals heterostructures, obtained by stacking two-dimensional (2D) materials, represent a novel platform for investigating physicochemical phenomena and applications. Here, the electrochemistry at the one-dimensional (1D) edge of a graphene sheet, sandwiched between two hexagonal boron nitride (hBN) flakes, is reported. When such an hBN/graphene/hBN heterostructure is immersed in a solution, the basal plane of graphene is encapsulated by hBN, and the graphene edge is exclusively available in the solution. This forms an electrochemical nanoelectrode, enabling the investigation of electron transfer using several redox probes, e.g., ferrocene(di)methanol, hexaammineruthenium, methylene blue, dopamine and ferrocyanide. The low capacitance of the van der Waals edge electrode facilitates cyclic voltammetry at very high scan rates (up to 1000 V s-1), allowing voltammetric detection of redox species down to micromolar concentrations with sub-second time resolution. The nanoband nature of the edge electrode allows operation in water without added electrolyte. Finally, two adjacent edge electrodes are realized in a redox-cycling format. All the above-mentioned phenomena can be investigated at the edge, demonstrating that nanoscale electrochemistry is a new application avenue for van der Waals heterostructures. Such an edge electrode will be useful for studying electron transfer mechanisms and the detection of analyte species in ultralow sample volumes.

Inertial measurement and heart-rate sensor-based dataset for geriatric fall detection using custom built wrist-worn device.

This paper describes a dataset acquired from 41 volunteers performing 16 Activities of daily livings (ADLs) and 8 Falls repeated 5 times. This data was collected using a custom wrist-worn end device. The dataset has data collected from Inertial measurement unit (IMU) and heart-rate sensors. The end device is built using Qualcomm Snapdragon 820c System on Chip (SoC) interfaced to the sensors via Interconnect Integrated Circuit (I2C) protocol. The data was sampled for every activity at a rate of 20 Hz for the motion sensors and at a rate of 1 Hz for the heart-rate sensor. The motion sensor comprised of a triaxial accelerometer, triaxial gyroscope, triaxial magnetometer and a linear accelerometer. The heart-rate sensor was medical grade and all sensors were calibrated for the wrist -worn position. The dataset is available on this website https://shamanx86.github.io/fall_detection_data/ and https://doi.org/10.5281/zenodo.10013090.

Orbital compartment syndrome following primary scleral buckle surgery.

PURPOSE: To illustrate a patient with orbital compartment syndrome following scleral buckle placement that was successfully treated with canthotomy and cantholysis. METHODS: Observational case report. RESULTS: A 26-year-old male underwent a primary scleral buckle repair for a chronic rhegmatogenous retinal detachment. On post-operative day four, the patient presented to the emergency room with pain and increased intraocular pressure (IOP). Initial treatment with conservative IOP lowering agents was unsuccessful. The patient was diagnosed with delayed orbital compartment syndrome and was successfully managed with lateral canthotomy and inferior cantholysis in addition to aggressive steroid and antibiotic medical management. CONCLUSION: Following scleral buckle placement with sub-tenon's anesthesia block, there may be a delayed presentation of orbital compartment syndrome. Recognition and management of this rare complication is important for preventing irreversible blindness.

A Narrative Review of the Use of Artificial Intelligence in Breast, Lung, and Prostate Cancer.

Artificial intelligence (AI) has been an important topic within radiology. Currently, AI is used clinically to assist with the detection of lesions through detection systems. However, a number of recent studies have demonstrated the increased value of neural networks in radiology. With an increasing number of screening requirements for cancers, this review aims to study the accuracy of the numerous AI models used in the detection and diagnosis of breast, lung, and prostate cancers. This study summarizes pertinent findings from reviewed articles and provides analysis on the relevancy to clinical radiology. This study found that whereas AI is showing continual improvement in radiology, AI alone does not surpass the effectiveness of a radiologist. Additionally, it was found that there are multiple variations on how AI should be integrated with a radiologist's workflow.

Volatile anesthetics inhibit presynaptic cGMP signaling to depress presynaptic excitability in rat hippocampal neurons.

Volatile anesthetics alter presynaptic function through effects on Ca2+ influx and neurotransmitter release. These actions are proposed to play important roles in their pleiotropic neurophysiological effects including immobility, unconsciousness and amnesia. Nitric oxide and cyclic guanosine monophosphate (NO/cGMP) signaling has been implicated in presynaptic mechanisms, and disruption of NO/cGMP signaling has been shown to alter sensitivity to volatile anesthetics in vivo. We investigated volatile anesthetic actions NO/cGMP signaling in relation to presynaptic function in cultured rat hippocampal neurons using pharmacological tools and genetically encoded biosensors and sequestering probes of cGMP levels. Using the fluorescent cGMP biosensor cGull, we found that electrical stimulation-evoked NMDA-type glutamate receptor-independent presynaptic cGMP transients were inhibited 33.2% by isoflurane (0.51 mM) and 26.4% by sevoflurane (0.57 mM) (p < 0.0001) compared to control stimulation without anesthetic. Stimulation-evoked cGMP transients were blocked by the nonselective inhibitor of nitric oxide synthase N-ω-nitro-l-arginine, but not by the selective neuronal nitric oxide synthase inhibitor N5-(1-imino-3-butenyl)-l-ornithine. Isoflurane and sevoflurane inhibition of stimulation-evoked increases in presynaptic Ca2+ concentration, measured with synaptophysin-GCaMP6f, and of synaptic vesicle exocytosis, measured with synaptophysin-pHlourin, was attenuated in neurons expressing the cGMP scavenger protein sponge (inhibition of exocytosis reduced by 54% for isoflurane and by 53% for sevoflurane). The anesthetic-induced reduction in presynaptic excitability was partially occluded by inhibition of HCN channels, a cGMP-modulated excitatory ion channel that can facilitate glutamate release. We propose that volatile anesthetics depress presynaptic cGMP signaling and downstream effectors like HCN channels that are essential to presynaptic function and excitability. These findings identify novel mechanisms by which volatile anesthetics depress synaptic transmission via second messenger signaling involving the NO/cGMP pathway in hippocampal neurons.