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Retreatability of Endosequence® BCS™ Hiflow Utilizing Both Chloroform and An Aqueous Solution
No full textPurpose: When RCT fails, retreatment of the case usually requires removal of the previous root canal fill (RCF). The aim of our research was to evaluate the retreatability of a root canal initially filled with gutta percha and EndoSequence® BCS™ HiFlow utilizing chloroform followed by 18% HCl, 18% HCl alone, chloroform alone or saline solution. Methods: 40 extracted single canal teeth were decoronated and obturated utilizing a single cone gutta percha technique and Endosequence BCS, stored one week in an incubator, and then we attempted to remove the previous RCF. Teeth were divided in 4 different groups (n=10). Canals were then cleaned using heat, rotary instruments, hand files and specific solutions. Group A - cleaned by using only saline solution, Group B - cleaned by using only chloroform solution, Group C - cleaned by using only 18% HCl solution, and Group D - cleaned by using chloroform + 18% HCl. Image J software was used to evaluate and quantify the amount of obturation material left in the canal after cleaning of the canals. Results: The pairwise comparison showed no significant difference between chloroform used alone and 18% HCl used alone (P = 0.82). However, chloroform + 18%HCl treatment showed a significant difference between chloroform alone (P = 0.026), 18% HCl alone (P = 0.021), and saline alone (0.003). Conclusion: The result of this study indicates that chloroform followed by 18% HCl was superior in removing the previous RCF Compared to the individual solutions used alone in canals filled with gutta-percha and BCS. However, regardless of the solution used, patency could be achieved
Higher incidence of dermatological immune-related adverse events in cancer patients treated with immune checkpoint inhibitors vs. other treatments: a TriNetX research network study
No full textNo risk of major adverse cardiovascular events after Mohs surgery using a large national database
No full textFilling the tank: A multicenter investigation of trauma survival after ultramassive transfusion
No full textINTRODUCTION: Ultramassive transfusion (UMT), transfusion of ≥ 20U of red blood cell products in the first 24 hours, is rare, requires significant resource utilization, and is associated with high mortality. The aim of this study was to describe the characteristics of trauma patients undergoing UMT and determine patterns associated with survival after UMT. METHODS: This retrospective, multicenter analysis from 11 high-volume trauma centers included traumatically injured patients older than 14 years who received UMT from 2016 to 2024. Demographic, clinical, and outcome data were obtained and compared between survivors and nonsurvivors. The primary outcome was survival with secondary outcome of need for specific operative interventions. RESULTS: A total of 1,155 patients received UMT with a mortality rate of 62.9%. Between survivors and nonsurvivors, there was no difference in mechanism of injury. Survivors presented were tachycardic (120 vs. 98 beats per minute, p \u3c 0.001) and had a higher initial Glasgow Coma Scale score (14 vs. 3, p \u3c 0.001), higher initial platelet count (189 vs. 149 103/μL, p \u3c 0.001), and smaller initial base deficit (8 vs. 11.8 mmol/L, p \u3c 0.001). Survivors underwent more extremity explorations (25.2% vs. 14.4%, p \u3c 0.001) and had more extremity vascular injuries (22.9% vs. 13.2%, p \u3c 0.001). The odds of mortality increased with age (odds ratio [OR], 1.026; 95% confidence interval [CI], 1.015-1.037; p \u3c 0.001), Injury Severity Score (OR, 1.025; 95% CI, 1.013-1.036; p \u3c 0.001), initial lactate (OR, 1.119; 95% CI, 1.079-1.161; p \u3c 0.001), and emergency department thoracotomy (OR, 3.92; 95% CI, 2.129-7.223; p \u3c 0.001). The odds of mortality decreased with higher Glasgow Coma Scale score (OR, 0.93; 95% CI, 0.897-0.962; p \u3c 0.001), heart rate (OR, 0.995; 95% CI, 0.990-0.9997; p = 0.04), and initial platelet count (OR, 0.998; 95% CI, 0.996-0.999; p = 0.04). CONCLUSION: This study affirms known factors influencing mortality in UMT and describes new patterns associated with reduced mortality including higher initial heart rate, extremity exploration, and concomitant extremity vascular injury. These findings can inform clinical decision making in the care of this challenging patient population. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III
Polymorphic α-Glucans as Structural Scaffolds in Cryptococcus Cell Walls for Chitin, Capsule, and Melanin: Insights From 13C and 1H Solid-State NMR
Get PDFCryptococcus species are major fungal pathogens responsible for life-threatening infections in approximately a million individuals globally each year, with alarmingly high mortality rates. These fungi are distinguished by a distinctive cell wall architecture further reinforced by two virulence-associated layers, melanin and capsule, rendering them insensitive to antifungal agents targeting the cell wall, such as echinocandins. The molecular interplay between these three biomolecular layers remains poorly understood. Here we employ solid-state NMR spectroscopy to examine intact cells of both wild-type and capsule-deficient strains of C. neoformans, along with melanized cells. High-resolution 13C and 1H data revealed five distinct structural forms of α-1,3-glucans that play versatile roles in forming the rigid cell wall scaffold by interacting with chitin microfibrils and chitosan, and in stabilizing the mobile matrix by associating with β-1,6-glucan and a small fraction of β-1,3-glucan. Two primary forms of α-1,3-glucans were distributed throughout the cell wall, hosting melanin deposition in the inner domain and capsule attachment on the cell surface. These findings offer a paradigm shift in understanding the cryptococcal cell wall and its interaction with two key virulence factors on opposite sides, raising critical biochemical questions that could inform the development of more effective antifungal treatments for cryptococcosis
Whole-Exome Sequencing Identified Molecular Variants Linked to the Progression of Gastric Precancerous Lesions in Patients from Southwestern Colombia—An Exploratory Approach.
Get PDFQualitative insights into drug use safety strategies and social support among sexual minority women who inject drugs in Baltimore, Maryland
Get PDFBackground: Sexual minority women (SMW) experience higher rates of substance use relative to heterosexual women in the U.S. but remain an under-studied population. SMW who inject drugs (SMWWID) navigate an unpredictable drug market and may experience complex relationships within their social spheres. We explore cisgender SMWWID’s strategies to maintain safety while injecting drugs, and the influence of their social support systems on those strategies. Methods: We conducted N = 16 phone-based, semi-structured, in-depth interviews with SMWWID in Baltimore, Maryland between June-October 2021. The interviews explored participants’ sexual orientation and gender identities, social networks and support systems, drug use behaviors and HIV risk, and experiences accessing services. Using an inductive thematic analysis approach, we examined emergent themes related to drug use, social support, safety, and HIV and identified key safety strategies and social support experiences for SMWWID. Results: SMWWID employed various strategies to “stay safe,” which they primarily interpreted as ensuring overdose safety (i.e., using drugs in the presence of others, carrying Naloxone, purchasing strategies), and additionally as infectious disease safety (i.e., avoiding syringe sharing, using sterile syringes) and avoiding threats of violence (i.e., maintaining situational awareness while using drugs). Romantic or sexual partners, family and friends, and the wider community were sources of social support for overdose safety, and family and friends also provided material support (e.g., financial, housing). Syringe sharing with romantic partners and threats of violence from people in the community detracted from SMWWID’s safety. Conclusion: SMWWID in this sample reported strong safety prioritization while using drugs, often facilitated by their social support systems. Harm reduction interventions that consider SMWWID’s relationships, including those that aim to improve social connectedness, may better meet the needs of SMWWID, thereby enhancing safety
Real-world treatment patterns and management gaps of lumbar disc herniation in the United States
Get PDFBACKGROUND: Lumbar disc herniation (LDH) affects approximately 1% to 3% of the population annually and leads to substantial physical burden, quality-of-life burden, and productivity loss. Commonly used interventions, including pharmacological and epidural steroid injections (ESIs), have limited high-quality evidence to support their effectiveness in the long-term for treating LDH beyond symptom relief. In general, there is a lack of consensus for timing of treatment after LDH onset and limited data on real-world treatment of LDH. The objective of this study was to describe current real-world treatment patterns and inform gaps in clinical management of patients with LDH. METHODS: A retrospective analysis was performed using data from January 01, 2018 through March 31, 2023 of a United States commercial health insurance claims database (IQVIA PharMetrics Plus). Patients aged 30-70 years with newly-diagnosed LDH and continuous insurance enrollment for ≥6 months before and ≥12 months after index (first) LDH diagnosis were included. Relevant billing codes were used to identify LDH, related treatments (nonpharmacologic, pharmacologic, invasive), and comorbidities. Demographic and clinical characteristics were summarized for the baseline (preindex) period. Treatment patterns were described over the follow-up period, up to 3 years after LDH diagnosis. Time from LDH diagnosis to ESI(s) and surgery(ies) were calculated. RESULTS: A total of 1,086,552 patients with LDH were included, with a mean age of 50.8 years. Patients had a mean follow-up of 27 months after LDH diagnosis. Nearly 20% of patients with LDH underwent ESI, with half of this group undergoing multiple ESIs. Multiple ESIs were associated with a greater likelihood of surgical intervention and repeat surgical intervention compared to those who only underwent single ESI. LDH surgery was performed on 7.2% of patients, approximately 10% of whom had multiple surgeries during follow-up. A large subset (44.1%) of patients who underwent LDH surgery did not have any ESI prior to surgery. General limitations of claims data analyses can include data misclassification, missing claims for diagnoses and procedures that were conducted, missing clinical information (severity of condition, insights into clinical decision making), and some missing patient demographics and characteristics. CONCLUSIONS: In this study, approximately one quarter of patients with LDH underwent ESI and/or surgery after conservative treatment. Opportunities exist to provide more guideline-concordant care to patients with LDH. In addition, unmet needs exist in the current treatment options for patients with LDH, potentially including the need for other nonsurgical treatment options for patients who do not fully respond to conservative treatment
IFI16 Mediates Deacetylation of KSHV Chromatin via Interaction with NuRD and Sin3A Co-Repressor Complexes
Get PDFIFI16 is a well-characterized nuclear innate immune DNA sensor that detects foreign dsDNA, including herpesviral genomes, to activate the inflammasome and interferon pathways. Beyond immune signaling, IFI16 also functions as an antiviral restriction factor, promoting the silencing of invading viral genes through transcriptional and epigenetic mechanisms. We recently demonstrated another role of IFI16, in which it interacts with and recruits the class I histone deacetylases, HDAC1 and 2, to the KSHV latency protein LANA, modulating its acetylation and function. In this study, we asked whether these IFI16-HDAC1/2 interactions contribute to broader epigenetic regulation of the KSHV chromatin. Our findings reveal that IFI16 associates with and facilitates the recruitment of the NuRD and Sin3A co-repressor complexes-both multiprotein, HDAC1/2-containing chromatin regulators-on KSHV episomes. Depletion of IFI16 led to reductions in NuRD and Sin3A occupancy on viral chromatin, accompanied by increased histone acetylation at lytic gene promoters. These results suggest that IFI16 plays a critical role in recruiting or stabilizing these HDAC-containing co-repressor complexes on the KSHV genome, thereby enforcing transcriptional silencing of lytic genes and maintaining latency in KSHV. Our study expands the known functions of IFI16 and identifies a novel epigenetic mechanism by which it modulates herpesviral chromatin states
The Dual-Port Approach to the Posterior Incisura: A Quantitative Cadaver Study of a Combined Endoscopic Paramedian Supracerebellar Infratentorial and Occipital Interhemispheric Transtentorial Approach
No full textBACKGROUND: The posterior incisura is a deep and surgically challenging area with complex neurovasculature. Endoscopic paramedian supracerebellar infratentorial approaches (EPSCITAs) have improved access and visualization of this region. However, endoscope and instrument conflict within this deep and narrow corridor remains a key limitation. This study evaluates the feasibility of a combined EPSCITA and endoscopic occipital interhemispheric transtentorial approach (EOIHTTA) with the aim of improving surgical freedom and visualization in this region. METHODS: Five embalmed and latex-injected cadaveric donors were dissected bilaterally (10 sides total). Measurements were taken at the EPSCITA port and then were repeated after addition of the EOIHTTA port. Measurements of surgical freedom at 3 anatomic targets, area of exposure, distance to the pineal gland, and angle at approach port, were obtained using stereotactic navigation. Statistical analyses were performed using 2-sample t-tests. RESULTS: Addition of the EOIHTTA port improved the vertical angle of approach from 15.07° to 58.96°, P \u3c 0.0001, and horizontal angle of approach from 28.1° to 50.02°, P \u3c 0.0001. The area of surgical freedom at each anatomic target increased notably, with the area at the pineal gland expanding from 663 mm to 1042 mm, P \u3c 0.005, the superior colliculus from 806 mm to 1090 mm, P \u3c 0.005, and the splenium from 415 mm to 902 mm, P \u3c 0.005. CONCLUSIONS: This dual-port approach enhances access to the posterior incisura, providing improved surgical exposure and maneuverability while reducing instrument conflict. This technique is an effective minimally invasive approach to this deep-seated region, addressing the limitations of traditional single-port techniques