Long-term risk of reintervention after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has surpassed surgical aortic valve replacement (SAVR) as the predominant mode of valve replacement for the treatment of severe aortic stenosis (AS). However, the long-term need for valvular reintervention after TAVR remains unknown. METHODS: Using data from the Medicare Fee for Service 100% dataset, all patients receiving TAVR between July 2011 and December 2020 were identified. Patients were categorized as receiving a valve reintervention (either surgical or transcatheter) or not using the appropriate International Classification of Diseases 10th Revision Procedure Coding System (ICD-10-PCS). A competing risk regression model was used to estimate the cumulative probability of valve reintervention. RESULTS: Of 230,644 TAVR patients were identified, of whom 1,880 received a reintervention. Patients receiving a reintervention were younger and more likely to be male. At 10 years, the crude rate of reintervention was 0.59% within a surviving cohort of 341 patients. After adjusting for the competing risk of death and other covariates, the adjusted cumulative incidence of reintervention at 10 years after TAVR was 1.63%. When the rate of reinterventions was compared between early (2011-2016) and later (2017-2020) time periods, the risk-adjusted rate of reintervention at 4 years had decreased over time (0.85% vs 0.51%). CONCLUSION: The 10-year risk of valve reintervention after TAVR is low and appears to be decreasing over time. Further research is necessary to determine the driving factors contributing to valve reintervention in the current era.

Integrative Conjugative Elements (ICEs) of the SXT/R391 family drive adaptation and evolution in γ-Proteobacteria.

Integrative Conjugative Elements (ICEs) are mosaics containing functional modules allowing maintenance by site-specific integration and excision into and from the host genome and conjugative transfer to a specific host range. Many ICEs encode a range of adaptive functions that aid bacterial survival and evolution in a range of niches. ICEs from the SXT/R391 family are found in γ-Proteobacteria. Over 100 members have undergone epidemiological and molecular characterization allowing insight into their diversity and function. Comparative analysis of SXT/R391 elements from a wide geographic distribution has revealed conservation of key functions, and the accumulation and evolution of adaptive genes. This evolution is associated with gene acquisition in conserved hotspots and variable regions within the SXT/R391 ICEs catalysed via element-encoded recombinases. The elements can carry IS elements and transposons, and a mutagenic DNA polymerase, PolV, which are associated with their evolution. SXT/R391 ICEs isolated from different niches appear to have retained adaptive functions related to that specific niche; phage resistance determinants in ICEs carried by wastewater bacteria, antibiotic resistance determinants in clinical isolates and metal resistance determinants in bacteria recovered from polluted environments/ocean sediments. Many genes found in the element hotspots are undetermined and have few homologs in the nucleotide databases.

Lymphovascular Invasion in Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Although there is a large body of literature regarding risk stratification and outcomes for perineural invasion (PNI) in cutaneous squamous cell carcinoma (cSCC), there is a relative paucity of studies exploring the role of lymphovascular invasion (LVI) in cSCC and a lack of clear evidence-based guidelines for how to manage patients with these tumors. OBJECTIVE: This article is intended to review the available literature regarding LVI in cSCC and formulate evidence-based recommendations for clinical management. METHODS AND MATERIALS: A literature review was conducted using PubMed to find relevant articles relating to outcomes and management of primary cSCC with LVI. RESULTS: The available literature suggests that LVI is a major risk factor for poor outcomes and increased morbidity and mortality in cSCC. CONCLUSION: Lymphovascular invasion is a very high-risk feature that should place these tumors in the highest-risk category, and management of these tumors should be similar to that of squamous cell carcinoma with PNI.

Use of iso-osmolar contrast media during endovascular revascularization is associated with a lower incidence of major adverse renal, cardiac, or limb events.

OBJECTIVE: We examined the association of iso-osmolar contrast media (IOCM) versus low-osmolar contrast media (LOCM) with major adverse renal, cardiovascular, or limb events in patients at high-risk of acute kidney injury (AKI) undergoing peripheral endovascular procedures. BACKGROUND: Procedural characteristics including iodinated contrast type and volume have been associated with adverse renal and cardiovascular outcomes in patients undergoing angiographic interventions. METHODS: Patients at high-risk of AKI, undergoing peripheral endovascular procedures were identified using the Premier Healthcare Database and separated into claudication and critical limb ischemia (CLI) cohorts. For each cohort, we compared IOCM versus LOCM for the primary endpoint of MARCE (major adverse renal or cardiovascular events) and secondary endpoints of major adverse renal events (MARE) and major adverse renal and limb events (MARLE). These outcomes were captured within the indexed hospitalization via adjusted multivariable regression analyses. RESULTS: Two procedure-based cohorts of high-risk patients were formed: claudication (N = 11,976) and CLI (N = 8713). Use of IOCM was associated with a significant absolute risk reduction (ARR) of 2.2% (p < 0.0001) for MARCE overall and in each cohort (claudication, 1.8%, p = 0.0070; CLI, 2.7%, p = 0.0054). The incidence of MARE and MARLE in the overall cohort was also lower with the use of IOCM: MARE (ARR = 1.4%, p = 0.0072) and MARLE (ARR = 2.0%, p = 0.0043). CONCLUSIONS: Using IOCM versus LOCM in patients at high-risk of adverse renal events undergoing peripheral endovascular procedures was independently associated with lower risk of MARCE, MARE, and MARLE.

The need for future coronary access following surgical or transcatheter aortic valve replacement.

The aim of the study was to estimate the percentage of Medicare patients needing coronary access for percutaneous coronary intervention (PCI) or coronary angiography following aortic valve replacement (AVR). Indications for TAVR have expanded to include younger and low-risk patients, raising the question of coronary access for future procedures. Medicare patients <80 years old with an AVR between 2011 and 2018 were included. Time-to-event analyses were conducted using Cox hazard models to estimate risk of coronary access up to 7 years after AVR. Model adjustments included age, sex, race, region, comorbidity, concomitant CABG, and smoking. A total of 13,469 Medicare patients (mean age 70.6) met inclusion criteria. Models estimated that 2.5% of patients at 1-year post-index and 17% at over 7 years would need coronary access. For patients who had SAVR (with or without CABG), estimates for coronary access were similar and over 15% after 6.5 years. For TAVR patients, with a previous PCI, 28% at 4.5 years required coronary access, which was higher than TAVR patients without a previous PCI. SAVR patients with and without CAD at baseline were similar; however, TAVR patients with CAD had a 22% rate of coronary access versus 7% for those without at 3 years. Approximately half of patients who needed coronary access returned to the same hospital as their initial AVR. Coronary access is required in a substantial portion of AVR patients especially those with PCI or a history of CAD undergoing TAVR. The need for coronary access may increase as transcatheter AVR becomes accessible to younger patients with a longer life expectancy.

Psychodermatology fellowship: is it time?

The fields of dermatology and psychiatry have overlap in the patient populations and diseases they treat. However, there are not currently fellowship opportunities for dermatologists or psychiatrists specifically interested in gaining expertise in psychodermatology. We discuss the logistics of a one-year psychodermatology fellowship, open to residents after completing either dermatology or psychiatry residencies, and the potential benefits that it could bring to both dermatology and psychiatry training programs across the county.

Utilizing o-Quinone Methide Chemistry: Synthesis of d9-Ivacaftor.

Lead time and cost are important factors for any pharmaceutical API. However, these issues become even more important when the drug substance contains an isotope such as deuterium, which has a natural abundance of only ∼0.016% of all hydrogen. Fewer suppliers and logistical barriers both play a role in driving up the cost. These factors can challenge the supply route used to manufacture d9-ivacaftor (17), requiring investigation into alternative routes. By adapting the work from Pettus et al., a synthetic approach utilizing a transient o-quinone methide allowed access to the deuterium-labeled o-tert-butylphenol moiety. This was developed and proven on pilot scale to significantly reduce the number of deuterated reagents used, leading to an overall reduction in cost by a factor of 10, while also providing the substantial benefit of applying prior process knowledge from the parent, nonisotopically enriched API ivacaftor (7).

Basomelanocytic Neoplasms: A Report of Two Similar Tumors With Divergent Treatments.

Basomelanocytic neoplasms are tumors consisting of elements of both basal cell carcinoma and melanoma. These tumors are exceedingly rare and present a unique challenge as to how the melanoma component should be classified. Due to the paucity of cases, there are no clear-cut evidence-based guidelines as to how these tumors should be staged and which treatment options provide the optimal outcome. We present 2 separate patients with similar cases of colonizing basomelanocytic tumors that were treated in drastically different ways, highlighting the differing approaches to treatment. We discuss theses treatment modalities and the challenges inherent to diagnosing and treating basomelanocytic neoplasms.

Rate of major adverse renal or cardiac events with iohexol compared to other low osmolar contrast media during interventional cardiovascular procedures.

OBJECTIVE: This study assessed the rate of major adverse renal or cardiac events (MARCE) when iohexol is used during interventional cardiovascular procedures compared to other low osmolar contrast media (LOCMs). BACKGROUND: Interventional cardiovascular procedures are often essential for diagnosis and treatment, the risk of MARCE should be considered. METHODS: Data were derived from the Premier Hospital Database January 1, 2010 through September 30, 2015. Patient encounters with an inpatient primary interventional cardiovascular procedure with a single LOCM (iohexol, ioversol, ioxilan, ioxaglate, or iopamidol) were included. The primary outcome was a composite endpoint of MARCE, which included: renal failure with dialysis, acute kidney injury (AKI) with or without dialysis, contrast induced AKI, acute myocardial infarction, angina, stent occlusion/thrombosis, stroke, transient ischemic attack, or death. Multivariable regression analysis was performed using the hospital fixed-effects specification to assess the relationship between MARCE and iohexol compared to other LOCMs, while controlling for patient demographics, comorbid conditions and reason for hospitalization. As a sensitivity analysis, direct comparisons of iohexol were made to other LOCMs. RESULTS: A total of 458,091 inpatient encounters met inclusion criteria of which 26% used iohexol and 74% used other LOCMs. Results of multivariable modeling revealed no differences in MARCE rates between iohexol and other LOCMs. When direct comparisons of iohexol vs. ioversol and iopamidol were modeled, no differences in MARCE nor the renal component of MARCE were found. CONCLUSIONS: In this retrospective multicenter study, there were no differences in MARCE events with iohexol compared to other LOCMs during inpatient interventional cardiovascular procedures.

A rare variant of extraskeletal osteosarcoma presenting as a clinically benign subcutaneous neoplasm.

Extraskeletal osteosarcoma (ESOS) is a rare variant of osteosarcoma that arises without attachment to the underlying skeleton. These cancers are typically found embedded in deeper tissues, most commonly the muscle or fascia, and are rarely found within the skin or subcutis. Most tumors are large in size upon initial presentation, and carry a poor prognosis. We discuss the case of a 48-year-old Caucasian woman who presented to a dermatology clinic with an asymptomatic, small, mobile, subcutaneous mass that appeared clinically benign. After elective removal and histopathologic examination, the patient was diagnosed with ESOS. ESOS presenting in this manner is exceedingly rare, and this case highlights the importance of sending all excised specimens, even those with a benign presentation, for pathologic examination.

Ulcerated tophaceous gout.

Gout is a common inflammatory arthropathy with a high prevalence worldwide. Increased levels of uric acid in the blood lead to deposition of monosodium urate crystals in the joints, inflammation, and pain. Acute gout attacks are often sudden, monoarticular, and typically resolve within a week, whereas chronic gout is often polyarticular with baseline pain between attacks. In chronic gout, depositions of uric acid known as tophi can form throughout the body. Despite the high prevalence of gout and the frequency with which tophi occur, ulceration over tophi is surprisingly rare. We report the case of a 38-year-old man, undiagnosed with gout, who presented to clinic for evaluation of ulcers with chalky white granules. The wounds were determined to be ulcerated tophaceous gout. Risk factors for ulceration over tophi and reported treatments are discussed.

Medical school ranking and dermatology match results: an analysis of the 2018 match data.

Dermatology is a specialty with fewer residency positions each year than total applicants, leading to increased competition in the match. Applicants tend to have substantial research experience and high national board scores. This study sought to explore whether there is a difference in the percentage of graduates matching into dermatology residencies based on the rank of the medical school. Publicly available match lists from highly ranked medical schools were compared to match lists from other allopathic schools to determine the proportion of graduates matching into dermatology. The data was analyzed using a chi square test and a significant difference was found between the percentage of students matching into dermatology from top schools (5.19%) compared to control schools (1.92%), (P<0.0001).

Bullous hemorrhagic lichen sclerosus of the breast: a report of two cases and review of the literature.

Lichen sclerosus (LS) is a chronic dermatologic condition characterized by atrophic porcelain-appearing plaques that can cause intense discomfort and eventually lead to destruction of local architecture. Lichen sclerosus most commonly arises in the anogenital area, but up to 20% of cases can present on extragenital skin. Rarely, LS can also present with hemorrhage and bullae; the mechanism by which this occurs is unknown. We report two cases of bullous hemorrhagic LS of the breast arising in 66-year-old and 77-year-old women. Bullous hemorrhagic LS of the breast is exceedingly rare, with few reported cases, and presents a diagnostic challenge to clinicians.

A sex-dependent change in behavioral temperature regulation in African house snakes (Lamprophis fuliginosus) challenged with different pathogens.

Behavioral fever in reptiles is often considered an adaptive response used to eliminate pathogens, yet empirical data showing the wide-spread use of this response is mixed. This behavioral change can be beneficial by enhancing the host's immune response and increasing the animal's chance of survival, but it can also be detrimental in terms of host energetic requirements and enzymatic performance. Thus, we examined whether captive-bred African house snakes (Lamprophis fuliginosus) employed behavioral fever in response to pathogen stimulus. Twenty-one African house snakes were injected separately with three different strains of ultraviolet (UV) light-killed bacteria (Escherichia coli, Staphylococcus aureus, Salmonella enterica). We found an increased variance of hourly cloacal temperatures following exposure to pathogens in male but not female house snakes. We did not, however, find a significant febrile response to pathogen exposure as measured via mean cloacal temperature. This research adds critical information to the field of reptilian physiology as this field remains understudied. Reptilian immune function and its relationship with thermal biology is ever more pertinent as new challenges arise, such as novel pathogens and changing climate.

Utilization and likelihood of radiologic diagnostic imaging in patients with implantable cardiac defibrillators.

PURPOSE: To examine imaging utilization in a matched cohort of patients with and without implantable cardioverter defibrillators (ICD) and to project magnetic resonance imaging (MRI) utilization over a 10-year period. MATERIALS AND METHODS: The Truven Health MarketScan Commercial claims and Medicare Supplemental health insurance claims data were used to identify patients with continuous health plan enrollment in 2009-2012. Patients with ICDs were identified using ICD-9 and CPT codes, and matched to patients with the same demographic and comorbidity profile, but no record of device implantation. Diagnostic imaging utilization was compared across the matched cohorts, in total, by imaging categories, and in subpopulations of stroke, back pain, and joint pain. MRI use in the nonimplant group over the 4-year period was extrapolated out to 10 years for ICD-indicated patients. RESULTS: A cohort of 18,770 matched patients were identified; average age 65.5 ± 13.38 and 21.9% female. ICD patients had significantly less MRI imaging (0.23 0.70 SD vs. 0.00 0.08 SD, P < 0.0001) than nonimplant patients. Among patients with records of stroke/transient ischemic attack (TIA) (ICD 5%, nonimplant 4%) and accompanying diagnostic imaging, 44% of nonimplant patients underwent MRI vs. 1% of ICD patients (P < 0.0001). Forecast models estimated that 53% to 64% of ICD-eligible patients may require an MRI within 10 years. CONCLUSION: MRI utilization is lower in ICD patients compared to nonimplant patients, yet the burden of incident stroke/TIA, back, and joint pain suggests an unmet need for MR-conditional devices.

The Rate of Magnetic Resonance Imaging in Patients with Deep Brain Stimulation.

BACKGROUND: For Parkinson's disease (PD), essential tremor (ET), and dystonia patients with deep brain stimulation (DBS) implants, magnetic resonance imaging (MRI) requires additional safety considerations due to potentially hazardous interactions. OBJECTIVE: A propensity-matched cohort of DBS-implanted patients was analyzed to determine the likelihood of needing MRI. METHODS: Patients with new DBS full-system implants (n = 576) were identified in the Truven Health MarketScan® Commercial Claims and Medicare Supplemental Databases (2009-2012). Patients diagnosed with PD, ET, or dystonia and no DBS implant were identified (DBS-indicated patients: n = 11,216). The DBS-indicated patients were continuously enrolled for 4 years and matched for age, gender, and propensity score based on comorbid conditions to DBS-implanted patients (n = 4,878 and 543, respectively). A Kaplan-Meier survival curve of time to first MRI was extrapolated to 10 years. RESULTS: An estimated 56-57% of DBS-indicated patients need an MRI within 5 years and 66-75% within 10 years after implantation. While 92% of DBS-implanted patients' MRI after implantation was of the head, for DBS-indicated patients, 62% of MRIs were of the body, potentially unrelated to the primary diagnosis. CONCLUSIONS: This analysis highlights the projected utilization of MRI in the DBS population for head and full-body images.

New developments concerning the proximal tubule in diabetic nephropathy: in vitro models and mechanisms.

The incidence of Type 2 diabetes is increasing rapidly worldwide, and understanding the mechanisms of its complications including diabetic nephropathy (DN) is important in the discovery of early biomarkers, understanding the causative mechanisms of its complications and identifying therapeutic targets. DN is characterized by glomerulosclerosis, tubulointerstitial fibrosis and tubular atrophy. The tubular component of the disease is important in progression of disease. In vitro models are a valuable alternative to animal studies and an effective way to explore mechanisms of human disease. Several proximal tubular cell lines have been used in studying mechanisms of DN. Key extracellular conditions that contribute to damage to the proximal tubule in DN include hyperglycaemia, proteinuria, and hypoxia and inflammation. According to current knowledge, these exert their effects through changes in transforming growth factor beta signalling, the renin-angiotensin system, dysregulation of pathways such as the polyol pathway, hexosamine pathway and protein kinase C pathway and through formation of advanced glycation end products. Studies in cell culture models have been instrumental in the delineation of these processes. However, all of the existing cell culture models have limitations including dedifferentiation. To bring research forward along with technological advances, such as major advances in 'omics' methodologies, a more suitable model is necessary. The RPTEC/TERT1 cell line is a promising alternative to previous proximal tubular epithelial cell lines due to features that resemble the cell type in vivo, such as its epithelial characteristics, maintenance of functional capabilities, glucose handling, expression of the primary cilium and transport activity including albumin. This cell line will facilitate identification of mechanisms of DN with potential to identify new therapeutic targets.