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Improving Vaccination Rates in Adult Solid Organ Transplant Candidates: Impact of an Infectious Diseases Pretransplant Clinic
No full textBACKGROUND: Despite guidelines recommending pretransplant immunizations for solid organ transplant candidates (SOTc), vaccine uptake is suboptimal. We evaluated the impact of an Infectious Disease Pretransplant (IDPT) clinic for improving vaccinations in SOTc.
METHODS: A retrospective quality improvement study of SOTc seen in the IDPT clinic between January 2020 and February 2021 at the Henry Ford Transplant Institute. Vaccination status before (pre-IDPT clinic visit) and 6 months after (post-IDPT clinic visit) were determined for influenza, pneumococcus, hepatitis B, hepatitis A, tetanus, and zoster vaccines. Differences in per-person year (PPY) vaccination rates and uptake of each vaccine type between the two time points were assessed. Factors associated with vaccine completion (at least one dose of six adult vaccines) in the post-IDPT clinic visit period were analyzed with logistic regression.
RESULTS: Of the 200 SOTc included, 60% were men. Vaccination rates were significantly higher in the post-IDPT clinic visit period; difference in median PPY vaccination rate was 0.61 (p \u3c 0.001). Uptake was statistically significant for all six vaccine classes. A total of 29% patients completed vaccination. Increasing age was associated with likelihood of vaccine completion (odds ratio [OR], 1.14; 95% CI 1.08-1.21). Heart and lung transplant candidates had significantly higher odds of vaccine completion than kidney candidates after IDPT clinic visits (Heart: OR, 7.01; 95% CI 2.39-20.55) (Lung: OR, 10.76; 95% CI 3.56-32.55).
CONCLUSION: IDPT clinic visits significantly increased vaccination rates in SOTc, especially in heart and lung transplant candidates. The IDPT clinic optimized vaccine completion for this highly vulnerable population
Targeted Overexpression of Mitochondrial ALDH2 in Coronary Endothelial Cells Mitigates HFpEF in a Diabetic Mouse Model
No full textHeart failure (HF) has become an epidemic, with a prevalence of ~7 million cases in the USA. Despite accounting for nearly 50% of all HF cases, heart failure with a preserved ejection fraction (HFpEF) remains challenging to treat. Common pathophysiological mechanisms in HFpEF include oxidative stress, microvascular dysfunction, and chronic unresolved inflammation. Our lab focuses on oxidative stress-mediated cellular dysfunction, particularly the toxic effects of lipid peroxidation products like 4-hydroxy-2-nonenal (4HNE). Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, plays a vital role in detoxifying 4HNE and thereby protecting the heart against pathological stress. ALDH2 activity is reduced in various metabolic stress-mediated cardiac pathologies. The dysfunction of coronary vascular endothelial cells (CVECs) is critical in initiating HFpEF development. Thus, we hypothesized that ectopic overexpression of ALDH2 in CVECs could mitigate metabolic stress-induced HFpEF pathogenesis. In this study, we tested the efficacy of intracardiac injections of the ALDH2 gene into CVECs in db/db mice-a model of obesity-induced type 2 diabetes mellitus (T2DM)-and their controls, db/m mice, by injection with ALDH2 constructs (AAV9-VE-cadherin-hALDH2-HA tag-P2A) or control constructs (AAV9-VE-cadherin-HA tag-P2A-eGFP). We found that intracardiac ALDH2 gene transfer increased ALDH2 levels specifically in CVECs compared to other myocardial cells. Additionally, we observed increased ALDH2 levels and activity, along with decreased 4HNE adducts, in the hearts of mice receiving ALDH2 gene transfer compared to control GFP transfer. Furthermore, ALDH2 gene transfer to CVECs improved diastolic function compared to GFP control alone. In conclusion, ectopic ALDH2 expression in CVECs can contribute, at least partially, to the amelioration of HFpEF
The Factors Influencing the Decision to Pursue Orthopaedic Surgery Residency Vary by Race and Gender: A Survey-Based Study
No full textBackground and objective: Despite ongoing efforts to increase diversity in the field, orthopaedic surgery continues to be the least diverse specialty in all of medicine. This study aimed to assess experiences in medical school and their impact on the decision to pursue orthopaedic surgery residency, and specifically, if these experiences varied by race, including underrepresented minority (URM), or gender. We hypothesized that male and Caucasian residents would report earlier exposure to orthopaedics and mentorship, contributing to earlier decisions to pursue the field.
Methods: A voluntary survey assessing factors influencing the decision to pursue orthopaedic surgery was sent to 2,122 orthopaedic surgery residents. We compared differences in response between male and female genders as well as three different racial groups (URM, Asian, and Caucasian). Differences in ordinal variables between independent groups were compared using independent t-tests for normally distributed data and Mann-Whitney U tests for non-normally distributed data. Differences in categorical data were analyzed using the χ2 test or Fisher\u27s exact test as appropriate.
Results: A total of 337 residents completed the survey, yielding a response rate of 15.9%. Males were more likely than females to agree that a role model or mentor of the same sex and race positively influenced their decision [median interquartile range: (IQR): 4 (2-5) vs. 2 (2-4); Mann-Whitney U=8807, p\u3c 0.001, r=0.32] and were more likely to disagree they experienced gender-based discrimination [1 (1-2) vs. 3 (2-4); U=7834, p\u3c 0.001, r=0.38). Interest in orthopaedics before medical school was higher in males (n=145, 64.7%) than females (n=56, 49.6%), while 15.0% (n=17) of females became interested during elective rotations compared to 7.1% (n=16) of males [χ²(3, N=337)=9.10, p=0.028, V=0.16]. More Caucasian residents (n=166, 64.3%) became interested in orthopaedic surgery before medical school compared to URM (n=22, 57.9%) and Asian (n=13, 31.7%) residents, while 7.7% (n=20) of Caucasians became interested during elective rotations compared to 12.2% (n=5) of Asians and 21.0% (n=8) of URM residents [χ²(6, N=337)=25.11, p\u3c 0.001, V=0.22].
Conclusions: There are several significant differences in the experiences of female and URM medical students who chose to pursue orthopaedic surgery relative to male and Caucasian students. The low response rate may reflect self-selection bias and should be taken into account when interpreting these findings
Activity of ampicillin-sulbactam, sulbactam-durlobactam, and comparators against Acinetobacter baumannii-calcoaceticus complex strains isolated from respiratory and bloodstream sources: results from ACNBio study
No full textInfections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC) are associated with high mortality rates and limited treatment options. This study aims to evaluate the in vitro activity of clinically utilized antimicrobials against a contemporary collection of ABC isolates with a predominant carbapenem-resistant phenotype. Geographically dispersed US medical centers (n = 22) provided non-duplicate respiratory and bloodstream ABC isolates for surveillance testing. Antimicrobial susceptibility testing was conducted by broth microdilution and interpreted according to Clinical & Laboratory Standards Institute (CLSI) and Food and Drug Administration (FDA) breakpoints. ABC isolates (n = 523) from respiratory tract (74.4%) and blood (25.6%) sources were recovered from patients (2023-2024). Forty percent were obtained from intensive care unit patients. Carbapenem non-susceptibility was observed in 76.9% of isolates and was more common among respiratory tract cultures. The addition of durlobactam to sulbactam decreased the MIC(90) by three-doubling dilutions from 32 to 4 µg/mL, increasing the susceptibility rate to 96.9% from 33.8%. Genome sequencing of sulbactam-durlobactam non-susceptible isolates (16/523; n = 3.1%) revealed MBL and non-enzymatic resistance mechanisms. Cefiderocol inhibited 93.5% and 76.1% of isolates at CLSI and FDA susceptible breakpoints, respectively. Minocycline susceptibility was \u3c 50%, while tigecycline and eravacycline MIC(50/90) were ½ and 0.5/1 µg/mL, respectively. Sulbactam-durlobactam displayed high activity against sulbactam (95.4%), carbapenem (96.3%), and cefiderocol (95.2%) non-susceptible isolates. Susceptibility rates of clinically utilized antimicrobials against a US collection of ABC isolates ranged from 23% to 97%, with meropenem displaying the lowest rate and sulbactam-durlobactam demonstrating the highest overall rate. Sulbactam-durlobactam activity was preserved against sulbactam, carbapenem, and cefiderocol non-susceptible isolates among respiratory tract and bloodstream isolates
Unplanned Healthcare Encounters in Drug-Resistant Urinary Tract Infections in Emergency Departments
No full textIntroduction: The treatment of extended-spectrum β-lactamase (ESBL)-producing urinary tract infections (UTIs) in the emergency department (ED) is challenging due to the limited oral treatment options available. The purpose of this study was to describe the treatment and outcomes of ESBL UTIs in the ED and to determine risk factors associated with secondary UTI-related unplanned healthcare encounters.
Methods: This was an institutional review board (IRB)-approved, retrospective cohort study of patients discharged from the ED with an ESBL UTI. The primary outcome was any UTI-related unplanned healthcare encounter within 30 days of the index ED visit. Unplanned healthcare encounters included phone/virtual visits, clinic visits, ED visits, and hospitalizations. Patients of ≥ 18 years of age treated for symptomatic UTI were included. Logistic regression was used to identify exposures independently associated with UTI-related unplanned healthcare encounters.
Results: A total of 162 patients were included, of which 103 (64%) experienced an unplanned healthcare encounter. The most common UTIs were complicated lower (71, 44%), complicated upper (57, 35%), catheter-related (24, 15%), and uncomplicated cystitis (10, 6%). Nitrofurantoin demonstrated to have in vitro activity in 121 (75%) patients, aminoglycosides in 117 (72%) patients, trimethoprim/sulfamethoxazole (TMP/SMX) in 66 (41%) patients, and fluoroquinolones in 62 (38%) patients. Of the 103 patients who experienced an unplanned healthcare encounter, 76 (74%) received inactive empiric antibiotic treatment. Oral β-lactams were most commonly prescribed, accounting for 66 (41%) of all initial prescriptions. Of the 81 patients with lower UTI, only 20 (25%) received a prescription for nitrofurantoin. Factors associated with UTI-related unplanned healthcare encounters included chronic kidney disease (CKD) (adjusted odds ratio {adjOR}, 3.4; 95% confidence interval {CI}, 1.2-9.5) and empiric oral β-lactam use (adjOR, 3.2; 95% CI, 1.5-6.6).
Conclusions: Patients with CKD or who received empiric oral β-lactam treatment more commonly experienced an ESBL UTI-related unplanned healthcare encounter. Prescribing first-line therapy with nitrofurantoin for lower UTI is a potential area for improvement
Hope Drives Quality of Life in Patients With Brain Metastases, But, the Hope Center Remains Elusive: An Analysis of NRG-CC003
No full textPURPOSE: NRG-CC003 randomized 393 patients with small cell lung cancer to prophylactic cranial irradiation (PCI) with or without hippocampal avoidance (HA). Hopefulness is a cognitive construct with 3 components: goals, pathways, and agency. Hope is measurable with validated instruments. Since hope is cognitive in nature, the existence of a hope center in the brain-most likely in the hippocampus-has been hypothesized. One exploratory objective of NRG-CC003 posited that if hope levels were better maintained in patients randomized to PCI + HA, then the hippocampus would be implicated in the mechanism of hopefulness.
METHODS AND MATERIALS: PCI consisted of 10 fractions of 2.5 Gy. The Adult Hope Scale (AHS) was administered at time-zero and at 6 months. Regarding patient-reported outcome measures, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 was administered at baseline and at 3, 6-, 12-, 18- and 24-month intervals. Comparisons of AHS scores by arm were made using Wilcoxon-Mann-Whitney tests, and correlation of AHS with EORTC QLQ-C30 by Pearson correlation coefficients.
RESULTS: Approximately 95% completed the AHS at baseline and 67% filled out the questionnaire at 6 months paralleling the completion rates of the conventional tools for QOL and neurocognition. When comparing hope levels (change from baseline to 6 months) there was no significant difference (P \u3e .05) between the 2 arms of the trial. There was a correlation for the components of hopefulness with QOL; specifically, between change in agency score and QLQ-C30 global health status (ρ = 0.27, P \u3c .0001) as well as between change in pathways score and QLQ-C30 global health status (ρ = 0.16, P = .022).
CONCLUSIONS: It is feasible to study hopefulness in the context of prospective trials conducted within the National Clinical Trials Network. The hippocampus could not be implicated as a critical structure in a central pathway that coordinates hopefulness. For the first time, validated tools established a relationship between hope and quality of life among cancer patients
Robot-assisted nephroureterectomy
No full textNephroureterectomy is the standard of care for high grade and recurrent low grade upper urinary tract urothelial cell carcinoma (UTUC). Robot-assisted nephroureterectomy (RANU) is an established technique for the minimally invasive performance of nephroureterectomy and has grown to be the favored approach over the past decade. The 3-dimensional vision, efficient wristed suturing, and precise movements of RANU offer advantages over laparoscopic nephroureterectomy (LNU). In addition to the expected benefits with reduced perioperative morbidity, available oncological outcomes are comparable to data associated with other published series. In this review we discuss the indications, preparation, technique, and oncologic outcomes of transperitoneal RANU
Socioeconomic disparities in prostate cancer screening: the impact of the Area Deprivation Index on PSA screening frequency
No full textOBJECTIVE: To investigate the impact of the Area Deprivation Index (ADI) on prostate-specific antigen (PSA) screening patterns in a North American cohort, as the influence of neighbourhood socioeconomic disadvantage on prostate cancer screening intensity has been scantly analysed.
PATIENTS AND METHODS: We included all men receiving care in Henry Ford Health System, aged 50-69 years and without previous prostate cancer diagnosis at the 31 December 2022. Each patient was assigned an ADI score based on their census block group, categorised into quartiles, with the fourth quartile (Q4, ADI 75-100) representing the most disadvantaged areas. The screening rate was calculated as the total number of PSA tests divided by the number of years patients were aged 50 years and older. Multivariable Poisson regression analysis tested the ADI\u27s influence on screening rate.
RESULTS: Among the 266 203 patients initially included, 75 958 patients had at least one PSA test at our institution. Overall, 20.9% were non-Hispanic Black. Patients in the most disadvantage quartile (Q4) were more likely to be non-Hispanic Black (P \u3c 0.001), had higher comorbidity rates (P \u3c 0.001) and lower probability of receiving two or more PSA tests (P \u3c 0.001) compared to the ones in the least disadvantaged quartile (first quartile [Q1]). At Poisson regression analysis, when compared to patients in Q4, patients from Q1, and the second and third quartile had a 1.87-, 1.70-, and 1.52-fold higher probability of receiving screening, respectively (P \u3c 0.001).
CONCLUSIONS: Living in more deprived areas was associated with lower rates of PSA screening frequency. These findings highlight how socioeconomic deprivation may limit access to preventive healthcare, reinforcing the need for more inclusive and targeted outreach strategies
Differences between allergy and dermatology in referral, evaluation, and management patterns for pediatric patients with atopic dermatitis
No full textINTRODUCTION: Allergists and dermatologists often take different approaches to caring for pediatric patients with atopic dermatitis (AD).
METHODS: A retrospective chart review was performed on patients \u3c 18 years old treated for AD within the University of Virginia health system from 2015 to 2020. Data were collected on patient and referring provider demographics as well as initial visit evaluation and management.
RESULTS: A total of 269 patients presented to allergy, 685 patients presented to dermatology, and 14 patients presented to a combined allergy-dermatology clinic as an initial visit with a primary diagnosis of AD. Both specialties were most often referred to by a generalist though dermatology received more specialty provider referrals. In addition, allergy ordered more diagnostic testing (IgE, allergens, complete blood count), while dermatology prescribed more medications (topical corticosteroids, topical calcineurin inhibitors, immunosuppressants). Patients seen in the combined dermatology-allergy clinic were more likely to receive diagnostic testing than patients seen in dermatology clinic and were more likely to be prescribed medications than patients seen in allergy clinic.
CONCLUSIONS: Our findings suggest allergists may focus more on identifying triggers of AD, while dermatologists largely focus on the prescription of therapies. Clinical care may be more comprehensive when allergists and dermatologists work synergistically
Characteristics and management of follicular events and contact dermatitis in patients using tapinarof cream for the treatment of atopic dermatitis or plaque psoriasis
No full textPurpose: Provide insights into the incidence, pre-sentation and management of follicular events and contact dermatitis in patients with plaque psoriasis or atopic dermatitis (AD) treated with tapinarof cream 1%.
Materials and methods: Key clinical trial publications for tapinarof were reviewed and augmented with the authors\u27 opinions based on real-world clinical experience.
Results: In the PSOARING and ADORING trials, discontinuation rates due to follicular events and contact dermatitis were low and most patients did not require dose modifications or treatment interruptions. In our experience, which includes the use of tapinarof in combination with other agents, tapinarof is generally well tolerated and if events of folliculitis or contact dermatitis occur, patients can be advised to temporarily discontinue application on affected sites until the event resolves, continuing application to other affected areas and body regions. Education on the correct application of tapinarof is important in the management of psoriasis and AD.
Conclusions: Tapinarof is a novel topical treatment option for adults with plaque psoriasis and patients with AD, with no restrictions regarding application sites and duration of use. Follicular events and contact dermatitis associated with tapinarof treatment are generally mild and self-limiting and rarely interfere with therapy.
Clinicaltrials.gov numbers: NCT05014568, NCT05032859, NCT05142774, NCT03956355, NCT03983980, NCT04053387