Extending duration of letermovir prophylaxis in haploidentical stem cell transplantation.

Not available.

ChatGPT Provides Unsatisfactory Responses to Frequently Asked Questions Regarding Anterior Cruciate Ligament Reconstruction.

PURPOSE: To determine whether the free online artificial intelligence platform ChatGPT could accurately, adequately, and appropriately answer questions regarding anterior cruciate ligament (ACL) reconstruction surgery. METHODS: A list of 10 questions about ACL surgery was created based on a review of frequently asked questions that appeared on websites of various orthopaedic institutions. Each question was separately entered into ChatGPT (version 3.5), and responses were recorded, scored, and graded independently by 3 authors. The reading level of the ChatGPT response was calculated using the WordCalc software package, and readability was assessed using the Flesch-Kincaid grade level, Simple Measure of Gobbledygook index, Coleman-Liau index, Gunning fog index, and automated readability index. RESULTS: Of the 10 frequently asked questions entered into ChatGPT, 6 were deemed as unsatisfactory and requiring substantial clarification; 1, as adequate and requiring moderate clarification; 1, as adequate and requiring minor clarification; and 2, as satisfactory and requiring minimal clarification. The mean DISCERN score was 41 (inter-rater reliability, 0.721), indicating the responses to the questions were average. According to the readability assessments, a full understanding of the ChatGPT responses required 13.4 years of education, which corresponds to the reading level of a college sophomore. CONCLUSIONS: Most of the ChatGPT-generated responses were outdated and failed to provide an adequate foundation for patients' understanding regarding their injury and treatment options. The reading level required to understand the responses was too advanced for some patients, leading to potential misunderstanding and misinterpretation of information. ChatGPT lacks the ability to differentiate and prioritize information that is presented to patients. CLINICAL RELEVANCE: Recognizing the shortcomings in artificial intelligence platforms may equip surgeons to better set expectations and provide support for patients considering and preparing for ACL reconstruction.

Into the unknown: The end of the coronavirus disease 2019 public health emergency in the United States and potential impacts on organ transplant recipients.

The public health emergency for coronavirus disease 2019 ended on April 11, 2023, 1 month earlier than its planned termination. The hasty cessation of emergency measures may negatively impact the care of solid organ transplant recipients and other immunosuppressed hosts. Accelerated pathways for drug and vaccine approvals, research funding, and insurance coverage for medical therapies and diagnostic testing are likely to be affected. Health care disparities that characterized the early pandemic may again be intensified. It is imperative that the transplant community promptly anticipate the impact of these changes and prepare accordingly to avoid disruptions in care for the most vulnerable patients.

Strategies to Mitigate the Drug-Drug Interaction between Nirmatrelvir/Ritonavir and Tacrolimus in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Azole Antifungals: Results of a Case Series.

INTRODUCTION: Nirmatrelvir/ritonavir (NIM/r) inhibits tacrolimus metabolism resulting in a profound drug-drug interaction that is further complicated by the use of azole antifungals. CASE PRESENTATIONS: We describe three strategies, in 4 patient cases, for the initiation of NIM/r in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients on tacrolimus at the time of diagnosis. Patients 1 and 2 (strategy 1) experienced prolonged, elevated tacrolimus concentrations after an empiric 33% reduction in tacrolimus dose and adjustment of azole antifungal at NIM/r initiation (strategy 1) and with complete discontinuation of tacrolimus and azole antifungal at NIM/r initiation (strategy 2). Patients 3 and 4 (strategy 3) did not experience elevated tacrolimus concentrations on NIM/r treatment with complete discontinuation of tacrolimus and azole antifungal and a 12-24-h delay in NIM/r initiation. Reinitiation of tacrolimus after NIM/r completion resulted in variable tacrolimus concentrations. CONCLUSION: NIM/r-tacrolimus is a serious drug-drug interaction which can be mitigated by early discontinuation of tacrolimus and azole antifungals, close monitoring, and reinitiation of tacrolimus and antifungal 48-72 h after completion of therapy.

Improvement of Pretibial Myxedema Following Administration of Teprotumumab.

Pretibial myxedema (PTM) is a rare complication of Graves' disease. It is characterized by non-pitting edema with hyperpigmented hyperkeratotic papules and plaques on bilateral lower legs. Effective treatments for patients with PTM are lacking. The etiology of PTM is unknown; however, it may be similar to the mechanism of thyroid-associated ophthalmopathy (TAO). Activated fibroblasts produce inflammatory cytokines and synthesize excessive glycosaminoglycans (GAG) that accumulate in the dermis and subcutaneous tissue. A recent, novel pathway implicates IGF-1 receptor as a mediator in this process. We present two patients with refractory PTM that improved following treatment with teprotumumab, an IGF-1 receptor inhibitor approved for use in TAO. J Drugs Dermatol. 2022;21(11):1252-1254. doi:10.36849/JDD.6854.

Respiratory Syncytial Virus.

Human respiratory syncytial virus (RSV) is a negative sense single-stranded RNA virus that can result in epidemics of seasonal respiratory infections. Generally, one of the two genotypes (A and B) predominates in a single season and alternate annually with regional variation. RSV is a known cause of disease and death at both extremes of ages in the pediatric and elderly, as well as immunocompromised populations. The clinical impact of RSV on the hospitalized adults has been recently clarified with the expanded use of multiplex molecular assays. Among adults, RSV can produce a wide range of clinical symptoms due to upper respiratory tract infections potentially leading to severe lower respiratory tract infections, as well as exacerbations of underlying cardiac and lung diseases. While supportive care is the mainstay of therapy, there are currently multiple therapeutic and preventative options under development.

Invasive aspergillosis in critically ill patients: Review of definitions and diagnostic approaches.

Invasive aspergillosis (IA) is an increasingly recognised phenomenon in critically ill patients in the intensive care unit, including in patients with severe influenza and severe coronavirus disease 2019 (COVID-19) infection. To date, there are no consensus criteria on how to define IA in the ICU population, although several criteria are used, including the AspICU criteria and new consensus criteria to categorise COVID-19-associated pulmonary aspergillosis (CAPA). In this review, we describe the epidemiology of IA in critically ill patients, most common definitions used to define IA in this population, and most common clinical specimens obtained for establishing a mycological diagnosis of IA in the critically ill. We also review the most common diagnostic tests used to diagnose IA in this population, and lastly discuss the most common clinical presentation and imaging findings of IA in the critically ill and discuss areas of further needed investigation.

Successful integration of a three-dimensional transthoracic echocardiography-derived model with an electroanatomic mapping system to guide catheter ablation of WPW.

Three-dimensional transthoracic echocardiography (3DE)-derived heart models have not previously been utilized to guide catheter ablation. In this case report, we describe the creation of a 3DE model from transthoracic echocardiography, import of the model into CARTO3, and successful use of the model as a guide during mapping and ablation of a right lateral accessory pathway. We believe this technique represents a valuable alternative to the integration of computed tomography or magnetic resonance imaging-derived anatomic data, and that it has the potential to improve the definition of the atrioventricular valve annuli during catheter ablation of accessory pathways.

Toward predictive modeling of catheter-based pulmonary valve replacement into native right ventricular outflow tracts.

BACKGROUND: Pulmonary insufficiency is a consequence of transannular patch repair in Tetralogy of Fallot (ToF) leading to late morbidity and mortality. Transcatheter native outflow tract pulmonary valve replacement has become a reality. However, predicting a secure, atraumatic implantation of a catheter-based device remains a significant challenge due to the complex and dynamic nature of the right ventricular outflow tract (RVOT). We sought to quantify the differences in compression and volume for actual implants, and those predicted by pre-implant modeling. METHODS: We used custom software to interactively place virtual transcatheter pulmonary valves (TPVs) into RVOT models created from pre-implant and post Harmony valve implant CT scans of 5 ovine surgical models of TOF to quantify and visualize device volume and compression. RESULTS: Virtual device placement visually mimicked actual device placement and allowed for quantification of device volume and radius. On average, simulated proximal and distal device volumes and compression did not vary statistically throughout the cardiac cycle (P = 0.11) but assessment was limited by small sample size. In comparison to actual implants, there was no significant pairwise difference in the proximal third of the device (P > 0.80), but the simulated distal device volume was significantly underestimated relative to actual device implant volume (P = 0.06). CONCLUSIONS: This study demonstrates that pre-implant modeling which assumes a rigid vessel wall may not accurately predict the degree of distal RVOT expansion following actual device placement. We suggest the potential for virtual modeling of TPVR to be a useful adjunct to procedural planning, but further development is needed.

Community-acquired respiratory viruses in solid organ transplant.

PURPOSE OF REVIEW: Respiratory viruses are common in solid organ transplant (SOT) recipients and recognized as a significant cause of mortality and morbidity. This review examines the literature on influenza and noninfluenza viruses in the SOT recipient. RECENT FINDINGS: Advances in immunosuppression and antimicrobial prophylaxis have led to improved patient and graft survival, yet respiratory viruses continue to be a common cause of disease in this population. Influenza viruses have received top priority regarding prevention and treatment, whereas advances in molecular diagnostic tests detecting an array of other respiratory viruses have expanded our knowledge about the epidemiology and impact of these viruses in both the general population and SOT patients. Effective treatment and prevention for noninfluenza respiratory viruses are only emerging. SUMMARY: Respiratory viruses can contribute to a wide array of symptoms in SOT, particularly in lung transplant recipients. The clinical manifestations, diagnosis, and treatment options for influenza and noninfluenza viruses in SOT patients are reviewed. PCR and related molecular techniques represent the most sensitive diagnostic modalities for detection of respiratory viruses. Early therapy is associated with improved outcomes. Newer classes of antivirals and antibodies are under continuous development for many of these community acquired respiratory viruses.

Investigating effect of standardized total body skin examination using sequence-networks.

This study employs sequence-network analysis to investigate the influence of instructing a standardized procedure on total-body skin examination (TBSE) performance. A between-subjects study was conducted with thirty-one participants comprising medical students and attending physicians. Among these participants, fifteen were randomly assigned to the uninstructed group and sixteen to the instructed group. The participants' gaze and field of view were recorded using eye tracking glasses while performing TBSE on a male and a female standardized patient. The recordings were then transcribed to depict the examination process. The instructed group missed significantly fewer body parts (p = 0.045) and had higher time efficiency (p = 0.007) while examining the female patient, but no significant difference was observed for the male patient examination. Furthermore, the examination sequences of the instructed group contained lesser variability than the uninstructed group. Hence, implementing a standard optimal procedure to perform TBSE could minimize the likelihood of missing body parts, increase examination efficiency, and improve performance consistency. This study demonstrated the potential of sequence-network analysis to study human performance in sequential tasks.

The burden of RSV, hMPV, and PIV amongst hospitalized adults in the United States from 2016 to 2019.

BACKGROUND: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus (PIV) hospitalize many people yearly. Though severe lower respiratory tract disease has been described in children, the elderly, and the immunocompromised, there is a gap in our understanding of RSV, hMPV, and PIV in hospitalized adults. We sought to evaluate the association of RSV, hMPV, and PIV with severe respiratory disease requiring noninvasive or mechanical ventilation and death in hospitalized adults in the United States. METHODS: We conducted a retrospective, pooled, cross-sectional study of general medicine hospitalizations in the United States from 2016 to 2019 using the National Inpatient Sample published by the Agency for Healthcare Quality and Research. We used multivariable Poisson regression to estimate the likelihood of severe respiratory disease or death. We used linear regression to estimate the mean difference in length of stay for those hospitalized with and without a respiratory virus. RESULTS: We found that RSV (incidence rate ratio [IRR]: 1.68, 95% confidence interval [CI]: 1.61-1.74, p < .001), hMPV (IRR: 1.82, 95% CI: 1.71-1.93, p < .001), and PIV (IRR: 1.81, 95% CI: 1.68-1.94, p < .001) were independently associated with severe respiratory disease, even after adjustment. Additionally, we found the presence of a respiratory virus prolonged hospitalizations by (0.79 ± 0.27 days, p < .003) for RSV, (0.88 ± 0.28 days, p < .002) for hMPV, and (1.43 ± 0.30 days, p < .001) for PIV. CONCLUSIONS: RSV, hMPV, and PIV have a significant burden on hospitalized adults, even without classic risk factors.

Adverse events associated with robotic-assistance in total hip arthroplasty: an analysis based on the FDA MAUDE database.

BACKGROUND: The Food and Drug Administration (FDA) maintains the Manufacturer and User Facility Device Experience (MAUDE) database for reporting adverse events associated with medical devices, including emerging technologies, such as robotic-assisted total hip arthroplasty (THA). Aim of this study was to evaluate the variation of adverse events associated with robotics in THA. METHODS: Medical device reports (MDRs) within the MAUDE database were identified between 2017 and 2021. For MDR identification the product class "orthopaedic stereotaxic equipment" and terms associated with THA were used. Individual adverse events were identified and organised by type and consequences, such as patient injury, surgical delay, or conversion to the manual technique. RESULTS: 521 MDRs constituting 546 discrete events were found. The most common reported complication was intraoperative hardware failure (304/546, 55.7%), among which the most common failure was a broken impaction handle/platform (110, 20.1%). Inaccurate cup placement was the second most common reported complication (63, 11.5%). Abandoning the robot occurred in 13.0% (71/521) of reports. A surgical delay was noted in 28% (146/521) of reports, with an average delay of 17.9 (range 1-60) minutes. CONCLUSIONS: Identifying complications that may occur with robotics in THA is an important first step in preventing adverse events and surgical delays. Database analysis provide an overview of the range of complications.

Persistent Impairment in Immune Reconstitution and Worse Survival Outcomes in Allogeneic Stem Cell Transplantation Patients with Early Coronavirus Disease 2019 Infection.

Patients undergoing allogenic hematopoietic stem cell transplantation (HSCT) are at an increased risk of mortality due to transplantation-related complications in the first year post-transplantation, owing in part to the profound immune dysregulation with T cell and B cell lymphopenia and functional impairment. Although several large studies have reported higher mortality rates from Coronavirus disease 2019 (COVID-19) in HSCT recipients, to date no study has focused on the impact of early COVID-19 infection on immune reconstitution post-transplantation and the correlation with transplantation outcomes. We retrospectively analyzed 61 consecutive adult patients who underwent their first allogeneic HSCT at our institution. Thirteen patients (21.3%) experienced early COVID-19 infection, with a median time to diagnosis of 100 days post-transplantation. In multivariable analysis, patients with early COVID-19 infection had significantly worse overall survival (adjusted hazard ratio [aHR], 4.06; 95% confidence interval [CI], 1.26 to 13.05; P = .019) and progression-free survival (aHR, 6.68; 95% CI, 2.11 to 21.11; P = .001). This was attributed mainly to higher nonrelapse mortality (NRM) among early COVID-19 patients (P = .042). Allogeneic HSCT recipients with early COVID-19 infection had significant delays in absolute lymphocyte count (95% CI, -703.69 to -56.79; P = .021), CD3+CD4+ cell (95% CI, -105.35 to -11.59; P = .042), CD3+CD8+ cell (95% CI, -324.55 to -57.13; P = .038), and CD3-CD56+ cell (95% CI, -193.51 to -47.31; P = .014) recovery compared to those without early COVID-19 infection. Our findings suggest that patients with early COVID-19 infection after allogeneic HSCT have higher NRM and worse survival, at least in part due to impaired immune reconstitution post-transplantation.

Charcot Neuroarthropathy Is Associated With Higher Rates of Phantom Limb After Lower Extremity Amputation.

BACKGROUND: The incidence of phantom limb pain in patients with Charcot neuroarthropathy who undergo major amputation is not well described. The purpose of this study was to determine whether patients with Charcot neuroarthropathy and diabetes who underwent either a below-knee amputation (BKA) or above-knee amputation (AKA) had an increased rate of phantom limb pain compared with those with a diagnosis of diabetes alone. METHODS: Using international classification of disease (ICD) and common procedural terminology (CPT) codes, the TriNetX research database identified 10 239 patients who underwent BKA and 6122 who underwent AKA between 2012 and 2022. Diabetic patients with and without Charcot neuroarthropathy were compared in terms of demographics and relative risk of developing phantom limb pain after AKA or BKA. RESULTS: Age, sex, ethnicity, and race did not significantly differ between groups. Charcot neuroarthropathy was associated with significantly increased risk of phantom limb pain following both BKA (risk ratio [RR]: 1.2, 95% confidence interval [CI]: 1.1-1.3, P < .01) and AKA (RR: 1.6, 95% CI: 1.2-2.3, P < .0068). CONCLUSION: Our results indicate that patients with a coexisting diagnosis of Charcot neuroarthropathy who require BKA or AKA may have an increased risk of developing phantom limb pain. LEVELS OF EVIDENCE: Level III.

Euclidean and Shape-Based Analysis of the Dynamic Mitral Annulus in Children using a Novel Open-Source Framework.

BACKGROUND: The dynamic shape of the normal adult mitral annulus has been shown to be important to mitral valve function. However, annular dynamics of the healthy mitral valve in children have yet to be explored. The aim of this study was to model and quantify the shape and major modes of variation of pediatric mitral valve annuli in four phases of the cardiac cycle using transthoracic echocardiography. METHODS: The mitral valve annuli of 100 children and young adults with normal findings on three-dimensional echocardiography were modeled in four different cardiac phases using the SlicerHeart extension for 3D Slicer. Annular metrics were quantified using SlicerHeart, and optimal normalization to body surface area was explored. Mean annular shapes and the principal components of variation were computed using custom code implemented in a new SlicerHeart module (Annulus Shape Analyzer). Shape was regressed over metrics of age and body surface area, and mean shapes for five age-stratified groups were generated. RESULTS: The ratio of annular height to commissural width of the mitral valve ("saddle shape") changed significantly throughout age for systolic phases (P < .001) but within a narrow range (median range, 0.20-0.25). Annular metrics changed statistically significantly between the diastolic and systolic phases of the cardiac cycle. Visually, the annular shape was maintained with respect to age and body surface area. Principal-component analysis revealed that the pediatric mitral annulus varies primarily in size (mode 1), ratio of annular height to commissural width (mode 2), and sphericity (mode 3). CONCLUSIONS: The saddle-shaped mitral annulus is maintained throughout childhood but varies significantly throughout the cardiac cycle. The major modes of variation in the pediatric mitral annulus are due to size, ratio of annular height to commissural width, and sphericity. The generation of age- and size-specific mitral annular shapes may inform the development of appropriately scaled absorbable or expandable mitral annuloplasty rings for children.

Deviations in RSV epidemiological patterns and population structures in the United States following the COVID-19 pandemic.

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory tract infection, with the greatest impact on infants, immunocompromised individuals, and older adults. RSV prevalence decreased substantially in the United States (US) following the implementation of COVID-19-related non-pharmaceutical interventions but later rebounded with abnormal seasonality. The biological and epidemiological factors underlying this altered behavior remain poorly defined. In this retrospective cohort study from 2009 to 2023 in Chicago, Illinois, US, we examined RSV epidemiology, clinical severity, and genetic diversity. We found that changes in RSV diagnostic platforms drove increased detections in outpatient settings post-2020 and that hospitalized adults infected with RSV-A were at higher risk of intensive care admission than those with RSV-B. While population structures of RSV-A remained unchanged, RSV-B exhibited a genetic shift into geographically distinct clusters. Mutations in the antigenic regions of the fusion protein suggest convergent evolution with potential implications for vaccine and therapeutic development.

Once-Daily Foscarnet Is Effective for Human Herpesvirus 6 Reactivation after Hematopoietic Stem Cell Transplantation.

Human herpesvirus 6 (HHV-6) reactivation is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with higher mortality and increased transplantation-related complications. We hypothesized that preemptive treatment with a short course of foscarnet at a lower cutpoint of plasma HHV-6 viral load would be effective in treating early HHV-6 reactivation, preventing complications and precluding hospitalization of these patients. We reviewed outcomes of adult patients (age ≥18 years) who received preemptive treatment with once-daily foscarnet 60 to 90 mg/kg for 7 days for HHV-6 reactivation after allo-HSCT at our institution between May 2020 and November 2022. Plasma HHV-6 viral load was monitored by quantitative PCR twice monthly in the first 100 days post-transplantation and twice weekly after reactivation until resolution. Eleven patients with a median age of 46 years (range, 23 to 73 years) were included in the analysis. HSCT was performed with a haploidentical donor in 10 patients and with an HLA-matched related donor in 1 patient. The most common diagnosis was acute leukemia (9 patients). Myeloablative and reduced-intensity conditioning regimens were used in 4 and 7 patients, respectively. Ten of the 11 patients received post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. The median follow-up was 440 days (range, 174 to 831 days), and the median time to HHV-6 reactivation was 22 days post-transplantation (range, 15 to 89 days). The median viral load at first reactivation was 3,100 copies/mL (range, 210 to 118,000 copies/mL), and the median peak viral load was 11,300 copies/mL (range, 600 to 983,000 copies/mL). All patients received a short course of foscarnet at either 90 mg/kg/day (n = 7) or 60 mg/kg/day (n = 4). In all patients, plasma HHV-6 DNA was undetectable at completion of 1 week of treatment. No HHV-6 encephalitis or pneumonitis occurred. All patients achieved neutrophil and platelet engraftment after a median of 16 days (range, 8 to 22 days) and 26 days (range, 14 to 168 days), respectively, with no secondary graft failure. No complications related to foscarnet administration were noted. One patient with very high HHV-6 viremia had recurrent reactivation and received a second course of foscarnet as an outpatient. A short course of once-daily foscarnet is effective in treating early HHV-6 reactivation post-transplantation and may reduce the incidence of HHV-6-related and treatment-related complications and preclude hospitalization in these patients.

Vancomycin Powder Is Highly Cost-Effective in Total Ankle Arthroplasty.

Prosthetic joint infection (PJI) is a costly and potentially fatal complication in total ankle arthroplasty (TAA). Some surgeons apply topical vancomycin powder to minimize the risk of infection during TAA procedures. The purpose of our study was to determine the cost-effectiveness of using vancomycin powder to prevent PJI following TAA and to propose an economic model that can be applied by foot and ankle surgeons in their decision to incorporate vancomycin powder in practice. Using our institution's records of the cost of 1 g of topical vancomycin powder, we performed a break-even analysis and calculated the absolute risk reduction and number needed to treat for varying costs of vancomycin powder, PJI infection rates, and costs of TAA revision. Costing $3.06 per gram at our institution, vancomycin powder was determined to be cost-effective in TAA if the PJI rate of 3% decreased by an absolute risk reduction of 0.02% (Number Needed to Treat = 5304). Furthermore, our results indicate that vancomycin powder can be highly cost-effective across a wide range of costs, PJI infection rates, and varying costs of TAA revision. The use of vancomycin powder remained cost-effective even when (1) the price of vancomycin powder was as low as $2.50 to as high as $100.00, (2) infection rates ranged from .05 to 3%, and (3) the cost of the TAA revision procedure ranged from $1000 to $10 000.Levels of Evidence: IV.