Patient and Parent Knowledge, Understanding, and Concerns After a New Diagnosis of Ehlers Danlos Syndrome.

Introduction: After diagnosis of Ehlers Danlos Syndrome (EDS), it is unclear what information patients and parents need and understand about EDS. The objective of this study is to characterize patient and parent knowledge and concerns about EDS after a diagnosis of EDS is made to determine patient and parent concerns and identify barriers that cause discomfort with the diagnosis. Methods: A convenience sample of patient and parent dyads were recruited after new diagnosis of EDS. Patients and parents completed questionnaires that assessed knowledge, comfort, and barriers of EDS before and after diagnosis, EDS education materials accessed, and additional clinical needs and concerns. Results: Seventy-two dyads completed the survey. Conclusion: Many respondents actively seek information on the diagnosis and management of EDS. Parents and patients look for information about EDS differently. Parents have more concerns after diagnosis and both want well-constructed, empirically supported educational materials delivered via multiple modalities, which makes clinical guidelines more essential.

Contextual Triggers and Tic Severity Across Life Periods: A Retrospective Analysis in Adults with Tic Disorders.

In tic disorders (TD), tic expression varies across the lifespan and as a function of contextual factors. This study explored connections between tic expression and contextual triggers across life periods in 74 adults (Mage = 23.2) with TDs. The Tic History and Coping Strategies form assessed retrospective self-reports of contextual antecedents, consequences, and tic severity during four life periods (middle school; 9th/10th grade; 11th/12th grade; college/work) and past month. Tics reportedly worsened during and after school in school-aged years and worsened in the evening during college/work years. Stress and anxiety were reported to consistently trigger tics across time. The impact of activities, places, and emotions did not differ across life periods. Attention-based consequences, most prevalent during middle school, were more common than escape- or avoidance-related consequences across all periods. Findings illuminate how contextual factors may influence tics across life periods and underscore the consistent impact of tic-triggering emotions and attention-related consequences.

Engineering of Rieske dioxygenase variants with improved cis-dihydroxylation activity for benzoates.

Rieske dioxygenases have a long history of being utilized as green chemical tools in the organic synthesis of high-value compounds, due to their capacity to perform the cis-dihydroxylation of a wide variety of aromatic substrates. The practical utility of these enzymes has been hampered however by steric and electronic constraints on their substrate scopes, resulting in limited reactivity with certain substrate classes. Herein, we report the engineering of a widely used member of the Rieske dioxygenase class of enzymes, toluene dioxygenase (TDO), to produce improved variants with greatly increased activity for the cis-dihydroxylation of benzoates. Through rational mutagenesis and screening, TDO variants with substantially improved activity over the wild-type enzyme were identified. Homology modeling, docking studies, molecular dynamics simulations, and substrate tunnel analysis were applied in an effort to elucidate how the identified mutations resulted in improved activity for this polar substrate class. These analyses revealed modification of the substrate tunnel as the likely cause of the improved activity observed with the best-performing enzyme variants.

Pediatric Treatment-Resistant Obsessive Compulsive Disorder: Treatment Options and Challenges.

Pediatric obsessive-compulsive disorder (OCD) is a chronic, potentially debilitating psychiatric condition. Although effective treatments exist, at least 10% of youth do not achieve remission despite receiving first-line treatments. This article reviews the extant, albeit limited, evidence supporting treatment approaches for youth with treatment-resistant OCD. A literature search for articles addressing pediatric treatment-resistant OCD was conducted through April 11, 2024. These results were augmented by searching for treatment-resistant OCD in adults; treatment strategies discovered for the adult population were then searched in the context of children and adolescents. In general, intensive treatment programs and antipsychotic augmentation of an antidepressant had the most substantial and consistent evidence base for treatment-resistant youth with OCD, although studies were limited and of relatively poor methodological quality (i.e., open trials, naturalistic studies). Several pharmacological approaches (clomipramine, antipsychotics [e.g., aripiprazole, risperidone], riluzole, ketamine, D-cycloserine, memantine, topiramate, N-acetylcysteine, ondansetron), largely based on supporting data among adults, have received varying levels of investigation and support. There is nascent support for how to treat pediatric treatment-resistant OCD. Future treatment studies need to consider how to manage the significant minority of youth who fail to benefit from first-line treatment approaches.

ChatGPT Is Moderately Accurate in Providing a General Overview of Orthopaedic Conditions.

Background: ChatGPT is an artificial intelligence chatbot capable of providing human-like responses for virtually every possible inquiry. This advancement has provoked public interest regarding the use of ChatGPT, including in health care. The purpose of the present study was to investigate the quantity and accuracy of ChatGPT outputs for general patient-focused inquiries regarding 40 orthopaedic conditions. Methods: For each of the 40 conditions, ChatGPT (GPT-3.5) was prompted with the text "I have been diagnosed with [condition]. Can you tell me more about it?" The numbers of treatment options, risk factors, and symptoms given for each condition were compared with the number in the corresponding American Academy of Orthopaedic Surgeons (AAOS) OrthoInfo website article for information quantity assessment. For accuracy assessment, an attending orthopaedic surgeon ranked the outputs in the categories of <50%, 50% to 74%, 75% to 99%, and 100% accurate. An orthopaedics sports medicine fellow also independently ranked output accuracy. Results: Compared with the AAOS OrthoInfo website, ChatGPT provided significantly fewer treatment options (mean difference, -2.5; p < 0.001) and risk factors (mean difference, -1.1; p = 0.02) but did not differ in the number of symptoms given (mean difference, -0.5; p = 0.31). The surgical treatment options given by ChatGPT were often nondescript (n = 20 outputs), such as "surgery" as the only operative treatment option. Regarding accuracy, most conditions (26 of 40; 65%) were ranked as mostly (75% to 99%) accurate, with the others (14 of 40; 35%) ranked as moderately (50% to 74%) accurate, by an attending surgeon. Neither surgeon ranked any condition as mostly inaccurate (<50% accurate). Interobserver agreement between accuracy ratings was poor (κ = 0.03; p = 0.30). Conclusions: ChatGPT provides at least moderately accurate outputs for general inquiries of orthopaedic conditions but is lacking in the quantity of information it provides for risk factors and treatment options. Professional organizations, such as the AAOS, are the preferred source of musculoskeletal information when compared with ChatGPT. Clinical Relevance: ChatGPT is an emerging technology with potential roles and limitations in patient education that are still being explored.

Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance.

H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple non-human mammalian species1,2. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera3-6. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here we use pseudovirus deep mutational scanning7 to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids, and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine strains. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.

Uncertainty cues amplify late positive potential responses to aversive emotional stimuli.

Uncertainty is unavoidable, and maladaptive responses to uncertainty may underlie the etiology and maintenance of psychopathology. A general tendency to associate uncertainty with aversive consequences, a type of covariation bias, can amplify aversive emotional experiences. To address questions about uncertainty during emotion regulation, we examined the Late Positive Potential (LPP) - an electrocortical marker of attention to and appraisal of motivationally relevant emotional stimuli - during a task designed to measure the effect of covariation bias and its emotional response consequences. Event-related potentials (ERPs) were recorded while participants (N = 52) were presented with a pre-stimulus cue that either conveyed information about the valence of an upcoming emotional image, or left them in ambiguity. We replicated findings that demonstrate expectancy biases in a priori and online expectancies of emotion-eliciting images, as well as in a posteriori estimates for concurrence of uncertainty cues and aversive images. Moreover, we demonstrate a novel finding that uncertainty cues amplify the LPP in response to subsequent aversive emotional stimuli. These findings advance research by conjoining existing emotion regulation research on the LPP with study of the effects of uncertainty on emotional appraisal and highlight the importance of accounting for stimulus uncertainty in emotion regulation research.

Evaluating increasing levels of sodium diformate in diets for nursery and finishing pigs on growth performance, fecal dry matter, and carcass characteristics.

Two studies were conducted to evaluate the effects of sodium diformate in swine diets. For Exp. 1, 360 barrows (DNA 200 × 400; initially 5.9 ±â€…0.06 kg) were used in a 38-d study. At weaning, pigs were randomly assigned to pens with five pigs per pen. Each pen was allocated to one of six treatments with 12 pens per treatment. Treatments were formulated to provide none, 0.40%, 0.60%, 0.80%, 1.00%, or 1.20% sodium diformate added at the expense of corn. Diets were fed in three phases: phase 1 from weaning to day 9, phase 2 from days 9 to 24, and phase 3 from days 24 to 38. From days 0 to 24 (phases 1 and 2), increasing sodium diformate increased (linear, P = 0.001) gain-to-feed (G:F). However, sodium diformate did not affect average daily gain (ADG) or average daily feed intake (ADFI). From days 24 to 38 (phase 3) and overall (days 0 to 38), there was no evidence of differences due to increasing sodium diformate for any growth response criteria. There was no evidence for differences in fecal dry matter (DM) on day 9. However, fecal DM decreased (linear, P < 0.05; quadratic, P = 0.097) as sodium diformate increased on day 24. In Exp. 2, 2,200 pigs (Duroc sire [PIC 800 or DNA 600] × PIC Camborough; initially 24.2 ±â€…0.30 kg) were used in a 117-d growth trial. Pens of pigs (25 pigs per pen) were randomly assigned to one of four treatments with 22 pens per treatment. Treatments were formulated with additions of none, 0.25%, 0.50%, or 0.75% sodium diformate. Diets were fed in six phases from 24 to 141 kg. For period 1 (days 0 to 32), ADFI tended to decrease then increase (quadratic, P = 0.081) with increasing sodium diformate, whereas G:F increased then decreased (quadratic, P < 0.001) with increasing sodium diformate. For period 2 (days 32 to 60), there was no evidence for differences in ADG or ADFI; however, there was a tendency for G:F to increase then decrease (quadratic, P = 0.093) with increasing sodium diformate. From days 60 to 93, increasing sodium diformate increased (linear, P < 0.01) ADG and ADFI. From days 93 to 117, increasing sodium diformate increased (linear, P < 0.05) ADG, ADFI, and G:F. Overall (days 0 to 117), pigs fed increasing sodium diformate had increased (linear, P < 0.01) ADG and a tendency for increased (linear, P = 0.075) ADFI; however, there was no evidence for differences in G:F. There were no treatment differences for any carcass characteristic. In summary, increasing sodium diformate may increase G:F in the early nursery and improve ADG after day 60 (approximately 82 kg) in the finishing period.

Dispelling the Myths of Isotretinoin and Implications for Rhinoplasty.

SUMMARY: Despite concerns from 1980s case reports, oral isotretinoin, a derivative of Vitamin A, has largely proven to be safe in surgical procedures with the exception of deep skin resurfacing. Isotretinoin modulates thinning skin and internal scarring in select rhinoplasty patients who may otherwise have poor definition and excessive scarring. A review of patients undergoing surgical interventions including rhinoplasty in the setting of concomitant isotretinoin was performed to examine safety and therapeutic potential. Forty-nine studies were reviewed. Isotretinoin use appears to be safe in a wide variety of surgical procedures relying on internal scar formation. In rhinoplasty, studies utilized oral isotretinoin to thin skin and improve appearance, patient and surgeon satisfaction. As such, the clinical potential for using oral isotretinoin in select rhinoplasty candidates such as those with thick glaborous sebaceous skin, ethnic, male, and/or revision patients, could mitigate internal scarring processes. Further studies examining the optimal dosing regimen and long-term benefits are warranted.

Effect of bone and analytical method on assessment of bone mineralization in response to dietary phosphorus, phytase, and vitamin D in finishing pigs.

A total of 882 pigs [PIC TR4 × (Fast LW × PIC L02); initially 33.2 ± 0.31 kg] were used in a 112-d study to evaluate the effects of different bones and analytical methods on the assessment of bone mineralization response to changes in dietary P, phytase, and vitamin D in growing pigs. Pens of pigs (20 pigs per pen) were randomized to 1 of 5 dietary treatments with 9 pens per treatment. Dietary treatments were designed to create differences in bone mineralization and included: 1) P at 80% of NRC (2012) standardized total tract digestible (STTD) P requirement, 2) NRC STTD P with no phytase, 3) NRC STTD P with phytase providing an assumed release of 0.14 % STTD P from 2,000 FYT/kg, 4) high STTD P (128% of the NRC P) using monocalcium phosphate and phytase, 5) diet 4 with additional vitamin D3 from 25(OH)D3. On d 112, one pig per pen was euthanized for bone, blood, and urine analysis. Additionally, 11 pigs identified as having poor body condition which indicated a history of low feed intake (unhealthy) were sampled. There were no differences between treatments for final body weight, average daily gain, average daily feed intake, gain to feed, or bone ash measurements (treatment × bone interaction) regardless of bone ash method. The response to treatment for bone density and bone mineral content was dependent upon bone sampled (density interaction, P = 0.053; mineral interaction, P = 0.078). For 10th rib bone density, pigs fed high levels of P had increased (P < 0.05) bone density compared with pigs fed NRC levels with phytase, with pigs fed deficient P, NRC levels of P with no phytase, and high STTD P with extra 25(OH)D3 intermediate, with no differences for metacarpals, fibulas, or 2nd ribs. Pigs fed extra vitamin D from 25(OH)D3 had increased (P < 0.05) 10th rib bone mineral content compared with pigs fed deficient P and NRC levels of P with phytase, with pigs fed industry P and vitamin D, and NRC P with monocalcium intermediate. Healthy pigs had greater (P < 0.05) serum Ca, P, vitamin D concentrations, and defatted bone ash than those unhealthy, with no difference between the two health statuses for non-defatted bone ash. In summary, differences between bone ash procedures was more apparent than differences between diets. Differences in bone density and mineral content in response to dietary P and vitamin D were most apparent with 10th ribs.

A review of calcium and phosphorus requirement estimates for gestating and lactating sows.

Calcium (Ca) and phosphorus (P) are minerals involved in biological functions and essential structural components of the skeleton. The body tightly regulates Ca and P to maintain homeostasis. Maternal needs for Ca and P increase during gestation and lactation to support conceptus growth and milk synthesis. Litter size and litter average daily gain (ADG) have a large effect on Ca and P requirements for sows because as they increase, the requirements increase due to a greater need from the sow. The objective of this review was to summarize published literature on Ca and P requirements in gestating and lactating sows derived from empirical data and factorial models. A total of nine empirical studies and seven factorial models were reviewed for determining the Ca and P requirements in gestation. For lactation, there were six empirical studies and seven factorial models reviewed. Empirical studies determined requirements based on the observed effect of Ca and P on bone mineralization, sow and litter performance, and milk characteristics. Factorial models generated equations to estimate Ca and P requirements using the main components of maintenance, fetal and placental growth, and maternal retention in gestation. The main components for factorial equations in lactation include maintenance and milk production. In gestation, the standardized total tract digestible phosphorus (STTD P) requirement estimates from empirical studies range from 5.4 to 9.5 g/d with total Ca ranging from 12.9 to 18.6 g/d to maximize bone measurements or performance criteria. According to the factorial models, the requirements increase throughout gestation to meet the needs of the growing fetuses and range from 7.6 to 10.6 g/d and 18.4 to 38.2 g/d of STTD P and total Ca, respectively, on day 114 of gestation for parity 1 sows. During lactation, STTD P requirement estimates from empirical studies ranged from 8.5 to 22.1 g/d and total Ca ranged from 21.2 to 50.4 g/d. For the lactation factorial models, STTD P requirements ranged from 14.2 to 25.1 g/d for STTD P and 28.4 to 55.6 g/d for total Ca for parity 1 sows with a litter size of 15 pigs. The large variation in requirement estimates makes it difficult to define Ca and P requirements; however, a minimum level of 6.0 and 22.1 g/d of STTD P during gestation and lactation, respectively, appears to be adequate to meet basal requirements. The limited data and high variation indicate a need for future research evaluating Ca and P requirements for gestating and lactating sows.

Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy.

BACKGROUND: Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality. METHODS: To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion IHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy. RESULTS: Capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib in both models. The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib extended survival and induced long-term progression-free survival when combined with radiotherapy in two complementary mouse models. Capmatinib treatment increased radiation-induced DNA double-strand breaks and delayed their repair. CONCLUSIONS: We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies, and insights into molecular mechanism underlying increased efficacy. Taken together, we demonstrate the groundbreaking efficacy of capmatinib and radiation as a highly promising concept for future clinical trials.

Alcaligenes faecalis corrects aberrant matrix metalloproteinase expression to promote reepithelialization of diabetic wounds.

Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to wound healing. Here, we focused on Alcaligenes faecalis, a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with A. faecalis accelerated healing during early stages. We investigated the underlying mechanisms and found that A. faecalis treatment promotes reepithelialization of diabetic keratinocytes, a process that is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found that A. faecalis treatment balances this overexpression to allow proper healing. This work uncovers a mechanism of bacterial-driven wound repair and provides a foundation for the development of microbiota-based wound interventions.

Amelioration of Anxiety Associated with Opioid Withdrawal by Activation of Spinal Mechanoreceptors Via Novel Heterodyned Whole Body Vibration.

Objectives: Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide. An important driving force for relapse is anxiety associated with opioid withdrawal. We hypothesized that our new technology, termed heterodyned whole-body vibration (HWBV) would ameliorate anxiety associated with OUD. Methods: Using a randomized, placebo (sham)-controlled, double-blind study design in an NIH-sponsored Phase 1 trial, we evaluated 60 male and 26 female participants diagnosed with OUD and undergoing treatment at pain and rehabilitation clinics. We utilized the Hamilton Anxiety Scale (HAM-A) and a daily visual analog scale anxiety rating (1-10) to evaluate anxiety. Subjects were treated for 10 min 5X/week for 4 weeks with either sham vibration (no interferential beat or harmonics) or HWBV (beats and harmonics). The participants also completed a neuropsychological test battery at intake and discharge. Results: In OUD subjects with moderate anxiety, there was a significant improvement in daily anxiety scores in the HWBV group compared to the sham treatment group (p=3.41 × 10-7). HAM-A scores in OUD participants at intake showed moderate levels of anxiety in OUD participants (HWBV group: 15.9 ± 1.6; Sham group: 17.8 ± 1.6) and progressively improved in both groups at discharge, but improvement was greater in the HWBV group (p=1.37 × 10-3). Furthermore, three indices of neuropsychological testing (mental rotations, spatial planning, and response inhibition) were significantly improved by HWBV treatment. Conclusions: These findings support HWBV as a novel, non-invasive, non-pharmacological treatment for anxiety associated with OUD.

Temperate phage-antibiotic synergy across antibiotic classes reveals new mechanism for preventing lysogeny.

A recent demonstration of synergy between a temperate phage and the antibiotic ciprofloxacin suggested a scalable approach to exploiting temperate phages in therapy, termed temperate phage-antibiotic synergy, which specifically interacted with the lysis-lysogeny decision. To determine whether this would hold true across antibiotics, we challenged Escherichia coli with the phage HK97 and a set of 13 antibiotics spanning seven classes. As expected, given the conserved induction pathway, we observed synergy with classes of drugs known to induce an SOS response: a sulfa drug, other quinolones, and mitomycin C. While some ß-lactams exhibited synergy, this appeared to be traditional phage-antibiotic synergy, with no effect on the lysis-lysogeny decision. Curiously, we observed a potent synergy with antibiotics not known to induce the SOS response: protein synthesis inhibitors gentamicin, kanamycin, tetracycline, and azithromycin. The synergy results in an eightfold reduction in the effective minimum inhibitory concentration of gentamicin, complete eradication of the bacteria, and, when administered at sub-optimal doses, drastically decreases the frequency of lysogens emerging from the combined challenge. However, lysogens exhibit no increased sensitivity to the antibiotic; synergy was maintained in the absence of RecA; and the antibiotic reduced the initial frequency of lysogeny rather than selecting against formed lysogens. Our results confirm that SOS-inducing antibiotics broadly result in temperate-phage-specific synergy, but that other antibiotics can interact with temperate phages specifically and result in synergy. This is the first report of a means of chemically blocking entry into lysogeny, providing a new means for manipulating the key lysis-lysogeny decision.IMPORTANCEThe lysis-lysogeny decision is made by most bacterial viruses (bacteriophages, phages), determining whether to kill their host or go dormant within it. With over half of the bacteria containing phages waiting to wake, this is one of the most important behaviors in all of biology. These phages are also considered unusable for therapy because of this behavior. In this paper, we show that many antibiotics bias this behavior to "wake" the dormant phages, forcing them to kill their host, but some also prevent dormancy in the first place. These will be important tools to study this critical decision point and may enable the therapeutic use of these phages.

Erythema dyschromicum perstans-like eruptions induced by epidermal growth factor receptor inhibitors in patients with lung cancer.

INTRODUCTION: Cutaneous adverse reactions to epidermal growth factor receptor inhibitors (EGFRi) are some of the most common side effects that patients experience. However, cutaneous adverse reactions that cause dyspigmentation in patients have been rarely reported. Erythema dyschromicum perstans (EDP) is a rare pigmentary condition that causes ashy-grey hyperpigmented macules and patches, with a few cases reported from EGFRi in the literature. The disfiguration caused by this condition may negatively impact patients' quality of life. Our study aimed to describe the clinical characteristics of EDP induced by EGFRi to better recognize and manage the condition. METHODS: We conducted a multicenter retrospective review at three academic institutions to identify patients with EDP induced by EGFRi from 2017 to 2023 and included sixteen patients in our study. RESULTS: The median age of patients was 66 years old, with 63% female and 37% male (Table 1). The majority of our patients were Asian (88%). All patients had non-small cell lung cancer and most patients received osimertinib. Median time to EDP was 6 months. The most common areas of distribution were the head/neck region, lower extremities, and upper extremities. Various topical ointments were trialed; however, approximately less than half had improvement in their disease and most patients had persistent EDP with no resolution. All patients desired treatment except one with EDP on the tongue, and there was no cancer treatment discontinuation or interruption due to EDP. Table 1 Patient demographics and clinical characteristics of 16 patients with EDP induced by EGFRi Case no Demographics: age, race, and sex Fitzpatrick skin type Cancer type EGFR therapy Concomitant photosensitive drug(s) Time to EDP (months) Clinical features Distribution Symptoms Treatments and clinical course EDP status from most recent follow up 1 47 y/o Asian male III Stage IV NSCLC Erlotinib None Unknown Brown-blue-gray hyperpigmented patches Bilateral shins Left thigh Xerosis Pruritus Triamcinolone 0.1% ointment for 4 months, improvement of blue discoloration Tacrolimus 0.1% BID for 9 months, improvement but no resolution Ongoing 2 62 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown hyperpigmented patches Bilateral arms Back Forehead Neck Right shin None Tacrolimus 0.1% ointment for 1 year with minor improvement Ongoing 3 69 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown macules and patches Chest Face Forehead Bilateral legs None Tacrolimus 0.1% ointment for 10 months, no improvement Ongoing 4 79 y/o White male II Stage IV NSCLC Osimertinib None 15 Mottled grey-blue hyperpigmented patches and plaques with mild scaling Bilateral arms Back Forehead Neck None Photoprotection, no improvement Ongoing 5 69 y/o Asian female III Stage IV NSCLC Osimertinib Ibuprofen 4 Blue-grey hyperpigmented macules and patches Abdomen Bilateral arms None Tacrolimus 0.1% ointment for 7 months, no improvement Ongoing 6 65 y/o Asian male III Stage IV NSCLC Osimertinib None 20 Hyperpigmented blue gray macules and patches Helix Bilateral shins None Photoprotection, no improvement Ongoing 7 66 y/o Asian female IV Stage IV NSCLC Erlotinib TMP-SMX 6 Ashy grey-brown thin plaques Back Forehead None 2.5% hydrocortisone ointment for 8 months, resolved Resolved 8 82 y/o Asian male III Stage III NSCLC Erlotinib Simvastatin 20 Ash-grey hyperpigmented patches Dorsal feet Forehead Scalp None Photoprotection Ongoing 9 57 y/o Asian female III Stage II NSCLC Erlotinib None 1 Bue-grey discoloration Tongue None No intervention Ongoing 10 51 y/o Asian female III Stage IV NSCLC Osimertinib None 9 Blue-grey hyperpigmented macules and patches Bilateral arms Axillae Groin Neck Trunk None 2.5% hydrocortisone ointment, triamcinolone 0.1% ointment, photoprotection with mild improvement Ongoing 11 67 y/o Asian male III Stage IV NSCLC Osimertinib None 7 Gray-blue macules and patches with mild background erythema and scaling Bilateral arms Ears Face Bilateral shins None Triamcinolone 0.1% ointment, protection for 6 months with mild improvement Ongoing 12 75 y/o Asian female IV Stage III NSCLC Osimertinib TMP-SMX 3 Gray-blue hyperpigmented patches Bilateral arms Abdomen Back Face Bilateral shins Pruritus Triamcinolone 0.1% and betamethasone 0.01% with relief of pruritus, lesions unchanged Triluma cream 6 months, mild improvement Ongoing 13 42 y/o Asian male IV Stage IV NSCLC Afatinib TMP-SMX 24 Grey-brown hyperpigmented patches Back Face None Hydroquinone 4% cream for 2 years with mild improvement Ongoing 14 74 y/o White female III Stage II NSCLC Osimertinib Atorvastatin 4 Grey-brown hyperpigmented patches Bilateral legs Trunk None Photoprotection Ongoing 15 64 y/o Asian female IV Stage IV NSCLC Osimertinib None 3 Gray-brown hyperpigmentation Abdomen Bilateral arms Back Bilateral legs Pruritus Triamcinolone 0.1% cream; No change, minimal concern to patient Ongoing 16 52 y/o Asian female IV Stage IV NSCLC Osimertinib None 42 Gray hyperpigmented patches with digitate shape Abdomen Bilateral flanks None Triamcinolone 0.1% cream Ongoing NSCLC, non-small cell lung cancer, TMP-SMX, Trimethoprim/Sulfamethoxazole CONCLUSIONS: We highlight the largest case series describing EDP from EGFR inhibitors, which mostly affected Asian patients with lung malignancy and on EGFR tyrosine kinase inhibitors. Clinicians should be able to recognize this condition in their patients and assess how it is affecting their quality of life, and refer to dermatology to help with management.

Improving Pneumococcal Vaccination Rates in Immunosuppressed Pediatric Patients with Rheumatic Disease.

Background: Patients with rheumatic diseases are at a high risk of invasive pneumococcal disease due to immunosuppression. We conducted a quality improvement project, and the first aim was to increase the percentage of patients with systemic lupus erythematosus and mixed connective tissue disease that is up to date on pneumococcal vaccinations from 9.6% to 80% within one year. Subsequently, the second aim was to increase the percentage of patients on immunosuppression with systemic lupus erythematosus, mixed connective tissue disease, juvenile dermatomyositis and systemic vasculitis that is up to date on pneumococcal vaccinations from 62.6% to 80% within one year. Methods: Two process measures were up-to-date vaccination status on (1) 13-valent pneumococcal conjugated vaccine (PCV13) and (2) 23-valent pneumococcal polysaccharide vaccine (PPSV23). Our outcome measure was being fully up to date on both pneumococcal vaccinations. Interventions included an immunization algorithm, reporting of eligible patients, education, reminders, and pre-visit planning. Results: There were shifts in the centerline for all quality measures in both phases of this project. The combined pneumococcal vaccination rate for Phase 1 increased from 9.6% to 91.1%, and this centerline was sustained. Pneumococcal vaccination rates also significantly increased for Phase 2: 68.8% to 93.4% for PCV13, 65.2% to 88.5% for PPSV23, and 62.6% to 86.5% for the combined pneumococcal vaccination rate. Conclusions: Quality improvement methodology significantly increased and sustained pneumococcal vaccination rates in our high-risk, immunosuppressed patients. We continue to prioritize this important initiative to mitigate the risk of invasive pneumococcal disease.

Acute and Long-Term Management of Blunt Cerebrovascular Injury at a Quaternary Referral Level 1 Trauma Center: The Memphis Experience and Comparison of a New Scoring System.

BACKGROUND AND OBJECTIVES: The management of blunt cerebrovascular injuries (BCVIs) remains an important topic within trauma and neurosurgery today. There remains a lack of consensus within the literature and significant variation across institutions. The purpose of this study was to evaluate management of BCVI at a large, tertiary referral trauma center. METHODS: Institutional Review Board approval was obtained to conduct a retrospective review of patients with BCVI at our Level 1 Trauma Center. Computed tomography angiography was used to identify BCVI for each patient. Patient information was collected, and statistical analysis was performed. With the included risk factors for ischemic complications, a novel scoring system based on ischemic risk, the "Memphis Score," was developed and evaluated to grade BCVI. RESULTS: Two hundred seventeen patients with BCVI from July 2020 to August 2022 were identified. The most common mechanism of injury was motor vehicle collision (141, 65.0%). Vertebral arteries were the most common vessel injured (136, 51.1%) with most injuries occurring at a high cervical location (101, 38.0%). Denver Grade 1 injuries (89, 33.5%) and a Memphis Score of 1 were most frequent (172, 64.6%), and initial anticoagulation with heparin drip was initiated 56.7% of the time (123). Endovascular treatment was required in 24 patients (11.1%) and was usually performed in the first 48 hours (15, 62.5%). While Denver Grade (P = .019) and Memphis Score (P < .00001) were significantly higher in those patients undergoing endovascular treatment, only the Memphis Score demonstrated a significant difference between those patients who had stroke or worsening on follow-up imaging and those who did not (P = .0009). CONCLUSION: Although BCVI management has improved since early investigative efforts, institutions must evaluate and share their data to help clarify outcomes. The novel "Memphis Score" presents a standardized framework to communicate ischemic risk and guide management of BCVI.

Psoas force recruitment in full-body musculoskeletal movement simulations is restored with a geometrically informed cost function weighting.

Simulations of musculoskeletal models are useful for estimating internal muscle and joint forces. However, predicted forces rely on optimization and modeling formulations. Geometric detail is important to predict muscle forces, and greater geometric complexity is required for muscles that have broad attachments or span many joints, as in the torso. However, the extent to which optimized muscle force recruitment is sensitive to these geometry choices is unclear. We developed level, uphill and downhill sloped walking simulations using a standard (uniformly weighted, "fatigue-like") cost function with lower limb and full-body musculoskeletal models to evaluate hip muscle recruitment with different geometric representations of the psoas muscle under walking conditions with varying hip moment demands. We also tested a novel cost function formulation where muscle activations were weighted according to the modeled geometric detail in the full-body model. Total psoas force was less and iliacus, rectus femoris, and other hip flexors' force was greater when psoas was modeled with greater geometric detail compared to other hip muscles for all slopes. The proposed weighting scheme restored hip muscle force recruitment without sacrificing detailed psoas geometry. In addition, we found that lumbar, but not hip, joint contact forces were influenced by psoas force recruitment. Our results demonstrate that static optimization dependent simulations using models comprised of muscles with different amounts of geometric detail bias force recruitment toward muscles with less geometric detail. Muscle activation weighting that accounts for differences in geometric complexity across muscles corrects for this recruitment bias.

Artificial Intelligence in Rhinology.

Rhinology, allergy, and skull base surgery are fields primed for the integration and implementation of artificial intelligence (AI). The heterogeneity of the disease processes within these fields highlights the opportunity for AI to augment clinical care and promote personalized medicine. Numerous research studies have been published demonstrating the development and clinical potential of AI models within the field. Most describe in silico evaluation models without direct clinical implementation. The major themes of existing studies include diagnostic or clinical decisions support, clustering patients into specific phenotypes or endotypes, predicting post-treatment outcomes, and surgical planning.