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Clozapine is primarily metabolized via cytochrome P450(CYP)1A2 and to a lesser extent CYP3A4, CYP2C19, and CYP2D6. Metabolic inhibitors of clozapine, such as fluvoxamine and ciprofloxacin, are important to recognize to avoid adverse drug events. Estrogen-containing oral contraceptives (eOCPs) are weaker CYP1A2 and CYP2C19 inhibitors but are associated with a 2-fold increase of clozapine concentrations. The potential for phenoconversion due to a CYP genetic polymorphism can add additional complexities when considering drug interactions. A case report is presented of a suspected interaction between newly initiated clozapine and a prescribed eOCP for which the patient's pharmacogenomic status was known. A 17-year-old, nonsmoking, White female with a history of schizophrenia was initiated on clozapine 12.5 mg at bedtime with a plan to increase by 25 mg every 4 days in the outpatient setting. The patient was a known rapid CYP1A2 metabolizer without identified sources of CYP1A2 induction and a CYP2C19 rapid metabolizer. Based on pharmacogenomic testing, there was no suspicion for significant gene-drug interactions. Yet, as the patient was prescribed an eOCP, a clozapine concentration was obtained after reaching 150 mg at bedtime. This steady-state clozapine concentration was found to be 560 ng/mL, correlating with worsening sedation and constipation. Given ongoing side effects, clozapine was lowered to 100 mg at bedtime; however, ongoing intolerance ultimately led to clozapine discontinuation. This case highlights the potential interaction between clozapine and eOCP in a CYP1A2 and CYP2C19 rapid metabolizer, leading to clozapine intolerance and discontinuation. The concomitant use of clozapine and eOCPs should be undertaken judiciously., (© 2024 AAPP. The Mental Health Clinician is a publication of the American Association of Psychiatric Pharmacists.)

Background: As pharmacy evolves, pharmacists have an increasing role in documentation. Publications examining the actions of other health professionals show that negative perception in written notes translates to patients receiving lower quality of care, resulting in worse health outcomes, suggesting that the use of stigmatizing language towards patients has concerning consequences., Objectives: To identify the prevalence of stigmatizing language in inpatient pharmacy progress. notes based on patient specific characteristics and diagnoses., Methods: This retrospective pilot study reviewed inpatient pharmacy progress notes of a Midwestern (United States) tertiary academic institution from May to June 2023. Stigmatizing words and phrases associated with specified disease states were separated into the categories of general language, substance use disorders, and mental health. Notes of patients on internal medicine, family medicine, kidney/pancreas transplant, liver transplant, and gastroenterology services were included., Results: Stigmatizing language was found in 22% (n = 43) of notes. The words "abuse" and "dependence" had the highest prevalence. Patients diagnosed with substance use disorders experienced stigmatizing language at a high rate, exaggerated further if their note lacked a documented diagnosis., Conclusions: This study demonstrated that stigmatizing language is present in pharmacy documentation. Providing context and resources of the proper documentation to reflect equitable healthcare is crucial for patient care., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The development of filler biomaterials with high hyaluronic acid concentrations, cohesiveness, and elastic modulus has become an option for chin augmentation, as the balance of these rheological properties promotes high lifting capacity, providing minimally invasive perceptible improvements in patient appearance., Presentation of Case: The present study reviewed clinical and anatomical aspects of patients referred for chin augmentation and created a flowchart to assertively diagnose patients with an indication of Juvéderm® Volux™ for defining the lower third of the face., Discussion: The chin is vital for facial proportions and attractiveness perception. Its relevance to facial appearance is noticed the most when chin size is less than ideal, making other facial areas seem larger or smaller. The adjacent soft tissues of the neck and jaw appear prematurely aged when chin projection or width is inadequate. Hyaluronic acid-based fillers have a confirmed history of safe and effective use for treating facial volume loss or deficiency., Conclusion: Juvéderm® Volux™ is a safe, effective, and long-lasting alternative for restoring and creating facial volume and sculpting, shaping, and contouring the chin and jaw., Competing Interests: Declaration of competing interest Dra. Alessandra Kuhn Dall'Magro is a consultant and speaker for Allergan/AbbVie. Dr. James Olding is a speaker for Allergan/AbbVie., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Many health care organizations offer pediatric infusions in outpatient infusion centers or, as in our organization, in a hospital-based outpatient Pediatric Infusion Therapy Center (PITC). When restrictions related to the COVID-19 pandemic decreased our PITC appointment capacity by 40%, other patient and family satisfaction issues were exacerbated. We implemented a new approach to pediatric infusions with the aim of improving patient and family satisfaction and reducing the amount of time in an appointment itinerary without negatively affecting patient safety. Methods: Our team used a phased approach to pilot the administration of short chemotherapy infusions in the same outpatient clinic examination rooms where consultation and routine office visits were conducted. Patients saw their specialist for an examination and, if clinically indicated, their infusion was administered in the same room. Appointment itineraries were then completed. The team tracked efficiency, satisfaction, and safety metrics related to the new process. Results: All efficiency metrics improved. No harm came to the 49 unique patients who received a total of 184 infusions. Patient appointment itineraries were shortened by an average of 1.03 hr. Satisfaction survey responses indicated a clear preference (93%) for the new process. Discussion: The novel approach of offering short infusions in outpatient clinic examination rooms provides an opportunity to ease capacity constraints and further increase patient and family satisfaction. This method may be especially helpful for health care organizations when external influences (e.g., lack of physical space, challenging patient volumes, and pandemics) necessitate a change.

Introduction: Acrocyanosis and erythema pernio are 2 dermatologic manifestations of vasospastic changes. Primary care providers should consider that these conditions can occur as primary or idiopathic conditions and as secondary conditions related to another disease or medication. Herein we describe a case of acrocyanosis and erythema pernio attributed to vincristine therapy., Case Description: A 22-year-old man was evaluated for discomfort and red lesions involving the toes of both feet for several weeks. He had completed chemotherapy 1 month earlier for Ewing sarcoma in the right femur. Local control for the primary tumor included wide local excision and reconstruction with a vascularized fibular allograft from the right fibula. On examination, his right foot was dark blue and cool. Toes on both feet had nonpainful erythematous papules. After the case was discussed with the patient's oncology team, the diagnosis was medication-induced acrocyanosis of the right foot and bilateral erythema pernio. Treatment consisted of supportive care to keep the feet warm and promote circulation to the feet. At 2-week follow-up, the patient's symptoms and the appearance of his feet had markedly improved., Discussion: Primary care clinicians should be able to recognize dermatologic manifestations of vasospastic changes, including acrocyanosis and erythema pernio, and rule out possible secondary causes, such as pharmacologic agents. This patient's history of therapy for Ewing sarcoma prompted consideration of medication-induced vasospastic changes most likely related to the adverse vasospastic effects of vincristine. Symptoms should improve with cessation of the offending medication.

Introduction and Importance: Cholangiocarcinoma is a malignant neoplasm with a difficult diagnosis and unfavorable prognosis that can appear anywhere in the biliary tree. Anatomically, it can be classified as intra- or extrahepatic, the latter being the most common primary malignancy of the biliary tract. Although bone tissue is the third most common target for metastases in general, metastatic lesions from cholangiocarcinomas are uncommon in the head and neck., Case Presentation: A 33-year-old female patient undergoing cancer treatment for cholangiocarcinoma was referred to the Oral and Maxillofacial Surgery and Traumatology Service (CTBMF) of the São Vicente de Paulo Hospital in Passo Fundo, Rio Grande do Sul, Brazil, for interdisciplinary follow-up. She presented trismus, dysphagia, pain, necrosis and drainage in the mental region, and an increased volume on the right side of the mandibular body in the region of teeth 47 and 48. An incisional biopsy was performed in this bulging region. The histopathological diagnosis was poorly differentiated carcinoma. The patient was followed-up weekly by the CTBMF team, receiving analgesia and palliative treatment for the extra- and intraoral lesions, controlling opportunistic infections, and improving food intake., Discussion: Metastatic cholangiocarcinomas in the mandible are rare, hence their diagnosis is often late, which may disfavor the prognosis of these conditions., Conclusion: Carefully examining patients with mandibular bone lesions is strongly suggested, especially patients with known or previous concomitant malignancy., Competing Interests: Declaration of competing interest The publication of this article does not generate any conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction and Importance: Orthognathic surgery aims to restore the functional and esthetic standards of the face and non-surgical or minimally invasive procedures have been optimizing the results of facial orthosurgical treatments. This case report aimed to show the use of minimally invasive techniques that, associated with orthognathic surgery, represent a trend in current oral and maxillofacial rehabilitation., Case Presentation: A female patient, 28 years old, white, sought care from the Dentistry team of the São Vicente de Paulo Hospital, in Passo Fundo, Brazil, complaining of mandibular prognathism, anteroposterior maxillary deficiency, dental crowding, malocclusion, functional and esthetic changes that negatively affected her psychosocial interactions and stomatognathic function. The treatment involved orthodontics, orthognathic surgery, and orofacial harmonization with dermal fillers., Clinical Discussion: The multidisciplinarity among the specialties of Oral and Maxillofacial Surgery and Traumatology, Orthodontics, and Orofacial Harmonization add and contribute to the process of planning and implementing the treatment proposed, as well as the prognosis toward patient satisfaction., Conclusion: The surgical procedure associated with minimally invasive facial harmonization not only corrected the functional complaint of the patient but also played an important role in improving facial harmony, contributing significantly to self-esteem., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: For decades, the management of chronic myelomonocytic leukemia (CMML) or juvenile myelomonocytic leukemia (JMML) has been largely inextricable from myelodysplastic syndromes (MDS), myeloproliferative neoplasms, and acute myeloid leukemia. Hallmarks of these diseases have been the emergence of unique genomic signatures and discouraging responses to available therapies. Here, we will critically examine the current options for management and review the rapidly developing opportunities based on advances in CMML and JMML disease biology., Recent Findings: Few clinical trials have exclusively been done in CMML, and in JMML, the rarity of the disease limits wide scale participation. Recent case series in JMML suggest that hypomethylating agents (HMAs) are a viable option for bridging to curative intent with allogeneic hematopoietic stem cell transplant or as posttransplant maintenance. Emerging evidence has demonstrated targeting the RAS-pathway via MEK inhibition may also be considered. In CMML, treatment with HMAs is largely derived from data inclusive of MDS patients, including a small number of patients with dysplastic CMML variants. Based on CMML disease biology, additional therapeutic targets being investigated include inhibitors of splicing, CD123/dendritic cell axis, inherent GM-CSF progenitor cell hypersensitivity, and targeting the JAK/STAT pathway. Current evidence is also expanding for oral HMAs. The management of CMML and JMML is rapidly evolving and clinicians must be aware of the genetic landscape and expanding treatment options to ensure these rare populations are afforded therapeutic interventions best suited to their needs.

To evaluate the correlation between an uncapped, actual body weight-based unfractionated heparin dosing strategy, we performed a body mass index-based subanalysis of a previously reported pediatric cohort. Nearly half (45%) of obese patients were supra-therapeutic on initial anti-FXa assessment. Obese patients achieved therapeutic anti-FXa significantly faster than nonobese patients (median 4 vs 12 hours, P = .0192) and were more likely to have any supra-therapeutic anti-FXa levels (77% vs 35%; P = .0021). There was no statistically significant difference in major or clinically relevant nonmajor bleeding rates between weight categories (P = .69). Prospective pediatric studies are warranted to confirm our findings., (© 2021 Wiley Periodicals LLC.)

Background: Extracorporeal photopheresis (ECP) is associated with few adverse effects. We have anecdotally noted patients treated with long-term ECP develop iron deficiency anemia (IDA)., Methods: We performed a retrospective chart review of adult patients who received ECP for any indication at Mayo Clinic Rochester and Mayo Clinic Arizona. The primary objective was to describe the cumulative incidence of IDA at 1 year of ECP therapy., Results: A total of 123 patients were eligible for analysis. Graft-vs-host disease was the most common indication for ECP (n = 76, 61.8%). At 1 year of ECP therapy, the cumulative incidence of IDA was 24.1% (95% CI, 14.2%-32.9%). At 5 years, the cumulative incidence of IDA was 68.3% (95% CI, 38%-83.8%). Risk factors for the development of IDA included: cumulative number of ECP sessions (HR 1.34, 95% CI, 1.05-1.73 per 10 additional sessions, P = .022), an indication for ECP of solid organ transplant rejection (compared to cutaneous T-cell lymphoma, HR 5.46, 95% CI, 2.06-14.49, P < .001), and proton pump inhibitor use at baseline (HR 2.15, 95% CI, 1.1-4.21, P = .03). Iron supplementation was initiated in 29 of 37 evaluable patients who developed IDA, with a cumulative incidence of supplementation in 77.2% patients within 3 months of recognition of IDA (95% CI, 55.8%-88.3%). Hemoglobin normalized in 50.1% of patients started on iron supplementation for IDA within 7 months (95% CI, 25.2%-66.7%)., Conclusions: Iron deficiency anemia is common in patients receiving long-term ECP and occurs throughout ECP therapy. IDA resolved with iron supplementation in half of patients., (© 2019 Wiley Periodicals, Inc.)

Purpose: The aim of the study was to investigate the activation of the PI3K/AKT (phosphatidylinositol-3-kinase) pathway after stimulation of TLR-4 (Toll-like receptor 4) with LPS (lipopolysaccharide) in FLT3-ITD (internal tandem duplication)-positive AML (acute myeloid leukemia) cells. TRAF6 (tumor necrosis factor receptor-associated factor 6), an E3 ubiquitin ligase, is critically involved in TLR-signaling. Based on the observation that TRAF6 might play a role in AKT phosphorylation, we hypothesized that TRAF6 can enhance the constitutive FLT3-ITD-driven activation of AKT after LPS stimulation., Materials and Methods: Human MV4-11 FLT3-ITD cells were silenced for TRAF6 by stable shRNA expression. Western blotting was used to analyze signal transduction by detection of phosphorylated proteins. LPS-induced activation of the NF-κB pathway was ensured by the induction of IκBα expression. To evaluate a potential functional role of TRAF6, we also performed chemosensitivity assays., Results: In MV4-11 cells, AKT was activated in response to LPS treatment. Surprisingly, shRNA-mediated knockdown of TRAF6 resulted in a significant increase in basal AKT phosphorylation. By LPS stimulation, the gain of AKT phosphorylation was more pronounced in the TRAF6 knockdown cell line than in the control. In addition, the concentration-dependent induction of apoptosis in response to treatment with the cytostatic drugs cytarabine or daunorubicin was significantly reduced in TRAF6-depleted MV4-11 cells., Conclusion: Our data strongly suggest that the E3 ubiquitin ligase TRAF6 plays an important functional role in signal transduction and survival of AML cells. We hypothesize that LPS-mediated stimulation of TLR-4 leads to the induction of NF-κB-mediated signaling. However, TRAF6 might prevent a synergistic activation of the PI3K/AKT pathway after activation of TLR-4 signaling in FLT3-ITD-positive cells.

Amphipathic polymers ("amphipols") were introduced several years ago (Tribet, C.; Audebert, R.; Popot, J.-L. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 15047-15050) as an alternative method for solubilizing integral membrane proteins in stable, nativelike conformations. However, direct maintenance of full membrane protein functionality in amphipol solutions has not previously been demonstrated in the absence of added lipid or detergent. In this contribution, the first zwitterionic amphipol "PMAL-B-100" is introduced. PMAL-B-100 not only maintains membrane protein structure and solubility, but also supports the full catalytic activity of an integral membrane enzyme, diacylglycerol kinase, in the complete absence of additional lipid or detergent. All of the roles which a lipid bilayer normally plays in maintaining diacylglycerol kinase's structure and in facilitating catalysis are satisfied by the environment and interactions supplied by PMAL-B-100.