Acquired perforating dermatosis: a clinical and dermatoscopic correlation.

Acquired Perforating Dermatosis (APD) is a perforating disease characterized by transepidermal elimination of dermal material [1,2]. This disease usually develops in adulthood. APD has been reported to occur in association with various diseases, but is most commonly associated with dialysis-dependent chronic renal failure (CRF) or diabetes mellitus (DM) [1,2,3,4]. Morton et al found that APD occurs in up to 10% of patients undergoing hemodialysis [5]. Additionally, Saray et al found that sixteen of twenty-two cases with APD were associated with CRF [3].

Postmortem Mitragynine Distribution in a Single Drug Fatality Case.

A 32-year-old Caucasian male was found unconscious at his sober-living home and pronounced dead after transportation to the emergency room. The decedent had a documented history of substance-use disorder and past suicide attempts, but according to his family, he was sober for the past year. Significant autopsy findings were cardiomegaly, hepatomegaly, congested lungs, cerebral edema, and obesity. The toxicology examination of blood and tissues using liquid chromatography tandem mass spectrometry detected only mitragynine in the central blood (7.5 mg/L), peripheral blood (3.3 mg/L), liver (42.2 mg/kg), and gastric contents (33.1 mg). The qualitative identification of 7-hydroxymitragynine was performed only on the central blood. The pathologist ruled the cause of death acute mitragynine intoxication combined with cardiomegaly with left ventricular hypertrophy, with severe hepatomegaly and obesity listed as other significant conditions. The mode, or manner, of death was determined to be an accidental overdose. To the authors' knowledge, this is the first reported case where mitragynine was the only drug detected. This case study will contribute to the understanding of mitragynine-only death investigation and provide valuable toxicology information for medical examiners and pathologists.

CF33-hNIS-anti-PD-L1 oncolytic virus followed by trastuzumab-deruxtecan in a patient with metastatic triple negative breast cancer: a case study.

Prognosis of metastatic triple negative breast cancer (mTNBC) remains poor despite recent advances in therapeutic options. Trastuzumab deruxtecan (T-DXd) has shown promising efficacy in patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer, which is defined by immunohistochemistry (IHC) 1+ or 2+ and lack of HER2 amplification by fluorescence in situ hybridization (FISH) testing. The purpose of the study is to evaluate the safety and initial evidence of efficacy of intratumoral administration of CF33-hNIS-anti-PD-L1 (CHECKvacc) against mTNBC. Oncolytic virus CHECKvacc intratumoral injection is currently undergoing investigation in patients with mTNBC as a single agent (NCT05081492). The patient was enrolled on the clinical trial CHECKvacc for the Treatment of Metastatic Triple Negative Breast Cancer, received a single dose of CHECKvacc, and discontinued the study due to lack of immediate response. We report a case of a patient with mTNBC who was heavily pretreated and presented with extensive dermal metastasis. Two dermal metastasis biopsies in 2021 showed HER2 0 by IHC. The patient received a single dose of CHECKvacc and discontinued the study due to lack of immediate response. Twenty-five days later, the patient received treatment with T-DXd, and her tumor regressed significantly. The patient's disease-free survival was 10 months (December 2021-October 2022). The sequential treatment with intratumoral injection of CHECKvacc followed by T-DXd may have significant clinical activity in select patients with heavily pretreated mTNBC. ClinicalTrials.gov NCT05081492.

Reflections of mentors and mentees on a national mentoring programme for pharmacists in the United Kingdom: An examination into organisational culture and systems.

BACKGROUND: There is no accepted or consistent model for delivering mentoring programmes, manifesting in some debate surrounding the ideal conducive system. Mentorship structures and culture within pharmacy can be advanced by researching experiences of mentors and mentees. OBJECTIVE: To explore lived experiences of participants in a nationwide mentoring programme in relation to motivations and barriers associated with engaging with mentoring, and what system changes and organisational culture shift could further support mentoring for pharmacy professionals. METHODS: This study adopted a constructivist research paradigm, with a qualitative design to focus on how participants interpreted the world and their experiences. Verbatim transcripts of recordings were examined using deductive and inductive thematic analysis. RESULTS: Participants in twenty one-to-one interviews appreciated the programme's allowance for organic relationships to occur, its contribution towards advancing the profession forward, its flexibility, and available resources. They discussed training needs and a more formal onboarding process into the programme that facilitated greater awareness of resources, as well as the need to evaluate and tweak it. System changes were highlighted so that mentoring can be part of the organisational culture, such as incorporating mentoring in job descriptions to increase capacity, senior members of the profession acting as role models, and linking mentoring to existing education and development structures. CONCLUSION: Data demonstrated the need for formal structure but that which allowed for informal and organic relationships to develop. It is paramount for sponsoring organisations to provide resources and continuously monitor the program. The rich information gathered on administrative support and structure of a mentoring programme, along with its organisational facets, should help organisations when implementing similar initiatives. An organisation sponsoring or administering a mentoring programme must take actions that help codify its mentoring culture and its advocacy of mentoring as key to advancement for its profession's members.

Reflections of mentors and mentees on a national mentoring programme for pharmacists: An examination into relationships, personal and professional development.

BACKGROUND: While mentorship programmes for professionals are growing in number, the lived experiences of mentor and mentee participants could be captured so as to better inform best practices and considerations for thriving relationships. OBJECTIVE: This study evaluated the lived experiences of mentors and mentees in a nationwide programme for pharmacists administered by a professional organisation in the United Kingdom, specifically examining the nature of relationships comprising those experiences. METHODS: A phenomenological approach was adopted, with semi-structured interviews conducted remotely between November 2019 and June 2020. Potential participants approached via a gatekeeper, employing purposive and convenience sampling. Transcribed data were examined using a combination of inductive and deductive thematic analysis and codes were assigned independently by two researchers, to increase rigour in analysis. RESULTS: A total of 20 participants described their perceived role in their respective mentoring partnerships, gave their own account of the definition of mentoring and discussed the crucial role of trust and understanding in developing a successful mentoring relationship. Mentors' beliefs on their perceived role in the relationship largely guided their approach to the structure of the interactions. The concepts of personal growth and development of peers were often discussed by the participants, along with the acknowledgment that mentoring is a relationship that ideally lasts potentially a lifetime, should the relationship be successful. Mentors felt a sense of pride in giving back to the profession. An unintentional unbalanced power dynamic was often reported and both mentors and mentees acknowledged frustrations when they perceived their partner was not showing the same level of engagement and commitment. CONCLUSIONS: Pharmacists participating in a nationwide mentoring programme expressed considerable enthusiasm with their contribution, underscoring the programme's flexibility, its emphasis of mentoring versus merely advising, and its responsibility for enhancing or reconnecting with their professional identity as well as fostering more positivity and liveliness in their professional roles. . The programme might consider additional training to mentors to promote their own self-efficacy in mentoring, which among other things could curtail perceived potential power imbalances within mentor-mentee dyads and lead to a more dynamic and contextualised mentoring experience.

Genomic Markers of CDK 4/6 Inhibitor Resistance in Hormone Receptor Positive Metastatic Breast Cancer.

Cyclin-dependent kinase 4/6 inhibitors are the standard of care for hormone receptor-positive metastatic breast cancer. This retrospective study reports on genomic biomarkers of CDK 4/6i resistance utilizing genomic data acquired through routine clinical practice. Patients with HR+ MBC treated with palbociclib, ribociclib, or abemaciclib and antiestrogen therapy were identified. Patients were grouped into early (<6 months); intermediate (6−24 months for 0−1 lines; 6−9 months for ≥2 lines); or late progressors (>24 months for 0−1 lines; >9 months PFS for ≥2 lines). NGS and RNA sequencing data were analyzed in association with PFS, and survival analysis was stratified by prior lines of chemotherapy. A total of 795 patients with HR+ MBC treated with CDK 4/6i were identified. Of these, 144 (18%) patients had genomic data and 29 (3.6%) had RNA data. Among the 109 patients who received CDK4/6i as 1st- or 2nd-line therapy, 17 genes showed associations with PFS (p-value ≤ 0.15 and HR ≥ 1.5 or HR < 0.5). Whole transcriptome RNAseq was analyzed for 24/109 (22%) patients with 0−1 prior lines of therapy and 56 genes associated with PFS (HR ≥ 4 or HR ≤ 0.25 and FDR ≤ 0.15). In this retrospective analysis, genomic biomarkers including FGFR1 amplification, PTEN loss, and DNA repair pathway gene mutations showed significant associations with shorter PFS for patients receiving CDK4/6 inhibitor therapy.

Association of Operating Room Costs With Head and Neck Surgical Instrumentation Optimization: A Surgeon-Led Quality Improvement Initiative.

Importance: In an era of increasing health care expenditure, reduction of redundant head and neck surgical instrumentation may minimize waste. Objective: To (1) optimize head and neck surgical instrument trays at a single large academic tertiary care center and (2) identify associated direct cost savings. Design, Setting, and Participants: This prospective quality improvement initiative was conducted at an academic tertiary care medical center from July 2017 through July 2021. Participants were a multidisciplinary surgical quality team consisting of head and neck surgeons, operating room nurses, surgical technicians, and supply chain analysts. Main Outcomes and Measures: The 4 primary surgical instrument trays (major otolaryngology [Oto], Oto plastics, direct laryngoscopy, and microdirect laryngoscopy) used in all head and neck procedures were reviewed by 10 head and neck surgical faculty with detailed case observation of instrument utilization performed by trained operating room nurses and surgical technologists. Instruments used in less than 40% of cases were excluded from surgical trays, and novel instrument trays were established based on faculty feedback and utilization. Data on instrument processing, utilization, and associated institutional direct costs were prospectively collected over a 3-year period. The primary outcome measure was change in operating room direct costs. Surgeon satisfaction with the quality improvement intervention was the secondary outcome. Direct cost savings were identified as a function of surgical volume, labor and supply costs, and instrument depreciation. Results: More than 1500 eligible surgical cases were reviewed during the preintervention period. Of the 149 instruments in the major Oto tray, only 118 (79%) instruments were used in more than 40% of cases. There were 58 (49%) and 32 (21%) instruments in this tray that were used in more than 40% of neck dissections and sentinel lymph node biopsies, respectively. Resulting intervention included development of a streamlined major Oto tray with 118 instruments and novel neck dissection and sentinel lymph node biopsy trays. Similar processes were applied to the remaining head and neck trays, with a total of 257 instruments removed. Over a 3-year postintervention period, streamlined surgical trays were used 9284 times with direct cost savings of $228 338 (95% CI, $227 817-$228 854). Overall surgeon satisfaction with the optimized head and neck surgical trays was 100%. Conclusions and Relevance: In this quality improvement study, surgeon-led elimination of redundant or rarely used instruments from surgical instrument trays was associated with reduced operating room direct costs while maintaining stakeholder satisfaction.

Necrolytic migratory erythema associated with a metastatic neuroendocrine tumor.

Necrolytic migratory erythema (NME) is a skin condition historically associated with pancreatic glucagonomas. Rarely it occurs in the absence of a pancreatic tumor, which has been described as pseudoglucagonoma syndrome. We describe a woman with a metastatic neuroendocrine tumor who developed NME 6 years after diagnosis of the tumor. Her laboratory data revealed essential fatty acid deficiency and a high level of glucagon. Although the pathogenesis of NME is not completely understood, zinc, essential amino acid, and fatty acid deficiencies have all been postulated as possible causative factors.

Prurigo pigmentosa: report of two cases in the United States and review of the literature.

Prurigo pigmentosa is a rare inflammatory skin disease of unknown etiology presenting as a pruritic truncal eruption of reticulated and symmetric macules and papules with the predilection for young Japanese females. Although cases of PP are increasingly reported in the non-Japanese literature, dermatologists may be unfamiliar with this entity. Here we report a Caucasian American female and a Chinese American female with PP and a discussion of the literature. The treatments of choice for prurigo pigmentosa are tetracyclines such as doxycycline and minocycline, as well as dapsone. The prognosis is excellent.

Design fundamentals of mentoring programs for pharmacy professionals (Part 2): Considerations for mentors and mentees.

Developing a mentoring program is multifactorial, and organizations developing such programs must be reflective in considering their own organizational culture to determine the goals and outcomes assessment of a mentoring program that aligns with the organization's mission and values. Part 1 of this series of papers on devising mentoring programs for pharmacy professionals paid mind to their structure, logistical concerns, and basic design consideration. Designing a program, though, cannot be successful without consideration of the people involved, and the very human process that is mentoring and being mentored. This Part 2 paper takes into account the human needs of mentors and mentees, both independently and as pairs or groups involved in a potentially intimate and caring relationship that lasts anywhere from several months, to potentially a lifetime should the relationship be successful. As such, this commentary pays careful attention to the evolving roles each person plays and what this means to administrators overseeing or assessing the results and implications from such a program so as to strive for maximum organizational effectiveness for employing institutions and self-actualization for persons involved in the program.

Design fundamentals of mentoring programs for pharmacy professionals (Part 1): Considerations for organizations.

Mentoring programs have been offered by organizations within and outside of healthcare for years. This commentary examines the literature under the prism of design fundamentals for these programs, drawing particular considerations for schemes aimed at pharmacy professionals. The central argument presented is that mentoring can be used as a vehicle to support pharmacists to learn from others and each other, to reinforce and own their professional identity so that the uniqueness of the pharmacy profession is established within a global health landscape of constant change. In this Part 1 of a series of papers, a wealth of literature, theories, and evidence are presented aiming to inform the general structure and logistical considerations for both in-person and distance mentoring programs.

Xanthogranulomatous reaction to trametinib for metastatic malignant melanoma.

Trametinib, a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, has demonstrated great promise in treating metastatic melanoma associated with BRAF V600E and V600K mutations; however, it also is highly associated with cutaneous adverse events (AEs). As both BRAF and MEK inhibitors become increasingly used to treat malignant melanoma, it is important to better characterize these AEs so that we can manage them. Herein, we present a case of a 66-year-old man who developed erythematous scaly papules on the face and bilateral upper extremities after beginning therapy with trametinib. The severity of the reaction worsened on trametinib monotherapy compared to combination therapy with a BRAF inhibitor. Biopsy revealed a xanthogranulomatous reaction.

Hypertrophy and heart failure in mice overexpressing the cardiac sodium-calcium exchanger.

BACKGROUND: The cardiac sodium-calcium exchanger (NCX1) is a key sarcolemmal protein for the maintenance of calcium homeostasis in the heart. Because heart failure is associated with increased expression of NCX1, heterozygous (HET) and homozygous (HOM) transgenic mice overexpressing NCX1 were developed and evaluated. METHODS AND RESULTS: The NCX1 transgenic mice display 2.3-fold (HET) and 3.1-fold (HOM) increases in exchanger activity from wild-type (WT) mice. Functional information was obtained by echocardiography and catheterizations before and after hemodynamic stress from pregnancy, treadmill exercise or transaortic constriction (TAC). HET and HOM mice exhibited hypertrophy and blunted responses with beta-adrenergic stimulation. Postpartum mice from all groups were hypertrophied, but only the HOM mice exhibited premature death from heart failure. HOM mice became exercise intolerant after 6 weeks of daily treadmill running. After 21 days TAC, HET, and HOM mice exhibited significant contractile dysfunction and 15% to 40% mortality with clinical evidence of heart failure. CONCLUSIONS: Hemodynamic stress results in a compensated hypertrophy in WT mice, but NCX1 transgenic mice exhibit decreased contractile function and heart failure in proportion to their level of NCX1 expression. Thus exchanger overexpression in mice leads to abnormal calcium handling and a decompensatory transition to heart failure with stress.

Financial implications of hospital response to bioterrorism based on diagnosis-related group analysis.

INTRODUCTION: During an infectious disease outbreak, the ability of a hospital to continue routine operations depends upon its ability to absorb expected losses in revenue when the routine charge base is replaced by infectious disease-related charges. OBJECTIVE: The purpose of this study was to determine the probable financial impact of a bioterrorism event or an infectious disease outbreak on an academic and a community hospital. METHODS: During the fiscal year 01 July 2002-30 June 2003, the average number of inpatient charges identified by the diagnosis-related-groups (DRGs) of an academic, tertiary care, Level-1 trauma center (PUH) and a community hospital (StM) were obtained retrospectively. Per diem charges were determined for patients with: (1) gastroenteritis; (2) sepsis; (3) meningitis; (4) tuberculosis (TB); and (5) pneumonia. These charges were used to simulate the financial coding of patients exposed to biological agents. RESULTS: The total average PUH per diem charges per patient for all 31,530 discharges was (US)$10,516. Specifically, the average changes were $20,499 for patients with transplants, $14,406 for receiving critical care services, $12,650 for the provision of cardiac care, $11,576 for trauma/orthopedic care, and $8,259 for services for patients who suffered a stroke. For patients with infectious diseases, the average per diem charges per patient were: (1) $6,184 for patients with gastroenteritis; (2) $7,842 for patients with sepsis; (3) $10,831 for patients with meningitis; (4) $6,118 for patients with TB; and (5) $4,586 for patients with pneumonia. Per patient per day, PUH would generate a potential net on average loss of: (1) $4,332 for gastroenteritis; (2) $2,674 for sepsis; (3) $4,398 for TB; and (4) $5,930 for pneumonia replaced an admission. Patients with meningitis on average generated a net gain ($315) compared to the average, but would not compensate for the denial of transplant, cardiac, trauma/orthopedic, and some critical care services during the event. Total average StM per diem charges per patient for all 10,470 discharges equaled $3,008. Specifically, $4,965 for critical care, $3,022 for cardiac care, $4,397 for trauma/orthopedic care, and $3,037 for stroke services. For infectious diseases, the average per diem charge per patient was: (1) $2,273 (+$735) for gastroenteritis; (2) $3,047 (+$39) for sepsis; (3) $2,504 (-$504) for meningitis; (4) $2,887 ($120) for TB; and (5) $2,652 (-$356) for pneumonia (net loss/gain in parenthesis). CONCLUSIONS: Through DRG analysis, the probable financial impact of a bioterrorist attack on a Health Care Delivery System is largely detrimental. Preparedness for a biological event must include an assessment of hospital capability and capacity to handle these types of patients, but also must consider the financial ability to absorb expected losses in charges or ways in which to recover the losses.

Evaluating the Efficacy of Photodynamic Therapy with 20% Aminolevulinic Acid and Microdermabrasion as a Combination Treatment Regimen for Acne Scarring: A Split-face, Randomized, Double-blind Pilot Study.

Acne scarring is a consequence of abnormal resolution of wound healing after damage that occurs in the sebaceous follicle during acne inflammation. No trial to date has evaluated the efficacy of the combination of microdermabrasion and photodynamic therapy for acne scarring. This single-center, double-blinded pilot study enrolled subjects with moderate-to-severe acne scarring who were randomly assigned in a blinded fashion to use aminolevulinic acid and vehicle in a split-face fashion after full-face treatment with microdermabrasion. On average, 80 percent of the patients displayed more improvement in scarring on the aminolevulinic acid split face versus the vehicle split face after five treatments. Using two different noninvasive mechanisms of targeting acne scarring provided for a safe treatment regimen characterized by more efficacious results with respect to higher rates of scarring improvement.