Retrospective operationalization of allostatic load in patients with cancer: A systematic review.

Allostatic load (AL) has been shown to impact cancer outcomes. At present, no gold standard exists surrounding AL computation. As such, a systematic review of the literature was performed to identify studies that retrospectively calculated AL in patients with cancer. The following variables were collected for each study: AL calculation method, including the biomarkers used and their cutoff values, number of biosystems represented, definition of high AL, and the use of proxy biomarkers. Thirteen articles were included for full-text review. The number of biomarkers used in the calculation of AL varied considerably, ranging from 6 to 16. Considerable variability was also observed in terms of utilized biomarkers and biosystem representation. This lack of standardization complicates retrospective AL calculation among patients with cancer. Nonetheless, determining AL in patients with cancer presents an important step in the optimization of patient care and outcomes.

The First Report of Multiple, Bilateral Axillary Epidermal Inclusion Cysts.

Epidermal inclusion cysts (EICs) are benign masses that often develop on the face, scalp, neck, and back. Typically, EICs occur secondary to acne or obstructed hair follicles. However, the development of multiple EICs is associated with various syndromes and invasive procedures. Despite their relatively benign nature, a small percentage of EICs have been found to undergo malignant transformation. The complete excision of EICs is essential for their definitive treatment because of their ability to rupture, causing pain and infection. We present the first reported case of a patient without a history of acne, axillary surgery, or genetic syndromes who presented with multiple, painless, bilateral axillary EICs.

Smart Watches Lack Skin Smarts: Current and Future Dermatologic Applications in Device Metrics.

INTRODUCTION: Smartwatches have proven life-saving in medical specialties such as cardiology. Smartwatches actively warn us of arrhythmia risk and loud noise exposure. However, dermatologic health metrics are rarely monitored, and users are never alerted of potential skin health issues. Furthermore, the role of these devices within dermatology has not been evaluated in the literature. This study aims to analyze the current data points monitored by smartwatches and discuss potential adaptations to support dermatologic patient education and improve clinical management.  Methods: The top three smartwatches per global market share were identified and analyzed to determine the health data points they monitor and the alerts they provide. These data points were grouped and compared based on their corresponding body systems.  Results: Cardiovascular health comprises the highest percentage of data points collected with an average of 41% while dermatologic health averaged only 11%.  Conclusion: Dermatology is grossly underrepresented in current smartwatch devices. There is an important need to expand the dermatologic health metrics tracked by adapting existing smartwatch technology. From proactive cancer prevention to disease-specific reactive interventions, smartwatches can play a significant role in improving dermatological health and reducing healthcare costs.

Drosophila tweety facilitates autophagy to regulate mitochondrial homeostasis and bioenergetics in Glia.

Mitochondria support the energetic demands of the cells. Autophagic turnover of mitochondria serves as a critical pathway for mitochondrial homeostasis. It is unclear how bioenergetics and autophagy are functionally connected. Here, we identify an endolysosomal membrane protein that facilitates autophagy to regulate ATP production in glia. We determined that Drosophila tweety (tty) is highly expressed in glia and localized to endolysosomes. Diminished fusion between autophagosomes and endolysosomes in tty-deficient glia was rescued by expressing the human Tweety Homolog 1 (TTYH1). Loss of tty in glia attenuated mitochondrial turnover, elevated mitochondrial oxidative stress, and impaired locomotor functions. The cellular and organismal defects were partially reversed by antioxidant treatment. We performed live-cell imaging of genetically encoded metabolite sensors to determine the impact of tty and autophagy deficiencies on glial bioenergetics. We found that tty-deficient glia exhibited reduced mitochondrial pyruvate consumption accompanied by a shift toward glycolysis for ATP production. Likewise, genetic inhibition of autophagy in glia resulted in a similar glycolytic shift in bioenergetics. Furthermore, the survival of mutant flies became more sensitive to starvation, underlining the significance of tty in the crosstalk between autophagy and bioenergetics. Together, our findings uncover the role for tty in mitochondrial homeostasis via facilitating autophagy, which determines bioenergetic balance in glia.

Use of Questionnaire-Based Research in Hand Surgery.

INTRODUCTION: Questionnaire-based research is ubiquitous, and careful survey design is paramount to obtaining meaningful results. This study characterizes the use of questionnaire-based studies in the current hand surgery literature. METHODS: We conducted a systematic review of questionnaire-based studies published between 2010 and 2020 in 4 major American journals. We included studies in which questionnaire results represented a primary outcome. Validation status of the survey instruments was assessed, and topics of study were categorized. Nonvalidated instruments were assessed for reporting of parameters to limit bias. RESULTS: Three hundred fifty-four studies were identified, including 186 (52.5%) using validated instruments, 98 (27.7%) using nonvalidated instruments, 64 (18.1%) using a combination, and 6 (1.7%) that sought to validate an instrument. Of the studies that used validated instruments, 84.9% focused on patient-reported outcomes and 15.1% focused on other patient-centered topics. In contrast, of studies that used nonvalidated instruments, 44.9% focused on physician practice, 30.6% were patient centered, and 13.3% focused on education. Among nonvalidated questionnaires, 74.5% did not report predistribution testing, 49.0% did not publish full survey questions, and 33.3% did not report response rates. CONCLUSIONS: Survey research is common in the hand surgery literature. Forty-six percent of examined studies included at least some nonvalidated elements. Techniques to limit bias in the design and reporting of studies based on nonvalidated surveys were not uniformly disclosed. Identified areas for improvement include (1) pilot testing to assess for question clarity; (2) publication of full texts to improve transparency; and (3) better reporting on sample selection, respondents, and nonrespondents.

Invisible palmar needles: thyroid disorder associated spiny keratoderma and the importance of proper light for visualization.

Spiny keratoderma is a rare skin condition that presents on the palmar and plantar surfaces of the hands and/or feet. This condition is difficult to appreciate under ambient lighting but can be both physically and emotionally distressing to patients. Furthermore, because of the association with various neoplasms and systemic diseases, timely diagnosis and appropriate follow-up is of importance. We evaluate a case of spiny keratoderma in a patient with recently diagnosed hypothyroidism and emphasize the importance of proper lighting during a dermatology-focused physical examination. The patient's palmar lesions were only appreciable under LED light and with physical examination. A biopsy of the lesions confirmed the diagnosis of spiny keratoderma.

Surgical prophylaxis in pediatric orthopedic patients with penicillin allergy: a multicentered retrospective prognostic study.

Up to 20% of orthopedic surgeons still avoid the use of cephalosporins in patients with penicillin allergies despite its reported safety in the adult and general surgery pediatric population. The primary objective is to determine the incidence of adverse effects and allergic reactions when using cephalosporins in pediatric orthopedic patients labeled as penicillin-allergic as compared to those without previously reported penicillin allergy. A multicenter retrospective chart review was performed across three level 1 trauma centers from January 2013 to February 2020 to identify penicillin-allergic as well as non-penicillin-allergic pediatric patients treated for orthopedic injuries. Data were collected regarding patient demographics, antibiotic administered, timing of antibiotic administration, reported drug allergy, and described allergic reaction. Postoperative or intraoperative allergic reactions to antibiotics, surgical site infections, and complications were recorded. A total of 2289 surgeries performed by four fellowship-trained surgeons were evaluated. Eighty-five patients diagnosed with penicillin allergy were identified and underwent 95 surgeries and 95 patients without previously reported penicillin allergy underwent 95 surgeries. One patient, with a documented history of anaphylaxis to cefazolin, sustained an anaphylactic reaction intraoperatively to cefazolin. There were no other reported reactions, surgical site infections, or complications. There was no statistically significant difference in rate of allergic reaction in patients with previously reported penicillin allergy treated with cefazolin and those with no previous reported reaction (P > 0.05). Prophylaxis with cephalosporins is not associated with increased risk for allergic reaction. Cephalosporins can be safely administered to pediatric patients with penicillin allergy undergoing orthopedic intervention. Level of evidence: Level II, Multicenter Retrospective Prognostic Study.

A Case Report of Generalized Non-pruritic Lichen Amyloidosis.

We evaluate the rare case of a patient who presented with generalized, non-pruritic lichen amyloidosis. There are three reported cases of generalized and non-pruritic lichen amyloidosis. The lichen amyloidosis subtype of primary localized cutaneous amyloidosis is characterized by keratinocyte-derived amyloid deposition in the papillary dermis, classically presenting as pruritic, hyperpigmented macules coalescing into plaques on the lower extremities. While the pathogenesis is likely multifactorial, chronic scratching has been proposed as an inciting factor. The patient's type of lichen amyloidosis challenges the proposed etiology of chronic scratching leading to amyloid deposition.

A Unilateral, Pruritic Papular Eruption Following Primigravida Pregnancy.

Linear lichen planus (LLP), also known as blaschkolinear or blaschkoid lichen planus, is a rare subtype of lichen planus that presents along the lines of Blaschko. While LLP has been associated with vaccinations, neoplasms, medications, and successive pregnancies, we present a case of LLP following a primary pregnancy. A 29-year-old G1P1 female presented to dermatology for the evaluation of an intensely pruritic, whorled rash confined to her left lower leg that appeared shortly after the birth of her first child. A biopsy of the lesion and subsequent histopathology confirmed the diagnosis of LLP. The patient was treated with topical steroids with minimal response to therapy and declined further treatment.

The social vulnerability index as a risk stratification tool for health disparity research in cancer patients: a scoping review.

PURPOSE: The social vulnerability index (SVI), developed by the Centers for Disease Control and Prevention, is a novel composite measure encompassing multiple variables that correspond to key social determinants of health. The objective of this review was to investigate innovative applications of the SVI to oncology research and to employ the framework of the cancer care continuum to elucidate further research opportunities. METHODS: A systematic search for relevant articles was performed in five databases from inception to 13 May 2022. Included studies applied the SVI to analyze outcomes in cancer patients. Study characteristics, patent populations, data sources, and outcomes were extracted from each article. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: In total, 31 studies were included. Along the cancer care continuum, five applied the SVI to examine geographic disparities in potentially cancer-causing exposures; seven in cancer diagnosis; fourteen in cancer treatment; nine in treatment recovery; one in survivorship care; and two in end-of-life care. Fifteen examined disparities in mortality. CONCLUSION: In highlighting place-based disparities in patient outcomes, the SVI represents a promising tool for future oncology research. As a reliable geocoded dataset, the SVI may inform the development and implementation of targeted interventions to prevent cancer morbidity and mortality at the neighborhood level.

Spiny keratoderma: A review of case reports and histopathological descriptions.

Spiny keratoderma (SpK) is a rare skin condition characterized by spine-like papules on the palms and soles. The condition is identified under several names such as "music box spine keratosis" and "palmoplantar filiform hyperkeratosis," creating ambiguity in the diagnostic and histopathologic features of the disease. In this study, we reviewed 84 cases of SpK to examine patient demographics, medical history, clinical and histopathological descriptions, and sporadic versus hereditary onset. Notably, the most used histopathological terms were "parakeratosis" and "hypogranulosis," and the most used clinical terms were "spine" and "hyperpigmented." The average age at presentation was 60.1 years with the majority of cases in males. Only 29.8% of cases were associated with a family history of SpK and underlying malignancies were present in 28.6% of cases. This review investigates the frequency of histopathologic and clinical terms used to describe SpK to provide insight into the clinical and histopathological characteristics of this rarely reported condition.

HRAS-driven cancer cells are vulnerable to TRPML1 inhibition.

By serving as intermediaries between cellular metabolism and the bioenergetic demands of proliferation, endolysosomes allow cancer cells to thrive under normally detrimental conditions. Here, we show that an endolysosomal TRP channel, TRPML1, is necessary for the proliferation of cancer cells that bear activating mutations in HRAS Expression of MCOLN1, which encodes TRPML1, is significantly elevated in HRAS-positive tumors and inversely correlated with patient prognosis. Concordantly, MCOLN1 knockdown or TRPML1 inhibition selectively reduces the proliferation of cancer cells that express oncogenic, but not wild-type, HRAS Mechanistically, TRPML1 maintains oncogenic HRAS in signaling-competent nanoclusters at the plasma membrane by mediating cholesterol de-esterification and transport. TRPML1 inhibition disrupts the distribution and levels of cholesterol and thereby attenuates HRAS nanoclustering and plasma membrane abundance, ERK phosphorylation, and cell proliferation. These findings reveal a selective vulnerability of HRAS-driven cancers to TRPML1 inhibition, which may be leveraged as an actionable therapeutic strategy.