Genomic characterization of vulvar squamous cell carcinoma reveals differential gene expression based on clinical outcome.

OBJECTIVE: The greatest challenge in the management of vulvar squamous cell carcinoma (VSCC) is treatment of recurrent disease where options for surgery and radiation have been exhausted, or treatment of disease where distant metastasis is present. Identification of mutations differentially expressed between tumor from patients who died of aggressive disease and tumor from patients with an indolent course could reveal novel prognostic indicators and guide development of therapeutic drugs. METHODS: From 202 consecutive patients with VSCC, patients who recurred and died of disease (group A) were identified and matched by age, tumor size, depth of invasion and nodal status with those whose disease did not recur (group B). Tumors from 21 patients were subjected to whole exome sequencing of DNA and RNA, immunohistochemistry (IHC) antibodies of PD-L1 and P16, and in-situ hybridization (ISH) for high-risk HPV. RESULTS: Analysis of DNA and RNA revealed six genes that were strongly differentially expressed between group A and B: TGM3, ACVR2A, ROS1, NFEL2, CCND1 and BCL6. Clinically relevant DNA mutations were significantly greater in group A versus B: 7 vs 2.3 mutations per patient. The most common genomic alterations were mutations in TP53 and the promoter region of TERT. Other common genomic events include alterations of FAT1, CDKN2A, PIK3CA, CCND1, and LRP1B. All samples were MSI stable and tumor mutational burden (TMB) was similar in groups A and B. Most VSCC specimens (81%) were positive for PD-L1. CONCLUSIONS: ACVR2A and TGM3 are significantly under-expressed in tumors with poor outcome, suggesting they may play a role in tumor suppression. Clinical outcome of VSCC appears independent of MSI, TMB, or PD-L1 status.

Implementing a nurse-led prehabilitation program for patients undergoing spinal surgery.

ABSTRACT: Prehabilitation, or "prehab," helps patients optimize strength, function, and nutrition before surgery. This evidence-based practice project presents strategies for implementing a prehab program to prepare patients for spinal surgery. Nurses play an integral role in educating patients preoperatively about the myriad lifestyle changes associated with spinal surgery.

Using a Harm Reduction Approach to Treat Inpatients With Substance Use Disorders.

OBJECTIVE: This study investigated harm reduction (HR) strategies at our institution to decrease the number of patients with a substance use disorder (SUD) who left against medical advice (AMA). BACKGROUND: HR is a public health strategy used for adult substance use problems for whom abstinence is not feasible. METHODS: An HR program was established at 1 institution to enhance the care of hospitalized patients with a SUD. RESULTS: Of the 1780 unique visits for patients with a diagnosis of SUD, 311 patients (17.5%) left our hospital AMA or eloped. The average length of stay for all patients evaluated by the HR team was 6.6 days compared with 4.0 days for those who left AMA. Patients with >1 hospital stay accounted for 22% of our population but represented 34% of the patients who left AMA. CONCLUSIONS: This study reports the approaches implemented to reduce the AMA rate of patients with a SUD and to promote patient-enhanced care.

Caring for behaviorally challenging patients in nonpsychiatric settings.

ABSTRACT: This article discusses a pilot study on the use of a behavior support plan to safely address patients who exhibit disruptive behaviors in the ED and nonpsychiatric medical settings while respecting their autonomy.

Impact of Screening for Sexual Trauma in a Gynecologic Oncology Setting.

OBJECTIVES: Sexual trauma poses a significant concern and is associated with heightened stress, negative health repercussions, and adverse economic effects. A history of abuse may increase a woman's risk of developing cancer, in particular cervical cancer. We analyzed the impact of screening for sexual abuse in a gynecologic oncology population. METHODS: Patients were screened for sexual trauma in a gynecologic oncology clinic over 5 and a half years (April 1, 2011, to September 30, 2016) in this cohort study. The screening questions were selected by behavioral oncology physicians and integrated into the gynecologic history component of the new patient assessment. Patients who screened positive for a history of sexual abuse or intimate partner violence were offered a behavioral oncology referral. Providers were also questioned about the effect of screening on their practice. RESULTS: Of the 1,423 consecutive patients screened for sexual trauma, a total of 164 patients (12%) disclosed a history of sexual abuse. Of the 133 patients who specified their age at the sexual trauma, the majority (107 [80%]) responded that they were a young child or early teen. Most patients (92%) declined counseling. Among individuals presenting with cancer, the distribution of cancer type was statistically different between those patients with and without a sexual trauma history (p = 0.0001). CONCLUSION: Screening for sexual trauma in a gynecologic oncologic population serves as a valuable opportunity to uncover a history of abuse that may increase a woman's susceptibility to cancer. This study demonstrates that screening for sexual abuse in a gynecologic oncology setting may be integrated into new patient interviews with minimal disruption. Identification of an undisclosed sexual trauma history allows for an opportunity to offer counseling and minimize the emotional distress that may be precipitated by treatment and exams.

Strategies to Enhance Comprehension in the Healthcare Setting for Patients With Dyslexia.

Dyslexia involves extreme difficulty with reading, writing, and spelling in your native language despite at least average intelligence. Health literacy refers to the ability to read, understand, and use health information to make appropriate health decisions. Dyslexia is rarely mentioned as a contributing factor to health literacy. Medical providers should be more aware of the special needs of dyslexic patients and implement interventions to allow them to successfully navigate the healthcare environment.

Decline in Physical Restraint Use Following Implementation of Institutional Guidelines.

OBJECTIVE: To investigate the strategies implemented at our institution to reduce medical restraint use. BACKGROUND: Restraints have been utilized to prevent agitation, self-extubations, and falls, although they are often associated with negative repercussions for nurses and patients. METHODS: The restraint data at our institution were compared with the National Database of Nursing Quality Indicators (NDNQI) benchmark. We also described the measures taken to improve restraint documentation. RESULTS: The number of patients in medical restraints, medical restraint hours, medical restraints/patient-days, and deaths in restraints at our institution all significantly decreased (P < 0.00001). There were 27 self-extubations of restrained patients compared with 11 self-extubations of nonrestrained patients. The percentage of inpatients with restraints in critical care and step-down areas declined and remained below the NDNQI benchmark. CONCLUSIONS: This study reports the processes implemented to reduce restraint use through enhanced communication and increased documentation. Further exploration into factors that may attain a restraint-free environment is warranted.

Urological Evidence of Tick Bites in Children.

ABSTRACT: Ticks pose a serious threat to individuals of all ages owing to numerous physical illnesses including chills, aches, and a rash. Tick-borne illnesses range from a mild fever that may be treated at home to a severe disease necessitating hospitalization. Children are at an increased risk of tick bites owing to to their exposure to tick-infested areas during the summer. We report 2 cases of boys aged 3 and 8 years who sustained tick bites to the hemiscrotum and penis. Overnight hospitalization and a course of antibiotics were mandatory. In the first case, the child experienced significant scrotal cellulitis with erythema and edema extending to the suprapubic area with induration of the right anterior scrotum at the site of the tick bite. A scrotal ultrasound demonstrated swelling of the scrotal wall. In the second case, considerable swelling and induration of the distal penis and glans, pruritis of the left groin and penis, and an erythematous rash over the entire anterior pelvis were observed. A high index of suspicion is warranted because a tick bite may present as penile edema. Pediatric emergency physicians should be aware of the risks associated with tick bites and accurately diagnose and initiate treatment to prevent morbidity and mortality.

The impact of COVID-19 on patient safety attendant use.

ABSTRACT: Patient safety attendants (PSAs) provide constant direct observation to patients who have cognitive impairments or thoughts. Some estimates report that an acute care hospital in the United States may spend more than $1 million annually on PSAs, an expenditure often not reimbursed. With no national defined standards to regulate or monitor PSA use, this study sought to determine the impact of COVID-19 on a PSA reduction program in a large Midwestern healthcare system.

Multidisciplinary approach to low-dose CT screening for lung cancer in a metropolitan community.

BACKGROUND: Lung cancer is the primary cause of cancer death in men and women in the USA, led by Kentucky. In 2015, the Centers for Medicare and Medicaid Services initiated annual lung cancer screening with a low-dose computed tomography (LDCT) scan. This observational cohort study evaluated the multidisciplinary approach to this screening in our metropolitan community. METHODS: We present the prospective findings of patients who underwent a screening lung LDCT scan over a 2-year period at our institution in Kentucky. Patients who fulfilled the screening criteria were identified during an office visit with their primary care provider. RESULTS: Of the 4170 patients who underwent a screening lung LDCT scan, a total of 838 (20.9%) patients had nodules >4 mm. Of the 70 patients diagnosed with lung cancer, Stage 1 non-small cell lung cancer was most commonly detected [38 cases (54.3%)]. A follow-up lung LDCT scan (n = 897), pulmonary function test (n = 157), positron emission tomography scan (n = 12) and a lung biopsy (n = 53) were performed for certain individuals who had anomalies observed on the screening lung LDCT scan. A total of 42% of patients enrolled in group tobacco cessation classes quit smoking. CONCLUSIONS: This study provides a unique perspective of a lung LDCT scan screening program driven by primary care providers in a state plagued by cigarette smoking and lung cancer deaths and offers a valuable message into the prevention, high-risk screening and diagnosis of lung cancer.

Multidisciplinary approach to enhancing provider well-being in a metropolitan medical group in the United States.

BACKGROUND: Physician burnout refers to depersonalization, emotional exhaustion, and a sense of lower personal accomplishment. Affecting approximately 50% of physicians in the United States, physician burnout negatively impacts both the physician and patient. Over a 3-year-period, this prospective study evaluated the multidisciplinary approach to decreasing provider burnout and improving provider well-being in our metropolitan community. METHODS: A multidisciplinary Well-Being Task Force was established at our Institution in 2017 to assess the myriad factors that may play a role in provider burnout and offer solutions to mitigate the stressors that may lead to decreased provider well-being. Four multifaceted strategies were implemented: (1) provider engagement & growth; (2) workflow/office efficiencies; (3) relationship building; and (4) communication. Providers at our Institution took the Mayo Clinic's well-being index survey on 3 occasions over 3 years. Their scores were compared to those of providers nationally at baseline and at 1 and 2 years after implementing organizational and individualized techniques to enhance provider well-being. Lower well-being index scores reflected better well-being. RESULTS: The average overall well-being index scores of our Institution's providers decreased from 1.76 at baseline to 1.32 2 years later compared to an increase in well-being index scores of physicians nationally (1.73 to 1.85). Both male and female providers' average well-being index scores at our Institution decreased over the 3 years of this study, from 1.72 to 1.58 for males and 1.78 to 1.21 for females, while physicians' scores nationally increased for both genders. The average well-being index scores were highest for providers at our Institution who graduated from medical school less than 5 years earlier (2.0) and who graduated 15-24 years earlier (2.3), whereas the average lowest scores were observed in providers who graduated ≥25 years earlier (1.37). Obstetricians/gynecologists and internal medicine physicians had the highest average well-being index scores (2.48 and 2.4, respectively) compared to other medical specialties. The turnover rate of our Institution's providers was 5.6% in 2017 and 3.9% in 2019, reflecting a 30% decrease. CONCLUSION: This study serves as a model to reduce provider burnout and enhance well-being through both organizational and individual interventions.

Dynamic response of microglia/macrophage polarization following demyelination in mice.

BACKGROUND: The glial response in multiple sclerosis (MS), especially for recruitment and differentiation of oligodendrocyte progenitor cells (OPCs), predicts the success of remyelination of MS plaques and return of function. As a central player in neuroinflammation, activation and polarization of microglia/macrophages (M/M) that modulate the inflammatory niche and cytokine components in demyelination lesions may impact the OPC response and progression of demyelination and remyelination. However, the dynamic behaviors of M/M and OPCs during demyelination and spontaneous remyelination are poorly understood, and the complex role of neuroinflammation in the demyelination-remyelination process is not well known. In this study, we utilized two focal demyelination models with different dynamic patterns of M/M to investigate the correlation between M/M polarization and the demyelination-remyelination process. METHODS: The temporal and spatial features of M/M activation/polarization and OPC response in two focal demyelination models induced by lysolecithin (LPC) and lipopolysaccharide (LPS) were examined in mice. Detailed discrimination of morphology, sensorimotor function, diffusion tensor imaging (DTI), inflammation-relevant cytokines, and glial responses between these two models were analyzed at different phases. RESULTS: The results show that LPC and LPS induced distinctive temporal and spatial lesion patterns. LPS produced diffuse demyelination lesions, with a delayed peak of demyelination and functional decline compared to LPC. Oligodendrocytes, astrocytes, and M/M were scattered throughout the LPS-induced demyelination lesions but were distributed in a layer-like pattern throughout the LPC-induced lesion. The specific M/M polarization was tightly correlated to the lesion pattern associated with balance beam function. CONCLUSIONS: This study elaborated on the spatial and temporal features of neuroinflammation mediators and glial response during the demyelination-remyelination processes in two focal demyelination models. Specific M/M polarization is highly correlated to the demyelination-remyelination process probably via modulations of the inflammatory niche, cytokine components, and OPC response. These findings not only provide a basis for understanding the complex and dynamic glial phenotypes and behaviors but also reveal potential targets to promote/inhibit certain M/M phenotypes at the appropriate time for efficient remyelination.

Standardized warfarin monitoring decreases adverse drug reactions.

BACKGROUND: While warfarin is the most commonly prescribed medication to prevent thromboembolic disorders, the risk of adverse drug reactions (ADR) poses a serious concern. This prospective study evaluated how primary care providers (PCP) and cardiologists at our Institution managed patients treated with warfarin with the goal of decreasing the number of warfarin ADRs. METHODS: A multidisciplinary anticoagulation task force was established at our Institution in 2014 to standardize warfarin monitoring and management. Between 2013 and 2017, we analyzed patients who were prescribed warfarin by their PCP or cardiologist upon hospital discharge and in the ambulatory setting to determine the international normalized ratio (INR) within 5, 10, and 30 days after discharge, time in therapeutic range (TTR), number of severe warfarin ADRs, and total and average cost reduction of all severe warfarin ADRs to determine whether there was an organizational cost savings following the implementation of standardized warfarin care. RESULTS: The warfarin ADR rate significantly decreased over the 5-year period, from 3.8 to 0.98% (p < 0.0001). The proportion of warfarin prescriptions out of all anticoagulants significantly decreased, from 72.2 to 42.1% (p < 0.001). The proportion of individuals who received an INR at 5, 10, and 30 days after hospital discharge compared to the total number of patients prescribed warfarin significantly increased (p < 0.001). The total cost of severe warfarin ADRs decreased by 57.6% between 2013 and 2017. CONCLUSIONS: This study serves as a model to reduce the number of severe warfarin ADRs by the following tactics: (1) educating PCPs and cardiologists about evidence-based guidelines for warfarin management, (2) increasing the use of our Institution's electronic warfarin module, and (3) enhancing patient compliance with obtaining INR.

Cloacal Anomalies in Monoamniotic, Monochorionic Twins with Complete Urinary Tract Obstruction.

Cloacal anomalies (persistent cloaca) represent the most severe form of anorectal malformations in girls where the rectum, urethra, and vagina remain fused together inside the pelvis and drain into a single common perineal orifice. Infants with cloacal anomalies often succumb to poor lung development due to oligohydramnios. Cloacal anomaly in discordant monozygotic twins has rarely been reported in the literature. In this review, we present the first case of persistent cloaca and complete urinary tract obstruction in discordant monoamniotic twins.

Pembrolizumab in Recurrent Squamous Cell Carcinoma of the Vulva: Case Report and Review of the Literature.

Advanced vulvar cancer is associated with a very poor prognosis. Surgical resection is the mainstay of treatment, with radiation indicated for areas at high risk for recurrence. When surgical and radiation options have been exhausted, the effectiveness of systemic chemotherapy is poor. No biologic or targeted agents have been approved for the management of advanced or recurrent vulvar cancer. Pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), has been successfully used as a target of tumor immune therapy in small cell lung cancer and melanoma. We present the first case in the literature of a patient with recurrent vulvar cancer who was treated successfully with pembrolizumab. Caris next-generation testing revealed a PD-L1 and PD-1 mutation (PD-L1 positive, 2+, 100%). She attained a complete clinical remission after 2 cycles, and a CT scan after 6 cycles revealed a significant response by RECIST criteria. After completing 10 cycles, treatment was stopped due to complications of severe malnutrition related to narcotic abuse. A CT scan 10 weeks after the final treatment revealed no adenopathy. Pembrolizumab is a safe and effective chemotherapeutic agent to treat recurrent vulvar carcinoma.

Xanthine calculi in a patient with Lesch-Nyhan syndrome and factor V Leiden treated with allopurinol: case report.

BACKGROUND: Lesch-Nyhan syndrome is a rare inborn error of purine metabolism marked by a complete deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Inherited as an X-linked recessive genetic disorder that primarily affects males, patients with Lesch-Nyhan syndrome exhibit severe neurological impairments, including choreoathetosis, ballismus, cognitive dysfunction, and self-injurious behavior. Uric acid levels are usually abnormally high, leading to kidney and bladder stones which often necessitate urological intervention. Factor V Leiden is an autosomal dominant disorder of blood clotting associated with hypercoagulability, thrombophilia, and renal disease. CASE PRESENTATION: We present the first reported case of xanthine calculi in a patient with Lesch-Nyhan syndrome and Factor V Leiden who was treated with allopurinol. A renal ultrasound and CT scan demonstrated bilateral staghorn calculi in the kidneys as well as nephrocalcinosis. Two years earlier the patient underwent cystoscopy with bilateral ureteroscopy and laser lithotripsy, and he was stone free afterwards. The patient subsequently underwent bilateral percutaneous nephrolithotomy (PCNL) and was stone free following the procedure. Patients with endogenous overproduction of uric acid who are being treated with allopurinol have a higher chance of developing xanthine stones. CONCLUSIONS: Pediatricians treating these children should be aware of these rare conditions and promptly manage the potential complications that may require medical or surgical intervention.

A Hospital-Based Neuroscience Nursing Course Designed to Improve Competence and Confidence.

After experiencing growth in a neuroscience service line, nurse leaders identified a need for increased competencies among clinical staff. This hospital met the need by developing a unique multidisciplinary neuroscience nursing course to improve the clinical competence, confidence, and professional development of bedside nurses.

Practical considerations of linear accelerator-based frameless extracranial radiosurgery for treatment of occipital neuralgia for nonsurgical candidates.

Occipital neuralgia generally responds to medical or invasive procedures. Repeated invasive procedures generate increasing complications and are often contraindicated. Stereotactic radiosurgery (SRS) has not been reported as a treatment option largely due to the extracranial nature of the target as opposed to the similar, more established trigeminal neuralgia. A dedicated phantom study was conducted to determine the optimum imaging studies, fusion matrices, and treatment planning parameters to target the C2 dorsal root ganglion which forms the occipital nerve. The conditions created from the phantom were applied to a patient with medically and surgically refractory occipital neuralgia. A dose of 80 Gy in one fraction was prescribed to the C2 occipital dorsal root ganglion. The phantom study resulted in a treatment achieved with an average translational magnitude of correction of 1.35 mm with an acceptable tolerance of 0.5 mm and an average rotational magnitude of correction of 0.4° with an acceptable tolerance of 1.0°. For the patient, the spinal cord was 12.0 mm at its closest distance to the isocenter and received a maximum dose of 3.36 Gy, a dose to 0.35 cc of 1.84 Gy, and a dose to 1.2 cc of 0.79 Gy. The brain maximum dose was 2.20 Gy. Treatment time was 59 min for 18, 323 MUs. Imaging was performed prior to each arc delivery resulting in 21 imaging sessions. The average deviation magnitude requiring a positional or rotational correction was 0.96 ± 0.25 mm, 0.8 ± 0.41°, whereas the average deviation magnitude deemed within tolerance was 0.41 ± 0.12 mm, 0.57 ± 0.28°. Dedicated quality assurance of the treatment planning and delivery is necessary for safe and accurate SRS to the cervical spine dorsal root ganglion. With additional prospective study, linear accelerator-based frameless radiosurgery can provide an accurate, noninvasive alternative for treating occipital neuralgia where an invasive procedure is contraindicated.

Quantifying isocenter measurements to establish clinically meaningful thresholds.

A dataset range of isocenter congruency verification tests have been examined from a statistical perspective for the purpose of establishing tolerance levels that are meaningful, based on the fundamental limitation of linear accelerator isocentricity and the demands of a high-precision stereotactic radiosurgery program. Using a laser-defined isocenter, a total of 149 individual isocenter congruency tests were examined with recorded values for ideal spatial corrections to the isocenter test tool. These spatial corrections were determined from radiation exposures recorded on an electronic portal imaging device (EPID) at various gantry, collimator, and treatment couch combinations. The limitations of establishing an ideal isocenter were quantified from each variable which contributed to uncertainty in isocenter definition. Individual contributors to uncertainty, specifically, daily positioning setup errors, gantry sag, multileaf collimator (MLC) offset, and couch walkout, were isolated from isocenter congruency measurements to determine a clinically meaningful isocenter measurement. Variations in positioning of the test tool constituted, on average, 0.38 mm magnitude of correction. Gantry sag and MLC offset contributed 0.4 and 0.16 mm, respectively. Couch walkout had an average degrading effect to isocenter of 0.72 mm. Considering the magnitude of uncertainty contributed by each uncertainty variable and the nature of their combination, an appropriate schedule action and immediate action level were determined for use in analyzing daily isocenter congruency test results in a stereotactic radiosurgery (SRS) program. The recommendations of this study for this linear accelerator include a schedule action level of 1.25 mm and an immediate action level of 1.50mm, requiring prompt correction response from clinical medical physicists before SRS or stereotactic body radiosurgery (SBRT) is administered. These absolute values were derived from considering relative data from a specific linear accelerator and, therefore, represent a means by which a numerical quantity can be used as a test threshold with relative specificity to a particular linear accelerator.

Guidelines for treatment naming in radiation oncology.

Safety concerns may arise from a lack of standardization and ambiguity during the treatment planning and delivery process in radiation therapy. A standardized target and organ-at-risk naming convention in radiation therapy was developed by a task force comprised of several Radiation Oncology Societies. We present a nested-survey approach in a community setting to determine the methodology for radiation oncology departments to standardize their practice. Our Institution's continuous quality improvement (CQI) committee recognized that, due to growth from one to three centers, significant variability existed within plan parameters specific to patients' treatment. A multidiscipline, multiclinical site consortium was established to create a guideline for standard naming. Input was gathered using anonymous, electronic surveys from physicians, physicists, dosimetrists, chief therapists, and nurse managers. Surveys consisted of several primary areas of interest: anatomical sites, course naming, treatment plan naming, and treatment field naming. Additional concepts included capitalization, specification of laterality, course naming in the event of multiple sites being treated within the same course of treatment, primary versus boost planning, the use of bolus, revisions for plans, image-guidance field naming, forbidden characters, and standard units for commonly used physical quantities in radiation oncology practice. Guidelines for standard treatment naming were developed that could be readily adopted. This multidisciplinary study provides a clear, straightforward, and easily implemented protocol for the radiotherapy treatment process. Standard nomenclature facilitates the safe means of communication between team members in radiation oncology. The guidelines presented in this work serve as a model for radiation oncology clinics to standardize their practices.