A Diagnostic Dilemma and Classification Conundrum: Atypical Histiocytic Neoplasm Presenting as a Calvarial Mass.

Histiocytic disorders are a wide range of disorders arising from abnormal proliferation and infiltration of dendritic cells. The Histiocyte Society has arranged the disorders into five main groups: L, C, M, R, and H. We present a case in which an elderly woman presented with a solitary osseous lesion in her skull in the right anterior calvarium. Biopsy and histological studies were strongly positive for cyclin D1; positive for CD68, S100, and ZBTB46; weakly positive for OCT2; and equivocal for ALK1 and CD163. Genomic studies also identified KRAS and GPS2 mutations. KRAS-positive genomic analysis favors a diagnosis of histiocytoma, while the solitary calvarium and spontaneous resolution with remission favor a diagnosis of Langerhans cell histiocytosis (LHC). Despite the strong clinical evidence favoring LCH, our patient's clinical and histologic features did not fit any of the five histiocytic categories and were classified as an atypical histiocytic disorder.

A Novel Therapy for a Rare Condition: Continuous Anakinra Infusion for a Patient With Macrophage Activation Syndrome.

Macrophage activation syndrome (MAS) is a type of hemophagocytic lymphohistiocytosis (HLH), which occurs due to excessive stimulation of the immune system. Common precipitants of MAS include disseminated infection or underlying rheumatologic disorders such as adult-onset Still's disease which is characterized as an inflammatory arthritis with daily fevers and a salmon-colored rash. We present a case of a patient with probable adult-onset Still's disease and subsequent disseminated cytomegalovirus (CMV) infection, who met the criteria for MAS based on the presence of a fever, cytopenia in multiple cell lines, elevated ferritin, presence of hemophagocytosis on bone marrow, low fibrinogen, and mild splenomegaly on physical exam. The patient responded to treatment with continuous anakinra infusion and ganciclovir for treatment of CMV. Though cytotoxic medications such as etoposide have traditionally been considered first-line treatment for HLH/MAS, interleukin-1 inhibitors such as anakinra are emerging as aless cytotoxic alternative.

A Rare Case of West Nile Virus-Associated Cardiomyopathy.

A 68-year-old man presented in late summer 2021 with fever, myalgias, generalized weakness, dizziness, and headache. Past medical history included rheumatoid arthritis treated with infliximab, congestive heart failure with preserved ejection fraction, and recent travel to Alaska. He was febrile, tachycardic, and tachypneic on admission. Physical exam and admission labs were overall unremarkable. On day 4, he complained of shortness of breath and central chest discomfort. Troponin was mildly elevated, electrocardiogram was unremarkable, and echocardiogram showed new global wall motion abnormalities and ejection fraction of 40%, which was 55% months prior. Serum West Nile IgM antibodies resulted positive near the end of hospitalization. Testing for SARS-CoV-2, influenza as well as multiple other viral, bacterial, and fungal organisms was negative. Overall, the patient recovered clinically including improvement in ejection fraction on echocardiogram with conservative management. West Nile virus (WNV) is associated with a myriad of symptoms and complications, most notably, neuroinvasive disease. However, cardiomyopathy secondary to WNV as illustrated in this case has been infrequently described. Clinicians should be aware of this potential rare complication in patients with WNV to improve rapid detection and treatment of myositis, associated cardiomyopathy, and related complications.

Integrated secure messaging to enhance medical education: a mixed methods study.

BACKGROUND: Instant messaging applications and texting are useful for educating and communicating with medical students; however, they present patient privacy concerns and do not address the challenge of student inclusion in patient care communication. EMR-integrated secure messaging offers an opportunity to include students on team communication, enhance their medical education, and ensure patient privacy. METHODS: Between July 2019 through March 2020, we performed a mixed method study to evaluate use of EPIC® Secure Chat as a means of enhancing student education and team communication. We promoted use of secure messaging in orientation, performed a pre- and post-rotation survey to assess perceptions of Secure Chat effect on communication, and directly reviewed and categorized messages. RESULTS: Twenty-four 3rd and 4th year students completed the pre-rotation survey, and 22 completed the post-rotation survey. Twelve (50%) students reported the quality of communication with faculty was either good or very good prior to internal medicine rotation, while 20 (91%) reported this post-rotation (p-value 0.001). There was a similar improvement in communication with ancillary staff. Nineteen (86%) students felt that secure messaging improved their communication with faculty. On message review, threads were frequently logistical, but also often included discussions of patient management. CONCLUSIONS: Students viewed Secure Chat as having a favorable effect on their communication with team members and reported communication on internal medicine to be improved compared to prior rotations. Messages included students on important patient care conversations. Secure messaging offers a novel medium to improve team communication, enhance student education, and maintain patient privacy.

Leadership Immersion and Aspiring Leader Programs Designed to Improve Nurses' Well-Being and Competence: Integral Features During the COVID-19 Pandemic.

Nurse leaders play integral roles in the health care system as they focus on patient quality of care and safety at a high level and lead teams of frontline staff. Nurse leadership turnover during COVID-19 poses challenges not only for continuity of patient care but also for organizations that may fail to meet their specific goals. When a nurse leader role is not filled, gaps in care delivery occur. Our institution developed the Leadership Immersion and Aspiring Leader Programs prior to COVID-19 that provide application to theory opportunities to new nursing leaders who are prepared to fill leadership positions.

Bullous fixed drug eruption following administration of the recombinant adjuvant Shingrix vaccine.

A 51-year-old woman with Crohn's disease presented with a bullous rash on her left arm and axilla 2 days after receiving her second dose of the recombinant adjuvant Shingrix vaccine. PCR for herpes simplex virus (HSV) 1, HSV 2 and varicella zoster virus was negative. Punch biopsy revealed changes that were consistent with a bullous fixed drug eruption. She was successfully treated oral prednisone and topical triamcinolone cream. This is the first known case of a bullous fixed drug eruption due to the recombinant adjuvant Shingrix vaccine.

Rhabdomyolysis Secondary to COVID-19 Vaccination.

Rhabdomyolysis has been described as a complication of coronavirus disease 2019 (COVID-19) infection, but few cases of rhabdomyolysis associated with COVID-19 vaccination have been reported. We described a case of an 80-year-old male who developed rhabdomyolysis two days after receiving his second dose of the Moderna COVID-19 vaccine. He presented with severe weakness, myalgias, and an initial creatinine kinase (CK) of 6,546 IU/L that improved with intravenous fluids. Common causes of rhabdomyolysis were excluded including statin use, strenuous exercise, and trauma. With the increasing immunization efforts against COVID-19, physicians should consider the possibility of rhabdomyolysis when a patient presents with neuromuscular complaints following vaccination.

Posterior Reversible Encephalopathy Syndrome in a Patient With SARS-CoV-2 Infection Treated With Tocilizumab.

As the world has struggled to adapt to the coronavirus disease (COVID-19) pandemic, new evidence has emerged suggesting that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may manifest with a wide variety of neurologic symptoms. We present the case of a 70-year-old patient hospitalized for COVID-19 related pneumonia who was treated with off-label interleukin (IL)-6 inhibitor tocilizumab and eventually developed prolonged delirium. MRI findings were consistent with posterior reversible encephalopathy syndrome (PRES). PRES was felt to be from SARS-CoV-2 infection, tocilizumab, or a combination. The patient received symptomatic treatment without success. These findings are consistent with few other recent reports, which have chronicled PRES findings in patients with SARS-CoV-2 infections. However, this is only the second example of PRES in a COVID-19 patient treated with tocilizumab. While cases of PRES have been noted to occur with other infectious diseases, clinicians should be aware of the association with SARS-CoV-2 infection and tocilizumab therapy, particularly when considering tocilizumab treatment outside its approved indication. Future research efforts are needed to establish evidence-based guidelines for the management of these patients.

Ex vivo delivery of Mirococept: A dose-finding study in pig kidney after showing a low dose is insufficient to reduce delayed graft function in human kidney.

The complement system plays a pivotal role in the pathogenesis of ischemia-reperfusion injury in solid organ transplantation. Mirococept is a potent membrane-localizing complement inhibitor that can be administered ex vivo to the donor kidney prior to transplantation. To evaluate the efficacy of Mirococept in reducing delayed graft function (DGF) in deceased donor renal transplantation, we undertook the efficacy of mirococept (APT070) for preventing ischaemia-reperfusion injury in the kidney allograft (EMPIRIKAL) trial (ISRCTN49958194). A dose range of 5-25 mg would be tested, starting with 10 mg in cohort 1. No significant difference between Mirococept at 10 mg and control was detected; hence the study was stopped to enable a further dose saturation study in a porcine kidney model. The optimal dose of Mirococept in pig kidney was 80 mg. This dose did not induce any additional histological damage compared to controls or after a subsequent 3 hours of normothermic machine perfusion. The amount of unbound Mirococept postperfusion was found to be within the systemic dose range considered safe in the Phase I trial. The ex vivo administration of Mirococept is a safe and feasible approach to treat DGF in deceased donor kidney transplantation. The porcine kidney study identified an optimal dose of 80 mg (equivalent to 120 mg in human kidney) that provides a basis for further clinical development.

Methods for delivering the UK's multi-centre prison-based naloxone-on-release pilot randomised trial (N-ALIVE): Europe's largest prison-based randomised controlled trial.

INTRODUCTION AND AIMS: Naloxone is an opioid antagonist used for emergency resuscitation following opioid overdose. Prisoners with a history of heroin use by injection have a high risk of drug-related death in the first weeks after prison-release. The N-ALIVE trial was planned as a large prison-based randomised controlled trial (RCT) to test the effectiveness of naloxone-on-release in the prevention of fatal opiate overdoses soon after release. The N-ALIVE pilot trial was conducted to test the main trial's assumptions on recruitment of prisons and prisoners, and the logistics for ensuring that participants received their N-ALIVE pack on release. DESIGN AND METHODS: Adult prisoners who had ever injected heroin, were incarcerated for ≥7 days and were expected to be released within 3 months were eligible. Participants were randomised to receive, on liberation, a pack containing a single 'rescue' injection of naloxone or a control pack with no naloxone syringe. The trial was double-blind prior to prison-release. RESULTS: We randomised 1685 prisoners (842 naloxone; 843 control) across 16 prisons in England. We stopped randomisation on 8 December 2014 because only one-third of administrations of naloxone-on-release were to the randomised ex-prisoner; two-thirds were to others whom we were not tracing. DISCUSSION AND CONCLUSIONS: Prevention RCTs are seldom conducted within prisons; we demonstrated the feasibility of conducting a multi-prison RCT to prevent fatality from opioid overdose in the outside community. We terminated the N-ALIVE trial due to the infeasibility of individualised randomisation to naloxone-on-release. Large RCTs are feasible within prisons.

A double-blind randomised controlled investigation into the efficacy of Mirococept (APT070) for preventing ischaemia reperfusion injury in the kidney allograft (EMPIRIKAL): study protocol for a randomised controlled trial.

BACKGROUND: Delayed graft function (DGF) is traditionally defined as the requirement for dialysis during the first week after transplantation. DGF is a common complication of renal transplantation, and it negatively affects short- and long-term graft outcomes. Ischaemia reperfusion injury (IRI) is a prime contributor to the development of DGF. It is well established that complement system activation plays a pivotal role in the pathogenesis of IRI. Mirococept is a highly effective complement inhibitor that can be administered ex vivo to the donor kidney just before transplantation. Preclinical and clinical evidence suggests that Mirococept inhibits inflammatory responses that follow IRI. The EMPIRIKAL trial (REC 12/LO/1334) aims to evaluate the efficacy of Mirococept in reducing the incidence of DGF in cadaveric renal transplantation. METHODS/DESIGN: EMPIRIKAL is a multicentre double-blind randomised case-control trial designed to test the superiority of Mirococept in the prevention of DGF in cadaveric renal allografts, as compared to standard cold perfusion fluid (Soltran®). Patients will be randomised to Mirococept or placebo (Pbo) and will be enrolled in cohorts of N = 80 with a maximum number of 7 cohorts. The first cohort will be randomised to 10 mg of Mirococept or Pbo. After the completion of each cohort, an interim analysis will be carried out in order to evaluate the dose allocation for the next cohort (possible doses: 5-25 mg). Immunosuppression therapy, antibiotic and antiviral prophylaxis will be administered as per local centre protocols. The enrolment will take approximately 24 months, and patients will be followed for 12 months. The primary endpoint is DGF, defined as the requirement for dialysis during the first week after transplantation. Secondary endpoints include duration of DGF, functional DGF, renal function at 12 months, acute rejection episodes at 6 and 12 months, primary non-function and time of hospital stay on first admission and in the first year following transplant. Safety evaluation will include the monitoring of laboratory data and the recording of all adverse events. DISCUSSION: The EMPIRIKAL trial is the first study to evaluate the efficacy of an ex vivo administered complement inhibitor (Mirococept) in preventing DGF in cadaveric human renal transplantation. Mirococept has a unique 'cytotopic' property that permits its retention in the organ microvasculature. TRIAL REGISTRATION: ISRCTN registry, ISRCTN49958194 . Registered on 3 August 2012.

An Unusual Case of Statin-Induced Myopathy: Anti-HMGCoA Necrotizing Autoimmune Myopathy.

Statins are some of the most widely prescribed medications, and though generally well tolerated, can lead to a self-limited myopathy in a minority of patients. Recently, these medications have been associated with a necrotizing autoimmune myopathy (NAM). Statin-associated NAM is characterized by irritable myopathy on electromyography (EMG) and muscle necrosis with minimal inflammation on muscle biopsy. The case presented is a 63-year-old woman who has continued elevation of creatine kinase (CK) after discontinuation of statin therapy. She has irritable myopathy on EMG and NAM is confirmed by muscle biopsy. She subsequently tests positive for an experimental anti-3-hydroxy-3-methylglutaryl-coenzyme A (anti-HMGCoA) antibody that is found to be present in patients with statin-associated NAM. Though statin-associated NAM is a relatively rare entity, it is an important consideration for the general internist in patients who continue to have CK elevation and weakness after discontinuation of statin therapy. Continued research is necessary to better define statin-specific and dose-dependent risk, as well as optimal treatment for this condition.

Operationalizing professionalism: a meaningful and practical integration for resident education.

OBJECTIVES/HYPOTHESIS: Review contemporary definitions of professionalism and apply them to resident evaluation and education. DATA SOURCES: Review of PubMed, Medline, and Google Scholar. REVIEW METHODS: Review of articles and bibliographies from 1980 to 2012 for professionalism definitions, evaluation, and education in resident training was performed. RESULTS: Our initial search returned 291 articles. Sixty-seven articles were included in the final review. Definitions of professionalism often focused on attitudes and traits such as honesty, altruism, self-reflection, reliability, and respect for others. The operationalization of such abstract definitions is challenging as they are subject to variable interpretations when translated into measurable behaviors. Despite the challenges, specific behavioral benchmarks can be developed and utilized for evaluation with available methods including patient/nurse surveys, faculty observation, objective structured clinical exams (OSCE), ethical reasoning tests, and completion of administrative tasks. Curriculums have often been lecture-based, limiting the ability to transmit professional values and behaviors. Professionalism is taught most effectively through multiple modalities including mentorship, faculty role modeling, self-reflection, and resident professionalism portfolios. For professionalism evaluation and education to be effective, the curriculum should be developed as a collaborative effort between residents and faculty. CONCLUSIONS: Professionalism training requires practical, behavior-based definitions of professional conduct. Once professional expectations are defined, multiple methods should be used to comprehensively evaluate the learner. Professionalism curriculums must be interactive and promote development through a variety of methods with the goal to improve resident performance in this critical core competency.

Exome resequencing identifies potential tumor-suppressor genes that predispose to colorectal cancer.

Inherited factors account for around one third of all colorectal cancers (CRCs) and include rare high penetrance mutations in APC, MSH2, MSH6, and POLE. Here, we sought novel tumor-suppressor genes that predispose to CRC by exome resequencing 50 sporadic patients with advanced CRC (18 diagnosed ≤35 years of age) at a mean coverage of 30×. To help identify potentially pathogenic alleles, we initially sought rare or novel germline truncating mutations in 1,138 genes that were likely to play a role in colorectal tumorigenesis. In total, 32 such mutations were identified and confirmed, and included an insertion in APC and a deletion in POLE, thereby validating our approach for identifying disease alleles. We sought somatic mutations in the corresponding genes in the CRCs of the patients harboring the germline lesions and found biallelic inactivation of FANCM, LAMB4, PTCHD3, LAMC3, and TREX2, potentially implicating these genes as tumor suppressors. We also identified a patient who carried a germline truncating mutation in NOTCH3, part of the Notch signaling cascade that maintains intestinal homeostasis. Our whole exome analyses provided further gene lists to facilitate the identification of potential predisposition alleles.

Sodium amobarbital: historical perspectives and neurorehabilitation clinical caveats.

The sodium amobarbital (amytal) (SA) interview is a technique that has been utilized in the treatment of a variety of disorders since its introduction in 1929. Since that time, there has been an assortment of research conducted showing its value in both differential diagnosis and treatment of multiple conditions. Notwithstanding the substantive amount of experience with the technique and its application to a myriad number of clinical conditions, it remains a seldom used procedure in clinical practice and certainly in neurorehabilitation. This paper will review the history of SA, as well as summarize the literature published over the past two decades on the clinical applications of SA to provide readers with a foundation for the utility of this agent, as well as the sodium amytal interview (SAI) in neurorehabilitation clinical practice. Special emphasis will be placed on the use of the SAI in individuals with functional disorders that may be seen in the neurorehabilitation setting, as well as various classes of pain disorders.

Evaluation of psychometric properties of the internet addiction scale in a sample of Turkish high school students.

The Internet Addiction Scale (IAS) is a self-report instrument based on the seven substance dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed., American Psychiatric Association, 1994) and two additional criteria recommended by Griffiths. The IAS was administered to 300 high school students along with the Beck Depression Inventory (BDI) and Submissive Acts Scale (SAS). For test-retest reliability, the IAS was administered a second time 7 days after the first administration. An interitem reliability reduced the initial scale from 31 to 27 items (with Cronbach's alpha of 0.94). The factor analysis suggests the existence mainly of one factor in the IAS. Correlation analyses indicated that BDI and SAS were significantly correlated positively with the IAS. One-week test-retest correlation for the IAS was highly significant. According to these results, the psychometric properties of the IAS are promising.

Development of a psychometrically sound internet addiction scale: a preliminary step.

The Internet Addiction Scale (IAS) is a self-report instrument based on the 7 Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) substance dependence criteria and 2 additional criteria recommended by Griffiths (1998). The IAS was administered to 233 undergraduates along with 4 measures pertaining to loneliness and boredom proneness. An item reliability analysis reduced the initial scale from 36 to 31 items (with a Cronbach's alpha of .95). A principal-components analysis indicated that the IAS consisted mainly of one factor. Multiple regression analyses revealed that Family and Social Loneliness and Boredom Proneness were significantly correlated with the IAS; Family and Social Loneliness uniquely predicted IAS scores. No evidence for widespread Internet addiction was found.