The differential role of SSa/SSb and Ro52 antibodies in defining clinical phenotypes in idiopathic inflammatory myopathies.

OBJECTIVE: In idiopathic inflammatory myopathies, anti-SSa/SSb and anti-Ro52 are associated with interstitial lung disease (ILD), yet few studies have compared their prognostic utility. Our study analyzes clinical phenotypes associated with anti-SSa/SSb and anti-Ro52 positivity in IIM and their association with ILD. METHODS: We performed a retrospective analysis of IIM patients >18-years-old, seen at Northwell Myositis Center 2007- 2018 who met 2017 EULAR/ACR criteria with available anti-SSa/SSb data. Patients who were anti-SSa/SSb(-) and anti-Ro52(+) were excluded from anti-SSa/SSb subgroup analysis but included in Ro52 subgroup analysis. Organ manifestations, pulmonary function tests (PFTs) and comorbidities were recorded. Statistical analyses included Chi-square, Fisher's Exact, Wilcoxon Rank Sum, McNemar's test. RESULTS: Of 94 patients included in the final analysis, 35% (33/94) were anti-SSa/SSb positive (+). Of 60 patients with anti-Ro52 data, 42% (25/60) were (+). ILD was more common in anti-SSa/SSb (+) versus anti-SSa/SSb negative patients and anti-Ro52(+) versus anti-Ro52 negative patients (58% vs 25%; p = 0.003 and 64% vs.26%; p = 0,004 respectively). Anti-SSa/SSb (+) was not associated with increased ILD severity based on PFTs. Anti-Ro52(+) group had lower DLCO than anti-Ro52(-) (47% vs 68%; p = 0.003). Anti-SSa/SSb positivity did not confer a difference in the frequency of other manifestations. Elevated rates of venous thromboembolism (VTE) (10%-12%) and osteoporosis (13-17%) were observed independent of anti-SSa/SSb or anti-Ro52 status. CONCLUSION: In IIM anti-SSa/SSb or anti-Ro52 positivity is associated with higher ILD rate. Both assays are useful to confer ILD risk, but anti-Ro52 is more predictive of severe ILD. High frequencies of osteoporosis and VTE were observed in all subgroups.

A multidisciplinary approach to treating a unique case of recurrent metastatic thymic carcinoma: case report.

Thymic carcinoma (TC) is a rare and aggressive malignancy of the thymus associated with less than 25% 5 years survivability. Our case report showcases the successful treatment of advanced metastatic TC using a multidisciplinary approach and the utility of checkpoint inhibitors in treatment of recurrent TC. A 50-year-old man presented with Raynaud's phenomenon and was found to have a stage IVb TC (T3N2M0). Eight months after management with neoadjuvant chemotherapy, surgical resection and adjuvant chemoradiotherapy, patient was diagnosed with metastasis of TC to the liver and a concurrent stage III (T2N1M0) primary sigmoid colon adenocarcinoma. Following complete resection of the colon adenocarcinoma, the patient started palliative-intent treatment for TC with pembrolizumab given PD-L1 tumor proportionate score of 100%. This resulted in a sustained complete response for 38 months. Our patient did have immune-related adverse events involving multiple organs but was able to continue pembrolizumab for a standard treatment duration of 2 years with multidisciplinary care. When recurrent disease was noted in a portocaval lymph node, pembrolizumab was reinitiated and a second complete response was achieved. The patient has maintained that complete response while maintaining an acceptable quality of life, showing that treatment with pembrolizumab is effective in patients after discontinuation with prior immunotherapy.

Fighting Thymic Carcinoma: A Story of Immunotherapy and Multidisciplinary Care Triumph The thymus is a gland located in the chest that plays a major role in the immune system, particularly before adulthood. Thymic carcinoma (TC) is a type of cancer affecting the thymus that is often challenging to treat given its inadequate response to chemotherapy and tendency to spread to other organs. A 50-year-old man was found to have advanced stage thymic carcinoma, which is associated with a less than 25% 5-year survival rate. Eight months after completing a rigorous treatment protocol of chemotherapy, surgery and radiation therapy, his original thymic cancer was found to have metastasized to the liver. Simultaneously, he was diagnosed with stage III sigmoid colon cancer. He underwent curative surgery for colon cancer and was started on pembrolizumab for thymic cancer. Pembrolizumab is an immunotherapy drug that boosts the body's own immune system to fight against the cancer. Inadvertently, it can turn immune cells against healthy tissues, which results in symptoms called immune-related adverse events (irAEs). Indeed, he experienced various irAEs involving multiple organs. These events were effectively managed by involving multiple specialists and initiating medications to calm the immune system and allow him to continue immunotherapy. He had a complete response to treatment and was able to complete the standard treatment course of two years. He retained a complete response for over three years before his tumor recurred. He was restarted on pembrolizumab and achieved a complete response again. This case highlights a unique presentation of metastatic TC and the utility of a multidisciplinary approach for treatment to maintain a high quality of life five years after diagnosis.

A rare case of Polyarteritis Nodosa associated with autoimmune hepatitis: a case report.

BACKGROUND: Polyarteritis nodosa is a type of vasculitis affecting medium- and small-sized arteries that has been associated with hepatitis B but does not have an established relationship with autoimmune hepatitis. Here we report the case of an adult patient with autoimmune hepatitis who, shortly after diagnosis, developed life-threatening polyarteritis nodosa. CASE PRESENTATION: A 45-year-old woman was diagnosed with autoimmune hepatitis after initially presenting with a two-month history of fatigue, nausea, and anorexia and a three-week history of scleral icterus. Her liver biopsy showed mild portal fibrosis and her liver chemistries improved with prednisone and azathioprine. Three months later, she presented to the emergency department with fever, bilateral ankle pain, rash, oral ulcers, and poor vision. Physical examination was notable for erythema nodosum, anterior uveitis, retinal vasculitis, and frosted branch angiitis (frosted branch angiitis (a widespread florid translucent perivascular exudate). She subsequently developed repeated episodes of ischemic acute bowel necrosis that required multiple surgeries and extensive small bowel resections. Surgical pathology of the small bowel resection revealed ischemic necrosis, medium and small vessel vasculitis with microvascular thrombi consistent with polyarteritis nodosa. Azathioprine was discontinued and she was treated with pulse steroids followed by a prednisone taper, cyclophosphamide, and intravenous immune globulin with overall improvement in her symptomatology. Since her hospitalization, she has been maintained on low-dose prednisone and mycophenolate mofetil. CONCLUSIONS: In patients with recent diagnosis of autoimmune hepatitis, there should be a modest suspicion for concomitant polyarteritis nodosa if symptoms and signs of multisystem vasculitis develop.

Implementation of an Interprofessional Nutrition Workshop to Integrate Nutrition Education into a Preclinical Medical School Curriculum.

Objective: The patient-physician encounter provides an ideal opportunity to assess a patient's dietary history and its impact on total health. However, nutrition assessments and counseling in physician-patient encounters is often lacking. Insufficient nutrition education during medical school may lead to insecurity in assessing and counseling patients.Methods: Physicians and registered dietitians (RD) co-developed and co-facilitated a nutrition workshop for first-year medical students. Goals included increasing recognition of nutrition's impact on health and promoting student confidence and skills when attaining a nutrition history, assessing risk factors, and advising.Results: Seventy percent of students attested to having "sufficient" knowledge to counsel a patient on nutrition after the session compared to 38% before (Z= -4.46, p < 0.001). Sixty eight percent felt comfortable completing a nutritional assessment after the session compared to 35% before (Z= -4.30, p < 0.001). Sixty-three percent felt confident in advising patients about nutrition after the session compared to 32% before (Z= -4.20, p < 0.001). Students also significantly outperformed a control cohort on a nutrition-related component of an Objective Standardized Clinical Examination.Conclusions: Clinical nutrition education can be successfully integrated into the medical school curriculum as early as the first year. Interprofessional collaboration with RDs provided evidence-based content and authentic clinical experience in both the development of the workshop and in facilitating student discussion.

Utilization of high-fidelity simulation to address challenges with the basic science immunology education of preclinical medical students.

BACKGROUND: Immune function and dysfunction are highly complex basic science concepts introduced in the preclinical medical school curriculum. A challenge for early learners is connecting the intricate details and concepts in immunology with clinical manifestations. This impedes relevance and applicability. The impetus in medical education reform is promoting consolidation of basic science and clinical medicine during the first two years of medical school. Simulation is an innovation now widely employed in medical schools to enhance clinical learning. Its use in basic science curriculums is largely deficient. The authors piloted simulation as a novel curricular approach to enhance fundamental immunology knowledge and clinical integration. METHODS: The authors introduced a Primary Immunodeficiency Disease (PIDD) simulation during a basic science immunology course for second-year medical students at the Zucker School of Medicine at Hofstra/Northwell. The simulation tasked small groups of students with evaluating, diagnosing and managing an infant with previously undiagnosed immunodeficiency. Joint facilitation by clinical and science faculty during terminal debriefings engaged students in Socratic discussion. Debriefing aimed to immerse basic science content in the context of the clinical case. Students completed a post-simulation Likert survey, assessing utility in reinforcing clinical reasoning, integration of basic science and clinical immunology, enhanced knowledge and understanding of immunodeficiency, and enhanced learning. A summative Immunodeficiency Objective Structured Clinical Examination (OSCE) question was created by faculty to assess students' recognition of a PIDD and clinical reasoning. RESULTS: The simulation was well received by students with > 90% endorsing each of the objectives on the post-simulation survey. The authors also determined a statistically significant score variance on the summative OSCE question. Higher scores were achieved by the cohort of students completing the OSCE post-simulation versus the cohort completing the OSCE pre-simulation. CONCLUSIONS: The innovative use of simulation in a highly complex basic science immunology course provides relevance and consolidation for preclinical learners. Additional data will be collected to continuously assess application of concepts and proficiency stemming from this novel curricular intervention. The authors advocate the initiation and/or expansion of simulation in non-clinical basic science courses such as immunology to bridge the gap between theory and practice.

Caring for Patients With Physical Disabilities: Assessment of an Innovative Spinal Cord Injury Session That Addresses an Educational Gap.

Despite the fact that one fifth of Americans live with disability, caring for these patients is not routinely part of the undergraduate medical student curriculum. An innovative session addressing care of patients with spinal cord injury was developed for medical students and led by physiatrists, faculty experts in communications, and individuals with spinal cord injury. A mixed-method design was used in evaluating students' knowledge, skills, and attitudes following this curriculum. Quantitative evaluation was performed with a written essay question and checklist items from an objective structured clinical examination station. The session was given to 296 students from 2016 to 2018. On the objective structured clinical examination, 94% asked about sexual function, 85% asked about activities of daily living, 77% asked about instrumental activities of daily living, and 47% of students evaluated skin health. Students demonstrated respectful (99%) and nonjudgmental (99%) attitudes with spinal cord injury standardized patients and 91% interacted with the standardized patients caretaker appropriately. Themes emerged from the student survey including the following: the value of having real patients present during the session, exposure to physical medicine and rehabilitation as a specialty, and the advantage of a small group format. This session provided students with tools necessary to care for patients with spinal cord injury.

Delivering Challenging News: An Illness-Trajectory Communication Curriculum for Multispecialty Oncology Residents and Fellows.

Introduction: Published curricula to teach communication skills for postgraduate fellows in oncology are few in number despite the fact that oncologists conduct many difficult discussions with their patients and their families. Such discussions may include disclosing initial diagnosis or relapse of a patient's cancer or relaying a poor prognosis or change to palliative care. Methods: An eight-module course on communication in oncology practice was delivered over 2 months for palliative and oncology fellows and radiation oncology residents. Learners were given a precourse survey in which they were asked to rate their proficiency in various communication tasks. Each learner then participated in a videotaped precourse objective structured clinical exam (OSCE) on breaking bad news with standardized patients (SPs). The course took place over 8 weeks with weekly didactics and role-play. At the end of the course, a second OSCE took place. After the course was completed, the fellows again filled out a proficiency survey. Results: Twenty-two learners participated over 2 years of this course. Participants reported a significant increase in perceived competence in all areas on the postcourse survey. SP feedback on OSCEs pre- and postcourse indicated improvement in skills for learners. Pre- and postcourse OSCE video assessment revealed a significant improvement in global communication skills. Discussion: Initial data show that this course successfully improved communication skills and increased fellows' comfort level across several domains of communication. Future directions include validating our assessment tool, expanding the topic base, and investigating the impact on practice after course completion.

Common Variable Immunodeficiency: A Standardized Patient Case for Second-Year Medical Students.

Introduction: Common variable immunodeficiency (CVID) is the most common symptomatic antibody deficiency, with a prevalence of 0.6-6.9 depending on the population studied. In contrast to other primary immunodeficiency diseases (PIDDs), symptoms may not appear until the third decade of life. Lack of recognition of CVID is a persistent problem. Myriad confounding clinical phenotypes and frequent infections, including autoimmunity, malignancy, chronic lung disease, granulomatous disease, and gastrointestinal disease, complicate the diagnosis. Often it is years before a diagnosis is made, leading to irreversible morbidities and mortality. Methods: Second-year medical students are introduced to CVID during their session on PIDDs that occurs during the immunology/rheumatology course. To assess students' recognition of CVID, a 15-minute OSCE encounter was created that included a simulation of lung sounds (rhonchi), physical exam cards (clubbing, otitis media with effusion), and moulage of skin (petechiae). A standardized patient (SP) portrayed a patient requesting antibiotics for a sinus infection. Students were tasked to both interview the patient and perform a hypothesis-driven physical exam. A postencounter exercise queried the students on their differential diagnosis and their rationale. Results: Item analysis of the case showed high levels of difficulty and strong discrimination between high- and low-performing students in both communication skills and clinical reasoning in CVID. Discussion: This SP encounter can be used in both formative and summative assessments to measure the recognition of CVID.

Measuring cognitive load: mixed results from a handover simulation for medical students.

INTRODUCTION: The application of cognitive load theory to workplace-based activities such as patient handovers is hindered by the absence of a measure of the different load types. This exploratory study tests a method for measuring cognitive load during handovers. METHODS: The authors developed the Cognitive Load Inventory for Handoffs (CLI4H) with items for intrinsic, extraneous, and germane load. Medical students completed the measure after participating in a simulated handover. Exploratory factor and correlation analyses were performed to collect evidence for validity. RESULTS: Results yielded a two-factor solution for intrinsic and germane load that explained 50 % of the variance. The extraneous load items performed poorly and were removed from the model. The score for intrinsic load correlated with the Paas Cognitive Load scale (r = 0.31, p = 0.004) and was lower for students with more prior handover training (p = 0.036). Intrinsic load did not, however, correlate with performance. Germane load did not correlate with the Paas Cognitive Load scale but did correlate as expected with performance (r = 0.30, p = 0.005) and was lower for those students with more prior handover training (p = 0.03). CONCLUSIONS: The CLI4H yielded mixed results with some evidence for validity of the score from the intrinsic load items. The extraneous load items performed poorly and the use of only a single item for germane load limits conclusions. The instrument requires further development and testing. Study results and limitations provide guidance to future efforts to measure cognitive load during workplace-based activities, such as handovers.

Targeting the complement system in systemic lupus erythematosus and other diseases.

The importance of the complement system in the pathogenesis of systemic lupus erythematosus (SLE) has long been recognized. However, despite an unprecedented amount of SLE clinical trial activities ongoing at this time, complement inhibitors have been omitted from the therapeutic assault on this disease. We review data generated from murine lupus that provide scientific support for the study of human SLE. Also reviewed is the sole study of a complement inhibitor, eculizumab, performed in patients with SLE. We conclude with a review of other inflammatory diseases where ongoing programs might provide the groundwork for the development of complement inhibitors in SLE.

Approach to septic arthritis.

Prompt diagnosis and treatment of infectious arthritis can help prevent significant morbidity and mortality. The acute onset of monoarticular joint pain, erythema, heat, and immobility should raise suspicion of sepsis. Constitutional symptoms such as fever, chills, and rigors are poorly sensitive for septic arthritis. In the absence of peripheral leukopenia or prosthetic joint replacement, synovial fluid white blood cell count in patients with septic arthritis is usually greater than 50,000 per mm3. Isolation of the causative agent through synovial fluid culture is not only definitive but also essential before selecting antibiotic therapy. Synovial fluid analysis is also useful to help distinguish crystal arthropathy from infectious arthritis, although the two occasionally coexist. Almost any microorganism can be pathogenic in septic arthritis; however, septic arthritis is caused by nongonococcal pathogens (most commonly Staphylococcus species) in more than 80 percent of patients. Gram stain results should guide initial antibiotic choice. Vancomycin can be used for gram-positive cocci, ceftriaxone for gram-negative cocci, and ceftazidime for gram-negative rods. If the Gram stain is negative, but there is strong clinical suspicion for bacterial arthritis, treatment with vancomycin plus ceftazidime or an aminoglycoside is appropriate. Evacuation of purulent material with arthrocentesis or surgical methods is necessary. Special consideration should be given to patients with prosthetic joint infection. In this population, the intraarticular cutoff values for infection may be as low as 1,100 white blood cells per mm3 with a neutrophil differential of greater than 64 percent.

Antisynthetase syndrome.

Autoantibodies to eight of the aminoacyl-transfer RNA synthetases-the most well-recognized of which is anti-histidyl (Jo-1)-have all been implicated in the pathogenesis of antisynthetase syndrome (AS). AS is characterized by varying degrees of interstitial lung disease, myositis, arthropathy, fever, Raynaud's phenomenon, and mechanic's hands, and the morbidity and mortality of the disease are usually linked to the pulmonary findings. The value of a lung biopsy in AS cannot be overemphasized, as it serves to describe the underlying etiology of the interstitial lung disease, guide therapy, and estimate prognosis. Muscle disease shares many clinical features of polymyositis, yet histologically, the inflammatory involvement resembles that of dermatomyositis. Because inflammatory arthritis mimics rheumatoid arthritis, AS should be considered in atypical cases. Corticosteroids are the mainstay of acute therapy, although treatment often requires immunosuppressant medications such as cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, or rituximab.

Design, implementation, and outcome of a hands-on arthrocentesis workshop.

INTRODUCTION: During a 4-week rheumatology elective at our institution, opportunities for internal medicine residents to perform arthrocentesis were limited, particularly for sites other than the knee. Consequently, residents were inadequately prepared and had less self-confidence to perform such procedures. To overcome these educational deficiencies, an arthrocentesis workshop was developed. We report our quality improvement data that was collected during the first year of workshop implementation. METHODS: We devised a structured half-day arthrocentesis workshop for rheumatology fellows as well as rotating internal medicine residents. This program consisted of a one hour lecture immediately followed by a hands-on workshop that used mannequin models for 5 anatomic sites. A self-assessment questionnaire and medical knowledge test were administered before and after each session. The accuracy of the self-assessment questionnaire was analyzed by comparing responses to an external objective measure of knowledge in the same content area. Finally, an optional postworkshop survey addressed resident satisfaction. RESULTS: Thirty-eight trainees participated in the workshop between July 2006 and June 2007. There were statistically significant improvements in self-confidence in 9 content areas (P < 0.0002), cognitive testing (P < 0.0001) and in self-assurance of procedural skill at all anatomic sites. A high degree of discordance was found between the perceived level of competence and the actual performance on the medical knowledge test during the preworkshop analysis. In contrast, the postworkshop analysis displayed modestly higher concordance. All residents completing a postworkshop survey believed that it was a useful exercise, and 96% stated that they would change their practice habits. CONCLUSION: The arthrocentesis workshop provided a solid foundation from which trainees can learn key concepts of joint injection, increase their self-confidence and refine their motor skills. The accuracy of resident self-reported confidence is poor and should therefore be used only to complement other means of competency assessment and medical knowledge acquisition.

C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy.

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias.

Rheumatic syndromes associated with complement deficiency.

Deficiency of an early component of the classical complement pathway, C1q, C1r/C1s, C4, or C2, regularly produces autoimmunity in man, especially systemic lupus erythematosus. It has long been suggested that disruption of this pathway would lead to the inappropriate handling of immune complexes. An intriguing hypothesis that builds on this idea relates to a defect in clearance of one's own cellular debris, namely apoptotic cells. An attractive feature of this emerging concept is that blebs on apoptotic cells are decorated with antigens to which much of the autoantibody specificity is directed in systemic lupus erythematosus. A second hypothesis, generated primarily from complement deficiencies, relates to an impairment in the humoral immune response or in the regulation of autoreactive B cells. This review begins by summarizing the recognized autoimmune manifestations of complement deficiency and then describes new data derived from targeted gene deletions of complement proteins.

Polymyalgia rheumatica/temporal arteritis: recent advances.

Polymyalgia rheumatica (PMR)/temporal arteritis (TA) frequently causes significant morbidity in patients older than 50 years of age. This review highlights recent trends in clinical findings, epidemiology, pathogenesis, and laboratory and radiologic assessment of the disease. Although steroids are the mainstay of therapy because of their effectiveness and ease of administration, they have numerous side effects, particularly in an aging population. Furthermore, recent evidence suggests that steroids only suppress clinical symptoms, while a smoldering level of damaging vascular inflammation persists. As a result, alternative agents are actively being investigated. We compare their successes and shortcomings and offer insight into their potential role in the treatment of this disease.