Seronegative Rheumatoid Arthritis Secondary to Immune Checkpoint Inhibitor in a Renal Cell Carcinoma Patient Encountered in a Rural Community-Based Rheumatology Clinic: A Case Report.

Immune checkpoint inhibitors (ICIs) are a widely used class of cancer immunotherapy. Those drugs have improved the treatment of cancer since its introduction in the 2000s. Nivolumab is an ICI that can be used for previously untreated renal cell carcinoma. Immune-related adverse events (irAEs) are a type of adverse event of immunotherapy that is associated with an overreactive immune system. We report a case of a 69-year-old Caucasian man with stage IV renal cell carcinoma who presented to a rural community-based rheumatology clinic referred by his oncologist, after starting to develop morning stiffness for at least three hours, joint swelling, warmth, and erythema five months after starting immunotherapy with nivolumab. The patient was diagnosed with seronegative rheumatoid arthritis secondary to ICIs and required a higher dose of prednisone (up to 40 mg per day) with methotrexate to achieve remission. With the widespread availability of ICIs, rheumatologic irAEs can be encountered in a rural community-based practice. Practicing physicians taking care of cancer patients need to be aware of the adverse effect of ICIs.

Reversible Autoimmune Cardiomyopathy Secondary to a Vaccine-Induced Multisystem Inflammatory Syndrome.

The Dominican government started an early booster protocol, including a heterogeneous vaccination sequence needed based on availability. We report a case of a 25-year-old male who presented with jaundice, and vomiting for 6 days, associated with maculopapular rash (Mucocutaneous features), elevated pro-B-type natriuretic peptide (pro-BNP), erythrocyte sedimentation rate (ESR), transaminitis (> 1000 U/L), thrombocytopenia, echocardiogram evidenced stigmata of heart failure after his third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. He was started on steroids and immunoglobulin therapy for multisystemic organ failure syndrome. A significant improvement was noticed, then was discharge; in the post-discharge clinic, he was asymptomatic, inflammatory markers improved, and the echocardiogram showed a recovered ejection fraction. An accurate anamnesis, including a proper chronologic gathering of the events, is essential to recognize a vaccine-multisystem inflammatory syndrome; its prompt assessment and therapy would directly improve the outcome.

Community engagement in patient-centered outcomes research: Benefits, barriers, and measurement.

INTRODUCTION: This study employed the Delphi method, an exploratory method used for group consensus building, to determine the benefits and challenges associated with community engagement in patient-centered outcomes research. METHODS: A series of email surveys were sent to the Patient-Centered Outcomes Research Institute (PCORI)-funded researchers (n = 103) in New England. Consensus was achieved through gathering themes and engaging participants in ranking their level of agreement over three rounds. In round one, participant responses were coded thematically and then tallied. In round two participants were asked to state their level of agreement with each of the themes using a Likert scale. Finally, in round three, the group was asked to rank the round two themes based on potential impact. RESULTS: Results suggested the greatest benefit of community engagement is that it brings multiple perspectives to the table, with 92% ranking it as the first or second most important contribution. Time was ranked as the most significant barrier to engaging community. Strategies to overcome barriers to community engagement include engaging key stakeholders early in the research, being kind and respectful and spending time with stakeholders. The most significant finding was that no researchers reported having specific measures to evaluate community engagement. CONCLUSION: Community engagement can enhance both research relevance and methodology when researchers are engaged in meaningful collaborations. Advancing the science of community engagement will require the development of evaluation metrics to examine the multiple domains of partnership.

Perceptions of Cancer Care and Clinical Trials in the Black Community: Implications for Care Coordination Between Oncology and Primary Care Teams.

BACKGROUND: Despite efforts to ameliorate disparities in cancer care and clinical trials, barriers persist. As part of a multiphase community-engaged assessment, an exploratory community-engaged research partnership, forged between an academic hospital and a community-based organization, set out to explore perceptions of cancer care and cancer clinical trials by black Bostonians. MATERIALS AND METHODS: Key informant interviews with health care providers and patient advocates in community health centers (CHCs), organizers from grassroots coalitions focused on cancer, informed the development of a focus group protocol. Six focus groups were conducted with black residents in Boston, including groups of cancer survivors and family members. Transcripts were coded thematically and a code-based report was generated and analyzed by community and academic stakeholders. RESULTS: While some participants identified clinical trials as beneficial, overall perceptions conjured feelings of fear and exploitation. Participants describe barriers to clinical trial participation in the context of cancer care experiences, which included negative interactions with providers and mistrust. Primary care physicians (PCPs) reported being levied as a trusted resource for patients undergoing care, but lamented the absence of a mechanism by which to gain information about cancer care and clinical trials. CONCLUSIONS: Confusion about cancer care and clinical trials persists, even among individuals who have undergone treatment for cancer. Greater coordination between PCPs and CHC care teams and oncology care teams may improve patient experiences with cancer care, while also serving as a mechanism to disseminate information about treatment options and clinical trials. IMPLICATIONS FOR PRACTICE: Inequities in cancer care and clinical trial participation persist. The findings of this study indicate that greater coordination with primary care physicians (PCPs) and community health center (CHC) providers may be an important step for both improving the quality of cancer care in communities and increasing awareness of clinical trials. However, PCPs and CHCs are often stretched to capacity with caring for their communities. This leaves the oncology community well positioned to create programs to bridge the communication gaps and provide resources necessary to support oncologic care along the cancer continuum, from prevention through survivorship.

BONCAT: metabolic labeling, click chemistry, and affinity purification of newly synthesized proteomes.

Metabolic labeling of proteins using classical radioisotope-labeled amino acids has enabled the analysis and function of protein synthesis for many biological processes but cannot be combined with modern high-throughput mass spectrometry analysis. This chapter describes the unbiased identification of a whole de novo synthesized proteome of cultured cells or of a translationally active subcellular fraction of the mammalian brain. This technique relies on the introduction of a small bioorthogonal reactive group by metabolic labeling accomplished by replacing the amino acid methionine by the azide-bearing methionine surrogate azidohomoalanine (AHA) or the amino acid homopropargylglycine (HPG). Subsequently an alkyne- or azide-bearing affinity tag is covalently attached to the group by "click chemistry"-a copper(I)-catalyzed [3+2] azide-alkyne cycloaddition. Affinity tag-labeled proteins can be analyzed in candidate-based approaches by conventional biochemical methods or with high-throughput mass spectrometry.

Racial discrimination & cardiovascular disease risk: my body my story study of 1005 US-born black and white community health center participants (US).

OBJECTIVES: To date, limited and inconsistent evidence exists regarding racial discrimination and risk of cardiovascular disease (CVD). METHODS: Cross-sectional observational study of 1005 US-born non-Hispanic black (n = 504) and white (n = 501) participants age 35-64 randomly selected from community health centers in Boston, MA (2008-2010; 82.4% response rate), using 3 racial discrimination measures: explicit self-report; implicit association test (IAT, a time reaction test for self and group as target vs. perpetrator of discrimination); and structural (Jim Crow status of state of birth, i.e. legal racial discrimination prior 1964). RESULTS: Black and white participants both had adverse cardiovascular and socioeconomic profiles, with black participants most highly exposed to racial discrimination. Positive crude associations among black participants occurred for Jim Crow birthplace and hypertension (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.28, 2.89) and for explicit self-report and the Framingham 10 year CVD risk score (beta = 0.04; 95% CI 0.01, 0.07); among white participants, only negative crude associations existed (for IAT for self, for lower systolic blood pressure (SBP; beta = -4.86; 95% CI -9.08, -0.64) and lower Framingham CVD score (beta = -0.36, 95% CI -0.63, -0.08)). All of these associations were attenuated and all but the white IAT-Framingham risk score association were rendered null in analyses that controlled for lifetime socioeconomic position and additional covariates. Controlling for racial discrimination, socioeconomic position, and other covariates did not attenuate the crude black excess risk for SBP and hypertension and left unaffected the null excess risk for the Framingham CVD score. CONCLUSION: Despite worse exposures among the black participants, racial discrimination and socioeconomic position were not associated, in multivariable analyses, with risk of CVD. We interpret results in relation to constrained variability of exposures and outcomes and discuss implications for valid research on social determinants of health.

Experiencia con rituximab en miopatía inflamatoria idiopática refractaria / Experience with rituximab in refractory idiopathic inflammatory myopathy

Se describe las características clínicas y de laboratorio de dos pacientes que recibieron rituximab por miopatía inflamatoria idiopática (MII). Ellas eran refractarias a tratamiento convencional con DARMES, por lo que recibieron rituximab 1 gramo cada 14 días, en dos infusiones en ciclo semestral. En las historias clínicas se obtuvo los datos clínicos de fuerza muscular proximal, lesiones cutáneas patognomónicas, elevación de CPK, TGO, DHL y VSG, resultados de electromiografía, biopsia muscular y de piel. Ninguno de los dos casos presentó reacción medicamentosa ni infecciones durante y posterior a las infusiones. Rituximab mostró efectividad en la respuesta clínica y enzimática en estas pacientes con dermatomiositis refractarias a corticoides y DARMES tradicionales.

Clinical and laboratory characteristics of two patients who received rituximab for refractory idiopathic inflammatory myopathy (IIM) are described. Patients were refractory to conventional treatment with disease-modifying antirheumatic drugs (DMARDs) so they received rituximab 1 g dose every 14 days in two biannual cycle infusions. Data of proximal muscle strength, pathognomonic skin lesions, CPK, SGOT, LDH and ESR, results of electromyography, muscle and skin biopsy were obtained from the medical records. None of the cases presented drug reaction or infections during and following infusions. Rituximab showed effectiveness in clinical and enzymatic response in patients with dermatomyositis refractory to corticosteroids and traditional DMARDs.

Infliximab en pacientes con enfermedad ocular inflamatoria, refractarios a DARMES / Infliximab in patients with inflammatory DMARDs-refractory eye disease

Se describe la experiencia con infliximab (anticuerpo monoclonal con una potente acción antiinflamatoria) en el tratamiento de enfermedades oculares inflamatorias secundarias a patologías reumáticas y refractarias a drogas antirreumáticas modificadoras de la enfermedad (DARMES). Se evaluó el caso de una paciente de 50 años con artritis reumatoide (AR) de fondo activo y una paciente de 37 años con vasculitis anticuerpos anticitoplasma de neutrófilos especifico para mieloperoxidasa (ANCA MPO) sin compromiso de órgano noble, ambas con escleritis bilateral y perforación con prolapso de iris del ojo izquierdo. Ellas recibieron infliximab EV en dosis de 3 a 5 mg/kg/dosis, según el esquema, a las 0, 2, 6 y 8 semanas. Infliximab resultó eficaz y seguro para el tratamiento de escleritis asociada a AR y vasculitis ANCA MPO positivo, refractaria a tratamiento con DARMES y corticoides en dosis altas. Los injertos de tejido esclerocorneal evolucionaron favorablemente con infliximab.

Experience with infliximab (monoclonal antibody with strong anti-inflammatory action) for treatment of ocular inflammatory disease secondary to rheumatic diseases and refractory to disease-modifying antirheumatic drugs (DMARDs) is described. We evaluated the cases of a 50 year-old patient with active rheumatoid arthritis (RA) and a 37 year-old patient with myeloperoxidase antineutrophil cytoplasmic vasculitis antibody (MPO ANCA) without noble organ affectation, both with bilateral scleritis and left eye corneal perforation with iris prolapse. They received infliximab 3-5 mg/kg IV at 0, 2, 6, and 8 weeks. Infliximab was effective and safe for treatment of scleritis associated to RA and MPO ANCA positive vasculitis refractory to treatment with both DMARDs and high dose corticosteroids. Corneoscleral tissue grafts developed favorably with infliximab.

Management of squamous cell carcinoma of the base of tongue with chemoradiation and brachytherapy.

BACKGROUND: Treatment of base of tongue (BOT) squamous cell carcinoma (SCC) has traditionally been associated with poor prognosis and significant morbidity. We report a program consisting of concurrent chemoradiation followed by brachytherapy for these patients. METHODS: We reviewed all patients in our institution with previously untreated BOT SCC (1996-2004) who received this treatment program. RESULTS: In 88 patients (median age, 60.2 years; 37 T1/T2; 51 T3/T4), cervical lymph node metastases were present in 71 patients (80.7%). Six patients had residual/subsequent cervical metastases requiring 7 neck dissections. Local recurrence occurred in 16 patients (18.2%) and distant metastases occurred in 9 patients (10.2%). Median follow-up time was 3.1 years (range, 0.5-7.8 years). Three-year overall survival was 80.9% (95% CI: 69.6% to 88.3%). Locoregional control rate was 79.9% and disease-specific survival was 69.5% at 3 years. CONCLUSIONS: Concurrent chemoradiotherapy followed with brachytherapy is a safe and effective method of treatment of SCC of the BOT.

Challenges of conducting community-based participatory research in Boston's neighborhoods to reduce disparities in asthma.

Boston is one of the preeminent health care and research centers in the world, but for much of its urban core, these resources are largely out of reach. Community Based Participatory Research (CBPR) provides a model with the potential to bridge the gaps between its research prominence and the health of its residents. We report here two case studies of major research projects that were partnerships between universities in Boston and community based organizations and city agencies. The Healthy Public Housing Initiative (HPHI) and the Asthma Center on Community Environment and Social Stress (ACCESS) are projects that provide numerous lessons about the potential and challenges of conducting CBPR. Ensuring that the projects were true partnerships emerged as key issues in both, especially with respect to funding mechanisms and distribution of resources, although the nature of the challenges differed substantially in the two projects. We note that both academic and community partners may harbor stereotypes about the other and that generalizations about broad populations, academics or community members, may not apply well to everyone. Aligning objectives and expectations emerged as another key lesson. In HPHI, tension between service delivery and research was both a source of conflict and a source of creative development that led to divergent but interesting outcomes. In ACCESS, the tensions revolved more around community capacity building while attempting to build and maintain a large cohort for epidemiological investigations. We conclude that open and frank discussion and a transparent process upfront about project direction, finances, expectations, and other dimensions are necessary but not sufficient to address the inherent challenges in CBPR, and that even so, there are likely to be differences in perspective in such partnerships that require honest negotiation throughout the process of the project.

Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii.

Toxoplasma gondii is a highly successful protozoan parasite in the phylum Apicomplexa, which contains numerous animal and human pathogens. T.gondii is amenable to cellular, biochemical, molecular and genetic studies, making it a model for the biology of this important group of parasites. To facilitate forward genetic analysis, we have developed a high-resolution genetic linkage map for T.gondii. The genetic map was used to assemble the scaffolds from a 10X shotgun whole genome sequence, thus defining 14 chromosomes with markers spaced at approximately 300 kb intervals across the genome. Fourteen chromosomes were identified comprising a total genetic size of approximately 592 cM and an average map unit of approximately 104 kb/cM. Analysis of the genetic parameters in T.gondii revealed a high frequency of closely adjacent, apparent double crossover events that may represent gene conversions. In addition, we detected large regions of genetic homogeneity among the archetypal clonal lineages, reflecting the relatively few genetic outbreeding events that have occurred since their recent origin. Despite these unusual features, linkage analysis proved to be effective in mapping the loci determining several drug resistances. The resulting genome map provides a framework for analysis of complex traits such as virulence and transmission, and for comparative population genetic studies.

Purine salvage pathways in the apicomplexan parasite Toxoplasma gondii.

We have exploited a variety of molecular genetic, biochemical, and genomic techniques to investigate the roles of purine salvage enzymes in the protozoan parasite Toxoplasma gondii. The ability to generate defined genetic knockouts and target transgenes to specific loci demonstrates that T. gondii uses two (and only two) pathways for purine salvage, defined by the enzymes hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK). Both HXGPRT and AK are single-copy genes, and either one can be deleted, indicating that either one of these pathways is sufficient to meet parasite purine requirements. Fitness defects suggest both pathways are important for the parasite, however, and that the salvage of adenosine is more important than salvage of hypoxanthine and other purine nucleobases. HXGPRT and AK cannot be deleted simultaneously unless one of these enzymes is provided in trans, indicating that alternative routes of functionally significant purine salvage are lacking. Despite previous reports to the contrary, we found no evidence of adenine phosphoribosyltransferase (APRT) activity when parasites were propagated in APRT-deficient host cells, and no APRT ortholog is evident in the T. gondii genome. Expression of Leishmania donovani APRT in transgenic T. gondii parasites yielded low levels of activity but did not permit genetic deletion of both HXGPRT and AK. A detailed comparative genomic study of the purine salvage pathway in various apicomplexan species highlights important differences among these parasites.

Brachytherapy in the treatment of Stage IV carcinoma of the base of tongue.

PURPOSE: Survival in patients with Stage IV carcinoma of the base of tongue (BOT) treated by surgery and radiotherapy remains poor. External beam radiotherapy (EBRT) and brachytherapy (BT) have been used as an alternative treatment. METHODS AND MATERIALS: Eighteen patients with Stage IV carcinoma of the BOT were treated by EBRT and BT. RESULTS: Local control is 89%. The 5-year overall (OS) and disease specific survival (DSS) rates are 52% and 67%. No neck node positive patient implanted in the neck developed cervical metastases. Two patients (11%) developed complications. CONCLUSIONS: Local regional control, survival, and complications in patients with Stage IV carcinoma of the BOT treated by EBRT and BT have been satisfactory. The use of brachytherapy for nodal metastases has eliminated the need for neck dissection. We recommend this approach in the treatment of Stage IV carcinoma of the BOT.

Quality of life, functional outcome, and costs of early glottic cancer.

OBJECTIVE: To analyze quality of life, functional outcome, and hidden costs by primary treatment with surgery or radiation therapy in patients with early glottic cancer. STUDY DESIGN: Retrospective study in a tertiary care facility. METHODS: A group of 101 patients with carcinoma in situ and T1 invasive squamous cell carcinoma treated primarily with either surgery or radiation, between January 1990 and December 2000, were identified from searching our tumor registry. Patients completed two previously validated questionnaires and one local questionnaire. Statistical significance was assessed with the rank sum test, chi2 test, or Fisher's Exact test. RESULTS: Questionnaires were completed in 59% (44 of 74) of the surgical cohort and 41% (11 of 27) of the radiation therapy cohort. The primary surgical treatments were endoscopic excision (86%), hemilaryngectomy (12%), and total laryngectomy (1%). Patient-reported problems with swallowing, chewing, speech, taste, saliva, pain, activity, recreation, and appearance showed no difference between the endoscopic excision or radiation therapy cohorts. Comparing endoscopic excision versus radiation therapy, respectively, median number of treatments (2 vs. 35), total median travel distance (150 vs. 660 miles), total median travel time (180 vs. 1440 min), and total median number of hours of work missed (76 vs. 24) all differed significantly (P <.01). CONCLUSIONS: Almost all patients with early glottic cancer, whether treated with surgery or radiation therapy, reported excellent quality of life outcomes and functional results. In addition to actual costs, the hidden costs for radiation therapy versus endoscopic excision were all greater in terms of total number of hours of work missed, total travel time, and total travel distance.

Functional outcomes after treatment of squamous cell carcinoma of the base of the tongue.

OBJECTIVE: To compare functional outcome and quality of life after various treatments for squamous cell carcinoma of the base of the tongue. DESIGN: Retrospective survey using statistical comparison. SETTING: Academic medical center, institutional practice. PARTICIPANTS: Patients treated for squamous cell carcinoma of the base of the tongue between 1976 and 2000. Living patients 3 or more months after treatment were eligible. Questionnaire packets including validated site-specific quality-of-life instruments were mailed to 105 qualifying patients. Sixty-one patients participated, forming a volunteer sample. Patient responses were grouped according to treatment modality, operative vs nonoperative. MAIN OUTCOME MEASURES: The planned outcome was that nonoperative therapy would result in better function than operative treatment. RESULTS: Most comparisons indicated no statistical difference in outcome between operative and nonoperative groups. Significant differences (95% confidence interval) were calculated for age, interval since treatment, and T stage. Group comparisons of patient responses revealed significant differences only in xerostomia and days hospitalized. CONCLUSIONS: The tongue remains dysfunctional after both surgical and nonoperative treatment. Nonoperative treatment might more adversely affect saliva. Surgery is associated with a longer hospital stay.

Persistent congenital isolation of the suprapatellar pouch mimicking patellofemoral disease.

A patient with congenital isolation of the suprapatellar bursa presented with pain suggestive of patellofemoral joint disease. At arthroscopy, injection filled only the bursa. The diagnosis of congenital isolation of the suprapatellar bursa was made by the injection of radiopaque material into the bursa. Excision of the bursa eliminated the symptoms. This case is instructive, as it documents an unusual congenital anomaly that can complicate arthroscopic technique and can be a rare cause of knee pain.