Iatrogenic ANA: An emerging source of expensive diagnostic confusion.

Intravenous immune globulin (IVIg) therapy has been shown to be useful in a multitude of disorders. IVIg is produced from pooled human plasma; therefore, autoantibodies found in the general population are also present in IVIg and transferred to those being transfused. This can prove a particular hazard for screening and diagnostic tests based on autoantibodies. We present a patient who was found to have a positive antinuclear antibody (ANA) titer after multiple IVIg transfusions, resulting in diagnostic confusion and unnecessary workup. A 45-year-old gentleman was diagnosed with atypical CIDP, initiated on a course of IVIg, and sent for inpatient rehabilitation. However, recovery was complicated by multiple readmissions for recurrent weakness, and as part of the workup for other etiologies, an ANA was found to be positive. Sub-serologies and paraneoplastic autoantibody panel were negative. In the absence of clinical symptoms, we recommended continued monitoring and repeat ANA testing 6 months after the last dose of IVIg; as any drug needs 5 half-lives to be eliminated from the body. Clinicians should consider any recent IVIg treatments when evaluating the pre-test probability of detecting an underlying connective tissue disease with ANA screening. Indiscriminate ANA levels in patients recently given IVIg lead to unnecessary and expensive further testing and consultation.

A case series of hydroxychloroquine exacerbating the dermatomyositis rash.

Hydroxychloroquine (HCQ) is an antimalarial agent that is commonly used in the management of rheumatic skin disease. Few reports exist documenting exacerbation of dermatomyositis (DM) related to HCQ. Herein, we describe three adult patients with worsening DM cutaneous disease after starting HCQ and resolution or improvement with cessation. The time to exacerbation ranged from two weeks to nine months after the initiation of HCQ 400mg/day. Two of the three patients had antibodies to transcription intermediary factor 1γ (TIF1γ) and the other had antibodies to anti-nuclear matrix protein 2 (NXP2). After discontinuation of HCQ, the time to improvement or resolution of cutaneous symptoms ranged from six weeks to six months. Hydroxychloroquine may be associated with worsening cutaneous features in DM. In patients who are not improving despite escalation of immunosuppressive medications, or are worsening, we recommend a trial of discontinuing HCQ.

Antecedent immunosuppressive therapy for immune-mediated inflammatory diseases in the setting of a COVID-19 outbreak.

BACKGROUND: Finite clinical data and understanding of COVID-19 immunopathology has led to limited, opinion-based recommendations for the management of patients with immune-mediated inflammatory disease (IMID) receiving immunosuppressive (IS) therapeutics. OBJECTIVE: To determine if IS therapeutic type affects COVID-19 risk among patients with IMID. METHODS: We conducted a retrospective cohort analysis of Henry Ford Health System patients tested for COVID-19 between February 1 and April 18, 2020, treated with IS medication for IMID. Therapeutic class of IS medication, comorbidities, and demographic factors were combined into multivariate models to determine predictors of COVID-19 infection, admission, ventilation, and mortality. RESULTS: Of 213 patients with IMID, 36.2% tested positive for COVID-19, and they had no greater odds of being hospitalized or requiring ventilation relative to the general population. No IS therapeutic worsened the course of disease after multivariate correction, although multidrug regimens and biologics predicted an increased and decreased rate of hospitalization, respectively, with the latter driven by tumor necrosis factor α inhibitors. LIMITATIONS: A single-center study somewhat limits the generalization to community-based settings. Only patients tested for COVID-19 were analyzed. CONCLUSION: IS therapies for IMIDs are not associated with a significantly greater risk of SARS-CoV-2 or severe sequelae when controlling for other factors, and tumor necrosis factor α inhibitors may decrease the odds of severe infection.

Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection.

Human pegivirus (HPgV) protects HIV+ people from HIV-associated disease, but the mechanism of this protective effect remains poorly understood. We sequentially infected cynomolgus macaques with simian pegivirus (SPgV) and simian immunodeficiency virus (SIV) to model HIV+HPgV co-infection. SPgV had no effect on acute-phase SIV pathogenesis-as measured by SIV viral load, CD4+ T cell destruction, immune activation, or adaptive immune responses-suggesting that HPgV's protective effect is exerted primarily during the chronic phase of HIV infection. We also examined the immune response to SPgV in unprecedented detail, and found that this virus elicits virtually no activation of the immune system despite persistently high titers in the blood over long periods of time. Overall, this study expands our understanding of the pegiviruses-an understudied group of viruses with a high prevalence in the global human population-and suggests that the protective effect observed in HIV+HPgV co-infected people occurs primarily during the chronic phase of HIV infection.

Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication.

Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood. This, heretofore unappreciated, hyperacute-phase microbial translocation was accompanied by sustained reduction of lipopolysaccharide (LPS)-specific antibody titer, intestinal permeability, increased abundance of CD4+CCR5+ T cell targets of virus replication, and T cell activation. To test whether increasing gastrointestinal permeability to cause microbial translocation would amplify viremia, we treated two SIV-infected macaque 'elite controllers' with a short-course of dextran sulfate sodium (DSS)-stimulating a transient increase in microbial translocation and a prolonged recrudescent viremia. Altogether, our data implicates translocating microbes as amplifiers of immunodeficiency virus replication that effectively undermine the host's capacity to contain infection.

Utilizing Chamber Music to Teach Non-Verbal Communication to Medical Students: A Pilot Initiative.

Introduction The importance of non-verbal cues in communication between physicians and patients is well published in the medical literature. However, few medical school curricula teach non-verbal communication. Chamber musicians employ non-verbal communication to coordinate musician intention. Observation of chamber musicians' use of non-verbal communication may improve the understanding of non-verbal communication among medical students. Methods A total of 72 medical students attended rehearsals of two world-renowned string quartets on a single date. Following a brief discussion and demonstration on non-verbal communication by musicians, students observed the non-verbal cues employed by the quartets during musical rehearsals. Authors provided pre- and post-surveys, which included closed and open-ended questions to assess understanding of non-verbal communication and confidence in identifying non-verbal cues with patients and healthcare providers. Close-ended questions used numerical scales. The authors used paired t-tests to compare mean numerical scores pre- and post-intervention and analyzed qualitative, open-ended responses thematically. Results Of the 72 students who attended the workshop, 63 (88%) completed both pre- and post-surveys. Comparison demonstrated significant improvement in students' ability to appreciate non-verbal interactions among healthcare teams (p<0.05) and patients (p<0.05). Following the workshop, students commented that they appreciated the similarities in non-verbal cues between musicians and medical professionals. Discussion Chamber musicians and physicians share similarities, e.g., working in teams and performing specialized tasks; good communication is crucial to both. Observation of chamber musicians may serve as a vehicle to instruct medical students on non-verbal communication. Next steps include determining the longer-term impact of the workshop on confidence in communication by resurveying participants and comparing responses with those students who did not attend the workshop. Future studies are needed to assess the clinical impact of chamber music observation on medical students' non-verbal communication skills.

Rapidly Progressive Acute Liver Failure in Relapsed Multiple Myeloma.

Multiple myeloma affects upwards of 30,000 people every year and has significant morbidity and mortality. Common complications of the disease involve lytic bone lesions, hypercalcemia, anemia, and acute renal failure. A rare, yet serious, complication includes acute liver failure secondary to hepatic plasma cell infiltration. While this is reported seldom in living patients, it is found in upwards of 40% of patients incidentally on imaging or during autopsy. Conscientious and meticulous monitoring of liver function tests allows for early detection of liver failure in multiple myeloma; thus, allowing for broader therapeutic options overall.

Barriers, beliefs, and practices regarding hygiene and vaccination among the homeless during a hepatitis A outbreak in Detroit, MI.

Appropriate hygiene practices and vaccine acceptance are key factors impacting the health of homeless individuals. A recent outbreak of hepatitis A in Michigan, especially impacting Detroit, prompted us to investigate the practices and attitudes of Detroit's homeless population toward hygiene measures and vaccinations, as well as barriers to such resources. We developed a questionnaire as a means to collect our data, and participants were interviewed at shelters and soup kitchens. While the majority of participants adhered to healthy hygiene practices, approximately 89% reported barriers to accessing public showers. More than half the participants (64%) reported receiving their hepatitis A vaccine prior to the study, while 23% reported previously refusing or hesitating to receive vaccinations. Despite an overall favorable adherence to hygiene practices, substantial barriers are yet to be overcome. Moreover, active measures should be taken to establish higher levels of trust between providers and the homeless to encourage vaccine acceptance.

Successful Treatment of Recalcitrant Mpox Lesions With Intralesional Cidofovir in a Patient With HIV/AIDS.

This case report describes a man in his 50s with HIV/AIDS who presented with widely scattered recalcitrant mpox lesions.

Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis.

Simian hemorrhagic fever virus (SHFV) causes a fulminant and typically lethal viral hemorrhagic fever (VHF) in macaques (Cercopithecinae: Macaca spp.) but causes subclinical infections in patas monkeys (Cercopithecinae: Erythrocebus patas). This difference in disease course offers a unique opportunity to compare host responses to infection by a VHF-causing virus in biologically similar susceptible and refractory animals. Patas and rhesus monkeys were inoculated side-by-side with SHFV. Unlike the severe disease observed in rhesus monkeys, patas monkeys developed a limited clinical disease characterized by changes in complete blood counts, serum chemistries, and development of lymphadenopathy. Viral RNA was measurable in circulating blood 2 days after exposure, and its duration varied by species. Infectious virus was detected in terminal tissues of both patas and rhesus monkeys. Varying degrees of overlap in changes in serum concentrations of interferon (IFN)-γ, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 were observed between patas and rhesus monkeys, suggesting the presence of common and species-specific cytokine responses to infection. Similarly, quantitative immunohistochemistry of livers from terminal monkeys and whole blood flow cytometry revealed varying degrees of overlap in changes in macrophages, natural killer cells, and T-cells. The unexpected degree of overlap in host response suggests that relatively small subsets of a host's response to infection may be responsible for driving hemorrhagic fever pathogenesis. Furthermore, comparative SHFV infection in patas and rhesus monkeys offers an experimental model to characterize host⁻response mechanisms associated with viral hemorrhagic fever and evaluate pan-viral hemorrhagic fever countermeasures.

Subclinical Infection of Macaques and Baboons with A Baboon Simarterivirus.

Simarteriviruses (Arteriviridae: Simarterivirinae) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteriviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simarterivirus pathogenesis by infecting olive baboons (n = 4) and rhesus monkeys (n = 4) with the simarterivirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation. Three animals (two rhesus monkeys and one olive baboon) became infected and sustained high levels of SWBV-1 viremia for the duration of the study. The course of SWBV-1 infection was highly predictable: plasma viremia peaked between 1 × 107 and 1 × 108 vRNA copies/mL at 3⁻10 days post-inoculation, which was followed by a relative nadir and then establishment of a stable set-point between 1 × 106 and 1 × 107 vRNA copies/mL for the remainder of the study (56 days). We characterized cellular and antibody responses to SWBV-1 infection in these animals, demonstrating that macaques and baboons mount similar responses to SWBV-1 infection, yet these responses are ineffective at clearing SWBV-1 infection. SWBV-1 sequencing revealed the accumulation of non-synonymous mutations in a region of the genome that corresponds to an immunodominant epitope in the simarterivirus major envelope glycoprotein GP5, which likely contribute to viral persistence by enabling escape from host antibodies.

Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques.

The specificity of the antibody response against Zika virus (ZIKV) is not well-characterized. This is due, in part, to the antigenic similarity between ZIKV and closely related dengue virus (DENV) serotypes. Since these and other similar viruses co-circulate, are spread by the same mosquito species, and can cause similar acute clinical syndromes, it is difficult to disentangle ZIKV-specific antibody responses from responses to closely-related arboviruses in humans. Here we use high-density peptide microarrays to profile anti-ZIKV antibody reactivity in pregnant and non-pregnant macaque monkeys with known exposure histories and compare these results to reactivity following DENV infection. We also compare cross-reactive binding of ZIKV-immune sera to the full proteomes of 28 arboviruses. We independently confirm a purported ZIKV-specific IgG antibody response targeting ZIKV nonstructural protein 2B (NS2B) that was recently reported in ZIKV-infected people and we show that antibody reactivity in pregnant animals can be detected as late as 127 days post-infection (dpi). However, we also show that these responses wane over time, sometimes rapidly, and in one case the response was elicited following DENV infection in a previously ZIKV-exposed animal. These results suggest epidemiologic studies assessing seroprevalence of ZIKV immunity using linear epitope-based strategies will remain challenging to interpret due to susceptibility to false positive results. However, the method used here demonstrates the potential for rapid profiling of proteome-wide antibody responses to a myriad of neglected diseases simultaneously and may be especially useful for distinguishing antibody reactivity among closely related pathogens.

Genome Sequence of a Novel Kunsagivirus (Picornaviridae: Kunsagivirus) from a Wild Baboon (Papio cynocephalus).

The picornaviral genus Kunsagivirus has a single member, kunsagivirus A, which was discovered in migratory bird feces. We report here the discovery of a novel kunsagivirus in wild yellow baboon (Papio cynocephalus) blood. The genomic sequence of this virus indicates the probable need for the establishment of a second kunsagivirus species.