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Myocarditis is a rare complication of Coronavirus Disease 2019 (COVID-19) vaccination. We report a case of an elderly female who presented initially with acute myocarditis, fulminant heart failure, and atrial fibrillation after receiving a modified ribonucleic acid (mRNA) vaccine (BNT162b2). Unlike other patients with vaccine-induced myocarditis, she developed persistent fever, sore throat, polyarthralgia, diffuse macular rash, and lymphadenopathy. After extensive investigation, she was diagnosed with post-vaccination Adult-Onset Still's Disease. The systemic inflammation gradually subsided after the use of non-steroidal anti-inflammatory drugs and systemic steroids. She was discharged from hospital with stable hemodynamics. Methotrexate was subsequently given to maintain long-term remission.

Human breastmilk is rich in T cells; however, their specificity and function are largely unknown. We compared the phenotype, diversity, and antigen specificity of T cells in the breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 mRNA vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor (TCR) sequence overlap was limited between blood and breastmilk. Overabundan t breastmilk clones were observed in all individuals, were diverse, and contained CDR3 sequences with known epitope specificity including to SARS-CoV-2 Spike. Spike-specific TCRs were more frequent in breastmilk compared to blood and expanded in breastmilk following a third mRNA vaccine dose. Our observations indicate that the lactating breast contains a distinct T cell population that can be modulated by maternal vaccination with potential implications for infant passive protection.One-Sentence SummaryThe breastmilk T cell repertoire is distinct and enriched for SARS-CoV-2 Spike-specificity after maternal mRNA vaccination.

Background The duration of rectal gonococcal and chlamydial infection remains unknown. This basic epidemiologic parameter is needed to understand transmission dynamics. Methods We conducted a prospective, longitudinal, observational cohort study of 140 men who have sex with men (MSM) at risk of gonorrhea and chlamydia acquisition. For 48 weeks, enrolled men collected rectal swabs (Aptima multi-test kit) at home and responded to an electronic survey about sexual behavior and health conditions weekly. Swabs remained untested until participants completed the study. We used Kaplan-Meier estimates to determine the median duration of infection, censoring infections for treatment, loss to follow-up, and end-of-study. We used log-rank test to compare duration of infection by human immunodeficiency virus (HIV) status, history of infection with gonorrhea or chlamydia, and coinfection with the other pathogen. Results 140 enrolled MSM contributed 70.5 person-years of follow-up. Eighteen men had 20 incident rectal gonococcal infections, which persisted for 2–23 weeks; 30% were censored for treatment. The estimated median duration of rectal gonorrhea was 9 weeks (95% confidence interval [CI]: 3–12 weeks). Twenty-four men experienced 32 rectal chlamydial infections, persisting between 2 and 42 weeks; 60% were censored. The estimated duration of rectal chlamydia was 13 weeks (95% CI: 6 weeks–undefined). There were no differences in the duration of rectal gonorrhea or chlamydia by HIV status, history of chlamydia/gonorrhea, or coinfection. Conclusions On average, rectal gonorrhea and chlamydial infections last 2–3 months, although some infections persisted for 6–11 months. Further understanding into predictors of persistence is needed.

Background Pharyngeal gonorrhea is relatively common. However, the duration of untreated pharyngeal gonorrhea is unknown. Methods From March 2016 to December 2018, we enrolled 140 men who have sex with men in a 48-week cohort study. Participants self-collected pharyngeal specimens and completed a survey weekly. Specimens were tested using a nucleic acid amplification test at the conclusion of the study. We estimated the incidence and duration of infection. We defined incident infections as 2 consecutive positive tests, and clearance as 2 consecutive negative tests; and, after visual inspection of the data, we reclassified up to 2 weeks of missing or negative tests as positive if they occurred between 2 episodes of infections. We used Kaplan-Meier estimates to define duration of infection. Finally, we report on the frequency of single-positive tests and the time between the last negative test and the positive test. Results Nineteen (13.6%) of 140 participants experienced 21 pharyngeal infections (incidence, 31.7/100 person-years; 95% confidence interval, 20.7–48.6/100 person-years). The estimated median duration of pharyngeal gonorrhea was 16.3 weeks (95% confidence interval, 5.1–19.7 weeks). Twenty-two men had 25 single-positive specimens, a median of 7 days (interquartile range, 7–10 days) after their last negative test. Conclusions The median duration of untreated pharyngeal gonorrhea is 16 weeks, more than double previous estimates. This long duration of infection likely contributes to high levels of gonorrhea transmission.

BACKGROUNDCoronavirus disease 2019 (COVID-19) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor (AT1R-Ab).METHODSWe compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or severe disease to age and sex matched negative controls.RESULTSThere were no significant differences between cases and controls. However, there were trends toward a higher proportion with AT1R-Ab positivity among severe cases versus controls (32% vs. 11%, p=0.1) and higher levels in those with mild COVID-19 compared to controls (median 9.5U/mL vs. 5.9U/mL, p=0.06).CONCLUSIONSThese findings suggest that AT1R-Ab are not consistently associated with COVID-19 but do not exclude a contribution to endothelial pathology in a subset of people.

The fate of protective immunity following mild SARS-CoV-2 infection remains ill defined. Here we characterize antibody responses in a cohort of participants recovered from mild SARS-CoV-2 infection with follow up to 6 months. We measure IgA, IgM, and IgG binding and avidity to viral antigens and assess neutralizing antibody responses over time. Further, we correlate the effect of fever, gender, age, and time since symptom onset with antibody responses. We observe that total anti-S trimer, anti-RBD, and anti-NP IgG are relatively stable over 6 months of follow-up and anti-S and anti-RBD avidity increases over time, and that fever is associated with higher levels of antibodies. However, neutralizing antibody responses rapidly decay and are strongly associated with declines in IgM levels. Thus, while total antibody against SARS-CoV-2 may persist, functional antibody, particularly IgM, is rapidly lost. These observations have implications for the duration of protective immunity following mild SARS-CoV-2 infection., Graphical Abstract, Harrington et al., report that in adults with mild COVID-19, IgG responses are maintained for over six months and are correlated with fever. Neutralization activity rapidly decays, correlating with the loss of anti-S-trimer IgM titers. Thus, neutralizing antibodies fade quickly after mild COVID-19 infection, despite the long-term maintenance of IgG.

Background Risky alcohol consumption is on the rise among older adults. Biomarkers such as phosphatidylethanol (PEth) have been used to evaluate the correspondence between an objective, laboratory-based biomarker and self-report of alcohol consumption. This study examined the relationship between PEth, self-report of alcohol consumption, and health indices in a sample of community-dwelling older to middle-age adults (aged 35 to 89) with healthy and risky levels of alcohol consumption. Methods Self-reports of alcohol consumption were collected using the Alcohol Use Disorders Identification Test (AUDIT) and Form 30. In addition, indices of health along with a blood sample to determine PEth values were collected (N = 183). Results PEth was correlated with age, AUDIT-C, AUDIT total, alcohol consumption, mood, and liver function measures but not with medical comorbidity or body mass index (J Gerontol B Psychol Sci Soc Sci 73, 2018, 633). Alcohol consumption over the past 30 days measured with Form 30 was the strongest predictor of PEth levels for both middle-age and older adults, with age a small contributing predictor. General alcohol consumption patterns for amount of alcohol consumed over a 30-day period revealed middle-age adults consumed larger amounts of alcohol compared with older adults, but older adults consumed alcohol on more days than middle-age adults. Middle-age participants evidenced higher PEth levels than older adults at comparable drinking rates. Conclusions Overall, findings suggest a strong relationship between alcohol consumption and PEth levels with age a small but contributing factor to predicting PEth levels.

Background The duration of untreated extragenital gonococcal (GC) and chlamydial infection (CT) infection is not well defined. Methods From March 2016 to December 2018, we enrolled 140 MSM in a 12-month cohort study. Men ≥18 years were eligible if they reported receptive anal intercourse and had ≥1 following risks in ≤12 months: 1) diagnosis of GC, CT or syphilis; 2) methamphetamine or poppers use; or 3) >2 sex partners in ≤2 months or >5 in ≤12 months. Enrolled men either tested negative for GC/CT at enrollment, or, tested positive, were treated and waited 2–3 weeks prior to data collection. Each week, men self-collected pharyngeal and rectal specimens and completed an electronic diary. Specimens were tested after study completion (Aptima, Hologic Inc). We defined incident infections as two consecutively positive tests and clearance as >2 consecutively negative tests. We used Kaplan Meier curves to estimate duration of infection censoring subjects for receipt of pathogen-specific antibiotic, positive swab in final week of study, or loss-to-follow-up. Results Forty-eight men were observed for 1,687 weeks and contributed 3,579 tested specimens. Twenty-four (50%) MSM had ≥1 incident GC/CT infection; 13 (27%) had >1 infection. Overall extragenital GC/CT incidence was 129 (95%CI: 94–172) infections per 100 person-years. Pharyngeal GC, and rectal GC and CT incidence were 35 (95%CI: 20–61), 37 (95%CI: 22–64) and 59 (95%CI: 38–91) per 100 person-years, respectively. 46% (6/13) pharyngeal GC, 43% (6/14) rectal GC, 81% (17/21) rectal CT were censored. The estimated median duration of pharyngeal GC, rectal GC and rectal CT were 15 (95%CI 3 – undefined), 12 (95%CI 2 – undefined) and >20 (95% CI 12 – undefined) weeks. Conclusion Among high-risk MSM, incident extragenital GC/CT occur frequently: >1 infection per person per year. Untreated, these infections persist for a median of 3 to 5 months. Disclosure No significant relationships.

Background Little is known about the natural history of rectal and pharyngeal Mycoplasma genitalium (MG). Methods From March 2016 to December 2018, we enrolled 140 high-risk MSM in a 12-month cohort study. Eligibility criteria included: age ≥18 years, report of receptive anal intercourse, and ≥1 of the following in ≤12 months: (1) gonorrhea, chlamydia or syphilis; (2) methamphetamine or popper use, or (3) ≥2 sex partners in ≤2 months or ≥5 in ≤12 months. Each week, men collected pharyngeal and rectal swabs and completed an electronic sex diary. We tested swabs for MG (Aptima, Hologic, Inc.) at study completion. Infection was defined as ≥2 consecutive positive tests; clearance was ≥2 consecutively negative tests. We calculated person-weeks-at-risk to estimate incidence and used Kaplan Meier curves to estimate duration of infection. We censored subjects who had a positive swab in the final study week, received doxycycline or azithromycin and obtained clearance in the following 3 weeks, or were lost-to-follow-up. None received moxifloxacin. Results At week 1, the prevalence of rectal and pharyngeal MG was 8% (4/48) and 2% (1/48), respectively. Among 48 men with results from 3,579 specimens, 12 (25%) had ≥1 rectal, and 5 (10%) had ≥1 pharyngeal MG infection. In 1,504 person-weeks-at-risk, rectal MG incidence was 38 (95%CI: 19–68) infections per 100 person-years. In 1,715 person-weeks-at-risk, pharyngeal MG incidence was 15 (95%CI: 5–35) per 100 person-years. Forty percent (6/15) of rectal and 50% (3/6) of pharyngeal infections were censored. Rectal and pharyngeal infections had estimated median durations of 30 (95%CI: 6 – undefined) and 16 (95%CI: 3 – undefined) weeks, respectively. Blips, single positive tests that did not meet criteria for infection, occurred in 8 (17%) men with 17 rectal and 4 (8%) men with 10 pharyngeal MG-positive tests. Conclusion xtragenital, MG, including pharyngeal infection, is common and persistent among high-risk MSM. Disclosure No significant relationships.

The clinical phenotypes of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity are heterogeneous with various presentations including time of symptom onset, organ involvements, and underlying pathophysiology. Having a correct diagnosis can be challenging. Understanding their respective mechanisms as well as developing a comprehensive classification and diagnostic algorithm are pivotal for appropriate management strategy. Treatment modalities are based on the subtypes and severity of hypersensitivity reactions. Insights into the phenotypes and endotypes of hypersensitivity reactions enable personalized management in patients with suboptimal control of disease. This review updated the recent evidence of pathophysiology, classification, diagnostic algorithm, and management of NSAID hypersensitivity reactions.

During the past decade, the medical community has expressed a growing concern over the high prevalence of postpartum depression and the tragic repercussions of untreated illness. However, many questions persist about the pathogenesis of postpartum depression, the natural course of the illness, and the safety and effectiveness of available treatments. To summarize the data on pharmacologic treatments for postpartum depression, we performed a systematic review of four major databases to identify original research published from 1960-September 2009 that featured pharmacologic treatments for depression detected in women during the 12 months after delivery. Pharmacologic treatments included prescription drugs (antidepressants and hormones), herbal remedies, and dietary supplements. Case reports, studies examining the prevention of postpartum depression, and those including diagnosed episodes of depression preceding the postpartum period (i.e., antepartum onset) were excluded. Treatment randomization or the presence of a control group was not required for inclusion in this review. Fourteen investigations met inclusion criteria. Nine studies examined the effects of prescription antidepressants, two investigated hormones, and three featured omega-3 fatty acid supplementation. Significant heterogeneity was evident in study design and prevented a pooled quantitative analysis of treatment effects. The power of most investigations was limited, and numerous confounding biases were evident. Therapeutic effects were documented for prescription antidepressants and hormone supplementation (estrogen derivatives). Tolerability of the interventions in depressed mothers and breastfed infants was not well described. The effectiveness of omega-3 fatty acids was not evident in postpartum depression trials, although significant limitations in study methodology were apparent. Postpartum depression is a common and serious medical problem, but most cases go undetected and untreated. The need to identify safe, effective, and convenient treatments for postpartum depression is urgent, but the current state of the medical literature describing pharmacologic interventions is not impressive. Preliminary evidence documenting the effectiveness of serotonergic antidepressants and hormone supplementation should serve as an impetus for rigorous controlled investigations in the future.

Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC) and its component phospholipid, 1-palmitoyl-2-epoxyisoprostane-sn-glycero-3-phosphorylcholine, induce endothelial cells (EC) to synthesize chemotactic factors, such as interleukin 8 (IL-8). Previously, we demonstrated a role for c-Src kinase activation in Ox-PAPC-induced IL-8 transcription. In this study, we have examined the mechanism regulating IL-8 transcription by Ox-PAPC downstream of c-Src. Our findings demonstrate an important role for JAK2 in the regulation of IL-8 transcription by Ox-PAPC. Treatment of human aortic EC with Ox-PAPC and 1-palmitoyl-2-epoxyisoprostane-sn-glycero-3-phosphorylcholine induced a rapid yet sustained activation of JAK2; activation of JAK2 by Ox-PAPC was dependent on c-Src kinase activity. Furthermore, pretreatment with selective JAK2 inhibitors significantly reduced Ox-PAPC-induced IL-8 transcription. In previous studies, we also demonstrated activation of STAT3 by Ox-PAPC. Here we provide evidence that STAT3 activation by Ox-PAPC is dependent on JAK2 activation and that STAT3 activation regulates IL-8 transcription by Ox-PAPC in human EC. Transfection with small interfering RNA against STAT3 significantly reduced Ox-PAPC-induced IL-8 transcription. Using chromatin immunoprecipitation assays, we demonstrated binding of activated STAT3 to the sequence flanking the consensus gamma-interferon activation sequence (GAS) in the IL-8 promoter; site-directed mutagenesis of GAS inhibited IL-8 transcription by Ox-PAPC. Finally, these studies demonstrate a role for STAT3 activation in atherosclerosis in vivo. We found increased staining for activated STAT3 in the inflammatory regions of human atherosclerotic lesions and reduced fatty streak formation in EC-specific STAT3 knock-out mice on the atherogenic diet. Taken together, these data demonstrate an important role for the JAK2/STAT3 pathway in Ox-PAPC-induced IL-8 transcription in vitro and in atherosclerosis in vivo.

Oxidized-1-palmitoyl-2-arachidonyl- sn -glycero-3-phosphorylcholine (Ox-PAPC), found in atherosclerotic lesions and other sites of chronic inflammation, activates endothelial cells (EC) to synthesize chemotactic factors, such as interleukin (IL)-8. Previously, we demonstrated that the sustained induction of IL-8 transcription by Ox-PAPC was mediated through the activation of sterol regulatory element–binding protein (SREBP). We now present evidence for the role of endothelial nitric oxide synthase (eNOS) in the activation of SREBP by Ox-PAPC. Ox-PAPC treatment of EC induced a dose- and time-dependent activation of eNOS, as measured by phosphorylation of serine 1177, dephosphorylation of threonine 495, and the conversion of l -arginine to l -citrulline. Activation of eNOS by Ox-PAPC was regulated through a phosphatidylinositol-3-kinase/Akt-mediated mechanism. These studies also demonstrated that pretreatment of EC with NOS inhibitor, N ω -nitro- l -arginine-methyl ester (L-NAME), significantly inhibited Ox-PAPC–induced IL-8 synthesis. Because SREBP activation had been previously shown to regulate IL-8 transcription by Ox-PAPC, we examined the effects of L-NAME on Ox-PAPC–induced SREBP activation. Our data demonstrated that Ox-PAPC–induced SREBP activation and expression of SREBP target genes were significantly reduced by pretreatment with L-NAME. Interestingly, treatment of EC with NO donor, S -nitroso- N -acetylpenicillamine, did not activate SREBP, suggesting that NO alone was not sufficient for SREBP activation. Rather, our findings indicated that superoxide (O 2 ·− ), in combination with NO, regulated SREBP activation by Ox-PAPC. We found that Ox-PAPC treatment generated O 2 ·− through an eNOS-mediated mechanism and that mercaptoethylguanidine, a peroxynitrite scavenger, reduced SREBP activation by Ox-PAPC. Taken together, these findings propose a novel role for eNOS in the activation of SREBP and SREBP-mediated inflammatory processes.

s / International Journal of Surgery 12 (2014) S13eS117 S38 0304: PROSPECTIVE AUDIT: IMPROVING RATES OF DAY CASE TONSILLECTOMIES IN THE ABSCENCE OF A DEDICATED DAY CASE UNIT Winnie Yeung, Helena Wilson. Royal Devon & Exeter NHS Foundation Trust