Infections Are Not Increased in Scleroderma Compared to Non-Inflammatory Musculoskeletal Disorders Prior to Disease Onset

The etiology of scleroderma (SSc) is unknown; immunogenic stimuli such as infections and vaccinations could theoretically be risk factors for scleroderma. Our objective was to assess the relationship between viral and bacterial infec-tions, and vaccinations, prior to diagnosis of SSc compared to non-inflammatory controls. Methods: A questionnaire was sent to individuals with SSc (n =83) and controls (n=351) with non-inflammatory musculoskeletal (MSK) disorders (os-teoarthritis, n = 204; tendonitis, n = 58; fibromyalgia, n= 89) from a rheumatology practice. Questions ascertained past in-fections, exposure to infectious agents and vaccination history. Results: The response rate was 78% (SSc) and 56% (MSK controls). The mean age was 56 ± 1.6 (SSc) and 58 ± 0.9 (MSK); 88% (SSc) and 82% (MSK) were female. No association between prior infections and SSc was observed. In fact, controls were more likely than SSc subjects to report any infec-tion within 1-year prior to disease diagnosis (35% vs. 16%, p<0.006), or to have suffered a trauma to affected joints prior to diagnosis (44% vs. 19%, p<0.0002). Within the 1-year prior to disease diagnosis, controls reported slightly more strep-tococcal infections (p<0.2), infections with diarrhea and vomiting (p<0.3), and antibiotic use (p<0.09), although none of these results were statistically significant. Histories of any hepatitis, rubella, any bacterial infection, and having had a pre-vious positive tuberculosis skin test were not significantly different between groups and were actually more often reported by the control subjects. SSc reported slightly more hepatitis B (p<0.08), more rheumatic fever (p<0.8) in past, and herpes zoster (p<0.4), although no differences reached significance. Conclusion: This study does not support that self-report of symptomatic infections are more likely to occur ever (prior to diagnosis) or within 1-year prior to symptom onset of SSc, or that vaccinations in adulthood trigger SSc

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium

Background The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. Methods For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. Findings Overall, 116 841 cases were analysed: 76 481 in 2018–19, before the pandemic, and 40 360 in 2020–21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40–0·55), H influenzae (0·51; 0·40–0·66) and N meningitidis (0·26; 0·21–0·31), while no significant changes were observed for S agalactiae (1·02; 0·75–1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145–55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. Interpretation COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. Funding Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization

Gone but Not Forgotten

A 52 -year-old healthy woman presented with a 1-week history of blurred vision and "soreness" in her left eye. Neuro-ophthalmic examination revealed a visual acuity of 20/20 OD, 20/40 OS, left RAPD and left superior arcuate defect on Humphrey visual field testing. Dilated fundus examination demonstrated a right "disc-at-risk" and moderate left optic disc edema. She reported having 2 cats at home with a recent scratch on her leg and also had symptoms suggestive of obstructive sleep apnea (OSA). A differential diagnosis of neuroretinitis, non-arteritic anterior ischemic optic neuropathy (NAION) and optic neuritis was considered, but infectious workup was negative and polysomnography was not diagnostic of OSA. She was treated empirically with ciprofloxacin for presumed cat-scratch neuroretinitis, but her left eye vision significantly worsened to no light perception (NLP) 2 weeks after the initial visit. There was now severe left optic disc edema, mild venous dilation and tortuosity and significant intraretinal fluid in the macula. MRI brain and orbits with contrast revealed longitudinally extensive thickening and enhancement of the left optic nerve with surrounding fat stranding and no signs of demyelination in the brain. This was thought to represent severe optic neuritis, but AQP4-IgG, MOG-IgG and vasculitis workup were negative and chest X-ray was normal. She was treated with intravenous methylprednisolone 1gram daily for 5 days followed by Prednisone 1mg/kg daily, but her vision remained NLP 1 week later. She was referred for plasmapheresis and after the first session, she had worsening left eye pain. Repeat examination demonstrated a visual acuity of NLP OS and worsening left optic disc edema, diffuse retinal edema and a cherry-red -spot, indicating the interval development of a central retinal artery occlusion (CRAO). Repeat MRI brain/orbits with contrast showed decreased enhancement within the left optic nerve. A diagnostic test was performed

Gone but Not Forgotten

A 52 -year-old healthy woman presented with a 1-week history of blurred vision and "soreness" in her left eye. Neuro-ophthalmic examination revealed a visual acuity of 20/20 OD, 20/40 OS, left RAPD and left superior arcuate defect on Humphrey visual field testing. Dilated fundus examination demonstrated a right "disc-at-risk" and moderate left optic disc edema. She reported having 2 cats at home with a recent scratch on her leg and also had symptoms suggestive of obstructive sleep apnea (OSA). A differential diagnosis of neuroretinitis, non-arteritic anterior ischemic optic neuropathy (NAION) and optic neuritis was considered, but infectious workup was negative and polysomnography was not diagnostic of OSA. She was treated empirically with ciprofloxacin for presumed cat-scratch neuroretinitis, but her left eye vision significantly worsened to no light perception (NLP) 2 weeks after the initial visit. There was now severe left optic disc edema, mild venous dilation and tortuosity and significant intraretinal fluid in the macula. MRI brain and orbits with contrast revealed longitudinally extensive thickening and enhancement of the left optic nerve with surrounding fat stranding and no signs of demyelination in the brain. This was thought to represent severe optic neuritis, but AQP4-IgG, MOG-IgG and vasculitis workup were negative and chest X-ray was normal. She was treated with intravenous methylprednisolone 1gram daily for 5 days followed by Prednisone 1mg/kg daily, but her vision remained NLP 1 week later. She was referred for plasmapheresis and after the first session, she had worsening left eye pain. Repeat examination demonstrated a visual acuity of NLP OS and worsening left optic disc edema, diffuse retinal edema and a cherry-red -spot, indicating the interval development of a central retinal artery occlusion (CRAO). Repeat MRI brain/orbits with contrast showed decreased enhancement within the left optic nerve. A diagnostic test was performed

Exploring the Mechanisms Controlling miRNA Expression During Prostate Cancer Progression

Purpose: Prostate cancer (PCa) is the most common neoplasm found in men. Understating its mechanism of progression is the foundation for developing a targeted therapy. miRNAs are small non-coding genes that post-transcriptionally control their targets. Recent evidence showed the involvement of miRNAs in PCa progression and the aggressive behavior related to it. The mechanism controlling miRNA expression remains largely unknown. We hypothesize that transcription factors (TF) are involved in regulating miRNA expression during PCa progression.Method: We searched the ChipBase database for TFs that bind to the promoters of miRNAs that are found dysregulated in PCa relapse and in the high Gleason grades. We next filtered our TFs to obtain PCa-specific TFs using the GENT Database. Finally, we assessed the prognostic significance of these TFs using cbioportal.Data and results: We identified a number of TFs which bind to miRNA promoters, including AR, ERG, TAF1, NFKB, GR. These TFs have positive correlation with their targeted miRNAs including miR20b, miR29c, miR141, and let-7a-3. TFs showed a divergent-effect pattern in which the same factor simultaneously affects multiple miRNAs. We also identified a number of feed forward loops where TFs affect miRNA and their common target genes. It is worth mentioning that expression levels of these TFs were found to correlate with PCa prognosis. Finally, the same TF was found to target a network of miRNA and non-miRNA targets.Conclusions: TFs can be potentially used as prognostic markers for prostate cancer. In addition, targeting these TFs can result in modifying the expression of their targeted miRNAs which can have therapeutic implication