Purpose
Coronavirus disease 2019 (COVID-19) caused a global pandemic with millions infected worldwide. Little is known on the ocular involvement associated with the disease. The aim of this study was ...to assess the clinical and molecular ocular involvement among patients with confirmed COVID-19 admitted to a tertiary care facility.
Methods
Consecutive patients admitted to the COVID-19 Ward of the Shamir Medical Center in Israel during March and April, 2020 were included. The control group included patients negative for COVID-19 admitted during a similar period to a different ward. Patients were examined by trained Ophthalmologists. SARS-CoV-2 conjunctival swab samples were obtained.
Results
Included were 48 patients, 16 with confirmed COVID-19 and 32 controls. Median patient age was 68.5 (interquartile range: 31.5, mean: 63 ± 21) years and 48% were male. Active conjunctival injection was present in three patients (19%) with COVID-19, compared to none in the controls (
p
= 0.034). Patients with COVID-19 were more likely to complain of foreign body sensation (31.3% vs 3.1%,
p
= 0.005) and redness of the eye (25% vs 0%,
p
= 0.003). Conjunctival injection was associated with loss of smell and taste (75% vs 7.7%,
p
= 0.018). Viral conjunctival swab tests all showed negative results for all three viral genes tested (E, N, and RdRp).
Conclusions
Among patients admitted to a tertiary referral center with confirmed COVID-19, active conjunctival injection was noted in one out of five cases, and was associated with loss of smell and taste. Conjunctival swabs for viral RNA were negative in patients with and without ocular involvement.
Abstract
A growing number of familial Mediterranean fever (FMF) patients in Israel do not have a single country of origin for all four grandparents. We aimed to predict the Mediterranean fever gene (
...MEFV
) variant most likely to be found for an individual FMF patient, by a machine learning approach. This study was conducted at the Sheba Medical Center, a referral center for FMF in Israel. All Jewish referrals included in this study carried an FMF associated variant in
MEFV
as shown by genetic testing performed between 2001 and 2017. We introduced the term ‘origin score’ to capture the dose and different combinations of the grandparents’ origin. A machine learning approach was used to analyze the data. In a total of 1781 referrals included in this study, the p.Met694Val variant was the most common, and the variants p.Glu148Gln and p.Val726Ala second and third most common, respectively. Of 26 countries of origin analyzed, those that increased the likelihood of a referral to carry specific variants were identified in North Africa for p.Met694Val, Europe for p.Val726Ala, and west Asia for p.Glu148Gln. Fourteen of the studied countries did not show a highly probable variant. Based on our results, it is possible to describe an association between modern day origins of the three most common
MEFV
variant types and a geographical region. A strong geographic association could arise from positive selection of a specific
MEFV
variant conferring resistance to endemic infectious agents.
Purpose
To determine whether meconium-stained amniotic fluid (MSAF) encountered in pregnancies complicated by preterm premature rupture of membranes (PPROM) is associated with adverse maternal and ...perinatal outcome.
Methods
A retrospective cohort study of all singleton pregnancies with PPROM and MSAF who delivered in a tertiary hospital at 24 + 0–36 + 6 weeks of gestation between 2007 and 2017. Women with PPROM–MSAF (study group) were compared to women with PPROM and clear amniotic fluid (control group). Controls were matched to cases according to age, gravidity, parity and gestational age at delivery in a 3:1 ratio. Primary outcome was defined as neonatal intensive care unit admission. Secondary outcomes were neonatal adverse outcomes, chorioamnionitis and placental abruption diagnosed clinically or by placental cultures and histology.
Results
Seventy-five women comprised the study group and were matched to 225 women representing the control group. A significantly higher rate of neonatal intensive care unit admissions was noted in the study group compared to controls (61.3% vs. 45.7%,
p
= 0.03). Multivariate analysis demonstrated that MSAF is an independent risk factor for neonatal intensive care unit admission (adjusted OR = 2.82, 95% CI 1.39–5.75,
p
= 0.004). MSAF was found to be associated to higher rates of cesarean and operative vaginal deliveries (30.7% vs. 24.4% and 5.3% vs. 2.7%,
p
= 0.057, respectively) as well as to chorioamnionitis and placental abruption (33.3% vs. 19.3%,
p
= 0.034 and 16.0% vs. 7.7%,
p
= 0.021, respectively).
Conclusion
MSAF is associated with higher frequencies of adverse perinatal outcome when compared to clear amniotic fluid in pregnancies complicated by PPROM.
Background
Systemic-lupus-nephritis is a chronic autoimmune disease characterized by immune complex deposition and a flare of autoantibodies and leading to renal injury.
Objectives
To expose ...anti-Dense-Fine-Speckled-70 (DFS70)-antibodies to genetically-prone-lupus-mice.
Methods
NZBXW/F1 female mice were monitored for the onset of glomerulonephritis by proteinuria upon infusion of anti-DFS70 (40 μg/mouse), commercial-human-IgG (cIgG) or phosphate-buffered-saline (PBS) as controls. The survival time was detected by mice death. Circulating anti-dsDNA were tested by ELISA. Proteinuria, was defined by a standard semi-quantitative-Bayer-Multistix-dipstick. Kidney histology was analyzed by periodic-acid–Schiff-PAS staining.
Results
A significantly higher percentage of anti-DFS70-infused mice exhibited prolonged survival time as compared with cIgG and PBS-subjected mice (p < 0.022). One mouse out of 10 mice injected with anti-DFS70-antibodies died at week 36, whereas, 6 out of 10 mice subjected with PBS found dead at this time. Eighty percent of anti-DFS70 injected mice did not show severe glomerulonephritis by histology.
Conclusions
anti-DFS70 attenuated the progression of glomerulonephritis and prolonged the survival time. Circulating anti-DFS70-autoantibodies may confer a protective role against renal injury in murine-lupus-nephritis. Our data may propose a novel therapy approach for lupus patients.
Streptococcus is well associated with a myriad of inflammatory diseases. Among others, this bacterium is linked to the triggering of psoriasis and to post-streptococcal reactive arthritis (PSRA), an ...arthritis which is typically confined to peripheral joints. Three patients who developed acute psoriatic spondyloarthritis (SpA) following a recent streptococcal infection are described in this article. We searched the existing literature for cases of axial involvement in PSRA and reviewed the association between streptococcal infection and psoriasis or psoriatic arthritis )PsA). In all patients, psoriatic SpA occurred within 7–10 days of a confirmed streptococcal infection. The main presenting syndrome was inflammatory back pain with evidence of acute axial spondyloarthritis on magnetic resonance imaging. One patient had guttate psoriasis, the second patient developed pustular psoriasis, and the third patient had exacerbation of pustular palmoplantar psoriasis. Two patients required treatment with tumor necrosis factor alpha (TNF-α) blockers. Axial involvement in PSRA is very rare. A potential association of streptococcal infection and development of PsA has been explored in several articles. However, to the best of our knowledge, acute psoriatic SpA as a manifestation of PSRA has yet to be described. Acute psoriatic SpA should be considered in the differential diagnosis of new-onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection.
Key Points
•
Our case series describes three cases of acute psoriatic spondyloarthritis that occurred within 7–-10 days of a confirmed streptococcal infection and progressed to full blown chronic disease
.
•
Acute psoriatic spondyloarthritis as a manifestation of post streptococcal reactive arthritis should be considered in the differential diagnosis of new onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection
.
The hygiene hypothesis claims that the lack of exposure to microorganisms in developed countries correlates with a rise in the incidence of autoimmune diseases. It was also found that helminths are ...able to modulate the immune response in hosts in order to survive. Consequently, several successful trials using helminths as a treatment for autoimmune patients have been reported. The helminth derivative, phosphorylcholine (PC), was discovered as an immunomodulatory molecule. We have recently shown in a murine model that when a conjugate of tuftsin and PC, termed TPC, is prophylactically administered before the onset of glomerulonephritis, it attenuates the development of systemic lupus erythematosus (SLE). The current study aimed to examine the TPC effect on the gut microbiome in a mouse model of lupus. TPC treatment altered the gut composition in the mice with active lupus, in correlation with a significant decrease in glomerulonephritis, followed by an increased level of anti-inflammatory interleukin 10 (IL-10), decreased levels of proinflammatory mediators, and expansion of the T regulatory cell population. Importantly, we found that TPC treatment altered the mouse gut microbiome composition, in correlation with a significant decrease in protein secretion and improved disease parameters. The major effects of TPC treatment on the gut microbiome included decreased abundances of
and increased abundance of several genera, including
, unclassified
, unclassified
,
,
, and
. Overall, our results associate microbial changes with the immunomodulation of glomerulonephritis in mice with lupus.
Recently, several papers referred to the association of different bacteria with lupus in mice and humans. This is the first report to demonstrate the effect of a compound derived from helminths on the induction of remission in mice with lupus and its association with a bacterial change. We show that several genera, including
, are associated with clinical and serological parameters of lupus, while other genera, including butyrate-producing bacteria, are associated with amelioration of disease following tuftsin and phosphorylcholine treatment.
Helminths or their products can immunomodulate the host immune system, and this phenomenon may be applied as the basis of new anti-inflammatory treatments. Previously, we have shown the efficacy of ...tuftsin-phosphorylcholine (TPC), based on a helminth product, in four animal models of autoimmune diseases: arthritis, colitis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis. We demonstrated that TPC reduced inflammatory process ex vivo in peripheral blood lymphocytes (PBLs) and in biopsies from giant-cell arteritis. In the present study, we assessed the therapeutic potential of TPC treatment on a chronic colitis murine model. C57BL/6 mice with chronic colitis were treated with TPC after the third cycle of 2% dextran sodium sulfate (DSS). Oral TPC treatment resulted in amelioration of the colitis clinical manifestations exemplified by reduced disease activity index (DAI) score, expansion of mesenteric lymph nodes (MLN) T regulatory cells (shown by Fluorescence Activated Cell Sorting (FACS)), significant reduction in the expression of pro-inflammatory cytokines (IL-1β, IL17, IL-6, TNFα), and elevation in the expression of anti-inflammatory cytokine IL-10 (shown by RT-PCR). This study demonstrated the potential immunomodulatory effects of oral administration of TPC in a chronic colitis murine model. Further clinical trials are needed in order to evaluate this novel approach for the treatment of patients with inflammatory bowel disease.
BACKGROUND
Intravenous immunoglobulins (IVIG) are a biologic product originally developed to treat immunocompromised patients. In the past decades, there has been increased utilization of IVIG in ...autoimmune conditions. The objectives were to evaluate the clinical use of IVIG in the largest tertiary medical center in Israel and to determine top uses, estimate off‐label usage, and assess consumption of this blood product.
STUDY DESIGN AND METHODS
We conducted an observational, retrospective study involving all patients who received IVIG from 2007 through 2015. Subjects were classified into five groups according to the indication for treatment.
RESULTS
A total of 1117 patients were identified. The mean (±SD) ages of adults and children were 55 ± 17 and 8 ± 7 years, respectively. Most common indication for treatment were immune‐mediated conditions (54%), followed by secondary immunodeficiency (28%), primary immunodeficiency (10%), infections (4%), and miscellaneous (4%). The main immune‐mediated conditions treated were hematologic disorders (305 patients, 27%), neurologic disorders (219 patients, 20%), and rheumatologic conditions (79 patients, 7%). Overall, a significant change in study period was observed in the number of patients (p < 0.001), consumption of IVIG (p < 0.01), and amount of IVIG administered per patient (p < 0.01). Fifty‐six percent of the IVIG infusions were given for off‐label Food and Drug Administration (FDA) indications.
CONCLUSION
In this study, we demonstrated that immune‐mediated conditions represent the majority of indications for treatment with IVIG. We observed a 417% increase in IVIG administration (g) over time, attributed mainly to autoimmune diseases. Many indications are still off‐label according to FDA recommendations.
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