•Many authorities recommend against antibiotic administration in STEC infections.•Antibiotics may increase Stx production in vitro; this effect is strain-specific.•TMP/SMX and b-lactams have been ...associated with the development of HUS.•Fosfomycin has been associated with favourable outcomes in Japanese studies.•Antibiotic therapy within 3 days of symptom onset appears to have the most benefit.
The administration of antibiotics in infections caused by Shiga toxin producing E. coli (STEC) strains, such as O157:H7, was and remains controversial, as it has been associated with the development of haemolytic uraemic syndrome (HUS). We conducted a literature review to better examine this association.
We searched the PubMed and Google Scholar databases for relevant articles, using the key words: ``haemolytic uraemic syndrome'', ``Shiga toxin'', ``E. coli O157:H7'', ``E. coli O104:H4'', ``STEC colitis'', ``STEC antibiotics'', ``STEC fosfomycin'', ``STEC trimethoprim sulfamethoxazole'', ``STEC fluoroquinolones'', ``STEC ciprofloxacin'', ``STEC rifaximin'', ``STEC gentamycin'', ``STEC colistin'', “Shiga toxin binding agent”, “Shiga toxin monoclonal antibody” and ``STEC Japan epidemic''.
Numerous studies report that antibiotics increase the risk of HUS development, while others report that antibiotics do not have any effect or can even reduce the rate of HUS development in STEC infections. The infecting STEC strain, the type of antibiotic as well as the timing of its administration appear to significantly affect the development of HUS in a STEC infected patient.
It appears that, while some antibiotics such as b-lactams and TMP/SMX may be detrimental, others appear to be safe and can prevent the development of HUS. Of note, fosfomycin appears to be the antibiotic with the most positive results from clinical studies, and may be able to avert HUS development, especially if administered within the first two or three days from diarrhoea onset. Fluoroquinolones have also shown positive outcomes in clinical studies, despite demonstrating unfavourable results in in vitro studies. Other agents, such as colistin, gentamycin and rifamycins, have shown promising results in in vitro studies and require further evaluation.
Multidrug-resistant bacteria have on overwhelming impact on human health, as they cause over 670,000 infections and 33,000 deaths annually in the European Union alone. Of these, the vast majority of ...infections and deaths are caused by only a handful of species-multi-drug resistant
,
,
,
spp.,
spp. and
. These pathogens employ a multitude of antibiotic resistance mechanisms, such as the production of antibiotic deactivating enzymes, changes in antibiotic targets, or a reduction of intracellular antibiotic concentration, which render them insusceptible to multiple antibiotics. The purpose of this review is to summarize in a clinical manner the resistance mechanisms of each of these 6 pathogens, as well as the mechanisms of recently developed antibiotics designed to overcome them. Through a basic understanding of the mechanisms of antibiotic resistance, the clinician can better comprehend and predict resistance patterns even to antibiotics not reported on the antibiogram and can subsequently select the most appropriate antibiotic for the pathogen in question.
Abstract
Objective
Cutaneous polyarteritis nodosa (CPAN) is a necrotizing vasculitis of the middle-size vessels, confined to the skin. We conducted a systematic review in order to identify studies ...evaluating the different treatment modalities used in CPAN.
Methods
This systematic review was conducted according to PRISMA guidelines, registered in PROSPERO: CRD42020222195. PubMed/Medline databases were searched from inception to December of 2020 using the terms: (Polyarteritis nodosaTitle/Abstract) AND ((therapyTitle/Abstract) OR (managementTitle/Abstract) OR (treatmentTitle/Abstract))’ and ‘Cutaneous arteritis Title/Abstract’. Articles evaluating pertaining to the management of CPAN in adults were eligible for inclusion.
Results
A total of seven eligible case series with 325 unique patients were included. No study included a control population. In general, systemic corticosteroids were widely used as induction treatment. Immunosuppressive agents combined with corticosteroids were AZA, hydroxychloroquine, sulfasalazine, sulphapyridine, CYC, MTX, mycophenolate, tacrolimus, rituxima and thalidomide. Other agents utilized in the studies were dapsone, colchicine, non-steroid anti-inflammatory drugs, salicylates, warfarin and clopidogrel. In some studies, the presence of ulcerations was associated with an increased risk of relapse.
Conclusion
The evidence available regarding the management of patients with CPAN is limited at best. Further studies are needed in order to evaluate the effect of treatment on disease remission, relapses and mortality.
Systemic Lupus Erythematosus (SLE) and lupus nephritis treatment is still based on non-specific immune suppression despite the first biological therapy for the disease having been approved more than ...a decade ago. Intense basic and translational research has uncovered a multitude of pathways that are actively being evaluated as treatment targets in SLE and lupus nephritis, with two new medications receiving FDA approval in the last 3 years. Herein we provide an overview of targeted therapies for SLE including medications targeting the B lymphocyte compartment, intracellular signaling, co-stimulation, and finally the interferons and other cytokines.
•Non-specific immune-suppression are still used for the treatment of Systemic Lupus Erythematosus and lupus nephritis.•Medications targeting B cells, Type I Interferons and Calcineurin have recently been approved for the treatment of SLE and LN.•Actively evaluated therapeutic targets include BLyS/APRIL, CD19/CD20, Jak, dendritic cells and co-stimulatory molecules.
ABSTRACT
Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability ...of the viral epitopes. The required percentage of immune individuals has been estimated to be 50–66% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.
The authors analyze factors regarding COVID-19 and herd immunity, such percentage of immune population, the length and effectiveness of immune response and stability of the viral epitopes.
We conducted a systematic review to identify cases of infection-induced anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
PubMed/Medline databases ...were searched from inception to July of 2020, according to PRISMA guidelines.
Among the 618 abstracts identified, 18 articles describing 23 patients (60.9% female, mean age 50.5 years) were included. Median time between infection and vasculitis development was 3 months. Five (21.7%) patients expired during follow-up. Vasculitis regressed after the resolution of infection in 12/23 (52.2%). ANCA titers decreased significantly on follow-up in 14/16 patients and in all survivors in which they were measured. Pathogens reported included Mycobacterium spp., Coccidioides spp., Rickettsia rickettsii, Staphylococcus spp., EBV, CMV and Dengue virus.
MPO-AAV can occur after infection and may regress after its resolution. Infection should be considered in cases of MPO-AAV, as immunosuppressive treatment can have catastrophic results if the infection is not adequately treated.
•Infections can lead to production of MPO-ANCA and development of vasculitis.•Pathogens include viruses, bacteria, mycobacteria and fungi.•In most cases, MPO-ANCA titers and vasculitis regress post-infection.•Consider infection, especially in immunosuppression-resistant cases of MPO-AAV•Immunosuppressant administration during an undiagnosed infection can be detrimental.
The objective of this study was to evaluate the prevalence and the clinical significance of lymphadenopathy and its histological subtypes in patients with systemic lupus erythematosus. We conducted a ...retrospective cohort study of patients with SLE diagnosed using the 1997 ACR criteria, who were followed at our institution between 2008 and 2022. Patients were grouped based on the presence of SLE-attributed LAD and its histological phenotype, then compared in terms of demographic, clinical and laboratory characteristics. Of the 255 patients, 33.7% had SLE-attributed, 0.8% lymphoma-related and 0.4% tuberculosis-related LAD. Univariate analysis identified significant associations between the presence of LAD and fever (
p
< 0.0001), weight loss (
p
= 0.009), pericarditis (
p
= 0.004), myocarditis (
p
= 0.003), myositis (
p
= 0.034), leukopenia (
p
= 0.004), lymphopenia (
p
= 0.003), membranous nephritis (
p
= 0.004), anti-RNP (
p
= 0.001), anti-Smith (
p
= < 0.0001), and SSB antibodies (
p
= 0.038), and hypocomplementemia (C3:
p
= 0.019; C4:
p
< 0.0001). Logistic regression confirmed the associations of LAD with fever (OR = 3.277, 95% C.I 1.657–6.481), pericarditis (OR = 4.146, 95% C.I:1.577–10.899), membranous nephritis (OR = 3.586, 95% C.I:1.305–9.854), and leukopenia (OR = 2.611, 95%C.I:1.319–5.166), but not with weight loss, myocarditis, or myositis. Biopsy in a subset of patients (33.7% of total) revealed reactive/proliferative (62.1%) or necrotizing (37.9%) histological patterns. When we compared the histologic patterns, necrotizing LAD was associated with fever (
p
= 0.052), sicca (
p
= 0.018), and malar rash (
p
= 0.005). Most patients received corticosteroids, hydroxychloroquine, and/or DMARDs with relatively quick clinical improvement. In conclusion, LAD is a common SLE manifestation, associated with constitutional symptoms, myo-/pericarditis, myositis, cytopenia, and membranous nephritis. Despite relatively high prevalence of LAD in SLE, a biopsy may still be needed to rule out lymphoma.
•There is insufficient number of well-designed studies evaluating CPPD treatment.•Treatment of CPPD is primarily based on empirical evidence and the treatment of gout.•Magnesium carbonate, ...hydroxychloroquine and methotrexate have been evaluated in RCTs.•Commonly used treatments (NSAIDs, colchicine) have not been adequately evaluated.•Anakinra and tocilizumab are promising options; cost and safety may limit their use.
Calcium pyrophosphate crystal deposition disease (CPPD) is a common cause of acute and chronic arthritis, especially in the elderly population. There is a paucity of data regarding the management of CPPD disease, which is currently based on expert opinion and evidence derived from the treatment of gout. We conducted a systematic literature review in order to identify the available treatment options for CPPD, and describe their efficacy and safety.
Online databases were searched from inception to May of 2020 using the search terms: (CPPD Title/Abstract OR CPDD Title/Abstract OR calcium pyrophosphate Title/Abstract OR chondrocalcinosis Title/Abstract) AND (treatment Title/Abstract OR management Title/Abstract OR therapy Title/Abstract). Articles evaluating the use of specific treatment agents for CPPD were eligible for inclusion. Case reports were excluded.
A total of 22 eligible studies and 403 unique patients were selected. We identified only 3 randomized, double-blind, controlled trials (RCTs) evaluating the use of methotrexate, hydroxychloroquine, and magnesium carbonate in CPPD, and these therapeutic options, with the exception of methotrexate, have shown efficacy and reduction of pain intensity. Further, 10 case series and 9 cohort studies were included. Intramuscular and intra-articular glucocorticoids, ACTH, as well as the biologic agents anakinra and tocilizumab appear to be efficacious in CPPD. Intra-articular injections of glycosaminoglycan polysulphate, hyaluronic acid and yttrium, as well as synovial membrane destruction by laser irradiation were associated with symptomatic improvement. Due to significant study heterogenicity, direct comparison between studies was not possible.
There are a limited number of studies evaluating the treatment of CPPD. High quality evidence is rather limited, while commonly administered agents such as NSAIDs, colchicine and corticosteroids have not been evaluated by RCTs. The need for high quality evidence supporting specific treatment modalities is urgent for this common yet neglected form of arthritis.
The neutrophil-to-lymphocyte ratio (NLR) emerged as a potential biomarker in SLE, but its association with several outcomes remains unclear. We aimed to evaluate the relationship between NLR and SLE ...disease activity, damage, depression, and health-related quality of life. A cross-sectional study was conducted, including 134 patients with SLE who visited the Division of Rheumatology between November 2019 and June 2021. Demographics and clinical data including NLR, Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus disease activity index (SELENA–SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), physician global assessment (PhGA), patient global assessment (PGA), patient health questionnaire (PHQ)-9, patient self-rated health, and lupus quality of life (LupusQoL) scores, were collected. Patients were stratified into two groups and compared using the NLR cut-off of 2.73, the 90th percentile value of healthy individuals. The analysis included t-test for continuous variables, χ
2
-test for categorical variables, and logistic regression adjusting for age, sex, BMI, and glucocorticoid use. Among the 134 SLE patients, 47 (35%) had an NLR ≥ 2.73. The NLR ≥ 2.73 group had significantly higher rates of severe depression (PHQ ≥ 15), poor/fair self-rated health, and the presence of damage (SDI ≥ 1). These patients also scored significantly lower in LupusQoL domains (physical health, planning, and body image), and higher in SELENA-SLEDAI, PhGA, and PGA. Logistic regression confirmed that high NLR is associated with severe depression (PHQ ≥ 15) (OR:7.23, 2.03–25.74), poor/fair self-rated health (OR:2.77,1.29–5.96), high SELENA-SLEDAI score(≥ 4) (OR:2.22,1.03–4.78), high PhGA (≥ 2) (OR:3.76, 1.56–9.05), and presence of damage (SDI ≥ 1) (OR:2.67, 1.11–6.43). High NLR in SLE may indicate depression, worse quality of life, active disease, and the presence of damage.
The administration of intravenous immunoglobulins (IVIG) is one of the adjunct therapies investigated and applied to sepsis patients, with the first studies being published nearly four decades ago. ...Intravenous immunoglobulin preparations have several mechanisms of action e.g. antigen neutralization, Fc-receptor blockade on phagocytic cells, modulation of cytokine responses and modulation of immune cell functions. The currently available evidence suggesting the use of intravenous immunoglobulins in sepsis is weak, but results from recent trials and systematic metanalyses seem more promising for the use of intravenous IgM-enriched immunoglobulins (IVIgGM) in septic patients. Nevertheless, the results of studies examining its value are contradicting. The purpose of this review is to summarize and present, clearly and thoroughly, the currently available data regarding established and future potential clinical uses of IVIgGM in patients with sepsis.
•The use of IVIgGM in sepsis syndrome has been evaluated for over 30 years.•A large body of literature exists regarding the use of IVIgGM in sepsis syndrome.•The additional cost for one additional life saved ranges between €5715 and €28,443.•Standard use of IVIgGM is not currently part of the SSC guidelines.•Large and well-designed RCTs are warranted before conclusive recommendations are made.
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