New and emerging therapies for systemic lupus erythematosus.

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.

The relationship of neutrophil-to-lymphocyte ratio with health-related quality of life, depression, and disease activity in SLE: a cross-sectional study.

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, χ2-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.

Prevalence and clinical significance of lymphadenopathy and its histological subtypes in patients with systemic lupus erythematosus: a retrospective cohort study.

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.

Seminoma in 46, XY Gonadal Dysgenesis: Rare Presentation and Review of the Literature.

Swyer syndrome is a rare congenital condition that serves as a risk factor for developing germ cell tumors. The condition belongs to the group of 46, XY Disorders of Sexual Development (DSD) is characterized by complete gonadal dysgenesis and is mostly manifested as delayed puberty and primary amenorrhea during adolescence. Individuals with Swyer syndrome are known to be phenotypically female with normal internal and external female genitalia at birth. 46, XY gonadal dysgenesis involves a high risk of gonadoblastoma development with malignant potential such that the onset is greatest at or after the event of puberty. This report of a 12-year-old phenotypic female with 46, XY gonadal dysgenesis, who developed an advanced metastatic seminoma, aims to emphasize the rarity of the development of a seminoma in the context of 46, XY CGD.

The impact of osteoporosis and vertebral compression fractures on mortality and association with pulmonary function in COPD: A meta-analysis.

OBJECTIVE: Osteoporosis is highly prevalent among patients with chronic obstructive pulmonary disease (COPD) and most commonly presents as a vertebral compression fracture (VCF). Our objective was to quantify the effect of osteoporosis and VCFs on the mortality and pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), of patients with COPD. METHODS: A PubMed/Medline search was conducted using the search terms "chronic obstructive pulmonary disease", "osteoporosis" and "vertebral compression fracture". Meta-analyses were conducted to evaluate the differences in mortality and PFTs between patients with COPD with and without osteoporosis or VCFs, according to PRISMA guidelines. PROSPERO registration: CRD42019120335. RESULTS: Of the 896 abstracts identified, 27 studies describing 7662 patients with COPD of which 1883 (24.6%) had osteoporosis or VCFs, were included. Random effects model analysis demonstrated that patients with COPD and osteoporosis or VCFs had an increased OR for mortality of 2.40 (95% CI: 1.24; 4.64, I2=89%, P<0.01), decreased FEV1/FVC with a mean difference of -4.80% (95% CI: -6.69; -2.90, I2=83%, P<0.01) and decreased FEV1, with a mean difference of -4.91% (95% CI: -6.51; -3.31, I2=95%, P<0.01) and -0.41 L (95% CI: -0.59; -0.24, I2=97%, P<0.01), compared to control subjects. Apart from FEV1 (liters) in subgroup 1 (P=0.06), all subgroup analyses found significant differences between groups, as did sensitivity analysis of low risk of bias studies. CONCLUSION: Osteoporosis and VCFs are associated with a significant reduction in survival and pulmonary function among patients with COPD.

Therapeutic options for cutaneous polyarteritis nodosa: a systematic review.

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 nodosa[Title/Abstract]) AND ((therapy[Title/Abstract]) OR (management[Title/Abstract]) OR (treatment[Title/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.

Bronchoscopy during the COVID-19 pandemic: effect on current practices and strategies to reduce procedure-associated transmission.

Introduction: Bronchoscopy and related procedures have unambiguously been affected during the Corona Virus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS COV-2). Ordinary bronchoscopy practices and lung cancer services might have changed over this pandemic and for the years to come.Areas covered: This manuscript summarizes the utility of bronchoscopy in COVID-19 patients, and the impact of the pandemic in lung cancer diagnostic services, in view of possible viral spread during these We conducted a literature review of articles published in PubMed/Medline from inception to November 5th, 2020 using relevant terms.Expert opinion: Without doubt this pandemic has changed the way bronchoscopy and related procedures are being performed. Mandatory universal personal protective equipment, pre-bronchoscopy PCR tests, dedicated protective barriers and disposable bronchoscopes might be the safest and simpler way to perform even the most complicated procedures.

Mechanisms of Antibiotic Resistance in Important Gram-Positive and Gram-Negative Pathogens and Novel Antibiotic Solutions.

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 Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp. and Klebsiella pneumoniae. 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.

Response to COVID-19 in Cyprus: Policy changes and epidemic trends.

OBJECTIVES: In late July, Cyprus experienced the second epidemic wave of COVID-19. We present the steps taken by the government and evaluate their effect on epidemic trends. MATERIALS: Cyprus Press and Information Office data were analysed. Using an R-based forecasting program, two models were created to predict cases up to 01/09/2020: Model 1, which utilised data up to 09/06/2020, when airports reopened to foreign travelers with COVID-19 screening; and Model 2, which utilised data until 24/06/2020, when screening for passengers from low-transmission countries was discontinued. RESULTS: PIO data revealed no significant policy changes between 24/06/2020 and 31/07/2020. Prediction models were robust and accurate (Model 1, R2  = 0.999, P < .001; Model 2, R2  = 0.998, P < .001). By August 30th, recorded cases exceeded those predicted by Model 1 by 24.47% and by Model 2 by 20.95%, with P values <.001 for both cases. CONCLUSIONS: The significant difference between recorded cases and those projected by Models 1 and 2 suggests that changes in epidemic trends may have been associated with policy changes after their respective dates. Discontinuation of major restrictions such as airport reopening, can destabilise the control of the epidemic, and may concomitantly necessitate a reevaluation of the current epidemic status. In the face of an evolving situation such as the COVID-19 pandemic, states are forced to balance the imposing of restrictions against their impact on the economy.

Management of calcium pyrophosphate crystal deposition disease: A systematic review.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Infection-induced myeloperoxidase specific antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis: A systematic review.

BACKGROUND: We conducted a systematic review to identify cases of infection-induced anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: PubMed/Medline databases were searched from inception to July of 2020, according to PRISMA guidelines. RESULTS: 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. CONCLUSIONS: 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.

Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge.

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.

Measles-associated pneumonia and hepatitis during the measles outbreak of 2018.

Background Between 2017 and 2018, Greece experienced a measles outbreak, affecting >3000 patients, most of which were unvaccinated. Measles-associated pneumonia (MAP) is the most common serious compilation of the disease, but very few recent reports regarding its presentation are available. Materials and Methods Between January and May 2018, 11 adult patients presented to our department with acute measles virus infection, hypoxia and findings on chest X-ray. Clinical, laboratory and radiological data were collected and assessed. Nine out of eleven patients had hypoxic respiratory failure. Other complications included hepatitis, cholestasis and myositis, which were observed in the majority of patients. All patients received supplementary oxygen administration, whereas five patients required continuous positive airway pressure ventilation. Scoring of the radiological examinations performed was most notable for the presence of reticular opacities and consolidations. Statistical analysis demonstrated a significant association between PaO2/FiO2 values and the presence of reticular opacities, with PaO2/FiO2 decreasing as the mean value of the reticular opacities score increased (P = .02). Conclusion To our knowledge, this is the first report demonstrating an association between PaO2/FiO2 values and the presence of reticular opacities in patients with MAP. MAP should be suspected in any patient presenting with acute onset hypoxaemia and a reticular pattern on radiological examination, especially in outbreak settings. What is known Measles infections are on the rise in Europe, with epidemics affecting several European countries, resulting from suboptimal immunisation. The most common serious complication of measles is pneumonia, which is more common in adult patients and can cause significant morbidity. It is the most common cause of death due to measles. What is new In this report, we present 11 adults with measles-associated pneumonia, who presented with the combination of acute measles virus infection, hypoxia and findings on chest X-ray. To our knowledge, this is the first report demonstrating an association between the severity of hypoxaemia and the presence of reticular opacities on chest imaging studies.

Granulomatous infective spondylitis in a patient presenting with progressive difficulty in walking: the differential between tuberculosis and brucellosis.

We report a case of infectious spondylitis in a 52-year-old woman who presented with progressive difficulty in walking. The patient had a 2-month long history of neurological symptoms, which progressed rapidly to paraplegia, following her admission. Imaging studies demonstrated the presence of vertebral lesions as well as additional tissue with inflammatory elements in the spinal canal, which caused a mass effect. In combination with the presence of increased cells and protein in the cerebrospinal fluid (CSF), the differential was steered towards causes of infectious spondylitis, primarily tuberculosis. However, brucellosis was also considered, as it is endemic in our area. Prompt surgical decompression produced biopsy samples, which confirmed the presence of granulomatous inflammation. The patient was started on an empiric regimen covering both for tuberculosis and brucellosis, and gradually regained full mobility in her lower limbs. The differential of infectious spondylitis is discussed, with an emphasis on the differentiation between tuberculosis and brucellosis.

Shiga toxin-induced haemolytic uraemic syndrome and the role of antibiotics: a global overview.

OBJECTIVES: 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. METHODS: 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''. RESULTS: 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. CONCLUSIONS: 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.

The utility of brain natriuretic peptides in septic shock as markers for mortality and cardiac dysfunction: A systematic review.

OBJECTIVE: To conduct a systematic review evaluating the utility of brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) as biomarkers in adult patients with septic shock. MATERIALS AND METHODS: Pubmed/Medline databases were searched from inception to November 2018 using the search terms: (septic[Title/Abstract] AND shock[Title/Abstract]) AND bnp[Title/Abstract]) and (septic[Title/Abstract]) AND shock[Title/Abstract]) AND natriuretic[Title/Abstract]). No restriction was applied regarding date of publication. Comparative observational studies evaluating BNP and NT-proBNP in patients with septic shock aged ≥18 years were eligible for inclusion. Bibliographies from the extracted articles were also reviewed to identify additional relevant publications. RESULTS: In total, 46 studies met all eligibility criteria and were included. A strong body of literature has demonstrated that in patients with septic shock, increased values of BNP and NT-proBNP are associated with increased mortality. An increase from baseline BNP values has also been associated with increased mortality, whereas decreases from baseline values are not related to worse outcome. Brain natriuretic peptides have also been associated with cardiac dysfunction in patients with sepsis. Moreover, BNP values have been found to be significantly elevated in septic shock, regardless of cardiac dysfunction, and have been used to distinguish between septic and cardiogenic shock. Furthermore, BNP and NT-proBNP are significantly increased in patients with septic shock, compared to patients with sepsis and severe sepsis. CONCLUSIONS: BNP and NT-proBNP appear to be reliable predictors of outcome in septic shock.

Porphyrias and photosensitivity: pathophysiology for the clinician.

Porphyrias are disorders caused by defects in the biosynthetic pathway of heme. Their manifestations can be divided into three distinct syndromes, each attributable to the accumulation of three distinct classes of molecules. The acute neurovisceral syndrome is caused by the accumulation of the neurotoxic porphyrin precursors, delta aminolevulinic acid, and porphobilinogen; the syndrome of immediate painful photosensitivity is caused by the lipid-soluble protoporphyrin IX and, the syndrome of delayed blistering photosensitivity, caused by the water-soluble porphyrins, uroporphyrin, and coproporphyrin. Porphyrias can manifest with one, or with a combination, of these syndromes, depending on whether one or more types of molecules are being accumulated. Iron plays a significant role in some of these conditions, as evidenced by improvements in both clinical manifestations and laboratory parameters, following iron depletion in porphyria cutanea tarda, or iron administration in some cases of X-linked erythropoietic protoporphyria. While the pathophysiology of a specific type of porphyrias, the protoporphyrias, appears to favor the administration of zinc, results so far have been conflicting, necessitating further studies in order to assess its potential benefit. The pathways involved in each disease, as well as insights into their pathobiological processes are presented, with an emphasis on the development of photosensitivity reactions.

The use of IgM-enriched immunoglobulin in adult patients with sepsis.

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.