Changes in Serum IL-12 Levels following the Administration of H1-Antihistamines in Patients with Chronic Spontaneous Urticaria.

INTRODUCTION: Research regarding the role of the IL-12 cytokine family in modulating immune and inflammatory responses is continuously evolving. In this study, the contribution of the p35 and p40 subunits as monomers (noted as IL-12p35 and IL-12p40) and heterodimers (noted as IL-12p70 or IL-12p35/p40) was analysed in the pathophysiology and progression of chronic spontaneous urticaria (CSU). MATERIALS AND METHODS: We conducted a longitudinal, case-control study involving 42 CSU cases and 40 control cases comprising adults without associated conditions. Serial measurements were performed to assess the serum levels of IL-12p70, IL-12p35, and IL-12p40 at the onset of the disease (pre-therapy phase) and 6 weeks after the initiation of the treatment (post-therapy phase). RESULTS: During the pre-therapeutic phase of CSU, elevated serum levels of IL-12 cytokine subtypes were detected compared to the control group. The relationship between IL-12 profiles and the course of CSU highlighted the pro-inflammatory role of IL-12p70 and the anti-inflammatory role of IL-12p35. Significant correlations were observed between IL-12p70 levels and the duration of the disease, as well as between IL-12 and the effectiveness of H1-antihistamines. CONCLUSIONS: The molecular background for the pleiotropic activities mediated by IL-12-derived cytokines in patients with CSU lies in the strict regulation of the production, signalling pathways, and cytokine-specific influences on the same pathophysiological events. The results of the present study suggest that the superficial layers of the skin serve as a cellular source of IL-12, a cytokine produced through antigenic stimulation. In patients with CSU, we identified independent, additive, or divergent functions of IL-12p70, IL-12p35, and IL-12p40, all relevant to systemic inflammation. These findings prove that the prototype programming of IL-12 is abnormal in CSU.

Blood stream Infections in chronic hemodialysis patients - characteristics and outcomes.

INTRODUCTION: Bloodstream Infections (BSI) are a major cause of death and hospitalization among hemodialysis (HD) patients. The rates of BSI among HD patients vary and are influenced by local patient and pathogen characteristics. Modifications in local infection prevention protocols in light of active surveillance of BSI has been shown to improve clinical outcomes. The aim of this study was to further explore factors associated with BSI in a contemporary cohort of HD patients at a public teaching hospital dialysis center in Israel. METHODS: This was a retrospective cohort study of HD patients with a BSI in the years 2014 to 2018. The primary outcome was the occurrence of BSI. Secondary outcomes were to describe the causative pathogens of BSI, and to assess for risk factors for BSI, and mortality. RESULTS: Included were 251 patients. The mean age was 68.5 ± 13.4 years, 66.9% were male. The mean time from initiation of dialysis was 34.76 ± 40.77 months, interquartile range (IQR) 1-47.5 months and the follow up period of the cohort was 25.17 ± 15.9 months. During the observation period, 44 patients (17.5%) developed 54 BSI events, while 10 of them (3.9% of the whole cohort) developed recurrent BSI events. Gram-negative microorganisms caused 46.3% of all BSI events. 31.4% of these BSI were caused by resistant bacteria. In a multivariate logistic regression analysis, patients receiving dialysis through a central line had a significantly increased risk for BSI adjusted Odds Ratio (aOR) 3.907, p = 0.005, whereas patients' weight was mildly protective (aOR 0.971, p = 0.024). CONCLUSIONS: We noted an increased prevalence of gram-negative pathogens in the etiology of BSI in HD patients. Based on our findings, additional empirical antibiotics addressing gram negative bacteria have been added to our empirical treatment protocol. Our findings highlight the need to follow local epidemiology for implementing appropriate preventative measures and for tailoring appropriate empiric antibiotic therapy.

Outcomes of ICU patients treated with intravenous immunoglobulin for sepsis or autoimmune diseases.

OBJECTIVES: To evaluate the outcomes of hospitalized patients in two intensive care units (ICU) treated with intravenous immunoglobulin (IVIg) added to standard-of-care therapy. The indications for IVIg therapy were sepsis or autoimmune disease. METHODS: We conducted a retrospective study involving adult patients with sepsis and autoimmune diseases, who received IVIg in the ICU at Wolfson and Sheba Medical Centers. A predefined chart was compiled on Excel to include a complete demographic collection, patient comorbidities, chronic medication use, disease severity scores (Charlson Comorbidity Index; SOFA and APACHE II index scores), indication and dosage of IVIg administration, duration of hospitalization and mortality rates. RESULTS: Patients (n - 111) were divided into 2 groups: patients with sepsis only (n-67) and patients with autoimmune disease only (n-44). Septic patients had a shorter ICU stay, received IVIg early, and had reduced mortality if treated with high dose IVIg. Patients with autoimmune diseases did not have a favorable outcome despite IVIg treatment. In this group, IVIg was administered later than in the sepsis group. CONCLUSIONS: IVIg therapy improved the outcomes for ICU patients with sepsis.

Screening for Medication Errors and Adverse Events Using Outlier Detection Screening Algorithms in an Inpatient Setting.

OBJECTIVES: To evaluate the potential of a novel system using outlier detection screening algorithms and to identify medication related risks in an inpatient setting. METHODS: In the first phase of the study, we evaluated the transferability of models refined at another medical center using a different electronic medical record system (EMR) on 3 years of historical data (2017-2019), extracted from the local EMR system. Following the retrospective analysis, the system's models were fine-tuned to the specific local practice patterns. In the second, prospective phase of the study, the system was fully integrated in the local EMR and after a short run-in period was activated live. All alerts generated by the system, in both phases, were analyzed by a clinical team of physicians and pharmacists for accuracy and clinical relevance. RESULTS: In the retrospective phase of the study, 226,804 medical orders were analyzed, generating a total of 2731 alerts (1.2% of medical orders). Of the alerts analyzed, 69% were clinically relevant alerts and 31% were false alerts. In the prospective phase of the study, 399 alerts were generated by the system (1.6% of medical orders). The vast majority of the alerts (72%) were considered clinically relevant, and 41% of the alerts caused a change in prescriber behavior (i.e. cancel/modify the medical order). CONCLUSION: In an inpatient setting of a 600 bed computerized decision support system (CDSS) -naïve medical center, the system generated accurate and clinically valid alerts with low alert burden enabling physicians to improve daily medical practice.

Cognitive Impairment, Sleep Disturbance, and Depression in Women with Silicone Breast Implants: Association with Autoantibodies against Autonomic Nervous System Receptors.

BACKGROUND: Silicone breast implants (SBIs) has been shown to be associated with an increased risk of autoimmune diseases. In the current study, we aimed to explore the potential association between circulating autoantibodies against the autonomic nervous system and cognitive impairment, memory deficit, and depressive symptoms reported by women with SBIs. METHODS: ELISA assays were used to quantify anti-adrenergic receptors (α1, α2, ß1, ß2), anti-muscarinic receptors (M1-M5), anti-endothelin receptor type A, and anti-angiotensin II type 1 receptor titers in the sera of 93 symptomatic female subjects with SBIs and 36 age-matched healthy female controls. RESULTS: A significant difference was detected in the level of autoantibodies against the autonomic nervous system receptors in women with SBIs who reported memory impairment, cognitive impairment, and sleep disturbance as compared with both women with SBIs who did not complain of these symptoms or with healthy individuals without SBIs. CONCLUSIONS: Clinical symptoms such as depression, cognitive impairment, and sleep disturbances were found to be associated with dysregulation of the levels of circulating autoantibodies targeting the autonomous nervous system receptors in women with SBIs. These autoantibodies may have diagnostic significance in diseases associated with breast implants.

Short- and long-term mortality in patients with urosepsis caused by Escherichia coli susceptible and resistant to 3rd generation cephalosporins.

BACKGROUND: The aim of this study was to compare short- and long-term mortality among patients with urosepsis caused by Escherichia coli susceptibile (EC-SC) and resistant (EC-RC) to 3rd generation cephalosporins. METHODS: A retrospective cohort study that included all patients with E. coli urosepsis admitted to a 700-bed hospital from January 2014 until December 2019. Mortality up to 30 days, 6 months and 1 year was assessed using logistic multivariate regression analysis and Cox regression analysis. RESULTS: A total of 313 adult were included, 195 with EC-SC and 118 patients with EC-RC. 205 were females (74%), mean age was 79 (SD 12) years. Mean Charlson score was 4.93 (SD 2.18) in the EC-SC group and 5.74 (SD 1.92) in the EC-RC group. Appropriate empiric antibiotic therapy was initiated in 245 (78.3%) patients, 100% in the EC-SC group but only 42.5% in the EC-RC group. 30-day mortality occurred in 12 (6.3%) of EC-SC group and 15 (12.7%) in the EC-RC group. Factors independently associated with 30-day mortality were Charlson score, Pitt bacteremia score, fever upon admission and infection with a EC-RC. Appropriate antibiotic therapy was not independently associated with 30-day mortality. Differences in mortality between groups remained significant one year after the infection and were significantly associated with the Charlson co-morbidity score. CONCLUSIONS: Mortality in patients with urosepsis due to E. coli is highly affected by age and comorbidities. Although mortality was higher in the EC-RC group, we could not demonstrate an association with inappropriate empirical antibiotic treatment. Mortality remained higher at 6 months and 1 year long after the infection resolved but was associated mainly with co-morbidity.

[ABDOMINAL PAIN AND SEIZURES - A COLORFUL TURN OF EVENTS].

INTRODUCTION: The porphyria diseases are inherited and may be exacerbated by environmental triggers. The most common symptoms are abdominal pain, constitutional symptoms, and mental symptoms. The diagnosis of acute intermittent porphyria is usually made during an attack. The initial diagnosis of porphyria is made with the help of biochemical tests in the blood, urine and feces. The best diagnostic approach for carriers of the genes for porphyria, regardless of the manifestation of symptoms, is a molecular test of the genetic mutations, according to which the porphyria can be divided into different types.

[AN UNUSUAL DIAGNOSIS OF CHRONIC URTICARIA].

INTRODUCTION: Cutaneous lupus is an autoimmune disease that can be represented individually or as part of the systemic disease, systemic lupus erythematosus (SLE). Initial presentation of skin manifestations, such as chronic urticatia, should raise the possibility that it might be the first manifestation of an active disease, for example SLE. Despite the broad differential diagnosis of chronic urticaria, other plausible diagnosis should be ruled out with complete anamnesis that includes family background, substance exposure, new and chronic drug therapy, serological and immunological blood tests, diagnostic biopsy of the skin and imaging as needed to rule out malignancy. We present a case of a patient with a family history of various autoimmune diseases, who presented with chronic urticatia and joint pain with partial response to steroid therapy over a period of several months.

Histiocytic Sarcoma

BACKGROUND: Histiocytic sarcoma (HS) is a rare hematopoietic malignancy originating from the monocyte/macrophage bone marrow lineage. HS can occur in isolation or in association with other hematological neoplasms such as non-Hodgkin lymphoma (NHL), myelodysplasia, or acute leukemia. Clinically, HS can affect lymph nodes, gastrointestinal tract, skin, bone marrow, and spleen as well as the central nervous system. Most cases of HS follow an aggressive clinical course, with most patients dying of progressive disease within one year of diagnosis.

Systemic lupus erythematosus: an expert insight into emerging therapy agents in preclinical and early clinical development.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic disease that is potentially fatal. There is no cure for SLE and the medications used are associated with toxic side effects. In the era of revolutionary emerging novel biologic agents, the design and investigation of targeted therapy for these patients is necessary. Novel therapies under investigation in phase II-III clinical trials showed promising results. Therapies can target various pathways involved in SLE including cytokines, signal transduction inhibitors, B-cell depletion and interference with co-stimulation. Of interest is the proof of concept of sequential therapy. AREAS COVERED: We performed an extensive literature search via PubMed, Medline, Elsevier Science and Springer Link databases between the years 2014-2020 using the following terms: SLE, novel treatments. We have reviewed 232 articles and selected those articles that (i) focus on phase II-III emerging therapies and (ii) offer new findings from existing therapies, which reveal breakthrough concepts in SLE treatment. EXPERT OPINION: It is still difficult to crack the puzzle of a successful SLE treatment approach. New strategies with potential may encompass the targeting of more than one protein. Another way forward is to identify each SLE patient and personalize therapy by clinical manifestations, disease activity, serology and activated protein.

The complexity of an overlap type resistant cryoglobulinemia: a case report and review of the literature.

Type I cryoglobulinemia is associated with B cell proliferative diseases, whereas essential mixed cryoglobulinemia is classically associated with infections, malignancy, and autoimmune diseases, but may be idiopathic. Prognosis in patients with grave manifestations and renal involvement is often poor. We report a case of a 40-year-old woman, 2 weeks post-partum for pre-eclampsia who was hospitalized with nephritic syndrome and acute renal failure. The patient harbored type I and type II cryoglobulinemia. Renal and cutaneous biopsies confirmed the diagnosis; however, an underlying etiology was not established. A bone marrow biopsy suggested monoclonal gammopathy of undetermined source (MGUS). Despite therapy with intravenous cyclophosphamide, rituximab, plasmapheresis, dialysis, and bortezomib, the patient succumbed after 8 months of hospitalization. We suggest that an overlap entity of types I and II cryoglobulinemia with severe multi-organ involvement not only is rare but also may be resistant to conventional therapy and fatal.