Vaccination recommendations for adult patients with autoimmune inflammatory rheumatic diseases

BACKGROUND: The number of individuals with autoimmune inflammatory rheumatic diseases (AIIRDs) treated with immunosuppressive drugs is increasing steadily. The variety of immunosuppressive drugs and, in particular, biological therapies is also rising. The immunosuppressants, as well as the AIIRD itself, increase the risk of infection in this population. Thus, preventing infections by means of vaccination is of utmost importance. New Swiss vaccination recommendations for AIIRD patients were initiated by the Swiss Federal Office of Public Health and prepared by a working group of the Federal Commission for Vaccination Issues as well as by consultation of international experts. METHODS: A literature search was performed in electronic databases (Cochrane, Medline, PubMed, Embase). In addition, unpublished literature was identified through a targeted website search of relevant organisations and international conferences dealing with vaccination, infectious diseases and rheumatology. RESULTS: Although data are scarce, the following main points were retrieved from the literature. Inactivated vaccines are safe, but their immunogenicity may be reduced in AIIRD patients, especially if they are under immunosuppressive therapy. Rituximab and abatacept appear to reduce significantly immune responses after vaccination. Live vaccines are generally contraindicated under immunosuppressive therapy owing to safety concerns. Specific exceptions, as well as time intervals for the administration of live vaccines after interruption of an immunosuppressive therapy, have been formulated in this article. CONCLUSION: More evidence regarding the immunogenicity and safety of vaccinations in AIIRD patients under various therapies is needed. Vaccination recommendations should be updated on a regular basis, as more scientific data will become available

Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03

Background: Gefitinib is active in patients with pretreated non-small-cell lung cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line treatment in advanced NSCLC followed by chemotherapy at disease progression. Patients and methods: In all, 63 patients with chemotherapy-naive stage IIIB/IV NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was replaced by cisplatin 80 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1, 8 for up to six 3-week cycles. Primary end point was the disease stabilization rate (DSR) after 12 weeks of gefitinib. Results: After 12 weeks of gefitinib, the DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP) was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n = 9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS was not reached after the follow-up of 21.6 months. In all, 41 patients received chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months. Conclusions: First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in an unselected patients population. Never smokers and patients with EGFR mutations tend to have a better outcome; hence, further trials in selected patients are warrante

The Swiss Systemic lupus erythematosus Cohort Study (SSCS) - cross-sectional analysis of clinical characteristics and treatments across different medical disciplines in Switzerland.

OBJECTIVES: To describe disease characteristics and treatment modalities in a multidisciplinary cohort of systemic lupus erythematosus (SLE) patients in Switzerland. METHODS: Cross-sectional analysis of 255 patients included in the Swiss SLE Cohort and coming from centres specialised in Clinical Immunology, Internal Medicine, Nephrology and Rheumatology. Clinical data were collected with a standardised form. Disease activity was assessed using the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), an integer physician's global assessment score (PGA) ranging from 0 (inactive) to 3 (very active disease) and the erythrocyte sedimentation rate (ESR). The relationship between SLE treatment and activity was assessed by propensity score methods using a mixed-effect logistic regression with a random effect on the contributing centre. RESULTS: Of the 255 patients, 82% were women and 82% were of European ancestry. The mean age at enrolment was 44.8 years and the median SLE duration was 5.2 years. Patients from Rheumatology had a significantly later disease onset. Renal disease was reported in 44% of patients. PGA showed active disease in 49% of patients, median SLEDAI was 4 and median ESR was 14 millimetre/first hour. Prescription rates of anti-malarial drugs ranged from 3% by nephrologists to 76% by rheumatologists. Patients regularly using anti-malarial drugs had significantly lower SELENA-SLEDAI scores and ESR values. CONCLUSION: In our cohort, patients in Rheumatology had a significantly later SLE onset than those in Nephrology. Anti-malarial drugs were mostly prescribed by rheumatologists and internists and less frequently by nephrologists, and appeared to be associated with less active SLE

Electrical coupling of neuro-ommatidial photoreceptor cells in the blowfly

A new method of microstimulation of the blowfly eye using corneal neutralization was applied to the 6 peripheral photoreceptor cells (R1-R6) connected to one neuro-ommatidium (and thus looking into the same direction), whilst the receptor potential of a dark-adapted photoreceptor cell was recorded by means of an intracellular microelectrode. Stimulation of the photoreceptor cells not impaled elicited responses in the recorded cell of about 20% of the response elicited when stimulating the recorded cell. This is probably caused by gap junctions recently found between the axon terminals of these cells. Stimulation of all 6 cells together yielded responses that were larger and longer than those obtained with stimulation of just the recorded cell, and intensity-response curves that deviated more strongly from linearity. Evidence is presented that the resistance of the axon terminal of the photoreceptor cells quickly drops in response to a light flash, depending on the light intensity. Incorporating the cable properties of the cell body and the axon, the resistance of the gap junctions, and the (adapting) terminal resistance, a theoretical model is presented that explains the measurements well. Finally, it is argued that the gap junctions between the photoreceptor cells may effectively uncouple the synaptic responses of the cells by counteracting the influence of field potentials.

Long-term outcomes in corticosteroid-refractory Graves' orbitopathy treated with tocilizumab.

Up to 20% of patients with moderate to severe Graves' orbitopathy (GO) do not respond to high-dose glucocorticoids (GC). A few studies, including a randomized trial, have demonstrated the efficacy of interleukin-6 (IL-6) blockade with tocilizumab (TCZ) in GC-refractory GO. However, data on predictors of response to TCZ and long-term outcomes are lacking. Observational single-center study on ten consecutive patients treated with TCZ for GC-refractory GO, between 2016 and 2020. Median (interquartile range) follow-up was 24 (12-36) months. Inflammation and exophthalmos improved dramatically in all patients within months after starting TCZ. Mean Clinical Activity Score decreased from 4.80 ± 1.13 to 0.70 ± 0.82 points at 6 months (mean change: -4.10 ± 1.52; p < .0001). Proptosis improved from 23.2 ± 2.1 to 20.6 ± 2.0 mm at 6 months (mean change: -2.9 ± 1.4 mm; p < .0001). Diplopia resolved in 7 patients. Thyroid receptor antibodies decreased markedly during TCZ treatment. Baseline serum IL-6 levels did not predict clinical response. TCZ was well-tolerated. During follow-up, 3 patients were diagnosed with cancer (breast cancer in 2 and urothelial cancer in 1). TCZ was rapidly effective and well-tolerated in our patients with GC-refractory GO. Four patients experienced mild/moderate adverse events as neutropenia, hyperlipidemia, and infections; nearly a third developed cancer during the follow-up. The increased incidence observed could be explained by the high prevalence of smokers, that are at higher risk for Graves' orbitopathy and solid malignancies as breast cancer. Thus, regular cancer screening could be proposed to this vulnerable population receiving high doses of immunosuppressants

The role of ocelli in cockroach optomotor performance

Insect ocelli are relatively simple eyes that have been assigned various functions not related to pictorial vision. In some species they function as sensors of ambient light intensity, from which information is relayed to various parts of the nervous system, e.g., for the control of circadian rhythms. In this work we have investigated the possibility that the ocellar light stimulation changes the properties of the optomotor performance of the cockroach Periplaneta americana. We used a virtual reality environment where a panoramic moving image is presented to the cockroach while its movements are recorded with a trackball. Previously we have shown that the optomotor reaction of the cockroach persists down to the intensity of moonless night sky, equivalent to less than 0.1 photons/s being absorbed by each compound eye photoreceptor. By occluding the compound eyes, the ocelli, or both, we show that the ocellar stimulation can change the intensity dependence of the optomotor reaction, indicating involvement of the ocellar visual system in the information processing of movement. We also measured the cuticular transmission, which, although relatively large, is unlikely to contribute profoundly to ocellar function, but may be significant in determining the mean activity level of completely blinded cockroaches

Autoimmune Hemolytic Anemia and Pulmonary Embolism: An Association to Consider.

Autoimmune hemolytic anemia (AIHA) is increasingly recognized as a strong risk factor for venous thrombosis. However, there are currently no guidelines on thromboembolism prevention and management during AIHA. Here, we describe the case of a patient with AIHA and pulmonary embolism and resume the current knowledge on epidemiology, risk factors, treatment, and pathophysiology of thrombosis during AIHA, as well as new therapeutic perspectives to prevent thrombus formation during AIHA

Lower circulating mitochondrial DNA and increased mitokines suggest significant mitochondrial dysfunction in systemic lupus erythematosus with renal involvement.

SLE is associated with significant morbidity, especially in the case of renal involvement. Mitochondrial dysfunction plays a significant role in SLE and may be assessed by measuring mitochondrial DNA (mtDNA) and cytokines reflecting mitochondrial stress (mitokines). Circulating mtDNA is a promising biomarker in SLE and appears to be reduced in severe SLE. However, measuring circulating mtDNA is challenging and reported methods are heterogenous. Our study aimed at evaluating whole blood mtDNA to nuclear DNA (nucDNA) ratio using droplet-digital PCR and circulating mitokines, growth differentiation factor 15 (GDF-15) and fibroblast growth factor 21 in SLE with and without renal involvement. Cross-sectional study involving 195 patients with SLE and age-matched healthy volunteers (HV) as control. Biomarkers were compared in patients with and without renal involvement (defined by estimated glomerular filtration rate <60 mL/min or proteinuria >0.5 g/day) and in those with active and inactive SLE. Compared with HV, patients with SLE displayed lower mtDNA/nucDNA ratios, especially in the case of renal involvement. Accordingly, mitokines were increased in patients with SLE with renal involvement. We found no correlation between mtDNA/nucDNA ratio and global disease activity. Mitokine levels, on the other hand, correlated with disease activity, in particular GDF-15 even after adjusting for renal involvement. Our findings suggest that lower whole blood mtDNA/nucDNA ratio, a surrogate marker for mitochondrial dysfunction, reflects renal damage, while GDF-15 may also reflect disease activity in SLE. Further studies are needed to assess the clinical value of these markers as predictors for active lupus nephritis