Lyme neuroborreliosis: Progressive cerebral vasculitis responsive to cyclophosphamide. A case report and review of the literature.

OBJECTIVES: Less than 1 % of patients with Lyme Neuroborreliosis (LNB) present with a cerebrovascular event. Ischaemic strokes occur more commonly than parenchymal or subarachnoid haemorrhages. If cerebral vasculitis due to LNB is suspected, antibiotic treatment should be started immediately, which will normally lead to remission. Very rarely progression and recurrent strokes are observed despite sufficient antibiotic therapy, even if steroids are added. Currently there are no guidelines on the adequate treatment of cerebral vasculitis due to LNB which is not responsive to antibiotics and steroids, but in very few reported cases cyclophosphamide led to disease stabilisation. We reviewed the literature regarding cyclophosphamide treatment in these patients and want to share our experience of cyclophosphamide therapy in progressive cerebral vasculitis due to LNB. RESULTS: We report a 71-year-old female patient with cerebral vasculitis and multiple strokes as a complication of LNB. Progression could only be halted by additional immunosuppressive treatment using cyclophosphamide. However, at that point the patient had already suffered severe ischaemic brain damage. Similarly, in existing case reports cyclophosphamide had been administered only at a time when patients already showed serious neurological deficits. CONCLUSION: Cerebral vasculitis in patients with LNB is very rare and normally responds to antibiotic treatment. A minority of patients show disease progression despite antibiotics and steroids. Our case report strengthens the recommendation that in those patients - even if signs of progressive vasculitis are only detectable on imaging and not clinically - cyclophosphamide should be considered without delay to prevent further cerebrovascular events.

Treatment of acquired thrombotic thrombocytopenic purpura without plasma exchange in selected patients under caplacizumab.

BACKGROUND: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy. Current standard of care is therapeutic plasma exchange, immunosuppression, and caplacizumab, an anti-von Willebrand factor nanobody, which is effective in treating aTTP episodes. PATIENTS/METHODS: Here we report on seven episodes of aTTP treated without plasma exchange in six female patients in Germany and Austria. Two episodes were initial presentations of aTTP; in five instances, patients experienced a relapse. In four episodes, moderate to severe organ dysfunction was observed; three cases presented with a mild course. All patients received caplacizumab immediately once aTTP was suspected or diagnosed, and plasma exchange was omitted based on shared decision making between patient and the treating physicians. RESULTS: We observed a rapid and robust increase of platelet counts already after the first dose of caplacizumab, leading to a doubling of platelet counts within 17 hours (median), platelet counts normalized (>150 G/L) after median 84 hours. Lactate dehydrogenase, as a surrogate parameter of organ damage, improved in parallel to the platelet counts, indicating resolving microangiopathy. CONCLUSIONS: In conclusion, in selected cases of acute bouts of aTTP, it seems feasible to delay or omit plasma exchange if platelet counts increase and organ function is stable after start of caplacizumab therapy.

Prescribed-Time Consensus and Containment Control of Networked Multiagent Systems.

In this paper, we present a new prescribed-time distributed control method for consensus and containment of networked multiple systems. Different from both regular finite-time control (where the finite settling time is not uniform in initial conditions) and the fixed-time control (where the settling time cannot be preassigned arbitrarily), the proposed one is built upon a novel scaling function, resulting in prespecifiable convergence time (the settling time can be preassigned as needed within any physically allowable range). Furthermore, the developed control scheme not only ensures that all the agents reach the average consensus in prescribed finite time under undirected connected topology, but also ensures that all the agents reach a prescribed-time consensus with the root's state being the group decision value under the directed topology containing a spanning tree with the root as the leader. In addition, we extend the result to prescribed-time containment control involving multiple leaders under directed communication topology. Numerical examples are provided to verify the effectiveness and the superiority of the proposed control.

Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome.

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed ß1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.

Collectively Rotating Formation and Containment Deployment of Multiagent Systems: A Polar Coordinate-Based Finite Time Approach.

This paper investigates the problem of achieving rotating formation and containment simultaneously via finite time control schemes for multiagent systems. It is nontrivial to maintain rotating formation where the desired formation structure is time-varying and only neighboring information is available. The underlying problem becomes even more complicated if containment is imposed yet finite time convergence is required at the same time. To tackle this problem, a polar coordinate-based approach is exploited in this paper. Finite time control protocols are established for leader agents and follower agents, respectively, such that three goals are achieved in finite time concurrently: 1) all the agents maintain a stable rotating motion around a common circular center with a common (possibly time-varying) angular velocity; 2) the leader agents form and maintain a prespecified rotating formation structure; and 3) the follower agents converge to the shifting convex hull shaped by the dynamically moving (circling) leaders. It is the polar coordinate expression that simplifies the formulation of the rotating formation-containment problem and facilitates the finite time control design process. The effectiveness of the proposed control scheme is illustrated via both formative mathematical analysis and numerical simulation.

Women's demand for late-term abortion--a social or psychiatric issue?

INTRODUCTION/AIM: Induced termination of unwanted pregnancy after 12th gestational week (late-term abortion) is legally restricted in Serbia as well as in many other countries. On the other hand, unwanted pregnancy very often brings women into the state of personal crisis. Psychiatric indications for legally approved late-term abortion on women's demand include only severe psychiatric disorders. The aim of this paper was to compare sociodemographic, psychological characteristics and claimed reasons for abortion in the two groups of women with late-term demand for abortion--the group of women satisfying legally prescribed mental health indications, and the group of women not satisfying these indications. The aim of the study was also to determine predictive validity of the abovementioned parameters for late-term abortion as the outcome of unwanted pregnancy. METHODS: A total of 62 pregnant women with demand for late-term abortion were divided into two groups according to the criteria of satisfying or not satisfying legally proposed psychiatric indications for late-term abortion after psychiatric evaluation. For the assessment of sociodemographic and psychological parameters sociodemographic questionnaire and symptom checklist-90 revised (SCL-90) scale were used, respectively. The outcome of unwanted pregnancy was followed 6 months after the initial assessment. RESULTS: The obtained results showed a statistically significant difference between the groups in educational level, satisfaction with financial situation, elevated anxiety and distress reactions. Unfavorable social circumstances were the main reason for an abortion in both groups and were predictive for an abortion. A 6-month follow-up showed that women had abortion despite legal restrictions. CONCLUSION: Pregnant women with psychiatric indication for late-term abortion belong to lower socioeconomic and educational level group compared to women without this indication who have more frequently elevated anxiety and distress reactions to unwanted pregnancy. It is necessary to have more accurate guidelines for mental health indications for legally approved late-term abortion, respecting social circumstances. Preventive measures are of great importance in order to lower the risk of illegally performed late-term abortions.