Extrahippocampal seizure and memory circuits overlap.

Seizures cause retrograde amnesia. We have previously demonstrated that seizures erode recently formed memories through shared ensembles and mechanisms in the CA1 region of the hippocampus. Here, we tested whether seizure circuits overlap spatial memory circuits outside of the CA. Spatial memory is consolidated by the hippocampal-cortical coupling that are connected via multiple pathways. We tested whether a seizure invades structures involved in memory consolidation by using the activity reporter TRAP2 mice. T-maze alternation learning activated neurons in the dentate gyrus, mediodorsal thalamus, retrosplenial cortex, and medial prefrontal cortex. This spatial memory relies on the plasticity of the AMPA receptor GluA1 subunit. GluA1 knockout/TRAP2 mice did not learn to alternate, and structures interposed between the hippocampus and the cortex were not active. A seizure prevented the recall of alternation memory and activated memory-labeled structures. There was a widespread overlap between learning-activated ensembles and seizure-activated neurons, which likely contributes to retrograde amnesia.Significance StatementWe propose that seizures cause retrograde amnesia by engaging the circuits that participate in memory consolidation.

Infliximab and biosimilar infliximab in psoriasis: efficacy, loss of efficacy, and adverse events.

Psoriasis is a chronic immune-mediated skin disease affecting multiple systems, and tumor necrosis factor-α (TNF-α) plays a significant role in the initiation and progression of the disease process. Psoriasis has a high prevalence rate in the Western world, especially in the USA and Australia; in China, although the prevalence rate is much lower, there is still a large number of patients suffering from psoriasis and its comorbidities. As TNF-α is thought to be crucial in the pathogenesis of psoriasis, specific therapy blocking TNF-α may be beneficial in the treatment of this disease. Infliximab, a murine-human monoclonal antibody, is highly efficacious in the treatment of moderate-to-severe psoriasis, with better skin clearance and faster onset of action than topical medications such as methotrexate, narrow-band ultraviolet B, and calcipotriol. Lack of adherence to infliximab therapy is mainly due to loss of response (LOR) over time and adverse events, particularly because infusion reactions are usually encountered. Anti-infliximab antibody is thought to be responsible for the LOR and infusion reactions. However, the mechanism underlying the formation of anti-infliximab antibody and its side effects remains unclear. Further studies identifying patients at risk for LOR will probably help clinicians to select the right patients for anti-TNF-α therapy and to increase the durability of the treatment. This review discusses the efficacy of infliximab as demonstrated by various clinical trials, LOR to infliximab, combatting LOR, as well as the adverse events usually faced during the use of infliximab therapy and the infliximab biosimilar Remsima®. We hope that we can discover a better way to use infliximab in the therapy of psoriasis from the current research data.

Scalp metastases as first presentation of pulmonary adenocarcinomas: a case report.

Cutaneous metastasis from primary visceral malignancy is a relatively uncommon clinical entity, with a reported incidence ranging from 0.22% to 12% of all malignancies. Here we report a 64-year-old asymptomatic female patient with Peutz-Jeghers syndrome presenting with multiple scalp metastases as the initial manifestation secondary to lung adenocarcinoma. Subsequent lung computed tomography scan showed large masses involving the left upper lobe associated with extensive mediastinal lymphadenopathy. After treatment with an epidermal growth factor receptor inhibitor gefitinib, the size of the tumor in the lung reduced significantly and the condition of the patient also gradually improved. Our case demonstrated that scalp metastasis could be the first sign of an internal malignancy. Asymptomatic elderly patients presenting with multiple, painless, immobile cutaneous nodules should be considered for further investigations to rule out the underlying primary cause. Metastasis to the skin is often a preterminal event that heralds poor prognosis.

Efficacy and safety of biologics targeting IL-17 and IL-23 in the treatment of moderate-to-severe plaque psoriasis: A systematic review and meta-analysis of randomized controlled trials.

Numerous biologics are currently licensed for the treatment of psoriasis, including new drugs targeting interleukin-17 (IL-17) and interleukin-23 (IL-23). This meta-analysis evaluated the short-term (12-16 weeks) efficacy and safety of biologics targeting IL-17 and IL-23 in the treatment of moderate-to-severe plaque psoriasis. Twenty-one randomized clinical trials met the defined inclusion criteria. Our results showed that Ixekizumab (160 mg wk0 + 80 mg q2w) had the greatest probability of achieving both PASI 75 (RR 21.32, 95% CI 15.48-29.36, P < 0.00001) and PASI 90 response (RR 59.76, 95% CI 32.41-110.19, P < 0.00001) at the primary endpoint times, followed by Ustekinumab and Secukinumab. Regarding the safety profile, Tildtakizumab (200 mg, q4w) was safest (RR 0.88, 95% CI 0.78-0.99, P = 0.04), while Ixekizumab (160 mg wk0 + 80 mg q2w) showed highest risk for one or more AE (RR 1.26, 95% CI 1.15-1.38, P < 0.00001). However, there was no significant difference between the two biologics regarding one or more SAEs. Comparing to the biologics targeting IL-23, the pooled effect size favored the biological agents targeting IL-17 in terms of the PASI 75 (PASI 75: RR 17.28, 95% CI 14.51-20.58, P < 0.00001) and PASI 90 (RR 37.19, 95% CI 26.91-51.41, P < 0.00001). The rate of overall AEs was significantly higher (P < 0.00001) in biologics targeting the IL-17 (RR 1.18, 95% CI 1.12-1.24, P < 0.00001) compared to biologics targeting IL-23 (RR 0.97, 95% CI 0.91-1.04, P = 0.44), and with respect to one or more SAEs, no difference was seen between biologics targeting IL-17 and IL-23. This meta-analysis found that Ixekizumab was the most effective short-term treatment, but was ranked as the most risk therapeutic choice among the biologics involved in this study, while Tildtakizumab was the best alternative in the case of safety. Furthermore, it demonstrated that biologics inhibiting IL-17 were superior to biologics targeting IL-23 in terms of the efficacy, but posed higher risk at the same time. This study might help the clinicians and guideline developers to choose the optimal one among these biologics for the treatment of moderate-to-severe plaque psoriasis.

Management of pediatric psoriasis with acitretin: A review.

Psoriasis is a chronic inflammatory disease of the skin which can occur at any age-group. Psoriasis in childhood is not uncommon and has genetic susceptibility but usually, an environmental trigger such as infection is thought to initiate the disease process. Pediatric psoriasis has profound effects on both physical and psychosocial health of the patient. Treatment of mild psoriasis can be done with topical therapies but those which do not respond to topical therapies can be treated with phototherapy and systemic therapies. The use of systemic therapies in childhood is mainly based on the published data, case series, expert opinion and the experience as there is the lack of controlled trials in the age group. Based on the experience retinoids are probably the second line drugs for the treatment of pediatric psoriasis which do not respond to topical therapies and phototherapy. Using acitretin in a low dose and with proper physical examinations and laboratory investigations will reduce the hazard of potential serious adverse events. This article gives the review of the use of acitretin in pediatric psoriasis.