Mario Negri Institute for Pharmacological Research

Background Serotonin syndrome is a rare and potentially fatal adverse drug reaction caused by serotonergic drugs and is due to an increase in serotonin concentration or activation of the 5-HT receptor in the central nervous system. We analysed adverse events in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data set to investigate the main drug classes related to reports of serotonin syndrome and the reporting risk in relation to age and sex. Methods We analysed data from the FAERS database to evaluate the main drug classes related to reports of the serotonin syndrome, and the reporting risk in relation to age and sex. Results We found 8,997 cases of serotonin syndrome; selective serotonin reuptake inhibitors (SSRIs) was the class of drugs with most reports, followed by opioids and other antidepressants. The highest Reporting Odds Ratios (ROR) for drug classes was for monoamine oxidase (MAO) inhibitors (45.99, 95% confidence interval (CI): 41.21–51.33) and SSRIs (32.66, 95% CI: 31.33–34.04), while the ten active substances with the highest ROR were moclobemide, isocarboxazid, oxitriptane, tranylcypromine, melitracen, phenelzine, linezolid, amoxapine, reboxetine and tryptophan; with values of ROR ranging from 44.19 (95% CI: 25.38–76.94) of tryptophan to 388.36 (95% CI: 314.58-479.46) of moclobemide. The ROR for the most commonly involved drugs was higher in the group of older adults (65 > years old), and higher in males. Conclusion Prescribers need to be vigilant about drugs that can raise serotonin concentration or influence serotonergic neurotransmission, also when using drugs with less well-known risk for serotonin syndrome, like linezolid and triptans.

Physicians often face difficulties in selecting appropriate medications for older adults with multiple comorbidities. As people age, they are more likely to be living with a number of chronic conditions (multimorbidity) and be prescribed a high number of medications (polypharmacy). Multimorbidity is frequent in nursing home (NH) residents and the use of potentially inappropriate medications, especially psychotropic drugs, is widespread. This retrospective cross-sectional cohort study examined the frequency of potentially inappropriate psychotropic drugs using the Beers, Screening Tool of Older Persons' Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) and Fit fOR The Aged (FORTA) criteria, and their association with mortality. This retrospective cross-sectional cohort study was conducted on a sample of long-term care NHs across Italy. Of the 34 NHs with an electronic medical records system, 27 met the inclusion criteria, with complete web-based case report forms (CRFs). Residents under the age of 65 years were excluded. We calculated the prevalence of potentially inappropriate psychotropics drugs (antipsychotics, antidepressants and anxiolytics/hypnotics) according to three criteria for prescriptive appropriateness. Univariate and multivariate correlations were examined, taking into account age, sex, comorbidities, and the number of psychotropic drugs, to analyse the relationship between inappropriate psychotropic use and mortality rates. The rate of inappropriate psychotropic prescriptions was calculated with the prevalence of residents receiving potentially inappropriate psychotropic drugs according to the three criteria. We used a logistic model to check for a possible predictive relationship between inappropriate use of psychotropics and mortality. The study evaluated differences in prescriptive appropriateness among NHs by analysing the proportions of potentially inappropriately treated residents at the last visit. Differences were compared with the overall sample mean using confidence intervals (CIs) calculated using Wald’s method. This study involved 2555 residents, of whom 1908 (74.7% of the total) were treated with psychotropic drugs; 186 (7.3% of the total) were exposed to at least one psychotropic drug considered potentially inappropriate according to the FORTA criteria. Analysis using the Beers criteria showed that 1616 residents (63.2% of the total) received at least one psychotropic drug considered potentially inappropriate. In line with the Beers recommendation, patients receiving at least three psychotropic drugs were also included and 440 were identified (17.2% of the total sample). According to the STOPP criteria, 1451 residents (56.8% of the total sample) were prescribed potentially inappropriate psychotropic drugs. No correlation was found between potentially inappropriate use of psychotropic drugs and mortality, in either univariate analysis or in a multivariate model adjusted for age, sex and comorbidity index. Different criteria for appropriate drug prescription identify very different percentages of patients in NHs exposed to psychotropics considered potentially inappropriate. The Beers and STOPP/START criteria identified a larger percentage of patients exposed in NHs than FORTA.

Background Supporting young ADHD patients in transition to adult services is essential. Yet, the low percentages of successful referrals and the issues reported by patients and clinicians stress the need for further attention to transitioning practices. The present study assessed the transitioning process of Attention-Deficit/Hyperactivity Disorder (ADHD) patients in Child and Adolescent Mental Health Services (CAMHS) and Adult Mental Health Services (AMHS) in the Italian territory. We asked child and adult psychiatrists to report the current state of services and their observations on limitations and possible future matters that must be addressed. Method Seventy-seven centers (42 CAMHS, 35 AMHS) filled in a web-based survey in which they reported the number of ADHD patients, how many transitioning patients they had within the past year, and how they structured transition. Results A fragmented picture emerged from the survey. Lack of resources, training, and communication between services hinder the transition process, and many adult patients remain under CAMHS’ care. While some services have a protocol, there is no structured guidance that can help improve integration and continuity of treatment. Conclusion The observed situation reflects a need for improvement and standard guidelines to enable a successful transition process, considering clinicians' and patients’ necessities.

The DNA damage response (DDR) is the cellular process of preserving an intact genome and is often deregulated in lymphoma cells. The ataxia telangiectasia and Rad3‐related (ATR) kinase is a crucial factor of DDR in the response to DNA single‐strand breaks. ATR inhibitors are agents that have shown considerable clinical potential in this context. We characterized the activity of the ATR inhibitor elimusertib (BAY 1895344) in a large panel of lymphoma cell lines. Furthermore, we evaluated its activity combined with the clinically approved PI3K inhibitor copanlisib in vitro and in vivo. Elimusertib exhibits potent anti‐tumour activity across various lymphoma subtypes, which is associated with the expression of genes related to replication stress, cell cycle regulation and, as also sustained by CRISPR Cas9 experiments, CDKN2A loss. In several tumour models, elimusertib demonstrated widespread anti‐tumour activity stronger than ceralasertib, another ATR inhibitor. This activity is present in both DDR‐proficient and DDR‐deficient lymphoma models. Furthermore, a combination of ATR and PI3K inhibition by treatment with elimusertib and copanlisib has in vitro and in vivo anti‐tumour activity, providing a potential new treatment option for lymphoma patients.

Importance Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are protected against disability because of greater capacity for repair. Objective To assess the incidence of and factors associated with progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS compared with typical adult-onset MS (AOMS) and late-onset MS (LOMS). Design, Setting, and Participants This cohort study on prospectively acquired data from the Italian MS Register was performed from June 1, 2000, to September 30, 2021. At the time of data extraction, longitudinal data from 73 564 patients from 120 MS centers were available in the register. Main Outcomes and Measures The main outcomes included age-related cumulative incidence and adjusted hazard ratios (HRs) for PIRA and RAW and associated factors. Exposures Clinical and magnetic resonance imaging features, time receiving disease-modifying therapy (DMT), and time to first DMT. Results After applying the inclusion and exclusion criteria, the study assessed 16 130 patients with MS (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared with AOMS and LOMS, patients with POMS had less disability, exhibited more active disease, and were exposed to DMT for a longer period. A first 48-week-confirmed PIRA occurred in 7176 patients (44.5%): 558 patients with POMS (40.4%), 6258 patients with AOMS (44.3%), and 360 patients with LOMS (56.8%) ( P < .001). Factors associated with PIRA were older age at onset (AOMS vs POMS HR, 1.42; 95% CI, 1.30-1.55; LOMS vs POMS HR, 2.98; 95% CI, 2.60-3.41; P < .001), longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P < .001), and shorter DMT exposure (HR, 0.69; 95% CI, 0.64-0.74; P < .001). The incidence of PIRA was 1.3% at 20 years of age, but it rapidly increased approximately 7 times between 21 and 30 years of age (9.0%) and nearly doubled for each age decade from 40 to 70 years (21.6% at 40 years, 39.0% at 50 years, 61.0% at 60 years, and 78.7% at 70 years). The cumulative incidence of RAW events followed a similar trend from 20 to 60 years (0.5% at 20 years, 3.5% at 30 years, 7.8% at 40 years, 14.4% at 50 years, and 24.1% at 60 years); no further increase was found at 70 years (27.7%). Delayed DMT initiation was associated with higher risk of PIRA (HR, 1.16; 95% CI, 1.00-1.34; P = .04) and RAW (HR, 1.75; 95% CI, 1.28-2.39; P = .001). Conclusions and Relevance PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study’s findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up. However, these data also reinforce the benefit for DMT initiation in patients with POMS, as treatment was associated with reduced occurrence of both PIRA and RAW regardless of age at onset.

Objective The objective of this systematic review was to evaluate the effect of different types of neoadjuvant chemotherapy regimens, in terms of optimal pathological response and oncological outcomes, in patients with locally advanced cervical cancer. Methods A systematic search of the literature was performed. MEDLINE through PubMed and Embase databases were searched from inception to June 2023. The study was registered in PROSPERO (ID number CRD42023389806). All women with a pathological diagnosis of locally advanced cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009 classification stages IB2-IVA), any age or histology, who underwent intravenous neoadjuvant chemotherapy before radical surgery, and articles only in English language, were included. We conducted a meta-analysis for optimal pathological response after surgery and survival outcomes. The risk of bias was assessed using the Newcastle-Ottawa scale and the Risk of Bias 2 (RoB) tools. The review methods and results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results 25 studies with a total number of 1984 patients fulfilled the eligibility criteria of our review and were included for data extraction and efficacy analysis. When compared with a two-drug regimen, the three-drug combination including cisplatin, paclitaxel, and ifosfamide or anthracyclines showed superior efficacy in terms of optimal pathological response with an odds ratio of 0.38 (95% CI 0.24 to 0.61, p<0.0001), with no difference in disease-free survival (hazard ratio (HR) 0.72, 95% CI 0.50 to 1.03, I ² =0%, p=0.07) and higher overall survival (HR 0.63, 95% CI 0.41 to 0.97, I ² =0%, p=0.03). Conclusions The three-drug combination of cisplatin, paclitaxel, and ifosfamide or anthracyclines showed a higher rate of complete or optimal partial response, with the triple regimens having an advantage over the platinum-based schedules in terms of overall survival. Neoadjuvant chemotherapy followed by radical surgery should not be considered a standard of care in locally advanced cervical cancer.

Current treatments for modulating the glial‐mediated inflammatory response after spinal cord injury (SCI) have limited ability to improve recovery. This is quite likely due to the lack of a selective therapeutic approach acting on microgliosis and astrocytosis, the glia components most involved after trauma, while maximizing efficacy and minimizing side effects. We have developed and characterized a new nanogel that can selectively release active compounds in microglial cells and astrocytes. We evaluated the degree of selectivity and subcellular distribution of the nanogel by applying an innovative super‐resolution microscopy technique, expansion microscopy. We then tested two different administration schemes in a SCI mouse model: in an early phase, the nanogel loaded with Rolipram, an anti‐inflammatory drug, achieved significant improvement in the animal's motor performance due to the increased recruitment of microglia and macrophages that were able to localize the lesion. Treatment in the late phase, however, gave opposite results, with worse motor recovery because of the widespread degeneration. These findings demonstrate that the nanovector can be selective and functional in the treatment of the glial component in different phases of SCI. They also open a new therapeutic scenario for tackling glia‐mediated inflammation after neurodegenerative events in the central nervous system. This article is protected by copyright. All rights reserved

Systemic light chain (LC) amyloidosis (AL) is a disease where organs are damaged by an overload of a misfolded patient-specific antibody-derived LC, secreted by an abnormal B cell clone. The high LC concentration in the blood leads to amyloid deposition at organ sites. Indeed, cryogenic electron microscopy (cryo-EM) has revealed unique amyloid folds for heart-derived fibrils taken from different patients. Here, we present the cryo-EM structure of heart-derived AL amyloid (AL59) from another patient with severe cardiac involvement. Its structure displays a stable core and two flexible segments adopting alternative conformations. Two confirmations are sterically incompatible and typically distributed on separate fibrils. Noteworthy, the fibril core harbours an extended constant domain fragment, thus ruling out the variable domain as sole amyloid building block. Surprisingly, the fibrils were abundantly concatenated with a proteinaceous polymer, here identified as collagen VI (COLVI) by immuno-electron microscopy (IEM) and mass-spectrometry. Cryogenic electron tomography (cryo-ET) showed how COLVI wraps around the amyloid forming a helical superstructure, likely stabilizing and protecting the fibrils from clearance. Thus, here we report the first structural evidence of interactions between amyloid and collagen, potentially signifying a novel pathophysiological mechanism of amyloid deposits.

Peritubular capillary rarefaction is a recurrent aspect of progressive nephropathies. We previously found that peritubular capillary density was reduced in BTBR ob/ob mice with type 2 diabetic nephropathy. In this model, we searched for abnormalities in the ultrastructure of peritubular capillaries, with a specific focus on the endothelial glycocalyx, and evaluated the impact of treatment with an angiotensin-converting enzyme inhibitor (ACEi). Mice were intracardially perfused with lanthanum to visualise the glycocalyx. Transmission electron microscopy analysis revealed endothelial cell abnormalities and basement membrane thickening in the peritubular capillaries of BTBR ob/ob mice compared to wild-type mice. Remodelling and focal loss of glycocalyx was observed in lanthanum-stained diabetic kidneys, associated with a reduction in glycocalyx components, including sialic acids, as detected through specific lectins. ACEi treatment preserved the endothelial glycocalyx and attenuated the ultrastructural abnormalities of peritubular capillaries. In diabetic mice, peritubular capillary damage was associated with an enhanced tubular expression of heparanase, which degrades heparan sulphate residues of the glycocalyx. Heparanase was also detected in renal interstitial macrophages that expressed TNF-α. All these abnormalities were mitigated by ACEi. Our findings suggest that, in experimental diabetic nephropathy, preserving the endothelial glycocalyx is important in order to protect peritubular capillaries from damage and loss.

The assessment of renal vasculature and renal blood flow (RBF) is extremely relevant in the diagnosis and monitoring of a range of renal diseases. Phase-contrast (PC) MRI, which does not require contrast media, allows non-invasive measurement of RBF in each renal artery in a single two-dimensional (2D) slice (2D PC-MRI), and recently also in the branches of the vessel of interest (four-dimensional (4D) flow MRI). Renal PC-MRI is not yet being routinely used in clincial practice, but several studies support its clinical potential. MR angiography (MRA) is routinely used to diagnose renal artery stenosis. Although usually requiring contrast agent administration, promising contrast-free sequences for MRA have recently been developed. This chapter provides a comprehensive overview of PC-MRI and MRA of the renal arteries, including patient preparation, physics and acquisition protocols, post-processing and data analysis methods, common issues and artifacts, and clinical applications, with the aim of fostering their wider adoption. Future multicenter studies are needed to define reference ranges, to provide additional evidence of renal PC-MRI and MRA clinical validity, and to demonstrate their clinical potential as part of a multiparametric renal MRI protocol, ultimately allowing their transfer to clinical practice.

Simple Summary Several naturally occurring substances, known as polyphenols, may be found in a variety of plant-based foods and drinks, including fruits, vegetables, whole grains, tea, and red wine. Several studies have shown that these molecules have many beneficial effects on human health, particularly in their ability to counteract tumor growth thanks to their capacity to dampen inflammatory processes. Furthermore, polyphenols can form complexes with certain metals, such as copper. This property is of great importance considering that copper is closely involved in both the early stages and progression of cancer. In this study, we investigated the capacity of hydroxytyrosol, a derivative of oleuropein found in the leaves and fruits of the Olea europaea plant, to complex with copper and, consequently, to counteract the progression of triple-negative breast cancer. We chose this type of cancer as it is the most aggressive subtype due to the lack of specific receptors, which results in the absence of targeted oncological therapy. Our results demonstrate that hydroxytyrosol forms a complex with copper, resulting in the reduction of its content within the triple-negative breast cancer cell, consequently reducing its aggressiveness and, eventually, its ability to form metastases. Abstract Polyphenols have gained increasing attention for their therapeutic potential, particularly in conditions like cancer, due to their established antioxidant and anti-inflammatory properties. Recent research highlights their ability to bind to transition metals, such as copper. This is particularly noteworthy given the key role of copper both in the initiation and progression of cancer. Copper can modulate the activity of kinases required for the epithelial–mesenchymal transition (EMT), a process fundamental to tumor cell dissemination. We have previously demonstrated the copper-binding capacity of oleuropein, a secoiridoid found in Olea europaea. In the present study, we investigated the effect of hydroxytyrosol, the primary oleuropein metabolite, on the metastatic potential of three triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-468, and SUM159). We found that hydroxytyrosol modulated the intracellular copper levels, influencing both the epithelial and mesenchymal markers, by downregulating copper-dependent AKT phosphorylation, a member of the EMT signaling cascade, through Western blot, RT-qPCR, and immunofluorescence. Indeed, by optical spectra, EPR, and in silico approaches, we found that hydroxytyrosol formed a complex with copper, acting as a chelating agent, thus regulating its homeostasis and affecting the copper-dependent signaling cascades. While our results bring to light the copper-chelating properties of hydroxytyrosol capable of countering tumor progression, they also provide further confirmation of the key role of copper in promoting the aggressiveness of triple-negative breast cancer cells.

Objective Sepsis and septic shock are major challenges and economic burdens to healthcare, impacting millions of people globally and representing significant causes of mortality. Recently, a large number of quality improvement programs focused on sepsis resuscitation bundles have been instituted worldwide. These educational initiatives have been shown to be associated with improvements in clinical outcomes. We aimed to evaluate the impact of a multi-faceted quality implementing program (QIP) on the compliance of a “simplified 1-h bundle” (Sepsis 6) and hospital mortality of severe sepsis and septic shock patients out of the intensive care unit (ICU). Methods Emergency departments (EDs) and medical wards (MWs) of 12 academic and non-academic hospitals in the Lombardy region (Northern Italy) were involved in a multi-faceted QIP, which included educational and organizational interventions. Patients with a clinical diagnosis of severe sepsis or septic shock according to the Sepsis-2 criteria were enrolled in two different periods: from May 2011 to November 2011 (before-QIP cohort) and from August 2012 to June 2013 (after-QIP cohort). Measurements and main results The effect of QIP on bundle compliance and hospital mortality was evaluated in a before–after analysis. We enrolled 467 patients in the before-QIP group and 656 in the after-QIP group. At the time of enrollment, septic shock was diagnosed in 50% of patients, similarly between the two periods. In the after-QIP group, we observed increased compliance to the “simplified rapid (1 h) intervention bundle” (the Sepsis 6 bundle – S6) at three time-points evaluated (1 h, 13.7 to 18.7%, p =0.018, 3 h, 37.1 to 48.0%, p =0.013, overall study period, 46.2 to 57.9%, p <0.001). We then analyzed compliance with S6 and hospital mortality in the before- and after-QIP periods, stratifying the two patients’ cohorts by admission characteristics. Adherence to the S6 bundle was increased in patients with severe sepsis in the absence of shock, in patients with serum lactate <4.0 mmol/L, and in patients with hypotension at the time of enrollment, regardless of the type of admission (from EDs or MWs). Subsequently, in an observational analysis, we also investigated the relation between bundle compliance and hospital mortality by logistic regression. In the after-QIP cohort, we observed a lower in-hospital mortality than that observed in the before-QIP cohort. This finding was reported in subgroups where a higher adherence to the S6 bundle in the after-QIP period was found. After adjustment for confounders, the QIP appeared to be independently associated with a significant improvement in hospital mortality. Among the single S6 procedures applied within the first hour of sepsis diagnosis, compliance with blood culture and antibiotic therapy appeared significantly associated with reduced in-hospital mortality. Conclusion A multi-faceted QIP aimed at promoting an early simplified bundle of care for the management of septic patients out of the ICU was associated with improved compliance with sepsis bundles and lower in-hospital mortality.

Background Gastric-cancer is a heterogeneous type of neoplastic disease and it lacks appropriate therapeutic options. There is an urgent need for the development of innovative pharmacological strategies, particularly in consideration of the potential stratified/personalized treatment of this tumor. All-Trans Retinoic-acid (ATRA) is one of the active metabolites of vitamin-A. This natural compound is the first example of clinically approved cyto-differentiating agent, being used in the treatment of acute promyelocytic leukemia. ATRA may have significant therapeutic potential also in the context of solid tumors, including gastric-cancer. The present study provides pre-clinical evidence supporting the use of ATRA in the treatment of gastric-cancer using high-throughput approaches. Methods We evaluated the anti-proliferative action of ATRA in 27 gastric-cancer cell-lines and tissue-slice cultures from 13 gastric-cancer patients. We performed RNA-sequencing studies in 13 cell-lines exposed to ATRA. We used these and the gastric-cancer RNA-sequencing data of the TCGA / CCLE datasets to conduct multiple computational analyses. Results Profiling of our large panel of gastric-cancer cell-lines for their quantitative response to the anti-proliferative effects of ATRA indicate that approximately half of the cell-lines are characterized by sensitivity to the retinoid. The constitutive transcriptomic profiles of these cell-lines permitted the construction of a model consisting of 42 genes, whose expression correlates with ATRA -sensitivity. The model predicts that 45% of the TCGA gastric-cancers are sensitive to ATRA. RNA-sequencing studies performed in retinoid-treated gastric-cancer cell-lines provide insights into the gene-networks underlying ATRA anti-tumor activity. In addition, our data demonstrate that ATRA exerts significant immune-modulatory effects, which seem to be largely controlled by IRF1 up-regulation. Finally, we provide evidence of a feed-back loop between IRF1 and DHRS3 , another gene which is up-regulated by ATRA. Conclusions ATRA is endowed with significant therapeutic potential in the stratified/personalized treatment gastric-cancer. Our data represent the fundaments for the design of clinical trials focusing on the use of ATRA in the personalized treatment of this heterogeneous tumor. Our gene-expression model will permit the development of a predictive tool for the selection of ATRA-sensitive gastric-cancer patients. The immune-regulatory responses activated by ATRA suggest that the retinoid and immune-checkpoint inhibitors constitute rational combinations for the management of gastric-cancer.

Early identification of sepsis is particularly important in the emergency department (ED). However, data on the diagnosis of sepsis in the ED are scanty, especially within the Italian context. To quantify sepsis incidence and recognition in the ED from Lombardy, Italy, we used EUOL data from the Regional Emergency Agency for the years 2017–2022. Sepsis was identified based on the ED discharge diagnosis; recognized sepsis cases were those assigned to a high-priority code at triage, while unrecognized ones were those assigned to a low priority code. Odds ratios (ORs) for sepsis recognition according to various patient characteristics were estimated using multivariable mixed-effects logistic regression models. The rate of sepsis diagnosis in ED was 1.9 per 1000 (6626 patients) in 2017 and increased to 3.4 per 1000 in 2022 (11,508 patients). In 2022, 67% of sepsis cases were correctly identified. Death in the ED was more frequent in patients with recognized sepsis (10.4%) than in those with unrecognized sepsis (2.3%). The probability of sepsis being recognized at ED admission was higher in men (multivariable OR: 1.06), in individuals with advanced age (OR: 1.71 for age ≥ 90 years vs < 60), and in those with access to the second (OR: 1.48) and third ED level (OR: 1.87). Conversely, it was lower in patients arriving at the ED through autonomous transportation (OR: 0.36). This large real-world analysis indicates an increase in sepsis cases referred to the ED in recent years. About one-third of sepsis cases are not correctly identified at triage, although more severe cases appear to be promptly recognized.

Rasmussen's encephalitis (RE) is a rare chronic neurological disorder, characterized by unilateral inflammation of the cerebral cortex, refractory focal epilepsy or epilepsia partialis continua, hemiparesis, and progressive cognitive decline. Interleukin-1 (IL-1) plays an important role in neuroinflammation as a key element in the activation of the inflammatory IL-1β-IL-1 receptor type 1 (IL-1R1) axis. Anakinra, an IL-1 inhibitor, is successfully used in patients with new onset refractory status epilepticus and febrile infection-related epilepsy syndrome. We present 38-year-old male with RE having right-sided hemiparesis and continuous spasms being unresponsive to immune modulatory therapies like pulse steroid, intravenous immunoglobulin and anti-seizure drugs. After treatment with anakinra for three weeks, the continuous spasms almost completely subsided, and his muscle strength returned to normal. Anakinra may be considered as a treatment option in patients with RE and refractory seizures.