Safety and usability of the MAK exoskeleton in patients with stroke.

BACKGROUND AND PURPOSE: Stroke is one of the leading causes of disability in adults worldwide, and one of the main objectives in the rehabilitation of these patients is to recover the gait. New technologies have emerged to cope with this issue, complementing conventional therapy with the use of devices such as exoskeletons. The Marsi Active Knee (MAK) exoskeleton (Marsi Bionics SL, Madrid, Spain) has already been tested, but an updated version was improved to allow the patients to perform functional exercises. The aim of this study was to assess the safety and usability of the MAK in the stroke population as well as its potential clinical effects. METHODS: A single-group open label intervention trial was conducted. The device was used twice a week for 5 weeks during 1 h per visit. During the visits, sit-to-stand transitions, walking, stair climbing, trunk rotations, and weight-transfer exercises were performed using the device. Adverse events were collected from participants and therapists to assess safety. The Quebec User Evaluation of the Satisfaction with assistive Technology (QUEST 2.0) was used by both therapists and participants to assess usability. To evaluate its clinical effects, active range of motion (ROM) and muscle strength were assessed in the lower limb. RESULTS: Six participants with stroke were recruited. The device was shown to be safe since no serious adverse events were reported neither by patients nor by therapists. Every proposed exercise was performed. Regarding clinical effects, overall muscle strength showed an increase after the treatment, although ROM measurements did not show any difference. DISCUSSION: Our results suggest that the MAK device is safe for stroke patients. Nevertheless, further changes to enhance usability are recommended, such as an improvement of the attachment system and an adaptation for the drop foot. Beneficial effects regarding increases in muscle strength were obtained. Further trials with a larger sample size, longer intervention periods, and a control group are needed to verify these results. Also, future research should focus on the usability of the MAK as an assistive technology.

Impact of Compensating Curves on Mastication of Complete Denture Wearers: A Randomised Triple-Blind Clinical Trial.

INTRODUCTION: The application of occlusal concepts in prosthodontics is still under debate.This study assessed the impact of compensating curves on the comminution of complete denture wearers. METHODS: Seven edentulous subjects, aged 64.6 ± 2.0 years, were rehabilitated with new muco-supported complete dentures and tested in two occlusal plane settings: with and without compensating curves. A randomised triple-blind clinical trial was conducted, considering one-week and one-month as adaptation periods for dentures. After each trial, the subjects were crossed over to their respective groups. One-week was also chosen as the washout period, and after that, the subjects were re-examined. The masticatory performance and swallowing threshold were determined while chewing Optocal test food. The multiple sieve method was used for fractionation and granulometry. RESULTS: During the masticatory performance and swallowing threshold estimates, no differences were found between the median particle sizes obtained with the both occlusal plane conditions (P ⟩ 0.05). However, the swallowing threshold improved after one month, resulting in smaller particle sizes. Moreover, the chewing rates for the both test foods were also increased (P ⟨ 0.05). CONCLUSIONS: These findings suggest that the compensating curves did not have an impact on the masticatory function of subjects wearing complete dentures.

Occlusal Loading Effect on Stress Distribution of Endodontically Treated Teeth: Finite Element Analysis Study.

AIM: Evaluate the influence of occlusal loading on the stress distribution of endodontically treated teeth after root canal preparation with different file's sizes and tapers by means of finite element analysis. METHODOLOGY: Seven three-dimensional models of a single-rooted, single-canal lower second premolar were established, one healthy control and six endodontically treated and restored models. The shape of root canal preparations followed file configurations 30/.05, 30/.09, 35/.04, 35/.06, 40/.04, and 40/.06. Von- Mises equivalent stresses were calculated by applying 30 N, 90 N and 270 N loads to the buccal cusp tip, each one at 90º, 45º and 20º angles from the occlusal plane simulating occlusion, dental interference and laterality, respectively. RESULTS: 45º loading was more prone to formation of higher stress values. The simulation of occlusion and laterality resulted in maximum stress areas located at the inner side of the root curvature, while under occlusal interference they were on the lingual surface over the tooth's long axis. CONCLUSIONS: The angulation of occlusal loading and magnitude were determinants for stress distribution on dental structure. Both variations of size and taper were not determinants for the increase in the maximum stress areas.

Microhemorragias cerebrales. Utilidad de las secuencias de susceptibilidad magnética (SWI) / Cerebral microbleeds. Utility of SWI sequences

Objetivo: Definir el concepto de microhemorragia cerebral y revisar las secuencias de resonancia magnética (RM) utilizadas para su valoración. Revisar cuáles son las patologías que presentan microhemorragias y que pueden beneficiarse del uso de secuencias de susceptibilidad magnética (SWI). Conclusión: Las SWI son útiles en la detección y caracterización de microhemorragias, venas y otras fuentes de susceptibilidad. La secuencia SWI mejora la sensibilidad diagnóstica con respecto a las secuencias convencionales potenciadas en T2* (eco de gradiente T2* [2D-GRE]). Las microhemorragias cerebrales pueden asociarse a diversas enfermedades, aparecer en contextos clínicos menos conocidos o servir como biomarcador tumoral en gliomas (ITTS) y como marcador de actividad inflamatoria en las placas de esclerosis múltiple (EM).(AU)

Objectives: Define the concept of cerebral microbleeds (CMB) and describe the most useful MRI sequences for detecting this finding. Review the entities that most frequently present with CMB and that may benefit from the use of susceptibility-weighted imaging (SWI) sequences. Conclusions: SWI is a useful MRI sequence for the detection and characterization of microhemorrhages, venous structures and other sources of susceptibility in imaging. SWI is particularly sensitive to local magnetic field inhomogeneities generated by certain substances and is superior to T2* GRE sequences for this assessment. CMB may be seen in different neurologic conditions, in certain infrequent clinical contexts and have a key role as a biomarker status in gliomas (ITTS) and as a marker of inflammatory activity in multiple sclerosis.(AU)

Cerebral microbleeds. Utility of SWI sequences.

OBJECTIVES: Define the concept of cerebral microbleeds (CMBs) and describe the most useful MRI sequences for detecting this finding. Review the entities that most frequently present with CMBs and that may benefit from the use of susceptibility-weighted imaging (SWI) sequences. CONCLUSIONS: SWI is a useful MRI sequence for the detection and characterization of microhemorrhages, venous structures and other sources of susceptibility in imaging. SWI is particularly sensitive to local magnetic field inhomogeneities generated by certain substances and is superior to T2* GRE sequences for this assessment. CMBs may be seen in different neurologic conditions, in certain infrequent clinical contexts and have a key role as a biomarker status in gliomas (ITTS) and as a marker of inflammatory activity in multiple sclerosis.

Analysis of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with monogenic PRKN and LRRK2 forms of Parkinson's disease.

INTRODUCTION: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is the most common surgical treatment for Parkinson's disease (PD). Patient selection and genetic background can modify the response to this treatment. The objective of this study was to compare both clinical and pharmacologic response of STN-DBS between patients with monogenic forms of PD and non-mutation carriers with idiopathic PD. METHODS: A retrospective analysis among 23 carriers of genetic mutations (8 PRKN and 15 LRRK2) and 74 patients with idiopathic PD was performed. The study included comparisons of Unified Parkinson's Disease Rating Scale (UPDRS) II and III scores, Schwab and England (S&E) scale values, Hoehn & Yahr (H&Y) stage scores, and equivalent doses of levodopa before and after the surgery (at 6 and 12 months) between both groups. RESULTS: The mean age at the time in which STN-DBS was performed was 59.5 ± 8.6. Linear mixed models showed the absence of statistically significant differences between mutation and non-mutation carriers regarding levodopa doses (p = 0.576), UPDRS II (p = 0.956) and III (p = 0.512) scores, and S&E scale scores (0.758). The only difference between the two groups was observed with respect to H&Y stage in OFF medication/ON stimulation status being lower in genetic PD at 6 months after surgery (p = 0.030). CONCLUSION: Clinical and pharmacological benefit of bilateral STN-DBS is similar in PRKN and LRRK2 mutation carriers and patients with idiopathic PD.

Order-disorder phase transition and molecular dynamics in the hybrid perovskite [(CH3)3NH][Mn(N3)3].

We present a temperature-dependent Raman scattering study of a [(CH3)3NH][Mn(N3)3] hybrid organic-inorganic azide-perovskite, in which we have analysed in detail the wavenumber and full width at half-maximum (FWHM) of lattice modes and internal modes of the NC3 skeleton, N3- and CH3 molecular groups. In general, the modes exhibited unusual behaviour during the phase transitions, including discontinuity in the phonon wavenumber, bandwidth, and unconventional shifts upon temperature variation. Spectral features on heating reveal the absence of significant distortions in the NC3 skeleton and a relatively restricted order-disorder process of the TrMA+ cations. On the other hand, linewidth anomalies of the δNC3 and νasNC3 modes have been attributed to the molecular dynamics of encapsulated cations. The unconventional blue shift of the symmetric stretching modes of azide ligands indicates the weakening of the intermolecular interactions between the TrMA+ cations and azido-bridges, and the strengthening of the intramolecular bonds. Additionally, we have used differential scanning calorimetry to confirm the subtle monoclinic to monoclinic (P21/c â†’ C2/c) phase transition at around 330 K; and the phase transition to trigonal structure (R3¯m) above 359 K, whose associated entropy variation turns to be |ΔS| ∼ 22.3 J·kg-1 K-1 and displays a barocaloric (BC) tunability |δTt/δP| ∼ 3.17 K kbar-1, according to our estimations using the Clausius-Clapeyron method. Although the obtained values of entropy change and BC tunability are very close to those reported on formate-perovskites and other important caloric materials, those parameters are much lower than the giant entropy change of ∼80 Jkg-1 K-1 and large BC tunability ∼12 K kbar-1 observed for the analogue azide-perovskite [(CH3)4N][Mn(N3)]3 (TMAMnN3). Very interestingly, our combined study shed light to understand such different behaviour, as they reveal that the hydrogen bonds created between the TrMA+ cations and the framework prevent an extensive order-disorder process that is needed to obtain large entropy changes and large BC coefficients as it occurs in the case of related azide-perovskites with no H-bonds between the A cations (for example TMA) and the framework.

Rol de enfermería en el área COVID en un hospital pediátrico de alta complejidad / The role of nurses in the COVID area in a pediatric tertiary-care hospital

Introducción: la pandemia por SARS-CoV-2 planteó un desafío para todo el equipo de salud. Fue necesario analizar y pensar en este contexto el rol de enfermería en la atención y cuidados del paciente y su familia. Los procesos asistenciales debieron adaptarse a nuevas y diversas situaciones que generaron la atención de pacientes en su mayoría con comorbilidades asociadas. El objetivo del trabajo fue describir el rol de enfermería y la implementación de diversos protocolos y procesos de atención de pacientes en salas de internación pediátrica del área COVID de un hospital de alta complejidad. Material y métodos: se realizó un estudio retrospectivo y descriptivo sobre el personal de enfermería que participó en la atención de casos sospechosos o confirmados de COVID-19 durante la pandemia y los protocolos implementados para los cuidados de enfermería. Resultados: solo el 52.5% (n 79) del personal tenía experiencia mayor a tres años, el 75% (n: 113) pertenecían al género femenino, el 47% (n: 71) eran licenciados en enfermería. Conclusiones: Los profesionales enfermeros han logrado mediante sus fortalezas disciplinares dar respuesta a las necesidades del paciente pediátrico y su familia frente a la crisis sanitaria. Las competencias desarrolladas en la administración de los recursos disponibles, la adaptación, flexibilidad a los procesos y líneas estratégicas en tiempo real, posicionan al enfermero como un valor fundamental en el cuidado asistencial (AU)

Introduction: The SARS CoV-2 pandemic posed a challenge for the entire healthcare team. It was necessary to analyze and reflect on the role of nursing in the care of patients and their families in this context. Care processes had to be adapted to new and diverse situations that were generated by the care for patients who usually had associated comorbidities. The aim of the study was to describe the nursing role and the implementation of different protocols and processes for patient care in pediatric inpatient wards in the COVID area of a tertiary-care hospital. Material and methods: a retrospective descriptive study was conducted in the nursing personnel involved in the care of suspected or confirmed cases of COVID-19 during the pandemic and the protocols implemented for nursing care. Results: only 52.5% (n: 79) of the personnel had more than three years of experience, 75% (n: 113) were female, and 47% (n: 71) had a nursing degree. Conclusions: Through their disciplinary strengths, nursing professionals have been able to respond to the needs of pediatric patients and their families in the face of the health crisis. The skills developed in the management of available resources, adaptation, and flexibility to processes and real-time strategies, have positioned nurses as a fundamental factor in healthcare (AU)

Effects of ATLAS 2030 gait exoskeleton on strength and range of motion in children with spinal muscular atrophy II: a case series.

BACKGROUND: Children with spinal muscular atrophy (SMA) present muscle weakness and atrophy that results in a number of complications affecting their mobility, hindering their independence and the development of activities of daily living. Walking has well-recognized physiological and functional benefits. The ATLAS 2030 exoskeleton is a paediatric device that allows gait rehabilitation in children with either neurological or neuromuscular pathologies with gait disorders. The purpose is to assess the effects in range of motion (ROM) and maximal isometric strength in hips, knees and ankles of children with SMA type II after the use of ATLAS 2030 exoskeleton. METHODS: Three children (mean age 5.7 ± 0.6) received nine sessions bi-weekly of 60 min with ATLAS 2030. ROM was assessed by goniometry and strength by hand-held dynamometer. All modes of use of the exoskeleton were tested: stand up and sit down, forward and backward walking, and gait in automatic and active-assisted modes. In addition, different activities were performed during the gait session. A descriptive analysis of all variables was carried out. RESULTS: The average time of use was 53.5 ± 12.0 min in all sessions, and all participants were able to carry out all the proposed activities as well as to complete the study. Regarding isometric strength, all the measurements increased compared to the initial state, obtaining the greatest improvements for the hip flexors (60.2%) and extensors muscles (48.0%). The ROM increased 12.6% in hip and 34.1% in the ankle after the study, while knee ROM remained stable after the study. CONCLUSION: Improvements were showed in ROM and maximal isometric strength in hips, knees and ankles after using ATLAS 2030 paediatric gait exoskeleton in all three children. This research could serve as a preliminary support for future clinical integration of ATLAS 2030 as a part of a long-term rehabilitation of children with SMA. TRIAL REGISTRATION: The approval was obtained (reference 47/370329.9/19) by Comunidad de Madrid Regional Research Ethics Committee with Medical Products and the clinical trial has been registered on Clinical Trials.gov: NCT04837157.

Risky business in Georgia's wild birds: contact rates between wild birds and backyard chickens is influenced by supplemental feed.

Backyard chickens are increasingly popular, and their husbandry varies widely. How backyard chickens are housed may influence the accessibility of chicken feed and water to wild birds, and thus, the contact rates between both groups. Increased contacts have implications for pathogen transmission; for instance, Newcastle disease virus or avian influenza virus may be transmitted to and from backyard chickens from contaminated water or feed. Given this potentially increased pathogen risk to wild birds and backyard chickens, we examined which wild bird species are likely to encounter backyard chickens and their resources. We performed a supplemental feeding experiment followed by observations at three sites associated with backyard chickens in North Georgia, USA. At each site, we identified the species of wild birds that: (a) shared habitat with the chickens, (b) had a higher frequency of detection relative to other species and (c) encountered the coops. We identified 14 wild bird species that entered the coops to consume supplemental feed and were considered high-risk for pathogen transmission. Our results provide evidence that contact between wild birds and backyard chickens is frequent and more common than previously believed, which has crucial epidemiological implications for wildlife managers and backyard chicken owners.

Improving the DNA Barcode Library of Mosquito Species With New Identifications and Discoveries in North-Central Argentina.

The family Culicidae is represented by 244 species in Argentina, many of them with epidemiological importance. DNA barcodes are effective tools for identifying mosquito species, for knowing genetic variability, and for establishing phylogenetic relationships. This work aims to explore mosquito diversity employing different species delimitation approaches and to establish formally a DNA barcode library for the Argentinian mosquito fauna. Barcode fragments of 80 specimens of Argentinian mosquitoes of 28 species of the genera Aedeomyia Theobald (Diptera: Culicidae), Anopheles Meigen (Diptera: Culicidae), Coquillettidia Dyar (Diptera: Culicidae), Culex L. (Diptera: Culicidae), Haemagogus Williston (Diptera: Culicidae), Mansonia Blanchard (Diptera: Culicidae), Nyssorhynchus Blanchard (Diptera: Culicidae), Ochlerotatus Lynch-Arribálzaga (Diptera: Culicidae), Psorophora Robinneau-Desvoidy (Diptera: Culicidae) and Uranotaenia Lynch-Arribálzaga (Diptera: Culicidae) were sequenced. Another 82 sequences were obtained from public databases to establish the phylogenetic relationships using Maximum Likelihood and Bayesian Inference, and the species boundaries based on three approaches (ABGD, GMYC, and mPTP). Sixteen of the 28 species sequenced were recovered as monophyletic, of which 12 were also recognized as molecular operational taxonomic units according to the three methodologies. The disparity between morphology and barcode-based identifications could be explained by synonymy, species complexes occurrence, hybridization, incomplete lineage sorting, or the effect of the geographical scale of sampling. Twenty of the 28 sequenced species are new barcodes for Argentina and 11 are the first for science. This increases from 31 to 52 (12.7 to 21.31%) and from six to 10 (28.57 to 47.62%) the number of species and genera, respectively, with barcode sequences in Argentina. New species records are provided.

Evaluation of point-of-care algorithms to detect diabetes during screening for latent TB infection.

BACKGROUND: Individuals with both diabetes mellitus (DM) and TB infection are at higher risk of progressing to TB disease.OBJECTIVE: To determine DM prevalence in populations at high risk for latent TB infection (LTBI) and to identify the most accurate point-of-care (POC) method for DM screening.METHODS: Adults aged ≥25 years were recruited at health department clinics in Hawaii and Arizona, USA, and screened for LTBI and DM. Screening methods for DM included self-report, random blood glucose (RBG), and POC hemoglobin A1c (HbA1c). Using HbA1c ≥6.5% or self-reported history as the gold standard for DM, we compared test strategies to determine the most accurate method while keeping test costs low.RESULTS: Of 472 participants, 13% had DM and half were unaware of their diagnosis. Limiting HbA1c testing to ages ≥30 years with a RBG level of 120-180 mg/dL helped identify most participants with DM (sensitivity 85%, specificity 99%) at an average test cost of US$2.56 per person compared to US$9.56 per person using HbA1c for all patients.CONCLUSION: Self-report was insufficient to determine DM status because many participants were previously undiagnosed. Using a combination of POC RBG and HbA1c provided an inexpensive option to assess DM status in persons at high risk for LTBI.

Laboratory Resolved Structure of Supercritical Perpendicular Shocks.

Supermagnetosonic perpendicular flows are magnetically driven by a large radius theta-pinch experiment. Fine spatial resolution and macroscopic coverage allow the full structure of the plasma-piston coupling to be resolved in laboratory experiment for the first time. A moving ambipolar potential is observed to reflect unmagnetized ions to twice the piston speed. Magnetized electrons balance the radial potential via Hall currents and generate signature quadrupolar magnetic fields. Electron heating in the reflected ion foot is adiabatic.

Change in opioid and analgesic use for headaches after aneurysmal subarachnoid hemorrhage over time.

BACKGROUND: Severe headache, a hallmark of aneurysmal subarachnoid hemorrhage (aSAH), affects up to 90% of patients during hospitalization. Opioids remain the guideline recommended mainstay of acute therapy despite their significant side effects and potential for tolerance and addiction. We evaluated time trends in opioid prescriptions, hypothesizing a decline with increasing recognition of the opioid crisis. METHODS: We performed a retrospective review of patients with aSAH admitted to a single tertiary care center between 2012 and 2019 and included patients with Hunt-Hess-Grade≤3 who were able to verbalize pain scores. Collected variables included mean and maximum daily headache scores, aneurysm treatment modality, and daily analgesic medication doses. RESULTS: Of 340 patients with aSAH, 114 (86 from 2012-2016 and 28 from 2017-2019) were included. Of the included patients, 86/114 (75.4%) were female. Patients in the 2012-2016 had a median age of 55 compared to 63 in the 2017-2019 group (P=0.02). Otherwise, there was no significant difference in demographic data including time in hospital, treatment option utilized, or aneurysm characteristics. Maximal daily headache score ranged from 6 to 8 for 2012-2016 and 5 to 8 for 2017-2019 cohorts. Average oral morphine equivalents (in mg) administered during hospitalization were similar between groups (2012-2016: 251±345 95% CI [178,323]; 2017-2019: 207±237 95% CI [119,295]; P=0.319). When prescribed, doses of opioids provided at discharge were less in the more recent group (2012-2016: 84.4±78.9 95% CI [57.5, 111]; 2017-2019: 38.1±20.2 95% CI [33.7, 42.5]; P=0.004) CONCLUSION: Despite recognition of important drawbacks of opioid use for headache control, and efforts to reduce opioid use during hospitalization, we found that utilization during hospitalization for SAH did not decrease over time. Maximal headache scores remained similar in the studied time periods, indicative of insufficient pain relief. This points out a pressing need to further investigate alternative opioid and narcotic sparing strategies for patients with SAH.

Edema cerebral idiopático de inicio tardío asociado a estimulación cerebral profunda / Idiopathic delayed-onset edema associated with deep brain stimulation

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HAE-AS: A Specific Disease Activity Scale for Hereditary Angioedema With C1-Inhibitor Deficiency.

BACKGROUND AND OBJECTIVE: The activity of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) varies between patients and within individual patients. Objective: This study aims to develop a disease activity scale for C1-INH-HAE (HAE-AS) with sound measurement properties. METHODS: Eleven countries participated in a prospective multicenter cohort study. A clinical questionnaire was self-completed by 290 adult patients with C1-INH-HAE. Patients also completed 2 quality of life scales, the SF-36v2 and the HAE-QoL. Rasch analysis and classic psychometric methods were used to preselect a series of clinical items: number of attacks by location and number of treated attacks, emergency room visits, psychological/psychiatric treatment, missed school/workdays in the previous 6 months; general health; and impairment in everyday work/activities due to pain. RESULTS: The mean (SD) age was 41.5 (14.7; range, 18-84) years, and 69% were females. The final 12-item Rasch model showed that the HAE-AS had satisfactory reliability (person separation index, 0.748), local item independence, unidimensionality, and no item bias by age or sex. The HAE-AS provided scores in a linear measure, with a mean of 10.66 (3.92; range, 0-30). Further analysis with classic psychometric methods indicated that the HAE-AS linear measure presented moderate-to-high convergent validity with quality of life scales (SF-36v2: physical component, r=-0.33; mental component, 0.555; HAE-QoL, -0.61), and good discriminative validity by age, sex, and disease severity (P<.05). CONCLUSIONS: The HAE-AS is a short, valid, reliable, and psychometrically sound measure of the activity of C1-INH-HAE that could prove useful for research studies.

Immune Checkpoint Inhibitor with or without Radiotherapy in Melanoma Patients with Brain Metastases: A Systematic Review and Meta-Analysis

Objective@#Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. @*Materials and Methods@#A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. @*Results@#Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44–61%); DCR, 57% (95% CI, 49–66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31–54%]; DCR, 85% [95% CI, 63–95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11–20%]; DCR, 26% [95% CI, 21– 32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52–67%) compared to ICI monotherapy (11%; 95% CI, 8–17%) and ICI combined with radiotherapy (4%; 95% CI, 1–19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). @*Conclusion@#ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.

Immune Checkpoint Inhibitor with or without Radiotherapy in Melanoma Patients with Brain Metastases: A Systematic Review and Meta-Analysis

Objective@#Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. @*Materials and Methods@#A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. @*Results@#Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44–61%); DCR, 57% (95% CI, 49–66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31–54%]; DCR, 85% [95% CI, 63–95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11–20%]; DCR, 26% [95% CI, 21– 32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52–67%) compared to ICI monotherapy (11%; 95% CI, 8–17%) and ICI combined with radiotherapy (4%; 95% CI, 1–19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). @*Conclusion@#ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.