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Metal-halide perovskites are recognized as cutting-edge solar energy technology, boasting remarkable absorption capabilities, minimal environmental impact, and cost-effectiveness. This study delves into the structural stability, mechanical stability, and optoelectronic properties of lead-free halide perovskites, specifically XMgI3 (X = Li/Na), by utilizing the CASTEP and WIEN2k software along with the GGA-PBE and Tran-Blaha modified Becke-Johnson (TB-mBJ) exchange-correlation functions to compare their electronic properties. The structural and mechanical stabilities were confirmed by assessing their tolerance factor and formation energy and by evaluating their elastic constants, respectively. Using the TB-mBJ exchange-correlation potential function, the calculated indirect band gap values for LiMgI3 and NaMgI3 were 2.474 and 2.556 eV, respectively. These band gaps are suitable for solar energy harvesting due to their broad optical absorption ranging from infrared to visible light. The partial density of states and the total density of states were determined to investigate the contribution of individual atoms. Consequently, this study can guide researchers focusing on the experimental synthesis of these materials at the laboratory scale for in-depth exploration, particularly in applications such as photovoltaics and various optoelectronic devices.
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Metal halide perovskites are crystalline materials with a sharp increase in popularity and rapidly becoming a major contender for optoelectronic device applications. In this work, we provide the optoelectronic features of a possible novel candidate, ZSnCl3 (Z = Na/K) Sn-based on a detailed numerical simulation. The output of the current computations is compared to the results that are currently available, and a respectable agreement is noted. The studied compounds were cubic in nature and structurally stabe. The mechanical properties reflect the mechanical stability and ductility of the proposed materials. The Sn-based single perovskite compounds proposed in this study are mechanically stable and ductile. The narrow direct band gap for NaSnCl3 and KSnCl3 are 1.36 eV and 1.47 eV, respectively, using the HSE06 hybrid function with the Boltztrp2 integrated in Quantum ESPRESSO (QE) software. The effective use of these compounds in perovskite solar cells and other optoelectronic applications was confirmed by optical absorption spectral measurements conducted in the photon energy range of 0-20 eV.
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Background: Multiple Sclerosis (MS) is a common neurological disease among white populations of European origin. Frequencies among Latin Americans continue to be studied, however, epidemiologic, and clinical characterization studies lack from Central American and Caribbean countries. Ethnicity in these countries is uniformly similar with a prevalent Mestizo population. Methods and results: Data from January 2014 to December 2019 from Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama, Dominican Republic, and Aruba on demographic, clinical, MRI and phenotypic traits were determined in coordinated studies: ENHANCE, a population-based, retrospective, observational study on incidence and clinical characteristics, and from the subgroup with MS national registries (Aruba, Dominican Republic, Honduras, and Panama), data on prevalence, phenotypes and demographics. Expanded Disability Status Scale (EDSS), and therapeutic schemes were included. ENHANCE data from 758 patients disclosed 79.8% of Mestizo ethnicity; 72.4% female; median age at onset 31.0 years and 33.2 at diagnosis. The highest incidence rate was from Aruba, 2.3-3.5 × 100,000 inhabitants, and the lowest, 0.07-0.15 × 100,000, from Honduras. Crude prevalence rates per 100,000 inhabitants fluctuated from 27.3 (Aruba) to 1.0 (Honduras). Relapsing MS accounted for 87.4% of cases; EDSS <3.0 determined in 66.6% (mean disease duration: 9.1 years, SD ± 5.0); CSF oligoclonal bands 85.7%, and 87% of subjects hydroxyvitamin D deficient. Common initial therapies were interferon and fingolimod. Switching from interferon to fingolimod was the most common escalation step. The COVID-19 pandemic affected follow-up aspects of these studies. Conclusion: This is the first study providing data on frequencies and clinical characteristics from 8 countries from the Central American and Caribbean region, addressing MS as an emergent epidemiologic disorder. More studies from these areas are encouraged.
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The quest for efficient thermoelectric materials has intensified with the advent of novel Janus monolayers exhibiting exceptional thermoelectric parameters. In this work, we comprehensively investigate the structural, electronic, transport, phonon, and thermoelectric properties of novel Janus γ -Pb 2 XY (X=S, Se; Y=Se, Te; X ≠ Y) monolayers using density functional theory combined with the Boltzmann transport equation. Our findings unveil the energetic, dynamic, thermal, and mechanical stability of these monolayers, along with their remarkable thermoelectric performance. Remarkably, the p-type γ -Pb 2 SeTe monolayer exhibits an outstanding figure of merit (ZT) of 6.88 at 800 K, attributed to its intrinsically low lattice thermal conductivity of 0.162 Wm - 1 K - 1 arising from strong phonon scattering, low group velocity, low phonon relaxation time, and a high Grüneisen parameter. Furthermore, these monolayers demonstrate high Seebeck coefficients and electrical conductivities, making them promising for efficient charge transport and thermoelectric energy conversion. Our results highlight the immense potential of Janus γ -Pb 2 XY monolayers as promising candidates for high-temperature thermoelectric applications and open up exciting avenues for further exploration of these novel two-dimensional materials in energy-related technologies.
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Importance: Postpancreatectomy hemorrhage is an uncommon but highly morbid complication of pancreaticoduodenectomy. Clinical evidence often draws suspicion to the gastroduodenal artery stump, even without a clear source. Objective: To determine the frequency of gastroduodenal artery bleeding compared to other sites and the results of mitigation strategies. Design, Setting, and Participants: This cohort study involved a retrospective analysis of data for consecutive patients who had pancreaticoduodenectomy from 2011 to 2021 at Memorial Sloan Kettering Cancer Center (MSK) and Thomas Jefferson University Hospital (TJUH). Exposures: Demographic, perioperative, and disease-related variables. Main Outcomes and Measures: The incidence, location, treatment, and outcomes of primary (initial) and secondary (recurrent) hemorrhage requiring invasive intervention were analyzed. Imaging studies were re-reviewed by interventional radiologists to confirm sites. Results: Inclusion criteria were met by 3040 patients (n = 1761 MSK, n = 1279 TJUH). Patients from both institutions were similar in age (median [IQR] age at MSK, 67 [59-74] years, and at TJUH, 68 [60-75] years) and sex (at MSK, 814 female [46.5%] and 947 male [53.8%], and at TJUH, 623 [48.7%] and 623 male [51.3%]). Primary hemorrhage occurred in 90 patients (3.0%), of which the gastroduodenal artery was the source in 15 (16.7%), unidentified sites in 24 (26.7%), and non-gastroduodenal artery sites in 51 (56.7%). Secondary hemorrhage occurred in 23 patients; in 4 (17.4%), the gastroduodenal artery was the source. Of all hemorrhage events (n = 117), the gastroduodenal artery was the source in 19 (16.2%, 0.63% incidence in all pancreaticoduodenectomies). Gastroduodenal artery hemorrhage was more often associated with soft gland texture (14 [93.3%] vs 41 [62.1%]; P = .02) and later presentation (median [IQR], 21 [15-26] vs 10 days [5-18]; P = .002). Twenty-three patients underwent empirical gastroduodenal artery embolization or stent placement, 7 (30.4%) of whom subsequently experienced secondary hemorrhage. Twenty percent of all gastroduodenal artery embolizations/stents (8/40 patients), including 13% (3/13 patients) of empirical treatments, were associated with significant morbidity (7 hepatic infarction, 4 biliary stricture), with a 90-day mortality rate of 38.5% (n = 5) for patients with these complications vs 7.8% without (n = 6; P = .008). Ninety-day mortality was 12.2% (n = 11) for patients with hemorrhage (3 patients [20%] with primary gastroduodenal vs 8 [10.7%] for all others; P = .38) compared with 2% (n = 59) for patients without hemorrhage. Conclusions and Relevance: In this study, postpancreatectomy hemorrhage was uncommon and the spectrum was broad, with the gastroduodenal artery responsible for a minority of bleeding events. Empirical gastroduodenal artery embolization/stent without obvious sequelae of recent hemorrhage was associated with significant morbidity and rebleeding and should not be routine practice. Successful treatment of postpancreatectomy hemorrhage requires careful assessment of all potential sources, even after gastroduodenal artery mitigation.
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Pancreaticoduodenectomia , Hemorragia Pós-Operatória , Humanos , Pancreaticoduodenectomia/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/epidemiologia , Duodeno/irrigação sanguínea , IncidênciaRESUMO
INTRODUCTION: Infratentorial glioblastoma(itGBM) is a rare and rapidly progressive form of GBM with poor prognosis. However, no studies have adequately examined itGBM outcomes in elderly patients (>65 years). Here, we used a national database to fill this knowledge gap. METHODS: SEER 18 registries were utilized to identify adult itGBM patients diagnosed between 2000-2016. itGBM cases were further divided into cerebellar and brainstem GBM as cGBM and bGBM, respectively. Kaplan-Meier analysis and Cox hazards proportional regression models were performed to assess factors associated with overall survival (OS). RESULTS: Among 137 (33%) elderly patients from the study cohort (N = 420), median age was 74 years, 38% were female, and 85% were white. Median OS in elderly itGBM patients was shorter than younger adults (10 vs. 5-months, p < 0.001). Multivariate analysis by tumor location revealed that older age was associated with poor survival for cGBM, but not for bGBM. Gross-total resection (GTR) was associated with better outcomes for both cGBM and bGBM. Radiotherapy had survival benefits for cGBM; meanwhile, chemotherapy prolonged OS in bGBM. In the elderly, advanced age (80 + years) was associated with poor outcomes, while GTR, CT and RT were all associated with improved survival. CONCLUSIONS: In our study, while elderly patients had worse survival compared to younger adults for both cGBM and bGBM, GTR improved OS in elderly itGBM, with CT and RT exhibiting a location-dependent survival benefit. Thus, elderly itGBM patients should undergo a combination of maximal resection and adjuvant treatment guided by infratentorial tumor location for maximal survival benefit.
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Neoplasias Encefálicas , Glioblastoma , Neoplasias Infratentoriais , Adulto , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Glioblastoma/patologia , Prognóstico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Modelos de Riscos Proporcionais , Estimativa de Kaplan-Meier , Resultado do TratamentoRESUMO
Simulation facilitates learning by imitating real-world systems or processes utilizing educational tools and models. Various fields, including business, aviation, and education use simulation for training. In healthcare, simulation provides trainees opportunities to develop procedural skills in a safe environment, building their understanding through hands-on interactions and experiences rather than passive didactics. Simulation is classified into low, medium, and high fidelity, based on how closely it mimics real-life experience. Its use in education is a valuable adjunct to instructional support and training with multiple potential benefits. Interventional radiology (IR) trainees can build technical and clinical proficiency prior to working directly on a patient. Simulation promotes experiential learning, constructivist learning, and student centeredness, thus giving students control over their learning and knowledge acquisition. More recently, the creative use of remote simulation has augmented traditional virtual didactic lectures, thereby further engaging international learners and enhancing remote collaboration. Despite the challenges to implementation, the addition of simulation in IR education is proving invaluable to supporting trainees and physicians in underserved regions.
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Drug repositioning seeks to leverage existing clinical knowledge to identify alternative clinical settings for approved drugs. However, repositioning efforts fail to demonstrate improved success rates in late-stage clinical trials. Focusing on 11 approved kinase inhibitors that have been evaluated in 139 repositioning hypotheses, we use data mining to characterize the state of clinical repurposing. Then, using a simple experimental correction with human serum proteins in in vitro pharmacodynamic assays, we develop a measurement of a drug's effective exposure. We show that this metric is remarkably predictive of clinical activity for a panel of five kinase inhibitors across 23 drug variant targets in leukemia. We then validate our model's performance in six other kinase inhibitors for two types of solid tumors: non-small cell lung cancer (NSCLC) and gastrointestinal stromal tumors (GISTs). Our approach presents a straightforward strategy to use existing clinical information and experimental systems to decrease the clinical failure rate in drug repurposing studies.
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Carcinoma Pulmonar de Células não Pequenas , Leucemia , Neoplasias Pulmonares , Humanos , Reposicionamento de Medicamentos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
PURPOSE: The population is aging, and age remains an important factor in deciding surgical candidacy for intracranial tumors. The natural history and surgical behavior of meningiomas in octogenarians are not well understood. We evaluated the surgical and functional outcomes, including survival, among octogenarians with intracranial meningiomas in a single institution. METHODS: The Tumor Registry (2004-2021) was used to identify octogenarian patients (ages 80-89) diagnosed with intracranial meningioma. Primary endpoints were 1-year survival and functional outcome measured with mRS postsurgery. Kaplan-Meier, univariable Log-rank tests, and multivariable Cox hazards proportional regression models were used for assessing factors associated with overall survival (OS) in octogenarians with meningiomas who underwent surgery; logistic regression and McNemar's were used to further characterize risk factors affecting functional surgical outcome at 1 year. RESULTS: Thirty octogenarians with intracranial meningioma who underwent surgery were identified. Median age was 82.5 years and 66.6% were female patients. The 1-year median postsurgical survival probability for all octogenarians with meningioma was 86.3% and no intraoperative mortality was observed. Frailty (mFI-5, p = 0.84), tumor grade (p = 0.11), tumor size (p = 0.22), extent of resection (p = 0.35), and Karnofsky scale on admission (p = 0.93) did not significantly affect the survival in octogenarians with meningiomas which were treated surgically. The 1-year postoperative functional status of octogenarian meningioma patients who underwent surgery was significantly improved compared to pre-op mRS (McNemar's chi-squared = 9.6, df = 1, p-value = 0.001946). CONCLUSION: In octogenarians with meningiomas, surgical intervention significantly improves the pre-operative modified Rankin Scale at 1 year postsurgery in this cohort.
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Neoplasias Meníngeas , Meningioma , Idoso de 80 Anos ou mais , Humanos , Feminino , Masculino , Meningioma/patologia , Octogenários , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection induces a spectrum of clinical manifestations that depend on the immune response of the patient, i.e., from an asymptomatic form to an inflammatory response with multiorgan deterioration. In some cases, severe cases of SARS-CoV-2 are characterized by an excessive, persistent release of inflammatory mediators known as a cytokine storm. This phenomenon arises from an ineffective T helper (Th)-1 response, which is unable to control the infection and leads to a reinforcement of innate immunity, causing tissue damage. The evolution of the disease produced by SARS-CoV2, known as COVID-19, has been of interest in several research fields. Asthma patients have been reported to present highly variable outcomes due to the heterogeneity of the disease. For example, the Th2 response in patients with allergic asthma is capable of decreasing Th1 activation in COVID-19, preventing the onset of a cytokine storm; additionally, IL-33 released by damaged epithelium in the context of COVID-19 potentiates either Th1 or T2-high responses, a process that contributes to poor outcomes. IL-13, a T2-high inflammatory cytokine, decreases the expression of angiotensin converting enzyme-2 (ACE2) receptor, hindering SARS-CoV-2 entry; finally, poor outcomes have been observed in COVID-19 patients with severe neutrophilic asthma. In other contexts, the COVID-19 lockdown has had interesting effects on asthma epidemiology. The incidence of asthma in the most populated states in Mexico, including Tamaulipas, which has the highest asthma incidence in the country, showed similar tendencies independent of how strict the lockdown measures were in each state. As described worldwide for various diseases, a decrease in asthma cases was observed during the COVID-19 lockdown. This decrease was associated with a drop in acute respiratory infection cases. The drop in cases of various diseases, such as diabetes, hypertension or depression, observed in 2020 was restored in 2022, but not for asthma and acute respiratory infections. There were slight increases in asthma cases when in-person classes resumed. In conclusion, although many factors were involved in asthma outcomes during the pandemic, it seems that acute respiratory infection is intimately linked to asthma cases. Social distancing during remote learning, particularly school lockdown, appears to be an important cause of the decrease in cases.
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Asma , COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Síndrome da Liberação de Citocina/epidemiologia , RNA Viral , Controle de Doenças Transmissíveis , Asma/epidemiologiaRESUMO
Plant growth-promoting rhizobacteria (PGPR) are members of the plant rhizomicrobiome that enhance plant growth and stress resistance by increasing nutrient availability to the plant, producing phytohormones or other secondary metabolites, stimulating plant defense responses against abiotic stresses and pathogens, or fixing nitrogen. The use of PGPR to increase crop yield with minimal environmental impact is a sustainable and readily applicable replacement for a portion of chemical fertilizer and pesticides required for the growth of high-yielding varieties. Increased plant health and productivity have long been gained by applying PGPR as commercial inoculants to crops, although with uneven results. The establishment of plant-PGPR relationships requires the exchange of chemical signals and nutrients between the partners, and polyamines (PAs) are an important class of compounds that act as physiological effectors and signal molecules in plant-microbe interactions. In this review, we focus on the role of PAs in interactions between PGPR and plants. We describe the basic ecology of PGPR and the production and function of PAs in them and the plants with which they interact. We examine the metabolism and the roles of PAs in PGPR and plants individually and during their interaction with one another. Lastly, we describe some directions for future research.
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BACKGROUND: The re-emergence of Monkeypox (MPX) and its related ophthalmic disease represent a clinical challenge in the initial stages because of the presence of lesions like those caused by varicella zoster, syphilis, and other infections due to other poxviruses. Human Immunodeficiency Virus (HIV) infection and secondary immunodepression raise the risk of severe and prolonged disease. PURPOSE: We present the case of a young immunosuppressed male patient with MPX, who presented with multiple skin lesions, also including risky ophthalmological manifestations due to extensive eyelid involvement. CONCLUSIONS: We describe a novel form of late-onset conjunctivitis and eyelid lesions, without active extraocular disease, highlighting the heterogeneous behavior of the new clinical form of MPX, that exhibits a wide spectrum of lesions in different stages of evolution.
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Infecções por HIV , Mpox , Sífilis , Humanos , Masculino , Mpox/diagnóstico , Mpox/patologia , América Latina , Pele/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Sífilis/patologiaRESUMO
We previously showed that specific polyamines (PAs) present in the extracellular environment markedly affect extracellular polysaccharide (EPS) production, biofilm formation and motility in Sinorhizobium meliloti Rm8530. We hypothesized that extracellular PA signals were sensed and transduced by the NspS and MbaA proteins, respectively, which are homologs of the PA-sensing, c-di-GMP modulating NspS-MbaA proteins described in Vibrio cholerae. Here we show that the decrease in biofilm formation and EPS production in the quorum-sensing (QS)-deficient S. meliloti wild-type strain 1021 in cultures containing putrescine or spermine did not occur in a 1021 nspS mutant (1021 nspS). The transcriptional expression of nspS in strain 1021 was significantly increased in cultures containing either of these polyamines, but not by exogenous cadaverine, 1,3-diaminopropane (DAP), spermidine (Spd) or norspermidine (NSpd). Cell aggregation in liquid cultures did not differ markedly between strain 1021 and 1021 nspS in the presence or absence of PAs. The S. meliloti QS-proficient Rm8530 wild-type and nspS mutant (Rm8530 nspS) produced similar levels of biofilm under control conditions and 3.2- and 2.2-fold more biofilm, respectively, in cultures with NSpd, but these changes did not correlate with EPS production. Cells of Rm8530 nspS aggregated from two- to several-fold more than the wild-type in cultures without PAs or in those containing Spm. NSpd, Spd and DAP differently affected swimming and swarming motility in strains 1021 and Rm8530 and their respective nspS mutants. nspS transcription in strain Rm8530 was greatly reduced by exogenous Spm. Bioinformatic analysis revealed similar secondary structures and functional domains in the MbaA proteins of S. meliloti and V. cholerae, while their NspS proteins differed in some residues implicated in polyamine recognition in the latter species. NspS-MbaA homologs occur in a small subset of soil and aquatic bacterial species that commonly interact with eukaryotes. We speculate that the S. meliloti NspS-MbaA system modulates biofilm formation, EPS production and motility in response to environmental or host plant-produced PAs.
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Poliaminas , Sinorhizobium meliloti , Poliaminas/metabolismo , Sinorhizobium meliloti/genética , Sinorhizobium meliloti/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes , Regulação Bacteriana da Expressão Gênica , Polissacarídeos Bacterianos/metabolismoRESUMO
In the treatment of non-small cell lung cancer (NSCLC), patients harboring exon 20 insertion mutations in the epidermal growth factor receptor (EGFR) gene (EGFR) have few effective therapies because this subset of mutants is generally resistant to most currently approved EGFR inhibitors. This report describes the structure-guided design of a novel series of potent, irreversible inhibitors of EGFR exon 20 insertion mutations, including the V769_D770insASV and D770_N771insSVD mutants. Extensive structure-activity relationship (SAR) studies led to the discovery of mobocertinib (compound 21c), which inhibited growth of Ba/F3 cells expressing the ASV insertion with a half-maximal inhibitory concentration of 11 nM and with selectivity over wild-type EGFR. Daily oral administration of mobocertinib induced tumor regression in a Ba/F3 ASV xenograft mouse model at well-tolerated doses. Mobocertinib was approved in September 2021 for the treatment of adult patients with advanced NSCLC with EGFR exon 20 insertion mutations with progression on or after platinum-based chemotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Camundongos , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutagênese Insercional , Mutação , Receptores ErbB , Éxons , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
BACKGROUND: Venous sinus stenosis (VSS) stenting has emerged as an effective treatment for patients with Idiopathic Intracranial Hypertension (IIH). However, stenting carries risk of in-stent stenosis/thrombosis and cumulative bleeding risk from long-term dual antiplatelet (DAPT) use. Thus, we investigated the potential safety and efficacy of primary balloon angioplasty as an alternative to stenting in IIH. METHODS: A prospectively maintained single-center registry of IIH patients undergoing endovascular procedures was queried. Inclusion criteria included patients with confirmed IIH and angiographically demonstrable VSS who underwent interventions from 2012- 2021. Patients were dichotomized into primary balloon angioplasty (Group A) and primary stenting (Group S), comparing clinical outcomes using bivariate analyses. RESULTS: 62 patients were included with median age of 33 [IQR 26-37], 74% females. Group A (9/62) and Group S (53/62) had similar baseline characteristics. Papilledema improvement was higher in Group S at 6 weeks and 6 months (44 vs. 93, p = 0.002 and 44 vs. 92%, p = 0.004), with similar improvements across all symptoms. Group S had higher mean post-procedure venous pressure gradient change (8 vs. 3 mmHg, p = 0.02) and a lower CSF opening pressure at 6 months (23 vs. 36 cmH2O, p < 0.001). VPS rescue rate was higher in Group A (44 vs. 2%, p = 0.001). There was only one procedural complications; a subdural hematoma in Group A. CONCLUSIONS: Primary VSS balloon angioplasty provides a marginal and short-lived improvement of IIH symptoms compared to stenting. These findings suggest a cautious and limited role for short-term rescue angioplasty in poor shunting and stenting candidates with refractory IIH.
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Angioplastia com Balão , Hipertensão Intracraniana , Pseudotumor Cerebral , Feminino , Humanos , Masculino , Pseudotumor Cerebral/diagnóstico por imagem , Pseudotumor Cerebral/cirurgia , Constrição Patológica/terapia , Constrição Patológica/complicações , Cavidades Cranianas/cirurgia , Resultado do Tratamento , Stents/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: Acute COVID-19 infection has been associated with neurological involvement. We report a case series of newly diagnosed patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) developed in a short period of time after acute COVID-19 infection. METHODS: New MS patients developing initial symptoms shortly after an acute COVID-19 infection were diagnosed based on the 2017 McDonald Criteria [Garcia-Ramos et al. in Cells, 2021]. The patients diagnosed with NMOSD met the 2015 International Panel criteria for the diagnosis of NMOSD (IPDN) [Thompson et al. in Lancet Neurol 17:162-173, 2018]. RESULTS FROM THE MS PATIENT GROUP: Ten patients were included who had developed initial MS symptoms after COVID-19 infection. Gender distribution was equal (50% male). The mean age was 28 (range 17-39) years. Average time to neurological presentation was between 2 and 6 weeks following acute COVID-19 infection. Partial transverse myelitis was the initial presentation in 40% of the cases, and 60% of patients had spinal cord lesions present at the moment of diagnosis. All patients showed enhancing lesions on brain magnetic resonance imaging (MRI). The presence of cerebrospinal fluid (CSF) oligoclonal bands was found in all six tested cases. The majority of patients (80%) were unvaccinated for COVID-19. The two vaccinated patients had received two doses of the monovalent COVID-19 messenger ribonucleic acid (mRNA) (Pfizer Biotech) vaccine and no booster, a year prior to contracting COVID-19. RESULTS FROM THE NMOSD GROUP: Two patients with NMOSD were included. Positive aquoporin-4 protein antibody (AQP-4 Ab) was detected in serum in both cases [one Enzyme Linked immunosorbent assay (ELISA) and one cell based]. Both patients had mild COVID-19 infection prior to presentation, initial neurologic symptoms presented between 3 and 6 weeks after COVID-19 infection. Neither patients were vaccinated. Both responded partially to steroids, one developed a relapse 40 days after diagnosis. CONCLUSION: COVID-19 infection has been linked to several neurological and immune-driven conditions. This study suggests that in susceptible individuals, acute COVID-19 infection may act as a trigger for developing MS and NMOSD.
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Identifying patients with hormone receptor-positive (HR+) early invasive breast cancer (EIBC) who benefit from adjuvant chemotherapy has improved with molecular signature tests. However, due to high cost and limited availability, alternative tests are used. The present study sought to evaluate the performance of the proliferation marker Ki-67 to identify these patients and explore its association with molecular signatures and risk stratification markers. From the San José TecSalud Hospital in Monterrey México, patients with HR+ EIBC as tested with EndoPredict or MammaPrint and Ki-67 index were identified. They were categorized into two groups: Group 1 (June 2016-August 2018) was evaluated using EndoPredict and Group 2 (June 2016-August 2018) with MammaPrint. A ≥20% Ki67 index cutoff was utilized to identify highly proliferative EIBC and an area under the receiver-operating characteristic curve and κ concordance were utilized to evaluate the performance of Ki-67 index compared to molecular signature tests. In the EndoPredict group, 54/96 patients were considered high-risk based on their EPclin score, while 57/96 patients had Ki-67 index ≥20%. However, there was no significant overall concordance between them (59.37%, κ=0.168, P=0.09), while the given risk of distant recurrence given in percentage by EPclin had a positive association with the Ki67 index (P=0.04). In the MammaPrint group, 21/70 patients were considered high-risk and 36/70 patients presented with a Ki-67 index ≥20% with a significant overall concordance (67.14%, κ=0.35, P<0.001). In addition, high Ki-67 index was associated with the Nottingham histological grade in both groups. In conclusion, there was a concordance between Ki-67 and MammaPrint risk stratification of HR+ EIBC and no concordance with the EndoPredict molecular signature, but a positive association with the given percentage of recurrence and the median Ki-67 index as the cutoff at our center. Cost-effectiveness analyses of these tests in developing countries are required; until then, the use of Ki-67 appears reasonable to aid clinical decisions, together with the other established clinicopathological variables.
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BACKGROUND: Medically refractory idiopathic intracranial hypertension (IIH) is frequently treated with venous sinus stenosis stenting with high success rates. Patient selection has been driven almost exclusively by identification of supraphysiological venous pressure gradients across stenotic regions based on theoretical assessment of likelihood of response. OBJECTIVE: To explore the possibility of benefit in low venous pressure gradient patients. METHODS: Using a single-center, prospectively maintained registry of patients with IIH undergoing venous stenting, we defined treatment groups by gradient pressures of ≤4, 5 to 8, and >8 mmHg based on the most frequently previously published thresholds for stenting. Baseline demographics, clinical, and neuro-ophthalmological outcomes (including optical coherence tomography and Humphrey visual fields) were compared. RESULTS: Among 53 patients, the mean age was 32 years and 70% female with a mean body mass index was 36 kg/m 2 . Baseline characteristics were similar between groups. The mean change in lumbar puncture opening pressure at 6 months poststenting was similar between the 3 groups (≤4, 5-8, and >8 mmHg; 13.4, 12.9, and 12.4 cmH 2 O, P = .47). Papilledema improvement was observed across groups at 6 months (100, 93, and 86, P = .7) as were all clinical symptoms. The mean changes in optical coherence tomography retinal nerve fiber layer (-30, -54, and -104, P = .5) and mean deviation in Humphrey visual fields (60, 64, and 67, P = .5) at 6 weeks were not significantly different. CONCLUSION: Patients with IH with low venous pressure gradient venous sinus stenosis seem to benefit equally from venous stenting compared with their higher gradient counterparts. Re-evaluation of our restrictive criteria for this potentially vision sparing intervention is warranted. Future prospective confirmatory studies are needed.