White Matter Hyperintensity is Associated with Malignant Cerebral Edema in Ischemic Stroke Treated with Thrombectomy.

BACKGROUND: White matter hyperintensity (WMH) burden may lead to poor clinical outcomes after endovascular thrombectomy (EVT). But the relationship between WMH burden and cerebral edema (CED) is unclear. PURPOSE: To examine the association between WMH burden and CED and functional outcome in patients treated with EVT. STUDY TYPE: Retrospective. SUBJECT: 344 patients with acute anterior circulation large-vessel occlusion stroke who received EVT at two comprehensive stroke centers. Mean age was 62.6 ± 11.6 years and 100 patients (29.1%) were female. FIELD STRENGTH/SEQUENCE: 3T, including diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) images. ASSESSMENT: The severity of WMH was evaluated using the Fazekas scale on a FLAIR sequence before EVT. The severity of CED was assessed using CED score (three for malignant cerebral edema [MCE]) and net water uptake (NWU)/time on post-EVT cranial CT. The impact of WMH burden on MCE, NWU/time, and 3-month poor outcome (modified Rankin scale >2) after EVT were assessed. STATISTICAL TESTS: Pearson's chi-squared test, Fisher exact test, 2-tailed t test, Mann-Whitney U test, multivariable logistic regression, multivariate regression analysis, Sobel test. A P value <0.05 was considered statistically significant. RESULTS: WMH burden was not significantly associated with MCE and parenchymal hemorrhage (PH) in the whole population (P = 0.072; P = 0.714). WMH burden was significantly associated with an increased risk of MCE (OR, 1.550; 95% CI, 1.128-2.129), higher NWU/time (Coefficient, 0.132; 95% CI, 0.012-0.240), and increased risk of 3-month poor outcome (OR, 1.434; 95% CI, 1.110-1.853) in the subset of patients without PH. Moreover, the connection between WMH burden and poor outcome was partly mediated by CED in patients without PH (regression coefficient changed by 29.8%). DATA CONCLUSION: WMH burden is associated with CED, especially MCE, and poor outcome in acute ischemic stroke patients treated with EVT. The association between WMH burden and poor outcome may partly be attributed to postoperative CED. TECHNICAL EFFICACY: Stage 5.

Extranodal Rosai-Dorfman disease manifesting as Sjögren's syndrome combined with panuveitis and hypertrophic pachymeningitis: a case report and review of literature.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by massive lymphadenopathy and systemic extranodal lesions. We present the case of a 28-year-old woman who presented with recurrent blurred vision in her right eye for 3 months. She developed blindness and atrophy in her left eye a decade prior to presentation. She subsequently developed headache, fever, and impaired mental status. Cranial magnetic resonance imaging indicated hypertrophic pachymeningitis (HP), and 18F-fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography revealed significant FDG uptake in the left dura mater. Autoimmune testing revealed elevated anti-nuclear, anti-SS-A, and anti-SS-B antibody levels. Incisional biopsy of the atrophic eyeball revealed RDD with marked polyclonal plasmacytosis. The patient was diagnosed with RDD accompanied by multisystem involvement, including Sjögren's syndrome (SS), panuveitis, and HP. Treatment with methylprednisolone for several weeks resulted in significant improvement. This is the first reported case of RDD presenting with SS in combination with panuveitis and HP. Although RDD is rarely diagnosed in young patients, interdisciplinary collaboration is essential to prevent a delayed diagnosis.

AKAP3-mediated type I PKA signaling is required for mouse sperm hyperactivation and fertility†.

The protein kinase A (PKA) signaling pathway, which mediates protein phosphorylation, is important for sperm motility and male fertility. This process relies on A-kinase anchoring proteins that organize PKA and its signalosomes within specific subcellular compartments. Previously, it was found that the absence of A-kinase anchoring protein 3 (AKAP3) leads to multiple morphological abnormalities in mouse sperm. But how AKAP3 regulates sperm motility is yet to be elucidated. AKAP3 has two amphipathic domains, here named dual and RI, in its N-terminus. These domains are responsible for binding regulatory subunits I alpha (RIα) and II alpha (RIIα) of PKA and for RIα only, respectively. Here, we generated mutant mice lacking the dual and RI domains of AKAP3. It was found that the deletion of these domains caused male mouse infertile, accompanied by mild defects in the fibrous sheath of sperm tails. Additionally, the levels of serine/threonine phosphorylation of PKA substrates and tyrosine phosphorylation decreased in the mutant sperm, which exhibited a defect in hyperactivation under capacitation conditions. The protein levels of PKA subunits remained unchanged. But, interestingly, the regulatory subunit RIα was mis-localized from principal piece to midpiece of sperm tail, whereas this was not observed for RIIα. Further protein-protein interaction assays revealed a preference for AKAP3 to bind RIα over RIIα. Collectively, our findings suggest that AKAP3 is important for sperm hyperactivity by regulating type-I PKA signaling pathway mediated protein phosphorylation via its dual and RI domains.

Risk factors for cough after pulmonary resection.

BACKGROUND: To investigate the risk factors for cough after pulmonary resection. METHODS: The PubMed, Embase, Web of Science, ClinicalTrials.gov, and China National Knowledge Network databases were searched from inception to November 2022. The Q tests and I2 statistic were used to evaluate the heterogeneity. Odds ratios (OR) were combined using the inverse variance method. All statistical analyses were performed by RevMan 5.4.1. RESULTS: Nineteen studies with 4755 patients were included, the incidence of postoperative cough was 21.1%-55.8%. The results showed that young age [OR = 0.66, 95% CI (0.46, 0.96), p = 0.03], female sex [OR = 1.69, 95% CI (1.07, 2.66), p = 0.02], preoperative cough [OR = 5.96, 95% CI (2.58, 13.73), p < 0.01], right lobe operation [OR = 2.14, 95% CI (1.44, 3.19), p < 0.01], lobectomy [OR = 3.70, 95% CI (1.73, 7.90), p < 0.01], subcarinal lymph node dissection [OR = 3.45, 95% CI (1.86, 6.39), p < 0.01], mediastinal lymph node removal [OR = 3.49, 95% CI (2.07, 5.89), p < 0.01], closure of bronchial stump with stapler [OR = 5.19, 95% CI (1.79, 15.07), p < 0.01], peritracheal lymph node resection [OR = 3.05, 95%CI (1.40,6.64), p < 0.01], postoperative acid reflux [OR = 11.07, 95%CI (4.38,28.02), p < 0.01] were independent risk factors for cough after pulmonary resection. CONCLUSIONS: Young age, female sex, preoperative cough, right lobe operation, lobectomy, subcarinal lymph node dissection, mediastinal lymph node removal, closure of bronchial stump with stapler, peritracheal lymph node resection, and postoperative acid reflux are independent risk factors for cough after pulmonary resection.

Prognostic value of consolidation-to-tumor ratio on computed tomography in NSCLC: a meta-analysis.

BACKGROUND: Although several studies have confirmed the prognostic value of the consolidation to tumor ratio (CTR) in non-small cell lung cancer (NSCLC), there still remains controversial about it. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases from inception to April, 2022 for eligible studies that reported the correlation between CTR and prognosis in NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and pooled to assess the overall effects. Heterogeneity was estimated by I2 statistics. Subgroup analysis based on the cut-off value of CTR, country, source of HR and histology type was conducted to detect the sources of heterogeneity. Statistical analyses were performed using STATA version 12.0. RESULTS: A total of 29 studies published between 2001 and 2022 with 10,347 patients were enrolled. The pooled results demonstrated that elevated CTR was associated with poorer overall survival (HR = 1.88, 95% CI 1.42-2.50, P < 0.01) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 1.42, 95% CI 1.27-1.59, P < 0.01) in NSCLC. According to subgroup analysis by the cut-off value of CTR and histology type, both lung adenocarcinoma and NSCLC patients who had a higher CTR showed worse survival. Subgroup analysis stratified by country revealed that CTR was a prognostic factor for OS and DFS/RFS/PFS in Chinese, Japanese, and Turkish patients. CONCLUSIONS: In NSCLC patients with high CTR, the prognosis was worse than that with low CTR, indicating that CTR may be a prognostic factor.

Multi-proteomic Analysis Revealed Distinct Protein Profiles in Cerebrospinal Fluid of Patients Between Anti-NMDAR Encephalitis NORSE and Cryptogenic NORSE.

New-onset refractory status epilepticus (NORSE) is rare but intractable. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and cryptogenic etiologies are the two major causes of NORSE with distinct clinical features. To elucidate the underlying mechanisms, 6 patients with anti-NMDAR encephalitis NORSE and 5 with cryptogenic NORSE (C-NORSE) were enrolled. Five patients of cerebrovascular disorders were used as controls. Quantitative proteomic analysis of the cerebrospinal fluid (CSF) samples of the patients revealed 101 and 56 proteins were changed, respectively. The average fold-change of the upregulated proteins, namely up-proteomic score in this study, was positively correlated with the severity and prognosis of the diseases, including ICU stay (r = 0.9308, P = 0.0035 in NMDAR group; r = 0.8977, P = 0.0193 in C-NORSE group), mRS score at discharge (r = 0.9710, P = 0.0111 in NMDAR group; r = 0.7071, P = 0.2000 in C-NORSE group), and time taken for patients awaking from a coma (r = 0.8823, P = 0.0100 in NMDAR group; r = 0.7906, P = 0.2000 in C-NORSE group). Pathways involved in humoral immune response, wound healing, and epigenetic regulation of transcription were upregulated in anti-NMDAR encephalitis NORSE. Pathways of innate and lymphocyte mediated immune response, synaptic functions, ubiquitination, and cell apoptosis were up-regulated in C-NORSE, which was consistent with a mouse model of status epilepticus. Fc receptor and B cell mediated immunity signaling pathways were downregulated in C-NORSE. Immunome microarray analysis demonstrated high autoantibody targeting 48 proteins in CSF samples of anti-NMDAR encephalitis NORSE. While the reaction was kept at a very low level in C-NORSE. There is no significant difference in inflammatory cytokine level between each group. The level of IL-4 (r = 0.7435, P = 0.0451), IL-13 (r = 0.7643, P = 0.0384), IFN-γ (r = 0.7973, P = 0.0287) and TNF-α (r = 0.8598, P = 0.0141) in NMDAR group, and IL-6 (r = 0.8479, P = 0.0348), IL-8 (r = 0.9076, P = 0.0166) in C-NORSE group were positively correlated with the up-proteomic score. The present study suggests that the up-proteomic score of CSF could be a promising indicator for assessment of the severity of anti-NMDAR encephalitis NORSE and C-NORSE. The distinct CSF proteomes imply different pathogenic mechanisms of the two diseases, and immunotherapy strategies as well.

Genetically predicted testosterone and cancers risk in men: a two-sample Mendelian randomization study.

OBJECTIVE: In observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men. METHODS: We performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty. RESULTS: Genetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09-1.26, P = 2.51E-05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48-0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36-0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001-1.0007, P = 0.0116). However, testosterone had no significant association with other cancers. CONCLUSION: This study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.

Predicting futile recanalization, malignant cerebral edema, and cerebral herniation using intelligible ensemble machine learning following mechanical thrombectomy for acute ischemic stroke.

Purpose: To establish an ensemble machine learning (ML) model for predicting the risk of futile recanalization, malignant cerebral edema (MCE), and cerebral herniation (CH) in patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) and recanalization. Methods: This prospective study included 110 patients with premorbid mRS ≤ 2 who met the inclusion criteria. Futile recanalization was defined as a 90-day modified Rankin Scale score >2. Clinical and imaging data were used to construct five ML models that were fused into a logistic regression algorithm using the stacking method (LR-Stacking). We added the Shapley Additive Explanation method to display crucial factors and explain the decision process of models for each patient. Prediction performances were compared using area under the receiver operating characteristic curve (AUC), F1-score, and decision curve analysis (DCA). Results: A total of 61 patients (55.5%) experienced futile recanalization, and 34 (30.9%) and 22 (20.0%) patients developed MCE and CH, respectively. In test set, the AUCs for the LR-Stacking model were 0.949, 0.885, and 0.904 for the three outcomes mentioned above. The F1-scores were 0.882, 0.895, and 0.909, respectively. The DCA showed that the LR-Stacking model provided more net benefits for predicting MCE and CH. The most important factors were the hypodensity volume and proportion in the corresponding vascular supply area. Conclusion: Using the ensemble ML model to analyze the clinical and imaging data of AIS patients with successful recanalization at admission and within 24 h after MT allowed for accurately predicting the risks of futile recanalization, MCE, and CH.

Cumulative Evidence for Relationships Between Multiple Variants in the TERT and CLPTM1L Region and Risk of Cancer and Non-Cancer Disease.

Background: Genetic studies previously reported that variants in TERT-CLPTM1L genes were related to susceptibility of cancer and non-cancer diseases. However, conclusions were not always concordant. Methods: We performed meta-analyses to assess correlations between 23 variants within TERT-CLPTM1L region and susceptibility to 12 cancers and 1 non-cancer disease based on data in 109 papers (involving 139,510 cases and 208,530 controls). Two approaches (false-positive report probability test and Venice criteria) were adopted for assessing the cumulative evidence of significant associations. Current study evaluated the potential role of these variants based on data in Encyclopedia of DNA Elements (ENCODE) Project. Results: Thirteen variants were statistically associated with susceptibility to 11 cancers and 1 non-cancer disease (p < 0.05). Besides, 12 variants with eight cancers and one non-cancer disease were rated as strong evidence (rs2736098, rs401681, and rs402710 in bladder cancer; rs2736100, rs2853691, and rs401681 in esophageal cancer; rs10069690 in gastric cancer; rs2736100 and rs2853676 in glioma; rs2242652, rs2736098, rs2736100, rs2853677, rs31489, rs401681, rs402710, rs465498, and rs4975616 in lung cancer; rs2736100 in idiopathic pulmonary fibrosis and myeloproliferative neoplasms; and rs401681 in pancreatic and skin cancer). According to data from ENCODE and other public databases, 12 variants with strong evidence might fall within putative functional regions. Conclusions: This paper demonstrated that common variants of TERT-CLPTM1L genes were related to susceptibility to bladder, esophageal, gastric, lung, pancreatic, and skin cancer, as well as to glioma, myeloproliferative neoplasms, and idiopathic pulmonary fibrosis, and, besides, the crucial function of the TERT-CLPTM1L region in the genetic predisposition to human diseases is elucidated.

Can We Cryopreserve the Sperm of COVID-19 Patients During the Pandemic?

An extreme strain has been placed on healthcare facilities in the COVID-19 era. Initial stage of the pandemic, national and international societies for reproductive medicine suggested the suspension of new IVF treatments and non-essential cryopreservation of gametes. Accordingly, the demands of cryopreservation of semen with COVID-19 patients also was suspended by some of cryobanks to protect staff and patients from unnecessary viral exposure at the acute stage. However, the pandemic may stay with us longer than expected. In addition, there will be some male COVID-19 patients with cancer or critically illness who needs to cryopreserve their semen before medical treatments, otherwise they might loss the chance of getting their own offspring. In this document, we summarize available evidence to deepen and expand awareness of feasibility of sperm cryopreservation and propose some suggestions to help cryobanks carry out sperm preservation procedure for COVID-19 male patients.

Subacute Balamuthia mandrillaris encephalitis in an immunocompetent patient diagnosed by next-generation sequencing.

Balamuthia mandrillaris is a free-living heterotrophic amoeba found in soil that causes a rare and usually fatal granulomatous amebic encephalitis. We report an immunocompetent patient infected with B. mandrillaris encephalitis diagnosed by next-generation sequencing (NGS). Clinical manifestations included sudden headache and epilepsy with disturbance of consciousness. The opening pressure of cerebrospinal fluid (CSF) was 220 mmH2O, with mildly elevated white blood cell numbers and elevated protein levels. Cranial magnetic resonance imaging revealed abnormal signals in the right frontal lobe, left parietal lobe, and left occipital lobe. CSF NGS detected B. mandrillaris. Albendazole and metronidazole combined with fluconazole were administered to the patient immediately, but his condition deteriorated and he eventually died. Encephalitis caused by B. mandrillaris is rare and has a high mortality rate. Clinical manifestations are complex and diverse, but early diagnosis is very important for successful treatment. This can be aided by the metagenomic NGS of CSF.

Risk Factors Associated with Impairment in Pulmonary Diffusing Capacity among Patients with Noncystic Fibrosis Bronchiectasis.

This study aims to investigate the risk factors associated with impaired pulmonary diffusing capacity among patients with noncystic fibrosis bronchiectasis (NCFB) and compare the predictive value of several scoring systems for the impairment in these patients. Between July 2019 and June 2021, patients who were admitted to the hospital and diagnosed with NCFB were included in this study. Clinical data were collected and analyzed retrospectively. A total of 175 NCFB patients were included in the analysis. Multivariate logistic regression analysis revealed that impaired pulmonary diffusing capacity diagnosed by carbon monoxide diffusing capacity (DLCO) <80% prediction was associated with age, Reiff score, body mass index (BMI), comorbid chronic obstructive pulmonary disease (COPD), and interstitial lung disease (ILD). Disease duration, frequency of exacerbation, hemoglobin level, and COPD were independent risk factors for impaired pulmonary diffusing capacity diagnosed by DLCO/alveolar volume (VA) <80% prediction. Age, Reiff score, and smoking status were independent risk factors for decreased VA diagnosed by VA <80% prediction. The areas under the curve (AUC) for discrimination of DLCO <80% prediction were 0.822 (0.760-0.885) for Bronchiectasis Severity Index (BSI), 0.787 (0.718-0.856) for FACED, 0.795 (0.729-0.863) for E-FACED, and 0.767 (0.694-0.839) for modified Medical Research Council (mMRC) scores; the AUC for discrimination of DLCO/VA <80% prediction was 0.803 (0.727-0.880) for BSI, 0.752 (0.669-0.835) for FACED, 0.757 (0.676-0.839) for E-FACED, and 0.762 (0.679-0.845) for mMRC, respectively. The BSI had the largest AUC, but the differences between those scoring systems had no statistical significance (P=0.181 for DLCO <80% prediction and P=0.105 for DLCO/VA <80% prediction). The mMRC score (up to 2 grades) showed a high specificity for discriminating diffusing dysfunction (88.3% for DLCO <80% prediction and 76.1% for DLCO/VA <80% prediction). In NCFB patients, several factors such as age, Reiff score, BMI, exacerbation frequency, disease duration, and comorbid COPD and ILD were associated with impaired pulmonary diffusing capacity, which requires more attention in managing those patients. In addition, several scoring methods, including a simple index of mMRC, showed a comparable and moderate performance for predicting pulmonary diffusing impairment and would facilitate the systematic evaluation of the diffusing capacity of NCFB patients.

Biological functions of miR-183 on chemosensitivity of laryngeal cancer cells.

PURPOSE: The purpose of this study was to investigate the effect of miR-183 on the sensitivity of laryngeal cancer cells to 5-fluorouracil (5-Fu) and its mechanism, so as to provide certain references for the clinical prevention of drug resistance in laryngeal cancer cells. METHODS: Cell proliferation was determined via 5-ethynyl-2'-deoxyuridine (EdU) staining. Colony formation assay was applied to test the colony-formation ability in each group of cells. In addition, the expression levels of apoptosis-related proteins were measured through Western blotting. Wound-healing assay and Transwell assay were performed to examine the migratory and invasive abilities. Furthermore, the tumor-forming ability in vitro was detected by subcutaneous tumor formation assay. RESULTS: MiR-183 declined remarkably in 5-Fu-RES group compared with that in Control group. After overexpressing miR-183, the DNA replication and colony forming abilities of the resistant human primary laryngeal cancer cells were weakened notably. MiR-183 overexpression could obviously up-regulate Bax and inhibit Bcl-2 in the resistant human primary laryngeal cancer cells. Moreover, the overexpression of miR-183 was able to repress the migratory and invasive abilities of the resistant human primary laryngeal cancer cells. Further, overexpression of miR-183 restrained the in vitro tumor-forming ability of the resistant human primary laryngeal cancer cells markedly. Finally, it was revealed that TBX3 in the resistant human primary laryngeal cancer cells was suppressed distinctly, while that of PTEN was up-regulated evidently after overexpressing miR-183. CONCLUSIONS: The overexpression of miR-183 can inhibit the drug resistance of the human primary laryngeal cancer cells to 5-Fu, promote cancer cell apoptosis and inhibit their invasive and migratory abilities at the same time, whose mechanism may be associated with the targeted regulation of the TBX3/PTEN signaling pathway by miR-183.

Paroxysmal Sympathetic Hyperactivity in Severe Anti-N-Methyl-d-Aspartate Receptor Encephalitis: A Single Center Retrospective Observational Study.

Background: Paroxysmal sympathetic hyperactivity (PSH) is a disorder with excessive sympathetic activity commonly recognized in patients with acquired brain injury. Autonomic instability is frequent in anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE). However, PSH in anti-NMDARE has gained little attention. Methods: We retrospectively reviewed 24 patients diagnosed with severe anti-NMDARE in the neuro-intensive care unit (NICU) between 2014 and 2019. Patients were assessed with the PSH assessment measure (PSH-AM) scale, and categorized into "PSH+" group and "PSH-" group. The clinical characteristics, hospital mortality, and functional outcome by modified Rankin Scale (mRS) score at six months after discharge were compared between the two groups. Among patients with PSH+, the clinical features and pharmacotherapy of PSH were summarized and compared. Results: Twenty-four patients were included in the study. Twelve of them (50%) were categorized as PSH+ based on PSH-AM scores. There were no significant differences in the demographic characteristic, GCS scores upon admission, incidence of status epilepticus, teratoma occurrence, hospital mortality, and 6-month mRS between PSH+ and PSH- groups. Patients with PSH+ had increased length of NICU stay, hospital stay and duration of mechanical ventilation. The most prominent clinical features of PSH in severe anti-NMDARE were tachycardia and hyperthermia, while posturing was the relatively mildest clinical feature. Propranolol and clonazepam were more commonly used than gabapentin in pharmacotherapy of PSH in severe anti-NMDARE. Conclusions: The incidence of PSH in severe anti-NMDARE patients was as high as 50%. Patients with PSH demonstrated prolonged NICU stay, hospital stay and increased duration of mechanical ventilation, while no effect on hospital mortality and functional outcome. Clinicians should be aware of the distinctive characteristics and treatment options of PSH in severe anti-NMDARE.

A refractory anti-NMDA receptor encephalitis successfully treated by bilateral salpingo-oophorectomy and intrathecal injection of methotrexate and dexamethasone: a case report.

INTRODUCTION: Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is an autoimmune-mediated disease that is common in young female patients with ovarian teratomas. With appropriate immunotherapy, most patients achieve a good prognosis. Nevertheless, some patients may be refractory to first- and second-line immunotherapy, thus alternative treatments are required for these patients.Case presentation: We present a case of anti-NMDA receptor encephalitis with ovarian teratoma. After the prompt removal of the teratoma and intense immunotherapy was administered, including an intravenous methylprednisolone pulse, intravenous immunoglobin, plasmapheresis, immunoadsorption, intravenous cyclophosphamide, and rituximab, the patient's neurologic status did not improve. Bilateral salpingo-oophorectomy was then conducted, and intrathecal injection of methotrexate (MTX) and dexamethasone (DXM) was performed. The patient's neurological symptoms improved dramatically, and she achieved a good prognosis after 23 months. CONCLUSIONS: Intrathecal injection of MTX and DXM may be beneficial for treatment of refractory cases of anti-NMDA receptor encephalitis. Additional research is required to elucidate the mechanisms of intrathecal treatment with this therapy.

Predictive value of serum creatinine/cystatin C in neurocritically ill patients.

OBJECTIVE: To explore the predictive value of serum creatinine (Cr) to cystatin C (CysC) ratio in neurocritically ill patients. METHODS: We conducted a retrospectively observational study of adult patients admitted to a neurocritical care unit (NCU) between Jan 2013 and Jan 2017. Patients were excluded if <18 years old, required neurocritical care <72 hr, did operation during hospitalization, had premorbid disability or acute kidney injury (AKI) at admission. The Cr/CysC ratio was obtained at NCU admission. Primary end points were short-term (30-day) mortality and long-term (6-month) poor outcome, with the latter defined as modified Rankin Scale (mRS) of 4-6. RESULTS: Of 538 eligible patients, the etiology included acute ischemic stroke (N = 193, 35.9%), intracranial hemorrhage (N = 116, 21.6%), encephalitis and/or meningitis (N = 85, 15.8%), and others (N = 144, 26.7%). Serum Cr/CysC ratio was significantly correlated with body mass index (BMI) (r = .161, p < .001), the length of NCU stay (r = -.161, p < .001), duration of mechanical ventilation (r = -.138, p = .001), and risk of tracheotomy (r = -.095, p = .028). During follow-up, 88 (16.4%), patients died within 30 days and 307 (57.1%) patients achieved good outcome at 6 months. In multivariate logistic regression analysis, we identified serum Cr/CysC ratio as an independent predictor of long-term functional outcome (OR: 0.989, 95% CI: 0.980-0.998, p = .015) but not 30-day mortality (p = .513). CONCLUSIONS: Serum Cr/CysC ratio at admission could be used as a predictor of long-term poor prognosis in neurocritically ill patients.