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Background: Although total joint arthroplasty is the most effective procedures for end-stage arthritis, the incidence of postoperative death and complications remains high. The association of additional peripheral nerve blocks (PNBs) to routine spinal or general anesthesia with major adverse events (including mortality and complication rates) in elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) has been subject to inconclusive findings. Methods: This retrospective observational single institution study included all patients ≧ 18 years undergoing their first elective THA or TKA from January 1, 2012 to December 31, 2021. A 1:2 propensity score matching (PSM) was performed to account for the baseline differences between two groups that were accepted to PNB or not. Kaplan–Meier curves were employed to estimate the effects of PNB on mortality. The associations of PNB and the complications were assessed by logistic regression models. Results: We identified 1328 patients, among whom 197 had PNB and 1131 had not. The 90-day all-cause mortality was significantly reduced in patients with PNBs (0 % vs 2.79 %, P = 0.041) after THA or TKA, when compared to the non-PNB group. PNB was also associated with a lower risk of pulmonary complications (odds ratio [OR], 0.430; 95%confidence interval [CI],0.216–0.857) and deep vein thrombosis (OR, 0.103; 95%CI, 0.011–0.954). Interpretation: The results of this observational, propensity score–matched cohort study suggested a strong association between the addition of PNBs to routine spinal or general anesthesia and decreased risks of major adverse events.

Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels. Nevertheless, the mechanism responsible for this dynamic insulin secretion has not been completely understood, particularly at the single islet level. In this study, we have successfully developed an easy microfluidic platform that allows for the exploration of dynamic glucose-stimulated insulin secretion (GSIS) at the single islet level. With the utilization of this platform, we evaluated dynamic GSIS from single islets isolated from both normal and diabetic rats. Our results demonstrate that islets can be categorized into three types based on their dynamic GSIS: Type I exhibits a biphasic GSIS profile with a fast first phase and flat second phase; Type II also has a biphasic GSIS profile with a fast first phase but a slow increased second phase; Type III displays only a slowly increased second phase and lacks a fast first phase. RNA sequencing analysis demonstrated that the cell type and exocytosis-specific genes are consistent with the proportion of cells and insulin release kinetics among the three types of islets, respectively. Moreover, our findings suggest that high expression of Atp5pb is anti-correlated with the first phase of insulin secretion. Furthermore, we revealed that diabetic islets exhibit only the type I GSIS response, indicating a deliberate impairment of the second phase of insulin secretion. Together, this device serves as a crucial tool in the research field of islets and diabetes, allowing researchers to investigate islet functional heterogeneity and identity at the single islet level.

Abstract Diabetes mellitus (DM) is a disease caused by dysfunction or disruption of pancreatic islets. The advent and development of microfluidic organoids-on-a-chip platforms have facilitated reproduce of complex and dynamic environment for tissue or organ development and complex disease processes. For the research and treatment of DM, the platforms have been widely used to investigate the physiology and pathophysiology of islets. In this review, we first highlight how pancreatic islet organoids-on-a-chip have improved the reproducibility of stem cell differentiation and organoid culture. We further discuss the efficiency of microfluidics in the functional evaluation of pancreatic islet organoids, such as single-islet-sensitivity detection, long-term real-time monitoring, and automatic glucose adjustment to provide relevant stimulation. Then, we present the applications of islet-on-a-chip technology in disease modeling, drug screening and cell replacement therapy. Finally, we summarize the development and challenges of islet-on-a-chip and discuss the prospects of future research. Graphical Abstract

BackgroundAppendiceal goblet cell carcinoma (aGCC) is a rare neoplasm with mixed endocrine and exocrine features. No paraneoplastic neurological syndromes or autoantibodies have been identified in cases of aGCC or even appendiceal tumors. Amphiphysin-immunoglobulin G (IgG) autoimmunity was first described in stiff-person syndrome with breast cancer. We firstly described the clinical course and pathological findings of a patient with aGCC-associated amphiphysin-IgG autoimmunity.Case presentationA 54-year-old man who developed aGCC was admitted for acute disturbance of consciousness, psychiatric symptoms, cognitive impairment, seizure and hypotension. Amphiphysin-IgG was detected in the patient’s serum and CSF by immunoblotting and tissue-based indirect immunofluorescence assay confirming the diagnosis of definite paraneoplastic amphiphysin-IgG-positive encephalitis. Histopathology revealed amphiphysin protein expression and accompanying immune cell infiltration (predominantly CD20+ B cells, CD3+ and CD8+ T cells) within the tumor tissue, suggesting a possible paraneoplastic origin of amphiphysin-associated paraneoplastic neurological syndromes (PNSs) in this case. Although the patient’s symptoms resolved after high-dose corticosteroid therapy, he experienced recurrence 6 months later, manifesting as paraneoplastic cerebellar dysfunction. Despite treatment with IV cyclophosphamide and oral mycophenolate mofetil, no improvement was noted.ConclusionsThis case suggests that aGCC may trigger amphiphysin-IgG autoimmunity.

Paraneoplastic neurological syndromes (PNSs) are a group of neurological disorders triggered by an underlying remote tumor. Ovarian teratoma (OT) is the most common histologic type of germ cell tumor in females. The most common PNSs associated with OT is anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, with the increasing number of new antibodies reported over the last decade, the clinical spectrum of OT-related PNSs is also expanding. Our knowledge of OT-related PNSs is still far from complete. Here, we provide a comprehensive review of the most recent findings in the field of OT-related PNSs, with a particular focus on their clinical and pathological characteristics. Overall, the description of neuronal antibodies in PNSs associated with OT strongly suggests that antibodies may be responsible for the clinical symptoms in some cases. OT-related PNSs are associated with various clinical manifestations, including anti-NMDAR encephalitis, limbic encephalitis, encephalomyelitis, progressive cerebellar syndrome and opsoclonus-myoclonus syndrome. The pathological characteristics of the OT suggest that the mechanism of PNSs is probably due to heteromorphic neurons in the tumor tissue, the ectopic expression of the antigens in neural tissue within the teratomas and patients’ unusual immune response. Despite the severity of the neurological syndromes, most patients with OT-related PNSs showed good neurologic response to early tumor resection combined with immunotherapy. To further advance the management of OT-related PNSs, additional studies are needed to explore this complex topic.

BackgroundA variety of regional analgesia methods are used during video-assisted thoracic surgery (VATS). Our network meta-analysis (NMA) sought to evaluate the advantages of various methods of localized postoperative pain management in VATS patients.MethodsPubMed, the Cochrane Library, and EMBASE were searched from their date of inception to May 2021 for randomized controlled trials (RCTs) comparing two or more types of locoregional analgesia in adults using any standardized clinical criteria. This was done using Bayesian NMA.ResultsA total of 3,563 studies were initially identified, and 16 RCTs with a total of 1,144 participants were ultimately included. These studies, which spanned the years 2014 to 2021 and included data from eight different countries, presented new information. There were a variety of regional analgesia techniques used, and in terms of analgesic effect, thoracic epidural anesthesia (TEA) [SMD (standard mean difference) = 1.12, CrI (Credible interval): (−0.08 to −2.33)], thoracic paravertebral block (TPVB) (SMD = 0.67, CrI: (−0.25 to 1.60) and erector spinae plane block (ESPB) (SMD = 0.34, CrI: (−0.5 to 1.17) were better than other regional analgesia methods.ConclusionOverall, these findings show that TEA, TPVB and ESPB may be effective forms of regional analgesia in VATS. This research could be a valuable resource for future efforts regarding the use of thoracic regional analgesia and enhanced recovery after surgery.Systematic Review RegistrationIdentifier [PROSPERO CRD42021253218].

BackgroundMechanical ventilation (MV) is commonly used in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients with serious conditions. However, little is known about the potential risk factors and long-term outcomes of anti-NMDAR encephalitis requiring MV, especially prolonged MV.MethodsThe data collected prospectively from 305 patients with anti-NMDAR encephalitis were retrospectively reviewed. The functional outcome was assessed using a modified Rankin scale (mRS) every 3 months.ResultsWe identified 62 (20.3%) patients who required MV. The most common reasons for MV were decreased consciousness and/or status epilepticus (SE). Among 60 patients analyzed, 27 patients required prolonged MV (>15 days). Prolonged MV primarily was based on the younger age, coma, tumor, and severe pneumonia. During the follow-up (median: 28 months, range: 3–87 months), 77% of patients required MV that exhibited a good outcome. In univariate analysis, prolonged MV, higher levels of C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) were found to be associated with poor neurological outcome at 6 months. Although the prolonged MV group exhibited a longer time to achieve a good outcome as compared to the short MV group (median duration 6 months vs. 3 months, p = 0.004), no significant difference was observed between the two groups about long-term outcomes.ConclusionIt is important to recognize that most anti-NMDAR encephalitis patients who required MV will achieve a favorable long-term outcomes, despite the longer duration of MV. Our results may help clinicians in the ventilator management of severe anti-NMDAR encephalitis patients.

Objective: To study the clinical characteristics of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis and anti-contactin-associated protein-like 2 (Caspr2) encephalitis and to investigate factors associated with poor long-term neurological functional outcomes and relapse among patients in western China. Methods: In this single-center prospective cohort study, we consecutively enrolled patients with anti-LGI1 encephalitis and anti-Caspr2 encephalitis from April 2014 to February 2021. Patient outcomes were assessed using the modified Rankin scale. Predictors of long-term functional outcomes and relapse were analyzed. Results: Forty-four anti-LGI1 encephalitis patients [median age: 44 years, range: 18–82 years; females: 25 (56.8%)], 35 anti-Caspr2 encephalitis patients [median age: 43 years, range: 14–80 years; females: 19 (54.3%)], and 5 dual-positive patients [median age: 44 years, range: 36–58 years; females: 5 (100%)] were enrolled. Overall, 86.4% anti-LGI1 encephalitis patients and 80% anti-Caspr2 encephalitis had a favorable neurological functional outcome (mRS 0-2). Tumor occurrence and weight loss were associated with poor long-term functional outcomes in anti-LGI1 encephalitis, whereas in anti-Caspr2 encephalitis, predictors included behavioral disorder at acute phase, abnormalities in brain magnetic resonance imaging, higher modified Rankin scale scores at onset, poor response to the initial immunotherapy at 4 weeks, age at onset

ObjectiveTo address the effects of high dose steroids on in-hospital infection and neurologic outcome in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients.MethodsWe retrospectively reviewed the clinical data of anti-NMDAR encephalitis patients in West China Hospital, the Third Hospital of Mianyang and Mianyang Central Hospital between October 2011 and August 2020. The development of infections, inflammatory factors, neurologic outcome at discharge and risk factors for in-hospital infection were assessed in patients with and without high dose steroid therapy before and after immunotherapy. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression models were established to assess risk factors for in-hospital infection.ResultsA total of 278 patients with anti-NMDAR encephalitis were included in the study. Thirty-four patients received high dose methylprednisolone (IVMP) therapy only, 84 patients received intravenous immunoglobulin (IVIG) therapy, and 160 patients received IVIG and IVMP therapy. Compared with the IVIG group, IVIG + IVMP group had a higher infection rate (64.38% vs 39.29%, P < 0.001), a higher incidence of noninfectious complications (76.25% vs 61.90%, P = 0.018) and a higher modified Rankin Scale (mRS) score at discharge from the hospital (3 vs 2, P < 0.001). Inflammatory indicators, including white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII), were higher (9.93 vs 5.65, 6.94 vs 3.47 and 1.47 vs 0.70, respectively, P < 0.001) in the IVIG + IVMP group than in the IVIG group. Moreover, lymphocyte-to-monocyte ratio (LMR) was lower (2.20 vs 2.54, P = 0.047) in the IVIG + IVMP group. The LASSO model showed that mRS score on admission, seizure, body temperature, uric acid (URIC), cerebrospinal fluid immunoglobulin G (CSF IgG), NLR and LMR were risk factors for in-hospital infection. The prediction model exhibited an area under the curve (AUC) of 0.885.ConclusionsHigh dose steroids therapy was significantly associated with higher in-hospital infectious complication rates and a poor short-term prognosis in relatively severe anti-NMDAR encephalitis patients. The established prediction model might be helpful to reduce the risk of in-hospital infection.

Abstract Objective To explore the diversity and composition of the fecal microbiota in patients with anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis. Methods We enrolled 10 patients in the acute stage with naïve treatment, seven patients with relapse, 13 patients without relapse in the remission phase, and 12 paired healthy controls. The fecal microbiota in different groups was compared by 16S ribosomal DNA (rDNA) gene pyrosequencing. Results Prominent dysbiosis in the gut microbiome of patients with anti‐NMDAR encephalitis was found. Our primary findings showed that the overall species richness (alpha diversity indexes) of the microbiota was higher in patients than in controls (P

ObjectiveTo explore the structure and composition of the fecal microbiota of patients with epilepsy.MethodsVariations in the fecal microbiota between patients with epilepsy and healthy controls (HCs) from the same household were investigated and validated by utilizing 16S ribosomal RNA sequencing in two independent cohorts [exploration cohort (N = 55 patients and N = 46 HCs) and validation cohort (N = 13 patients and N = 10 HCs)].ResultsThe alpha diversity indexes of the specimens from patients with epilepsy were much lower than those from the HCs (p < 0.05). The structure and composition of the fecal microbiota differed between patients with different clinical prognoses and between patients and HCs (Adonis: p < 0.05). Microbiome alterations in patients with epilepsy included increases in Actinobacteria and Verrucomicrobia and decreases in Proteobacteria at the phylum level and increases in Prevotella_9, Blautia, Bifidobacterium, and others at the genus level [linear discriminant analysis (LDA): 3.5] Patients with drug-resistant epilepsy showed enrichment of bacterial taxa in Actinobacteria, Verrucomicrobia, and Nitrospirae and the genera Blautia, Bifidobacterium, Subdoligranulum, Dialister, and Anaerostipes (Kruskal-Wallis test: p < 0.05). Analysis of gut microbiome indicated predictive ability for disease diagnosis, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.97 (95% CI, 0.84–0.98). Applying the model to our validation cohort resulted in an AUC of 0.96 (95% CI, 0.75–0.97). Notably, the model could distinguish drug-resistant from drug-sensitive epilepsy (AUC = 0.85, 95% CI: 0.69–0.94).ConclusionPatients with epilepsy exhibit substantial alterations of fecal microbiota composition, and specific gut commensal strains are altered depending on different clinical phenotypes and thus could serve as potential biomarkers for disease diagnosis.

Objective: To measure mortality, identify predictors of death and investigate causes of death in patients with anti-gamma-aminobutyric-acid B receptor (anti-GABABR) encephalitis.Methods: Prospective analysis of anti-GABABR encephalitis cases diagnosed between June 2013 and August 2018 in West China Hospital of Sichuan University, with assessment of factors associated with mortality.Results: A total of 28 patients (11 females) with anti-GABABR encephalitis were included in this study. After a maximum time of 52 months (median 11 months, range 2–52) of follow-up, 9 (32.1%) patients died, with a median survival time of 6.5 months. Five patients died of tumor progression, one patient died of convulsive status epilepticus, one patient died of septic shock, and two patients died of severe pneumonia. Predictors of death were older age at onset (P = 0.025), presence of a tumor (66.7 vs. 15.8%, P = 0.013), the number of complications (2.6 vs. 1.0, P = 0.009) and deep venous thrombosis (33.3% vs. 0, P = 0.026).Conclusion: Patients with GABABR encephalitis have a high mortality rate within 5 years. Older age at onset, presence a tumor, the number of complications, and deep venous thrombosis are associated with death.