An Opportunity for Change: Principles for Reforming Internal Medicine Inpatient Conferences.

Inpatient educational conferences are a key part of internal medicine residency training. Many residencies made conferences virtual during the COVID-19 pandemic, and are now returning to in-person sessions. As we navigate this change, we can seize this opportunity to re-evaluate the role that inpatient conferences serve in resident education. In this paper, we briefly review the history of inpatient educational conferences before offering five recommendations for improvement. Our recommendations include grounding conference formats in educational theory, leveraging the expertise of all potential educators, broadening content to include health equity and justice throughout all curricula, and explicitly focusing on cultivating community among participants. Recognizing that each residency program is different, we anticipate that these recommendations may be implemented differently based on program size, available resources, and current institutional practices. We also include examples of prior successful curricular reforms aligned with our principles. We hope these recommendations ensure inpatient conferences continue to be a central part of residency education for future generations of internal medicine residents.

Use of machine learning approaches to predict transition of retention in care among people living with HIV in South Carolina: a real-world data study.

Maintaining retention in care (RIC) for people living with HIV (PLWH) helps achieve viral suppression and reduce onward transmission. This study aims to identify the best machine learning model that predicts the RIC transition over time. Extracting from the enhanced HIV/AIDS reporting system, this study included 9765 PLWH from 2005 to 2020 in South Carolina. Transition of RIC was defined as the change of RIC status in each two-year time window. We applied seven classifiers, such as Random Forest, Support Vector Machine, eXtreme Gradient Boosting and Long-short-term memory, for each lagged response to predict the subsequent year's RIC transition. Classification performance was assessed using balanced prediction accuracy, the area under the curve (AUC), recall, precision and F1 scores. The proportion of the four categories of RIC transition was 13.59%, 29.78%, 9.06% and 47.57%, respectively. Support Vector Machine was the best approach for every lag model based on both the F1 score (0.713, 0.717 and 0.719) and AUC (0.920, 0.925 and 0.928). The findings could facilitate the risk augment of PLWH who are prone to follow-up so that clinicians and policymakers could come up with more specific strategies and relocate resources for intervention to keep them sustained in HIV care.

Validating visual evoked potentials as a preclinical, quantitative biomarker for remyelination efficacy.

Many biomarkers in clinical neuroscience lack pathological certification. This issue is potentially a significant contributor to the limited success of neuroprotective and neurorestorative therapies for human neurological disease-and is evident even in areas with therapeutic promise such as myelin repair. Despite the identification of promising remyelinating candidates, biologically validated methods to demonstrate therapeutic efficacy or provide robust preclinical evidence of remyelination in the CNS are lacking. Therapies with potential to remyelinate the CNS constitute one of the most promising and highly anticipated therapeutic developments in the pipeline to treat multiple sclerosis and other demyelinating diseases. The optic nerve has been proposed as an informative pathway to monitor remyelination in animals and human subjects. Recent clinical trials using visual evoked potential have had promising results, but without unequivocal evidence about the cellular and molecular basis for signal changes on visual evoked potential, the interpretation of these trials is constrained. The visual evoked potential was originally developed and used in the clinic as a diagnostic tool but its use as a quantitative method for assessing therapeutic response requires certification of its biological specificity. Here, using the tools of experimental pathology we demonstrate that quantitative measurements of myelination using both histopathological measures of nodal structure and ultrastructural assessments correspond to visual evoked potential latency in both inflammatory and chemical models of demyelination. Visual evoked potential latency improves after treatment with a tool remyelinating compound (clemastine), mirroring both quantitative and qualitative myelin assessment. Furthermore, clemastine does not improve visual evoked potential latency following demyelinating injury when administered to a transgenic animal incapable of forming new myelin. Therefore, using the capacity for therapeutic enhancement and biological loss of function we demonstrate conclusively that visual evoked potential measures myelin status and is thereby a validated tool for preclinical verification of remyelination.

[Analysis of the relationship between embryo quality at different developmental stages and secondary sex ratio of single live births].

Objective: To investigate the effect of embryo quality at different developmental stages on the secondary sex ratio (SSR) of single live birth neonates. Methods: Data for patients with singleton live births after embryo transferred between January 2016 and January 2022 were retrospectively analyzed. The effect of embryo quality at different development stages on the SSR of 11 713 singleton live births were investigated. The association of SSR and embryo quality at different development stages was examined in univariate analysis and in a multivariate logistic regression model, after adjustment for confounders, using two models (Ⅰ and Ⅱ). Results: The age of both male and female, body mass index of both male and female, basal follicle stimulating hormone and estradiol, smoking of male, methods of insemination, methods of sperm extraction, types of transfer cycle and the number of embryo transferred were not related with SSR (all P>0.05). After adjustment for confounders, the probability of a male live birth was higher after transfer of good-quality blastula than after transfer of poorer-quality blastula (model Ⅰ: aOR=0.73, 95%CI: 0.65-0.82, P<0.001; model Ⅱ: aOR=0.73, 95%CI: 0.65-0.82, P<0.001). The quality of cleavage stage embryo was not associated with SSR (model Ⅰ: aOR=0.99, 95%CI: 0.87-1.13, P=0.937; model Ⅱ: aOR=0.99, 95%CI: 0.87-1.13, P=0.899). Conclusions: The SSR of singleton live births after embryo transfer is not correlated with the quality of cleavage stage embryo, but is correlated with the quality of blastula. Good-quality blastula transfer is more likely to result in a male live birth.

Plasma neurofilament light chain levels suggest neuroaxonal stability following therapeutic remyelination in people with multiple sclerosis.

BACKGROUND: Chronic demyelination is a major contributor to axonal vulnerability in multiple sclerosis (MS). Therefore, remyelination could provide a potent neuroprotective strategy. The ReBUILD trial was the first study showing evidence for successful remyelination following treatment with clemastine in people with MS (pwMS) with no evidence of disease activity or progression (NEDAP). Whether remyelination was associated with neuroprotection remains unexplored. METHODS: Plasma neurofilament light chain (NfL) levels were measured from ReBUILD trial's participants. Mixed linear effect models were fit for individual patients, epoch and longitudinal measurements to compare NfL concentrations between samples collected during the active and placebo treatment period. RESULTS: NfL concentrations were 9.6% lower in samples collected during the active treatment with clemastine (n=53, geometric mean=6.33 pg/mL) compared to samples collected during treatment with placebo (n=73, 7.00 pg/mL) (B=-0.035 [-0.068 to -0.001], p=0.041). Applying age- and body mass index-standardised NfL Z-scores and percentiles revealed similar results (0.04 vs 0.35, and 27.5 vs 33.3, p=0.023 and 0.042, respectively). Higher NfL concentrations were associated with more delayed P100 latencies (B=1.33 [0.26 to 2.41], p=0.015). In addition, improvement of P100 latencies between visits was associated with a trend for lower NfL values (B=0.003 [-0.0004 to 0.007], p=0.081). Based on a Cohen's d of 0.248, a future 1:1 parallel-arm placebo-controlled study using a remyelinating agent with comparable effect as clemastine would need 202 subjects per group to achieve 80% power. CONCLUSIONS: In pwMS, treatment with the remyelinating agent clemastine was associated with a reduction of blood NfL, suggesting that neuroprotection is achievable and measurable with therapeutic remyelination. TRIAL REGISTRATION NUMBER: NCT02040298.

Selection influences naive CD8+ TCR-ß repertoire sharing.

Within each individual, the adaptive immune system generates a repertoire of cells expressing receptors capable of recognizing diverse potential pathogens. The theoretical diversity of the T-cell receptor (TCR) repertoire exceeds the actual size of the T-cell population in an individual by several orders of magnitude - making the observation of identical TCRs in different individuals extremely improbable if all receptors were equally likely. Despite this disparity between the theoretical and the realized diversity of the repertoire, these 'public' receptor sequences have been identified in autoimmune, cancer and pathogen interaction contexts. Biased generation processes explain the presence of public TCRs in the naive repertoire, but do not adequately explain the different abundances of these public TCRs. We investigate and characterize the distribution of genomic TCR-ß sequences of naive CD8+ T cells from three genetically identical mice, comparing non-productive (non-functional sequences) and productive sequences. We find public TCR-ß sequences at higher abundances compared with unshared sequences in the productive, but not in the non-productive, repertoire. We show that neutral processes such as recombination biases, codon degeneracy and generation probability do not fully account for these differences, and conclude that thymic or peripheral selection plays an important role in increasing the abundances of public TCR-ß sequences.

[Three dimensional nephrometry system for partial nephrectomy: Our initial exploration].

OBJECTIVE: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. METHODS: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. RESULTS: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm3 and (33.0±36.4) cm3, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. CONCLUSION: Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.

[Evaluating continence recovery time after robot-assisted radical prostatectomy].

OBJECTIVE: To evaluate urinary continence recovery time and risk factors of urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RARP). METHODS: From January 2019 to January 2021, a consecutive series of patients with localized prostate cancer (cT1-T3, cN0, cM0) were prospectively collected. RARP with total anatomical reconstruction was performed in all the cases by an experienced surgeon. Lymph node dissection was performed if the patient was in high-risk group according to the D'Amico risk classification. The primary endpoint was urinary continence recovery time after catheter removal. Postoperative and pathological variables were analyzed. Continence was rigo-rously analyzed 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after catheter removal. Continence was evaluated by recording diaper pads used per day, and all the patients were instructed to perform the 24-hour pad weight test until full recovery of urinary continence. The patient was defined as continent if no more than one safety pad were needed per day, or no more than 20-gram urine leakage on the 24-hour pad weight test. Time from catheter removal to full recovery of urinary continence was recorded, and risk factors influencing continence recovery time evaluated. RESULTS: In total, 166 patients were analyzed. The mean age of the enrolled patients was 66.2 years, and the median prostate specific antigen (PSA) was 8.51 µg/L. A total of 59 patients (35.5%) had bilateral lymphatic dissection, and 28 (16.9%) underwent neurovascular bundle (NVB) preservation surgery. Postoperative pathology results showed that stage pT1 in 1 case (0.6%), stage pT2 in 77 cases (46.4%), stage pT3 in 86 cases (51.8%), and positive margins in 28 patients (16.9%). Among patients who underwent lymph node dissection, lymph node metastasis was found in 7 cases (11.9%). Median continence recovery time was one week. The number of the continent patients at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 65 (39.2%), 32 (19.3%), 34 (20.5%), 24 (14.5%), and 9 (5.4%). Two patients remained incontinent 24 weeks after catheter removal. The continence rates after catheter removal at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 39.2%, 58.4%, 78.9%, 93.4%, and 98.8%, respectively. Univariate COX analysis revealed that diabetes appeared to influence continence recovery time (OR=1.589, 95%CI: 1.025-2.462, P=0.038). At the end of 48 hours, 4 weeks, 12 weeks, and 24 weeks after catheter removal, the mean OABSS score of the continent group was significantly lower than that of the incontinent group. CONCLUSION: RARP showed promising results in the recovery of urinary continence. Diabetes was a risk factor influencing continence recovery time. Bladder overactive symptoms play an important role in the recovery of continence after RARP.

[Establishment and consistency verification of the standard operation procedure for laboratory detection of immunoglobulin G oligoclonal bands in cerebrospinal fluid].

Objective: To establish the standard operation procedure (SOP) for detection of oligoclonal band (OCB) in cerebrospinal fluid (CSF) and verify consistency by using this SOP in different laboratories. Methods: The SOP for detection of CSF-OCB fluid was successfully established by an expert feedback approach. Neuroimmunology laboratories in 3 representative Chinese three-tier research hospitals were selected for this study, and commercially available protein electrophoresis automation systems and detection SOP were set up. The quality control product was provided by the College of American Pathologists (CAP) and Sebiacompany were used for interior quality and compared to each other, respectively. Seventeen serum and CSF paired samples were tested and compared using the same SOP. Kappa test or Kendall W test were adopted to evaluate the inter-laboratory consistency among different hospitals. Results: The results of repeated testings in a single hospital suggested that the 2-and 4-fold dilution for CSF-OCB were reported as positive, while 64-and 128-fold dilution were reported as negative. Positive or negative inconsistencies were reported in 8-, 16-, and 32-fold dilution. After increasing the number of repetitions, the results showed that both 16-and 32-fold dilution were reported as negative, and 8-fold dilution exhibited negative results (2 positive results for 40 repetitions, coincidence rate=95%).The results of multi-center inter-laboratory quality assessment showed that the detection consistency rate among 3 hospitals was 100% (Kappa value =1). Conclusions: The SOP to detect CSF-OCB established in this study demonstrates a good repeatability and stability. Therefore,such SOP would be a good reference for diagnostic laboratories to detect CSF-OCB in China.

POGLUT1 biallelic mutations cause myopathy with reduced satellite cells, α-dystroglycan hypoglycosylation and a distinctive radiological pattern.

Protein O-glucosyltransferase 1 (POGLUT1) activity is critical for the Notch signaling pathway, being one of the main enzymes responsible for the glycosylation of the extracellular domain of Notch receptors. A biallelic mutation in the POGLUT1 gene has been reported in one family as the cause of an adult-onset limb-girdle muscular dystrophy (LGMD R21; OMIM# 617232). As the result of a collaborative international effort, we have identified the first cohort of 15 patients with LGMD R21, from nine unrelated families coming from different countries, providing a reliable phenotype-genotype and mechanistic insight. Patients carrying novel mutations in POGLUT1 all displayed a clinical picture of limb-girdle muscle weakness. However, the age at onset was broadened from adult to congenital and infantile onset. Moreover, we now report that the unique muscle imaging pattern of "inside-to-outside" fatty degeneration observed in the original cases is indeed a defining feature of POGLUT1 muscular dystrophy. Experiments on muscle biopsies from patients revealed a remarkable and consistent decrease in the level of the NOTCH1 intracellular domain, reduction of the pool of satellite cells (SC), and evidence of α-dystroglycan hypoglycosylation. In vitro biochemical and cell-based assays suggested a pathogenic role of the novel POGLUT1 mutations, leading to reduced enzymatic activity and/or protein stability. The association between the POGLUT1 variants and the muscular phenotype was established by in vivo experiments analyzing the indirect flight muscle development in transgenic Drosophila, showing that the human POGLUT1 mutations reduced its myogenic activity. In line with the well-known role of the Notch pathway in the homeostasis of SC and muscle regeneration, SC-derived myoblasts from patients' muscle samples showed decreased proliferation and facilitated differentiation. Together, these observations suggest that alterations in SC biology caused by reduced Notch1 signaling result in muscular dystrophy in LGMD R21 patients, likely with additional contribution from α-dystroglycan hypoglycosylation. This study settles the muscular clinical phenotype linked to POGLUT1 mutations and establishes the pathogenic mechanism underlying this muscle disorder. The description of a specific imaging pattern of fatty degeneration and muscle pathology with a decrease of α-dystroglycan glycosylation provides excellent tools which will help diagnose and follow up LGMD R21 patients.

Modified staging system for gastric neuroendocrine carcinoma based on American Joint Committee on Cancer and European Neuroendocrine Tumor Society systems.

BACKGROUND: The prognostic values of the AJCC staging system for gastric cancer (GC-AJCC), the AJCC staging system for gastric neuroendocrine tumours (NET-AJCC) and the European Neuroendocrine Tumor Society (ENETS) system for gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma (MA)NEC remain controversial. METHODS: Data on patients with (MA)NEC from 21 centres in China were analysed. Different staging systems were evaluated by performing Kaplan-Meier survival analysis and calculating the concordance index (C-index) and Akaike information criterion (AIC). Based on three existing systems, a modified staging system (mTNM) was developed. RESULTS: A total of 871 patients were included. In the GC-AJCC system, an overlap was noticed for pT2 and pT3 categories. Patients with stage IIIC disease had a similar prognosis to those with stage IV disease. The pT categories of the NET-AJCC system had a lower C-index and higher AIC than those of the other systems. In the ENETS system, there was a low proportion (0·2 per cent) of patients with stage IIIA and a high proportion (67·6 per cent) of stage IIIB disease. The mTNM system adopted the NET-AJCC pT and GC-AJCC pN and pM definitions, and was developed based on the ENETS stage definitions. The proportion of patients in each stage was better distributed and the mTNM system showed improved prognostic performance in predicting overall and disease-free survival. CONCLUSION: The mTNM system offers more accurate prognostic value for gastric (MA)NEC than the AJCC or ENETS staging systems.

Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas.

BACKGROUND: The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G-NECs) or mixed adenoneuroendocrine carcinomas (G-MANECs). METHODS: The study included patients with G-NECs or G-MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan-Meier method. RESULTS: In total, 804 patients with resectable G-NECs or G-MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no-chemotherapy group. Among patients with G-NECs, survival in the fluorouracil (5-FU)-based chemotherapy group and the non-5-FU-based chemotherapy group was similar to that in the no-chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G-NECs. Among patients with G-MANECs, OS in the non-5-FU-based chemotherapy group was worse than that in the no-chemotherapy group. Patients with G-MANECs did not have better OS when platinum-based chemotherapy was used. CONCLUSION: There was no survival benefit in patients who received adjuvant chemotherapy for G-NECs or G-MANECs.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G-NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G-MANECs). MÉTODOS: Se incluyeron pacientes con G-NECs y G-MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan-Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento. RESULTADOS: En total, se incluyeron en el estudio 804 pacientes con G-NECs y G-MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G-NECs, la supervivencia en los grupos con quimioterapia basada en 5-FU (fluorouracilo) y de quimioterapia sin 5-FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G-NECs. En pacientes con G-MANECs, la OS del grupo con quimioterapia sin 5-FU fue peor que la del grupo sin quimioterapia. Los pacientes con G-MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos. CONCLUSIÓN: La administración de quimioterapia adyuvante en pacientes con G-NECs y G-MANECs no mejoró la supervivencia.

Perimysial microarteriopathy in dermatomyositis with anti-nuclear matrix protein-2 antibodies.

BACKGROUND AND PURPOSE: Dermatomyositis (DM) with anti-nuclear matrix protein-2 (NXP-2) antibodies usually shows multifocal ischaemic lesions in muscle. Here, we aimed to investigate the microarteriopathy underlying muscle ischaemia in anti-NXP-2-positive DM. METHODS: A total of 16 patients diagnosed with anti-NXP-2-positive DM were investigated by muscle biopsy. A total of 13 patients with DM with other myositis-specific antibodies and 11 normal controls were included for comparison. Immunofluorescence assays were performed to localize endothelial cells, smooth muscle cells and pericytes, and to determine lesions in myofibers and microvessels by vascular endothelial growth factor and myxovirus resistance protein A (MxA). Electron microscopy was carried out to assess ultrastructure alterations. RESULTS: Subcutaneous edema, severe muscle weakness and dysphagia together with elevated creatine kinase, D-dimer and triglyceride levels, and decreased albumin levels were found in anti-NXP-2-positive DM. Muscle ischaemia included regional muscle edema, perifascicular atrophy, microinfarcts and focal punched-out vacuoles. The density of arterioles was higher in anti-NXP-2-positive DM (P ï¼œ 0.05). Perimysial arterioles with thickened vascular wall, thrombosis and lipid accumulation were found in the vascular wall of diseased perimysial arterioles. The frequency of diseased arterioles and thrombosis was higher in anti-NXP-2-positive DM (P < 0.05). Sarcoplasmic vascular endothelial growth factor and MxA expression was observed in multifocal ischaemic lesions. MxA was present in endothelial and smooth muscle cells of the diseased arterioles and pericytes. Electron microscopy confirmed damaged capillaries and tubuloreticular structures. CONCLUSIONS: Our research suggested that perimysial arterioles were most commonly involved in anti-NXP-2-positive DM, which led to muscle ischaemia.

Cine magnetic resonance urography for postoperative evaluation of reconstructive urinary tract after ileal ureter substitution: initial experience.

AIM: To report the initial experiences with functional cine magnetic resonance urography (cine MRU) and assess its usefulness as a novel postoperative evaluation method of ileal ureter substitution. MATERIALS AND METHODS: The medical records of 17 patients from who underwent cine MRU during June 2010 to December 2019 during their follow-up after ileal ureter substitution were collected. The cine MRU videos of reconstructive urinary tract were observed, and the luminal diameter, contraction ratio, peristaltic waves, and ureteral jets were measured. RESULTS: Seventeen patients underwent cine MRU after ileal ureter substitution during their follow-up. Based on their cine MRU videos assessing the morphology and the peristaltic motility of the reconstructive urinary tract, there was resolution of preoperative hydronephrosis, which matched their ameliorative renal function. Clearly, peristaltic motility of the ileal graft was observed in 14 patients with obvious peristaltic waves and ureteral jets. CONCLUSION: This study is the first to assess the clinical utility of functional cine MRU during the patient follow-up after ileal ureter substitution. Cine MRU is a radiation-free, non-invasive imaging method that can clearly show the morphology and the peristaltic motility of the ileal graft. Therefore, cine MRU, as a novel technique, will be extremely useful in the postoperative evaluation of patients after ileal ureter substitution.

Gradient subthalamic neurodegeneration and tau pathology in the hypoglossal nucleus as essential pathological markers of progressive supranuclear palsy - Richardson syndrome.

Progressive supranuclear palsy - Richardson syndrome (PSP-RS) was first described in 1964 by Steele et al. Tau pathology has not been reported in the hypoglossal nuclei of PSP-RS patients, whereas Steele et al. described gliosis with no remarkable neuronal losses in the hypoglossal nucleus. This study aimed to investigate the distribution and degree of tau pathology-associated neurodegeneration, with an emphasis on the hypoglossal nucleus, in patients with PSP-RS. Six clinicopathologically proven PSP-RS cases were included in this study. All patients were clinicopathologically and immunohistochemically re-evaluated. This study confirmed the following neuropathological characteristics of PSP-RS: (1) neurodegeneration usually affects the striatonigral system and cerebellar dentate nucleus; (2) the cerebellar afferent system in PSP-RS is affected by absent-to-mild neurodegeneration; and (3) the extent of tau distribution throughout the central nervous system is greater than the extent of neurodegeneration. Furthermore, we found that subthalamic neurodegeneration was more prominent in the ventromedial region than in the dorsolateral region. Nevertheless, the tau pathology showed no remarkable differences between these two sites. Interestingly, the tau pathology was frequently observed in the hypoglossal nuclei of PSP-RS patients. Gradient neurodegeneration of the subthalamus and tau pathology in the hypoglossal nucleus could be regarded as essential pathological features of PSP-RS.

[Correlation study on anti-Ro52 antibodies frequently co-occur with other myositis-specific and myositis-associated autoantibodies].

OBJECTIVE: Anti-Ro52 antibodies are frequently co-occur with other myositis-specific and myositis-associated autoantibodies, we here to study this phenomenon in Chinese patients suspected with inflammatory myopathies. METHODS: In the study, 1 509 patients clinically suspected with inflammatory myopathies were tested for 11 kinds of myositis-specific and myositis-associated autoantibodies (including: anti-Jo-1, PL-7, PL-12, EJ, OJ, Mi-2, SRP, Ku, PM-Scl 75, PM-Scl 100, and Ro52 antibo-dies) by line-blot immunoassay from 2010 to 2016 in Peking University First Hospital. This retrospective study was to analyze these results to reveal the characteristics of anti-Ro52 antibodies co-occuring with other myositis autoantibodies. The data were analyzed using SPSS 17.0 and Graph Pad PRISM for Chi-square test, independent t-test, Pearson's correlation analysis, and drawing statistical graphs. Significance level was set at P < 0.05. RESULTS: The positive rate of anti-Ro52 antibodies was 18.3% (276/1 509 cases), which was the most frequently detected myositis antibodies in our center. 51.8% (143/276) of the patients with anti-Ro52 antibodies were combined with the other myositis antibodies, and the most common co-occurred antibodies were anti-SRP antibodies (18.8%, 52/276), and the second common co-occurred antibodies were anti-Jo-1 antibodies (13.0%, 36/276). Anti-Ro52 antibodies were the most common antibodies that co-occurred in other myositis antibodies positive patients except in anti-OJ antibodies positive group. The co-positive rate with anti-Ro52 antibodies was the lowest in anti-PM-Scl 75 positive group (30.4%, 31/102), and the highest in anti-EJ positive group (80.0%, 12/15). The positive rate of anti-Ro52 antibodies in anti-synthase antibodies (including anti-Jo-1, EJ, OJ, PL-7, and PL-12 antibodies) positive group was 57.3% (75/131), which was significantly higher than that in the other antibodies (including: anti-Mi-2, SRP, Ku, PM-Scl 75, and PM-Scl 100 antibodies) positive group with 35.2% (119/338) (χ2=18.916, P < 0.001). The intensity of anti-Jo-1, EJ, and SRP antibodies in the group of the patients that co-occurred with anti-Ro52 antibodies was significantly higher than that in the other group without anti-Ro52 antibodies respectively (P < 0.05). The intensity of anti-SRP antibodies was significantly correlated with that of anti-Ro52 antibodies (r=0.44, P=0.001). CONCLUSION: Anti-Ro52 antibodies were commonly associated with other myositis-specific and myositis-associated autoantibodies, especially with anti-synthase antibodies, and the co-presence of anti-Ro52 antibodies may be correlated with the myositis antibody intensity.

[Robot-assisted laparoscopic upper urinary tract reconstruction surgery: A review of 108 cases by a single surgeon].

OBJECTIVE: To summarize the experiences and outcomes of 108 robot-assisted laparoscopic upper urinary tract reconstruction surgeries conducted by a single surgeon. METHODS: We consecutively and retrospectively reviewed 108 patients who underwent robot-assisted laparoscopic upper urinary tract reconstruction surgeries by a single surgeon from November 2018 to January 2020. The patient demographics, perioperative variables, postoperative complications and follow-up data were recorded. Fifty-three modified dismembered pyeloplasties (MDP), 11 spiral flap pyeloplasties (SFP), 11 ure-teroureterostomies (UUT), 4 lingual mucosal onlay graft ureteroplasties (LMU), 5 appendiceal onlay flap ureteroplasties (AU), 11 ureteral reimplantations (UR), 6 Boari flap-Psoas hitch surgeries (BPS) and 7 ileal ureter replacements (IUR) were enrolled finally. The success was defined as the improvement in subjective pain levels, and the improvement in the degree of hydronephrosis at ultrasound. RESULTS: All the surgeries were successfully completed without open or laparoscopic conversion. The median operative time was 141 min (range: 74-368 min), median blood loss was 20 mL (range: 10-350 mL) and median hospital stay was 4 d (range: 3-19 d) in MDP group, with the success rate of 94.3%. The median operative time was 159 min (range: 110-222 min), median blood loss was 50 mL (range: 20-150 mL) and median hospital stay was 5 d (range: 3-8 d) in SFP group, with the success rate of 100%. The median operative time was 126 min (range: 76-160 d), median blood loss was 20 mL (range: 10-50 mL) and median hospital stay was 5 d (range: 4-9 d) in UUT group, with the success rate of 100%. The median operative time was 204 min (range: 154-250 min), median blood loss was 30 mL (range: 10-100 mL) and median hospital stay was 6 d (range: 4-7 d) in LMU group, with the success rate of 100%. The median operative time was 164 min (range: 135-211 min), median blood loss was 75 mL (range: 50-200 mL) and median hospital stay was 8.5 d (range: 6-12 d) in AU group, with the success rate of 100%. The median operative time was 149 min (range: 100-218 min), median blood loss was 20 mL (range: 10-50 mL) and median hospital stay was 7 d (range: 5-10 d) in UR group, with the success rate of 90.9%. The median operative time was 166 min (range: 137-205 min), median blood loss was 45 mL (range: 20-100 mL) and median hospital stay was 5 d (range: 4-41 d) in BPS group, with the success rate of 83.3%. The median operative time was 270 min (range: 227-335 min), median blood loss was 100 mL (range: 10-100 mL) and median hospital stay was 7 d (range: 5-26 d) in IUR group, with the success rate of 85.7%. CONCLUSIONS: The surgeon performed and modified numerous complicated upper urinary tract reconstruction surgeries by the robotic platform, which facilitated the development of the standardized upper urinary tract reconstruction surgical technique.

Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis.

BACKGROUND: Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS: Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS: Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS: Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE.

Cartilage oligomeric matrix protein, C-terminal cross-linking telopeptide of type II collagen, and matrix metalloproteinase-3 as biomarkers for knee and hip osteoarthritis (OA) diagnosis: a systematic review and meta-analysis.

OBJECTIVE: This study was design to examine the diagnostic performance of cartilage oligomeric matrix protein (COMP), C-terminal cross-linking telopeptide of type II collagen (CTX-II), and matrix metalloproteinase-3 (MMP-3) as biomarker for knee and hip OA. METHODS: Systematic search on multiple databases was completed in January 2018 using certain keywords. COMP, CTX-II, MMP-3 levels in knee and hip OA patients and healthy individuals were collected and calculated. Differences between subgroups were expressed as standardized mean differences (SMD). Subgroup analyses were performed to compare COMP, CTX-II, and MMP-3 performance between measuring sources, genders, large and small sample size and diagnostic criteria for OA patients. RESULTS: A moderate performance of COMP in distinguishing between knee (SMD: 0.68; 95% confidence intervals (CI): 0.43-0.93; P < 0.0001) or hip (SMD: 0.25; 95% CI, 0.10, 0.40; P = 0.0008) OA patients and controls were found. CTX-II showed a moderated standardised mean differences (SMD) of 0.48 (95% CI, 0.32, 0.64; P < 0.0001) in the detection of knee OA and a large SMD of 0.76 (95% CI, 0.09, 1.42; P = 0.03) in diagnosing hip OA. A small SMD of 0.32 (95% CI, -0.03, 0.67; P = 0.07) was found for MMP-3 performance and the results did not reach statistic significance. Progression study revealed potential effectiveness of serum COMP in predicting OA progression. Subgroup analysis showed that serum COMP and urinary CTX-II performed better in male than female. Study size and diagnostic criteria did not significantly influence the pooled SMD, but they might be the sources of heterogeneity among studies. CONCLUSION: The overall results indicates that serum COMP and urinary CTX-II can distinguish between knee or hip OA patients and control subjects. Serum COMP is effective in predicting OA progression.Further researches with rigorous study design and a larger sample size are required to validate our findings.

[Propensity-matched comparison of laparoscopic and open radical cystectomy for female patients with bladder cancer].

OBJECTIVE: To compare the perioperative and oncologic outcomes of female patients receiving laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC). METHODS: Retrospective review of 91 consecutive female patients with urothelial carcinoma of bladder undergoing radical cystectomy at a single academic institution from 2006 to 2017. Those female patients received open radical cystectomy were matched to the patients who underwent laparoscopic radical cystectomy by using propensity score matching in 1 ∶1 ratio. The matching factors included age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, pathologic stage and pathologic nodal stage. The perioperation and oncology characteristics were compared, and Kaplan-Meier method was used to analyze the overall survival (OS), cancer specific survival (CSS) and progression-free survival (PFS) estimates. Finally, we did a sensitive analysis by using multivariable COX regression of all the patients, adjusting for the matching factors. RESULTS: There were 65 ORC and 26 LRC patients identified in this cohort with urothelial carcinoma of bladder, the median follow-up time was 38 months (interquartile range 18-69). The age (P<0.001) and ASA scores (P=0.018) were less for LRC before being matched. There were 22 LRC and 22 ORC patients matching successfully. Before being matched, the estimate blood loss (P=0.005), transfusion rate (P<0.001) and total complications rate (P=0.015) were less for LRC, and the lymph nodes yield was greater for LRC, but there were no differences in OS (P=0.698), CSS (P=0.942) and PFS (P=0.837) between the two groups. After being matched, the estimate blood loss (P=0.009), transfusion rate (P=0.001) and total complications rate (P=0.040) were less for LRC, but there was no difference in the lymph nodes yield. Besides, there were no statistic differences in OS (P=0.432), CSS (P=0.429) and PFS (P=0.284) between the two groups. In addition, in multivariable COX regression analysis, surgical approaches (LRC/ORC) were not found to be a predictor of OS (HR 1.134, 95%CI 0.335-3.835, P=0.839), CSS (HR 1.051, 95%CI 0.234-4.719, P=0.949) and PFS (HR 0.538, 95%CI 0.138-2.095, P=0.371) of the female patients with urothelial carcinoma of bladder. CONCLUSION: It is advantageous for laparoscopic radical cystectomy in terms of estimating blood loss, transfusion rate and complication rate. But there was no evidence that laparoscopic radical cystectomy for female patients with bladder cancer had a better oncologic prognosis than open radical cystectomy from this study.