Thiazolidinediones Decrease the Recurrence of Intracerebral Hemorrhage in Type 2 Diabetes Mellitus Patients: A Nested Case-Control Study.

INTRODUCTION: Preclinical evidence demonstrated the therapeutic potential of TZDs for the treatment of intracerebral hemorrhage (ICH). The present study conducted an investigation of cerebrovascular and cardiovascular outcomes following ICH in patients with type 2 diabetes mellitus (T2DM) treated with or without TZDs. METHODS: This retrospective nested case-control study used data from the Taiwan National Health Insurance Research Database. A total of 62,515 T2DM patients who were hospitalized with a diagnosis of ICH were enrolled, including 7,603 TZD users. Data for TZD non-users were extracted using propensity score matching. Primary outcomes included death and major adverse cardiovascular events (MACEs), which were defined as a composite of ischemic stroke, hemorrhagic stroke (HS), acute myocardial infarction (AMI), and congestive heart failure (CHF). Patients aged < 20 years with a history of traumatic brain injury or any prior history of MACEs were excluded. RESULTS: TZD users had significantly lower MACE risks compared with TZD non-users following ICH (adjusted hazard ratio [aHR]: 0.90, 95% confidence interval [CI]: 0.85-0.94, p < 0.001). The most significant MACE difference reported for TZD users was HS, which possessed lower incidence than in TZD non-users, especially for the events that happened within 3 months following ICH (aHR: 0.74, 95% CI: 0.62-0.89 within one month, p < 0.01; aHR: 0.68, 95% CI: 0.54-0.85 between 1-3 month). CONCLUSION: The use of TZD in patients with T2DM was associated with a lower risk of subsequent HS and mortality following ICH.

Comparing the Long-Term Cardiovascular Outcomes of Lumbo-Peritoneal, Ventriculo-Peritoneal, or Non-Shunting Treatment after Idiopathic Normal Pressure Hydrocephalus: A Nationwide Retrospective Cohort Study.

Purpose: With advances in medical technology, the average lifespan has increased, leading to a growing significance of idiopathic normal pressure hydrocephalus (iNPH), particularly in the elderly population. Most patients with iNPH have been treated either with ventriculo-peritoneal shunts (VPS) or conservative measures. However, lumbo-peritoneal shunts (LPS) have emerged as an alternative treatment option for iNPH in recent decades, extensive research still lacks comparing outcomes with LPS to those with VPS or non-surgical treatment. The aim of the resent study is to disclose the long-term therapeutic outcomes of LPS, VPS, and non-shunting in patients with iNPH. Methods: We used the National Health Insurance Research Database in Taiwan to assess the long-term outcomes of these treatment options. We enrolled 5,537 iNPH patients who received shunting surgery, of which 5,254 were VPS and 283 were LPS. To compare the difference between each group, matching was conducted by propensity score matching using a 1:1 ratio based on LPS patients. Primary outcomes included death and major adverse cardiovascular events (MACEs) Results: Our findings show that VPS resulted in significantly more MACEs than non-surgical treatment (Odds ratio: 1.83, 95% confidence interval: 1.16-2.90). In addition, both VPS and LPS groups had significantly lower overall mortality rates than non-shunting group. Moreover, LPS had lower overall mortality but similar MACEs rates to VPS. Conclusions: Based on these findings, we propose that the LPS is preferable to the VPS, and surgical treatment should be considered the primary choice over conservative treatment unless contraindications are present.

Machine Learning Assisting the Prediction of Clinical Outcomes following Nucleoplasty for Lumbar Degenerative Disc Disease.

BACKGROUND: Lumbar degenerative disc disease (LDDD) is a leading cause of chronic lower back pain; however, a lack of clear diagnostic criteria and solid LDDD interventional therapies have made predicting the benefits of therapeutic strategies challenging. Our goal is to develop machine learning (ML)-based radiomic models based on pre-treatment imaging for predicting the outcomes of lumbar nucleoplasty (LNP), which is one of the interventional therapies for LDDD. METHODS: The input data included general patient characteristics, perioperative medical and surgical details, and pre-operative magnetic resonance imaging (MRI) results from 181 LDDD patients receiving lumbar nucleoplasty. Post-treatment pain improvements were categorized as clinically significant (defined as a ≥80% decrease in the visual analog scale) or non-significant. To develop the ML models, T2-weighted MRI images were subjected to radiomic feature extraction, which was combined with physiological clinical parameters. After data processing, we developed five ML models: support vector machine, light gradient boosting machine, extreme gradient boosting, extreme gradient boosting random forest, and improved random forest. Model performance was measured by evaluating indicators, such as the confusion matrix, accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC), which were acquired using an 8:2 allocation of training to testing sequences. RESULTS: Among the five ML models, the improved random forest algorithm had the best performance, with an accuracy of 0.76, a sensitivity of 0.69, a specificity of 0.83, an F1 score of 0.73, and an AUC of 0.77. The most influential clinical features included in the ML models were pre-operative VAS and age. In contrast, the most influential radiomic features had the correlation coefficient and gray-scale co-occurrence matrix. CONCLUSIONS: We developed an ML-based model for predicting pain improvement after LNP for patients with LDDD. We hope this tool will provide both doctors and patients with better information for therapeutic planning and decision-making.

Analysis of the clinical and radiological outcomes of percutaneous cervical nucleoplasty: A case-control study.

BACKGROUND: Percutaneous cervical nucleoplasty (PCN) is a simple, safe, and effective treatment for contained cervical herniated intervertebral disc (CHIVD). However, few studies have compared the actual benefits of PCN against conservative treatment (CT), either clinically or radiographically. PURPOSE: The present study sought to analyze and to compare the outcomes of symptomatic contained CHIVD treated with PCN or CT. METHODS: The present study was designed as a case-control comparative study. Patients who indicated for PCN after a failed CT for more than 6 months were recruited. After the exclusion of some patients who did not meet the selection criteria of the study, we finally enrolled 71 patients treated with PCN. In addition, another 21 patients who indicated for PCN but finally chose to receive CT continuously were also enrolled and categorized as the control group. All patients completed the 6-month follow-up. Pain levels and functional outcomes were evaluated pre- and post-operatively by assessing the visual analog scale (VAS), Oswestry Disability Index (ODI), and Neck Disability Index (NDI). Radiographic images of 72 of 104 intervened segments were collected to measure disc height and other cervical spinal alignments, such as range of motion, C2-7 Cobb's angle, and C2-7 sagittal vertical axis. RESULTS: Compared with the CT group, the PCN group showed significantly better outcomes on VAS, ODI, and NDI at the 1-month post-operative follow-up, which continued through at least the 6-month follow-up (P < 0.01 for VAS and P < 0.05 for ODI and NDI). The mean disc height significantly decreased, from 6.04 ± 0.85 mm to 5.76 ± 1.02 mm, 3 months after PCN treatment (P = 0.003). However, the degree of disc height decrease did not correlate with the changes of the substantial VAS improvement. CONCLUSIONS: To provide therapeutic benefits for symptomatic contained CHIVD patients after an invalid CT for 6 months, PCN seems to be a better option than CT. The reduced disc heights did not alter the clinical outcomes of PCN.

Surgical interventions for Bertolotti's syndrome: case report and review of unsatisfactory cases in the literature.

BACKGROUND: Bertolotti's syndrome (BS) is characterized by the enlargement of transverse processes in caudal lumbar segments, causing chronic and persistent low back pain or sciatica. The present study aimed to describe our surgical technique for BS treatment and to review existing literature describing unsatisfactory outcomes. CASE PRESENTATION: We report a patient who complained of lower back pain and soreness that intermittently radiated to his left leg for longer than 10 years. Based on an examination of his symptoms and signs, including imaging and electrical physiology assessments, in addition to the report of temporary pain relief after a local steroid injection to a diagnostic trigger site (articulation between the transverse process and the sacral ala or iliac crest), the patient was diagnosed with BS. The applied surgical techniques included minimally invasive, three-dimensional C-arm guidance, a tubing approach, and microscopic and bone cavitron ultrasonic surgical aspirator-assisted operations. After surgery, improvements were reported on the visual analog scale (from 8 to 2 points on a 10-point scale) and the straight leg raising test for the left leg (20° to 90°) within 3 days. The patient gained an ordinary life and returned to work within one week of surgery, with no observed postoperative complications. CONCLUSIONS: Minimally invasive tubular microscopic decompression and disarticulation is an effective method for treating BS. However, to achieve a successful outcome, it is recommended to use physician-proficient techniques that are in line with the patient's diagnosis.

Primary osseous chondrosarcoma in the lumbar spine: case report and literature review with analysis.

Primary spinal chondrosarcoma (CS) is rare. Only a few previous case reports have included a detailed description of the surgical process used to treat the CS. In addition, a paucity of documentation exists comparing differences in the outcomes between the approaches in en bloc resection. Here, we present a case of CS in the lumbar (L) spine treated with two-stage (anterior and posterior approach) en bloc surgery and analyze the differences between one-stage and two-stage approaches in the treatment of primary lumbar CS. A 30-year-old male patient with an L3 vertebral body CS presented with back pain and lower limb weakness. Lumbar spine magnetic resonance imaging (MRI) showed an L3 vertebral body tumor with cord and root compression. Two-stage surgery comprising posterior total laminectomy and transpedicular screw fixation over L2-L4 in the first stage, with subsequent anterior corpectomy, cage implantation, and anterior lumbar interbody fusion was performed to achieve total tumor removal and stabilization. The patient's symptoms improved postoperatively, with no recurrence as of the 2-year follow-up. The analysis of previous similar cases showed that two-stage surgery, compared with one-stage surgery, appears to be beneficial in lumbar spine multisegment disease, providing a lower recurrence rate.

Effects of Diatomaceous Earth on House Dust Mite Sensitization in BALB/c Mice.

BACKGROUND: House Dust Mite (HDM) is associated with hypersensitivity such as asthma. Patients with asthma benefit from improved living environment by reducing HDM exposure. In this study, we examined the effects of commercialized diatomaceous earth product, Casaggia® used as construction materials, on hypersensitivity in HDM-sensitized mice. METHODS: Male mice were sensitized with house dust mite extract for 7d and then housed in diatomaceous earth (DE)-coated cages for 14 days at Animal Center of the Taichung Veterans General Hospital, Taichung, Taiwan in 2014. Levels of cytokine were determined using ELISA. White blood cell counts were recorded over 21d. Histological analysis was conducted to determine the remodeling of respiratory tract. RESULTS: Exposure to DE resulted in a suppression in elevated eosinophilia induced by HDM in mice. In addition, elevated serum IgE responding to HDM sensitization were restored in the presence of DE. DE ameliorated the inflammation progression in airway. CONCLUSION: Environmental exposure to DE is suggested to benefit patients with hypersensitivity through relieving inflammatory symptoms. In a sense of prevention, DE represents a potential material against development of asthma.

Nebulized salbutamol diminish the blood glucose fluctuation in the treatment of non-oliguric hyperkalemia of premature infants.

BACKGROUND: Hyperkalemia is a risky and potentially life-threatening condition in pre-term infants. Glucose-insulin infusion has been considered a major therapeutic way for non-oligouric hyperkalemia but affects the stability of blood sugar level. We aimed to evaluate the effectiveness of salbutamol nebulization compared to glucose-insulin infusion for the treatment of non-oliguric hyperkalemia in premature infants. METHODS: Forty premature infants (gestation age ≤36 weeks) with non-oliguric hyperkalemia (central serum potassium level greater than 6.0 mmol/L) within 72 h of birth were enrolled in this study. These infants were randomly assigned into two groups. One group received a regular insulin bolus with glucose infusion (Group A; n = 20), and the other received salbutamol (Ventolin) by nebulization (Group B; n = 20). Potassium level, blood sugar, heart rate, and blood pressure were recorded for each group before treatment and at 3, 12, 24, 48, and 72 h post-treatment. RESULTS: The serum potassium levels were reduced after treatment in both groups. No significant changes in heart rate or blood pressure were observed in either group. The fluctuation in glucose levels was gentler in the salbutamol-treated group than in the glucose-insulin infusion group. CONCLUSION: Salbutamol nebulization is not only as effective as glucose-insulin infusion for treating non-oliguric hyperkalemia in premature infants but can avoid potential side effects such as vigorous blood glucose fluctuations.

[Network pharmacological study of Schizonepetae Herba and Saposhnikoviae Radix in treatment of ulcerative colitis].

The aim of this paper was to screen the active targets of Schizonepetae Herba and Saposhnikoviae Radix in the treatment of ulcerative colitis by means of network pharmacology,and to investigate their mechanism of action. The effective components of Schizonepetae Herba and Saposhnikoviae Radix were screened out by traditional Chinese medicine systematic pharmacological( TCMSP)database,with oral bioavilability( OB) ≥30% and drug-like( DL) ≥18% selected as the thresholds. Target PPI network was built between the main components and their corresponding targets. One hundred and eighty-two human genes corresponding to the medicine target sites were obtained from Uniprot database; 3 874 genes corresponding to ulcerative colitis were obtained from Genecard database.A total of 115 intersection genes were screened from disease genes and medicine genes,and the PPI interaction analysis was conducted by using String tool. Disease-target PPI network was drawn by using Cytoscape software,and component-target-disease network was constructed. One hundred and eight nodes and 1 882 connections were found,and then Cytoscape software was used to merge the networks and filter the core network for gene GO function analysis and KEGG pathway enrichment analysis. The mechanism of Schizonepetae Herba and Saposhnikoviae Radix was then verified by animal experiment. Gene GO functional analysis suggested that biological process,molecular functions and cell components were involved,and it was found that ulcerative colitis might be related to transcription factor activity,and cytokine receptor binding,etc. Gene KEGG pathway enrichment analysis showed that the mechanism of ulcerative colitis might be associated with TNF and Toll-like receptors( TLRs) signaling pathway-mediated cytoinflammatory factors interleukin-1( IL-1) and interleukin-6( IL6). The possible mechanism of the effective components of Schizonepetae Herba and Saposhnikoviae Radix in treating ulcerative colitis might be related to intervening the cytokine receptor binding of TNF and TLRs signaling pathways,reducing the transcription of nuclear factor-kappaB( NF-κB),and inhibiting the secretion of intestinal inflammatory factors IL-1 and IL-6.

Acetazolamide alleviates sequelae of hyperglycaemic intracerebral haemorrhage by suppressing astrocytic reactive oxygen species.

Hyperglycaemia is associated with the poor outcome after intracerebral haemorrhage (ICH). Acetazolamide (AZA), a kind of carbonic anhydrogenase (CA) inhibitor, its effectiveness in ICH had been reported. However, the connections between AZA and ICH, especially in hyperglycaemia condition had never been defined. In this study, adult Sprague-Dawley rats were administered with vehicle or streptozotocin (STZ) to render them into normoglycaemic (NG) or hyperglycaemic (HG), respectively. Collagenase was then injected into the striatum. The NG or HG ICH rats treated with vehicle control or 5 mg/kg AZA (oral gavage) underwent haemorrhagic area assessments on the 1st, 4th, and 7th day after ICH. The coverage of pericytes was examined by immunohistochemistry. Reactive oxygen species (ROS) levels were assessed in mouse astrocyte cell line treated with vehicle or 20 µmol/L of AZA in culture media according to two different glucose concentrations. AZA reduced the haematoma size, improved neurobehavioral functions, suppressed astrocytic ROS production in vitro, and preserved cerebral pericytes coverage, which are even more remarkable in HG conditions. The present study indicates that AZA may alleviate some sequelae after ICH, especially in poorer prognostic HG rats through the suppression of astrocytic ROS production.

Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage.

Neurological deterioration of intracerebral hemorrhage (ICH) mostly occurs within the first 24 hours. Together with the microglia/macrophages (MMΦ), astrocytes are important cell population responsible for many brain injuries but rarely being highlighted in acute stage of ICH. In present study, we induced rats ICH either by collagenase or autologous blood injection. Experimental groups were classified as vehicle or Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3) treatment group (n = 9, each group). MRI assessments after ICH were used to evaluate the hematoma progression and blood-brain barrier (BBB) integrity. The glia cells accumulations were examined by GFAP and Iba1 immunohistochemistry, respectively. Abundant astrocytes but few MMΦ were observed in hyperacute and acute ICH. Upon suppression of astrocyte activity, ICH rats exhibited decreased size of hematoma expansion, less BBB destruction, reduced astrocyte accumulation in perihematomal regions, postponed course of hemoresolution and gain better outcomes. These finding provide evidence that activated astrocytes are crucial cell populations in hyperacute and acute ICH, and their modulation may offer opportunities for novel therapy and patient management.

R-apomorphine protects against 6-hydroxydopamine-induced nigrostriatal damage in rat.

Objective The aim of the present study was not only to assess the retrograde degenerative changes in the dopaminergic neurons of the substantia nigra (SN) and ventral tegmental area (VTA) after injection of 6-hydroxydopamine (6-OHDA) into the striatum, but also to use this 6-OHDA model of Parkinson's disease to explore the possible neuroprotective effect of R-apomorphine (R-APO). Methods The partial lesion was obtained by intrastriatal administration of 6-OHDA. R-APO administration (10 mg/kg, s.c.) started 15 min prior to lesioning and continued daily for another 22 days post surgery. Testing was carried out 5 weeks after lesioning. We investigated the histology and associated behavior and neurochemical changes. Structural and functional deficits were quantified by tyrosine hydroxylase (TH) / Nissl-staining cell number counting, striatal dopamine (DA) content determination and amphetamine-induced rotation analysis. Results R-APO-treatment attenuated the amphetamine-induced ipsiversive rotation 5 weeks after the lesion induction. R-APO administration for 22 days significantly reduced the size of the lesion at the level of the SN from 50% (control group) to 69%. Moreover, the cell shape resembled that observed in the intact animals. R-APO treatment significantly increased the number of cells in both the lesion and the intact sides of VTA by 60%, suggesting selective neurotrophic effect of R-APO in this area. Finally, R-APO-treatment significantly attenuated the 6-OHDA-induced striatal DA depletion and normalized dihydroxyphenylacetic acid (DOPAC)/DA ratios. Conclusion We conclude that R-APO has neuroprotective and possible neurotrophic effect on a striatal lesion with 6-OHDA, suggesting that this drug may have rescuing properties in patients with early stage Parkinson's disease. These effects are more pronounced in VTA and enhance with duration of treatment.

[Experimental study on the prevention of epidural scar adhesion with polycaprolactone/polylactic acid membrane].

OBJECTIVE: To evaluate the ability of a polycaprolactone/polylactic acid (PCL/PLA) membrane to inhibit epidural scar adhesion after laminectomy, and observe the responsive changes of the pain media in the spinal cord. METHODS: L(1), L(3) laminectomies were performed on 96 Wistar rats. The rats were divided into 3 groups: None-implant Control Group (NC), Autologous free fat graft group (AFFG) and PCL/PLA membrane group (PCL/PLAm). The rats were killed at 1, 3, 6, and 12 weeks postoperatively. Epidural scar formation and adhesion were observed grossly and histologically. Reverse transcription polymerase chain reaction (RT-PCR) were used to analyses the expression of Transforming growth factor beta (TGF-beta) in the epidural scar. Immunohistochemistry stain and RT-PCR were performed to evaluate the expression of the substance P and the c-fos gene in the relevant spinal cord, and the results were analyzed statistically. RESULTS: Gross evaluation and histological evaluation showed that in the NC lamina defect site had much scar tissue and had wide and tight adhesions to the dura; in the AFFG, with the fat degrading gradually, the adhesions were increased; whereas in the PCL/PLAm group, there were slightly adhesions to the dura. RT-PCR showed that the expression of the TGF-beta was much less in the PCL/PLAm group than in the NC group. The insertion of the PCL/PLA membrane and the fat patch reduced the expression of the substance P and the c-fos gene in the spinal cord. CONCLUSION: The insertion of the PCL/PLA membrane reduces scar formation and separates fibrosis tissue from the dura, the results indicate that PCL/PLA membrane is an effective way of reducing peridural scar formation and preventing the failed back surgery syndrome.