急性脑梗死中医治疗现状的思考

简要论述急性脑梗死中医治疗的现状,提出现代中医治疗急性脑梗死应关注的问题,并指出急性脑梗死的发病主要由肝肾不足、脾气亏虚而引发。临床治疗中应重视气虚、肾虚与血瘀的关系,并对活血、凉肝、清热解毒、化痰祛瘀等治法的运用进行探讨。     

Effect of patient age on glioblastoma perioperative treatment costs: a value driven outcome database analysis

Introduction

Identification of groups of patients or interventions with higher associated treatment costs may be beneficial in efforts to decrease the overall financial burden of glioblastoma (GBM) treatment. The authors’ objective was to evaluate perioperative surgical treatment cost differences between elderly and nonelderly patients with GBM using the Value Driven Outcome (VDO) database.

Methods

The authors obtained data from a retrospective cohort of GBM patients treated surgically (resection or biopsy) at their institution from August 2011 to February 2018. Data were compiled using medical records and the VDO database.

Results

A total of 181 patients with GBM were included. Patients were grouped into age?<?70 years at time of surgery (nonelderly; n?=?121) and?≥?70 years (elderly; n?=?60). Costs were approximately 38% higher in the elderly group on average (each patient was mean 0.68% of total cohort cost vs. 0.49%, p?=?0.044). Higher age significantly, but weakly, correlated with higher treatment cost on linear regression analysis (p?=?0.007; R²?=?0.04). Length of stay was significantly associated with increased cost on linear regression (p?<?0.001, R²?=?0.84) and was significantly longer in the elderly group (8.7?±?11.3 vs. 5.2?±?4.3 days, p?=?0.025). The cost breakdown by facility, pharmacy, supply/implants, imaging, and laboratory costs was not significantly different between age groups. Elderly patients with any postoperative complication had 2.1 times greater total costs than those without complication (p?=?0.094), 2.9 times greater total costs than nonelderly patients with complication (p?=?0.013), and 2.3 times greater total costs than nonelderly patients without complication (p?=?0.022).

Conclusions

GBM surgical treatment costs are higher in older patients, particularly those who experience postoperative complications.

     

Traumatic Event Exposure,Posttraumatic Stress Disorder,and Sleep Disturbances in a National Sample of U.S. Adults

Posttraumatic stress disorder (PTSD) is a highly prevalent, debilitating disorder found to develop after exposure to a potentially traumatic event (PTE). Individuals with PTSD often report sleep disturbances, specifically nightmares and insomnia, which are listed within the criteria for PTSD. This research examined prevalence of insomnia and nightmares within a national sample of 2,647 adults (data weighted by age and sex to correct for differences in sample distribution) who had been exposed to one or more PTEs. Prevalence of self‐reported sleep disturbance, sleep disturbances by PTE type, and gender differences were examined. All participants completed a self‐administered, structured online interview that assessed exposure to stressful events and PTSD symptoms. Among individuals who met DSM‐5 criteria for PTSD, a large majority (more than 92%) reported at least one sleep disturbance. Insomnia was relatively more prevalent than PTE‐related nightmares among individuals with PTSD and among all PTE‐exposed individuals. A higher number of PTEs experienced significantly increased the likelihood of both trauma‐related nightmares and insomnia, McFadden's pseudo R² = .07, p < .001. Women exposed to PTEs were more likely to endorse experience of insomnia, χ²(1, N = 2,647) = 99.13, p < .001, φ = .194, and nightmares compared to men, χ²(1, N = 2,648) = 82.98, p < .001, φ = .177, but this gender difference was not significant among individuals with PTSD, ps = .130 and .050, respectively. Differences in sleep disturbance prevalence by PTE type were also examined. Implications for treatment and intervention and future directions are discussed.     

Dermatologic rituximab dosing: treatment of refractory pemphigus vulgaris in an adolescent male

Rituximab is a chimeric monoclonal antibody against CD20 that mediates B-cell depletion. It has been shown to be effective in a variety of autoimmune-related diseases, including pemphigus vulgaris. Most reports of pemphigus treatment utilize the weekly dosing regimen designed for the treatment of B-cell malignancy. The authors report a case of successful treatment of refractory pemphigus vulgaris in an adolescent male using three infusions of rituximab spread over a four-month period of time. The authors also discuss recent updates in rituximab's mechanism of action in autoimmune disease. Rituximab acts to destroy auto-reactive B-cells prior to their development into auto-antibody producing plasma cells. More recent reports have shown that rituximab also indirectly leads to a decrease of autoreactive CD4+ T cells via depletion of B-cells that are necessary for antigen presentation. Monthly to bi-monthly rituximab infusion dosing may be a more appropriate dosing strategy for autoimmune disease that minimizes potential side effects while generating remission of disease. Dermatology continues to see an increase in use of medications designed for treatment of rheumatologic disease and malignancy. Additional studies should focus on the appropriate dosing of these medications for dermatologic conditions that limit the risk of adverse effects while preserving therapeutic benefit.     

Effects of Multimodal Analgesia on the Success of Mouse Embryo Transfer Surgery

Multimodal analgesia is promoted as the best practice pain management for invasive animal research procedures. Universal acceptance and incorporation of multimodal analgesia requires assessing potential effects on study outcome. The focus of this study was to assess effects on embryo survival after multimodal analgesia comprising an opioid and nonsteroidal antiinflammatory drug (NSAID) compared with opioid-only analgesia during embryo transfer procedures in transgenic mouse production. Mice were assigned to receive either carprofen (5 mg/kg) with buprenorphine (0.1 mg/kg; CB) or vehicle with buprenorphine (0.1 mg/kg; VB) in a prospective, double-blinded placebo controlled clinical trial. Data were analyzed in surgical sets of 1 to 3 female mice receiving embryos chimeric for a shared targeted embryonic stem-cell clone and host blastocyst cells. A total of 99 surgical sets were analyzed, comprising 199 Crl:CD1 female mice and their 996 offspring. Neither yield (pups weaned per embryo implanted in the surgical set) nor birth rate (average number of pups weaned per dam in the set) differed significantly between the CB and VB conditions. Multimodal opioid–NSAID analgesia appears to have no significant positive or negative effect on the success of producing novel lines of transgenic mice by blastocyst transfer.Abbreviation: CB, carprofen–buprenorphine; ES cell, embryonic stem cell; ET, embryo transfer; NSAID, nonsteroidal antiinflammatory drug; VB, vehicle–buprenorphineSurgical transfer of mouse embryos (embryonic transfer, ET) to surrogate dams is currently standard procedure in producing transgenic mouse models for research; the technique also is used to reestablish pathogen-free stocks of mice.²⁵ The procedure is invasive, in that it penetrates the peritoneal cavity and reproductive tract, often requires bilateral flank incisions through skin and muscle (each equivalent in length to approximately 10% of the snout–anus length), entails externalization and traction of internal organs, and requires wound closure. The ideal analgesia regimen for rodent ET would safely manage pain in the recipient female mouse without adversely affecting the quality or number of offspring from implanted embryos. Studies to date have found no effect of either the opioid buprenorphine or the nonsteroidal antiinflammatory drug (NSAID) flunixin on the number of embryos surviving after ET when compared with those after untreated or saline-placebo mice.^17,20 Furthermore, no study to date has looked at whether a multimodal combination of opioid and NSAID might either improve or decrease embryo survival.In the present study, we sought to compare reproductive outcomes of NSAID–opioid analgesia compared with opioid alone in embryo-transfer recipient mice by comparing outcomes from surrogate dams treated with carprofen and buprenorphine (CB) with those from dams treated with vehicle and buprenorphine (VB). We performed our analgesic comparison in the context of ongoing work in the University of California–San Francisco Transgenics Core. The Core receives targeted embryonic stem (ES) cell clones from laboratories and microinjects them into 8-cell embryos obtained from superovulated B6D2F1/Crl and Swiss Webster mice. The Core then surgically places these embryos into 1 to 3 recipient female mice, resulting in the generation of mice chimeric for the targeted ES cells and host blastocyst cells. To minimize any effects of learning curves, disruption of routine, and variability to ongoing research, the surgeon was instructed not to deviate from Core protocol in regard to animal anesthesia, handling, or housing. Therefore, the only change was to substitute buprenorphine with either carprofen–buprenorphine or vehicle–buprenorphine.Measured outcomes were the average number of weaned offspring produced per embryo implanted in the surgical set (that is, yield) and the average number of weaned offspring produced per dam in the surgical set (that is, birth rate).     

Morphological anomalies in two Lutzomyia (Psathyromyia) shannoni (Diptera: Psychodidae: Phlebotominae) specimens collected from Fort Rucker, Alabama, and Fort Campbell, Kentucky

This report describes two male specimens of the sand fly species Lutzomyia shannoni (Dyar) (Diptera: Psychodidae: Phlebotominae) collected at Fort Rucker, AL, and Fort Campbell, KY, in dry ice-baited light traps during September 2005. The specimens were observed to have anomalies to the number of spines on the gonostyli. The taxonomic keys of Young and Perkins (Mosq. News 44: 263-285; 1984) use the number of spines on the gonostylus in the first couplet to differentiate two major groupings of North American sand flies. The two anomalous specimens were identified as L. shannoni based on the following criteria: (1) both specimens possess antennal ascoids with long, distinct proximal spurs (a near diagnostic character of L. shannoni in North America), (2) the sequences of the partial cytochrome c oxidase subunit 1 gene from both specimens indicated L. shannoni, and (3) the sequences of the internal transcribed spacer 2 molecular marker from both specimens indicated L. shannoni. The anomalous features are fundamentally different from each other as the Fort Rucker specimen possesses a fifth spine (basally located) on just one gonostylus, whereas the Fort Campbell specimen possesses five spines (extra spines subterminally located) on both gonostyli. Because the gonostyli are part of the external male genitalia, anomalies in the number of spines on the gonostyli may have serious biological consequences, such as reduced reproductive success, for the possessors. These anomalies are of taxonomic interest as the specimens could easily have been misidentified using available morphological keys.     

Different cellular p16(INK4a) localisation may signal different survival outcomes in head and neck cancer

Background:

Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status.

Methods:

Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS).

Results:

A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20–82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status.

Conclusion:

Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status.     

Functional characterization of the 19q12 amplicon in grade III breast cancers

Introduction

The 19q12 locus is amplified in a subgroup of oestrogen receptor (ER)-negative grade III breast cancers. This amplicon comprises nine genes, including cyclin E1 (CCNE1), which has been proposed as its 'driver'. The aim of this study was to identify the genes within the 19q12 amplicon whose expression is required for the survival of cancer cells harbouring their amplification.

Methods

We investigated the presence of 19q12 amplification in a series of 313 frozen primary breast cancers and 56 breast cancer cell lines using microarray comparative genomic hybridisation (aCGH). The nine genes mapping to the smallest region of amplification on 19q12 were silenced using RNA interference in phenotypically matched breast cancer cell lines with (MDA-MB-157 and HCC1569) and without (Hs578T, MCF7, MDA-MB-231, ZR75.1, JIMT1 and BT474) amplification of this locus. Genes whose silencing was selectively lethal in amplified cells were taken forward for further validation. The effects of cyclin-dependent kinase 2 (CDK2) silencing and chemical inhibition were tested in cancer cells with and without CCNE1 amplification.

Results

19q12 amplification was identified in 7.8% of ER-negative grade III breast cancer. Of the nine genes mapping to this amplicon, UQCRFS1, POP4, PLEKHF1, C19ORF12, CCNE1 and C19ORF2 were significantly over-expressed when amplified in primary breast cancers and/or breast cancer cell lines. Silencing of POP4, PLEKHF1, CCNE1 and TSZH3 selectively reduced cell viability in cancer cells harbouring their amplification. Cancer cells with CCNE1 amplification were shown to be dependent on CDK2 expression and kinase activity for their survival.

Conclusions

The 19q12 amplicon may harbour more than a single 'driver', given that expression of POP4, PLEKHF1, CCNE1 and TSZH3 is required for the survival of cancer cells displaying their amplification. The observation that cancer cells harbouring CCNE1 gene amplification are sensitive to CDK2 inhibitors provides a rationale for the testing of these chemical inhibitors in a subgroup of patients with ER-negative grade III breast cancers.     

Safety and pharmacokinetic analysis of methotrexate administered directly into the fourth ventricle in a piglet model

We have developed a piglet model to assess chemotherapy administration directly into the fourth ventricle as a potential treatment for medulloblastoma and other malignant posterior fossa tumors. The objective of this study was to assess safety and pharmacokinetics after methotrexate infusions into the fourth ventricle. Catheters were inserted into the fourth ventricle and lumbar cistern in five piglets. Two milligrams of Methotrexate (MTX) was infused into the fourth ventricle on five consecutive days. Safety was assessed by neurological examination, 4.7 T MRI, and post-mortem pathological analysis. MTX levels in serum and cerebrospinal fluid (CSF) were measured, and area under the concentration–time curve (AUC) was calculated for CSF samples. No neurological deficits were caused by MTX infusions. One piglet died from complications of anesthesia induction for MRI scanning. MRI scans showed accurate catheter placement without signal changes in the brainstem or cerebellum. One piglet had asymptomatic ventriculomegaly. Pathological analysis demonstrated meningitis and choroid plexitis consisting predominantly of CD-3 positive T-lymphocytes in all piglets and a small focal area of subependymal necrosis in one. In all piglets, mean peak MTX level in fourth ventricular CSF exceeded that in lumbar CSF by greater than five-fold. Serum MTX levels were undetectable or negligible. Statistically significant differences between fourth ventricle and lumbar AUC were detected at peaks (P = 0.01) and at all collection time points (P = 0.01) but not at troughs (P = 0.36). MTX can be infused into the fourth ventricle without clinical or radiographic evidence of damage. An inflammatory response without clinical correlate is observed. Significantly higher peak MTX levels are observed in the fourth ventricle than in the lumbar cistern.     

MosquitoMap and the Mal-area calculator: new web tools to relate mosquito species distribution with vector borne disease

Background  

Mosquitoes are important vectors of diseases but, in spite of various mosquito faunistic surveys globally, there is a need for a spatial online database of mosquito collection data and distribution summaries. Such a resource could provide entomologists with the results of previous mosquito surveys, and vector disease control workers, preventative medicine practitioners, and health planners with information relating mosquito distribution to vector-borne disease risk.