Exploring Chemovar-Specific Cannabis Extracts Quantification and Evaluation of Cytotoxic Compounds for Targeting Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) represents one of the most aggressive and metastatic brain tumors, with a dismal success rate of less than three percent after five years, particularly in tumors with active immune checkpoints. This necessitates the development of targeted endogenous agents for precise GBM treatment. Previous experiments utilizing Chemovar Specific Cannabis Extractions (CSCEs), fractionated with polar solvents and quantified using Liquid and Gas Column Chromatography combined with Mass Spectrometry (LC/GCMS), have shown reduced viability and motility in human GBM cell lines. However, the complexity of the botanical substance has hindered the personalization of standard cannabis medicines for GBM due to unknown synergistic effects of multiple compounds. To address this limitation, our study focuses on exposing AM251 cells to chemovar fractions extracted using a non-polar solvent, thereby isolating a broader spectrum of constituents. By employing LC/GCMS in conjunction with Nuclear Magnetic Resonance (NMR), we have identified and quantified nine* compounds present in the non-polar CSCE that exhibit significant efficacy (0.1 μM) in inducing cytotoxicity* in GBM tumor cells. Conversely, the polar fraction in our experiment did not demonstrate efficacy against UM251 cells. The quantification of individual compounds within a cannabis extraction that selectively induces cell death in brain tumors holds promise for guiding future research and facilitating the development of a standardized CSCE for GBM therapy.

Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy

AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.

Outcomes of percutaneous coronary intervention in patients ≥ 75 years： one-center study in a Chinese patient group

ObjectiveTo 调查临床并且病人 &#x02265 的 perioperative 特征；75 经历经皮的冠的干预(一种总线标准) 并且从 2011 年 12 月经历了一种总线标准到 2013 年 11 月的连续题目被划分在这特定的病人 group.Methods1,035 评估与短期的一种总线标准以后的死亡有关的风险因素成四个范畴：(1 ) 有稳定的咽峡炎(SA ) 的病人 &#x02265；75 年(n = 58 ) ；(2 ) 有 SA &#x0003c 的病人；75 年(n = 218 ) ；(3 ) 有急性冠的症候群(交流) 的病人 &#x02265；75 年(n = 155 ) ；(4 ) 有交流 &#x0003c 的病人；75 年(n = 604 ) 。multivariable 逻辑回归分析被进行在病人 &#x02265 检测六月的死亡的风险因素；75 年经历了一种总线标准。临床的 comorbidities，在里面医院生物化学的指示物， perioperative 数据，在里面医院和六月的结果与更年轻的组，一起在四 groups.ResultsCompared 之中被分析并且比较病人 &#x02265；75 年是更可能的有高血压，中风的历史，长期的妨碍的肺的疾病，外部脉管的疾病，心脏性的吃惊和恶意的心律不齐，并且他们与相对更低的重量，血红素，白朊， triglyceride，更高的 creatinine，尿酸，脲氮和 pro-BNP 进入医院。左主要动脉损害，多容器，钙化的损害，长期完全吸藏也是更可能的在老组被看。Univariate 分析揭示了那年龄 &#x02265；在承认，紧急情况一种总线标准，优先的击和长期的肾疾病的 85 年，心脏性的吃惊或严重心律不齐与在老病人 &#x02265 的六月的死亡有关；75 年经历了一种总线标准。Multivariable 逻辑回归证明在承认，长期的肾疾病和优先的击的心脏性的吃惊或严重心律不齐是在老病人 &#x02265 预言六月的死亡的独立风险因素；75 年经历了 PCI.ConclusionsOur 数据的人，显示出那与在 75 年下面的病人相比，老病人(&#x02265；75 年) 经历了一种总线标准的人，有经常伴有 multi-comorbidities， severer 承认条件和复杂冠的损害的死亡，和更多的相对更高的风险。因素和更多强烈地在乎的风险的更好的评估应该被带去病人 &#x02265；75 年经历了一种总线标准治疗减少复杂并发症。

Vanishing bile duct syndrome in human immunodeficiency virus infected adults:A report of two cases

Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes.

Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients

AIM:To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus(HCV)liver transplant(LT)recipients.METHODS:We retrospectively compared the liver biopsies of well-matched HCV LT recipients under calcineurin inhibitors(CNI group,n=21)and mycophenolate(MMF group,n=15)monotherapy,with those patients who successfully withdrawn immunosuppression(IS)therapy from at least 3 years(TOL group,n=10).To perform the well-matched analysis,all HCV transplanted patients from December 1993 were screened.Only those HCV patients who reached the following criteria were considered for the analysis:(1)at least3 years of post-operative follow-up;(2)patients with normal liver graft function under low dose CNI monotherapy(CNI group);(3)patients with normal liver graft function under antimetabolite(Micophenolate Mofetil or coated mycophenolate sodium)monotherapy(MMF group);and(4)recipients with normal liver function without any IS.We excluded from the analysis recipients who were IS free or under monotherapy for<36 mo,recipients with cirrhosis or with unstable liver function tests.RESULTS:Thirty six recipients were enrolled in the study.Demographics,clinical data,time after LT and baseline liver biopsies were comparable in the three groups.After six years of follow-up,there was no worsening of hepatic fibrosis in the MMF group(2.5±1.5Ishak Units vs 2.9±1.7 Ishak Units,P=0.5)and TOL group(2.7±10.7 vs 2.5±1.2,P=0.2).In contrast,a significant increase in the fibrosis score was observed in the CNI group(2.2±1.7 vs 3.9±1.6,P=0.008).The yearly fibrosis progression rate was significantly worse in the CNI group(0.32±0.35)vs MMF group(0.03±0.31,P=0.03),and TOL group(-0.02±0.27,P=0.02).No differences have been reported in grading scores for CNI group(2.79±1.9,P=0.7),MMF group(3.2±1.5,P=0.9)and TOL group(3.1±1.4,P=0.2).Twenty four patients were treated with low dose ribavirin(8TOL,7 MMF,9 CNI).The hepatitis C titers were comparable in the three groups.No episodes of rejection have been reported despite differences of liver function test in the three groups during the observational period.CONCLUSION:IS withdrawal and MMF monotherapy is safe and seems to be associated with the slowest fibrosis progression in HCV LT recipients.

Single vs dual(en bloc) kidney transplants from donors ≤ 5 years of age: A single center experience

AIM: To compare outcomes between single and dual en bloc(EB) kidney transplants(KT) from small pediatric donors. METHODS: Monocentric nonprospective review of KTs from pediatric donors ≤ 5 years of age. Dual EB KT was defined as keeping both donor kidneys attached tothe inferior vena cava and aorta, which were then used as venous and arterial conduits for the subsequent transplant into a single recipient. Donor age was less useful than either donor weight or kidney size in decision-making for kidney utilization as kidneys from donors < 8 kg or kidneys < 6 cm in length were not transplanted. Post-transplant management strategies were standardized in all patients.RESULTS: From 2002-2015, 59 KTs were performed including 34 dual EB and 25 single KTs. Mean age of donors(17 mo vs 38 mo, P < 0.001), mean weight(11.0 kg vs 17.4 kg, P = 0.046) and male donors(50% vs 84%, P = 0.01) were lower in the dual EB compared to the single KT group, respectively. Mean cold ischemia time(21 h), kidney donor profile index(KDPI; 73% vs 62%) and levels of serum creatinine(SCr, 0.37 mg/d L vs 0.49 mg/d L, all P = NS) were comparable in the dual EB and single KT groups, respectively. Actuarial graft and patient survival rates at 5-years follow-up were comparable. There was one case of thrombosis resulting in graft loss in each group. Delayed graft function incidence(12% dual EB vs 20% single KT, P = NS) was slightly lower in dual EB KT recipients. Initial duration of hospital stay(mean 5.4 d vs 5.6 d) and the one-year incidences of acute rejection(6% vs 16%), operative complications(3% vs 4%), and major infection were comparable in the dual EB and single KT groups, respectively(all P = NS). Mean 12 mo SCr and abbreviated MDRD levels were 1.17 mg/d L vs 1.35 mg/d L and 72.5 m L/min per 1.73 m^2 vs 60.5 m L/min per 1.73 m^2(both P = NS) in the dual EB and single KT groups, respectively. CONCLUSION: By transplanting kidneys from young pediatric donors into adult recipients, one can effectively expand the limited donor pool and achieve excellent medium-term outcomes.

Season of the year influences infection rates following total hip arthroplasty

AIM To research the influence of season of the year on periprosthetic joint infections.METHODS We conducted a retrospective review of the entire Medicare files from 2005 to 2014. Seasons were classified as spring, summer, fall or winter. Regional variations were accounted for by dividing patients into four geographic regions as per the United States Census Bureau(Northeast, Midwest, West and South). Acute postoperative infection and deep periprosthetic infections within 90 d after surgery were tracked. RESULTS In all regions, winter had the highest incidence of periprosthetic infections(mean 0.98%, SD 0.1%) and was significantly higher than other seasons in the Midwest, South and West(P < 0.05 for all) but not the Northeast(P = 0.358). Acute postoperative infection rates were more frequent in the summer and were significantly affected by season of the year in the West.CONCLUSION Season of the year is a risk factor for periprosthetic joint infection following total hip arthroplasty(THA). Understanding the influence of season on outcomes following THA is essential when risk-stratifying patients to optimize outcomes and reduce episode of care costs.

Tissue engineering for neuromuscular disorders of the gastrointestinal tract

The digestive tract is designed for the optimal processing of food that nourishes all organ systems.The esophagus,stomach,small bowel,and colon are sophisticated neuromuscular tubes with specialized sphincters that transport ingested food-stuffs from one region to another.Peristaltic contractions move ingested solids and liquids from the esophagus into the stomach;the stomach mixes the ingested nutrients into chyme and empties chyme from the stomach into the duodenum.The to-and-fro movement of the small bowel maximizes absorption of fat,protein,and carbohydrates.Peristaltic contractions are necessary for colon function and defecation.

Current state of endohepatology: Diagnosis and treatment of portal hypertension and its complications with endoscopic ultrasound

The diagnosis and management of cirrhosis and portal hypertension(PH)with its complications including variceal hemorrhage,ascites,and hepatic encephalopathy continues to evolve.Although there are established“standards of care”in liver biopsy and measurement of PH,gastric varices remain an area without a universally accepted therapeutic approach.The concept of“Endo Hepatology”has been used to describe of the applications of endoscopic ultrasound(EUS)to these challenges.EUS-liver biopsy(EUS-LB)offers an alternative to percutaneous and transjuglar liver biopsy without compromising safety or efficacy,and with added advantages including the potential to reduce sampling error by allowing biopsies in both hepatic lobes.Furthermore,EUS-LB can be performed during the same procedure as EUS-guided portal pressure gradient(PPG)measurements,allowing for the collection of valuable diagnostic and prognostic data.EUS-guided PPG measurements provide an appealing alternative to the transjugular approach,with proposed advantages including the ability to directly measure portal vein pressure.In addition,EUS-guided treatment of gastric varices(GV)offers several possible advantages to current therapies.EUS-guided treatment of GV allows detailed assessment of the vascular anatomy,similar efficacy and safety to current therapies,and allows the evaluation of treatment effect through doppler ultrasound visualization.The appropriate selection of patients for these procedures is paramount to ensuring generation of useful clinical data and patient safety.

Prognostic implications of type 2 myocardial infarctions

Purpose: A type 2 myocardial infarction (MI) is due to ischemia from increased oxygen demand or decreased supply. It is not an infrequent complication following non-cardiac surgery or in the setting of acute medical illness. The purpose of this study was to determine whether type 2 MIs had a worse prognosis than a type 1 MI. Methods: The hospital database of a large terti-ary-level academic medical center was queried for all patients with a troponin I ≥ 1.6 ng/mL during a one-year period. The outcomes of patients with a type 2 MI were compared to those with a type 1 MI. Results: This retrospective study found that a type 2 MI is more lethal than the usual type 1 MI, particularly among women and the elderly. There was no statistical difference in outcomes between those that occurred in the post-operative setting compared to those that occurred in the setting of acute medical illness. Conclusions: Type 2 MIs are common and are associated with increased mortality, as compared with type 1 MIs. To date, no guidelines exist for the management of this type of MI. Further research into underlying mechanisms resulting in type 2 MI as well as potential treatment strategies is needed.

Analytical Calculation of the Compton Single Scatter Component of Pencil Beam Scatter Kernel for Scatter Correction in kV Cone Beam CT (kV-CBCT)

The accuracy of conventional superposition or convolution methods for scatter correction in kV-CBCT is usually compromised by the spatial variation of pencil-beam scatter kernel (PBSK) due to finite size, irregular external contour and heterogeneity of the imaged object. This study aims to propose an analytical method to quantify the Compton single scatter (CSS) component of the PBSK, which dominates the spatial distribution of total scatter assuming that multiple scatter can be estimated as a constant background and Rayleigh scatter is the secondary source of scatter. The CSS component of PBSK is the line integration of scatter production by incident primary photons along the beam line followed by the post-scattering attenuation as the scattered photons traverse the object. We propose to separate the object-specific attenuation term from the line integration and equivalently replace it with an average value such that the line integration of scatter production is object independent but only beam specific. We derived a quartic function formula as an approximate solution to the spatial distribution of the unattenuated CSS component of PBSK. The “effective scattering center” is introduced to calculate the average attenuation. The proposed analytical framework to calculate the CSS was evaluated using parameter settings of the On-Board Imager kV-CBCT system and was found to be in high agreement with the reference results. The proposed method shows highly increased computational efficiency compared to conventional analytical calculation methods based on point scattering model. It is also potentially useful for correcting the spatial variant PBSK in adaptive superposition method.

Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cryoballoon ablation outcomes for paroxysmal atrial fibrillation

BACKGROUND Cryoballoon ablation(CBA)is recommended for patients with paroxysmal atrial fibrillation(AF)refractory to antiarrhythmic drugs.However,only 80%of patients benefit from initial CBA.There is growing evidence that pretreatment with angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs)decreases the recurrence of AF postablation,particularly in nonparoxysmal AF undergoing radiofrequency ablation.The role of ACEIs and ARBs in patients with paroxysmal AF in CBA remains unknown.We decided to investigate the role of ACEIs and ARBs in preventing the recurrence of atrial arrhythmia(AA)following CBA for paroxysmal AF.AIM To investigate the role of ACEIs and ARBs in preventing recurrence of AA following CBA for paroxysmal AF.METHODS We followed 103 patients(age 60.6±9.1 years,29%women)with paroxysmal AF undergoing CBA 1-year post procedure.Recurrence was assessed by documented AA on electrocardiogram or any form of long-term cardiac rhythm monitoring.A multivariable Cox proportional hazard model was used to assess if ACEI or ARB treatment predicted the risk of AA recurrence.RESULTS After a 1-year follow-up,19(18.4%)participants developed recurrence of AA.Use of ACEI or ARB therapy was noted in the study population.Patients on ACEI/ARB had a greater prevalence of hypertension and coronary artery disease.On a multivariate model adjusted for baseline demographics and risk factors for AF,ACEI or ARB therapy did not prevent recurrence of AA following CBA(P=0.72).Similarly,on Kaplan–Meier analysis pretreatment with ACEI/ARB did not predict the time to first recurrence of AA(P=0.2173).CONCLUSION In our study population,preablation treatment with an ACEI or ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.

The Xu＇s chart for prostate biopsy： a visual presentation of the added value of biomarkers to prostate-specific antigen for estimating detection rates of prostate cancer

Elevated serum prostate-specific antigen （PSA） level is the primaryindication for prostate biopsy for detection of prostate cancer （PCa） in the modern era. The detection rate of PCa from biopsy is typically below 30%, especially among patients with PSA levels at 4-10 ng ml-1. In the past several years, additional biomarkers, such as Prostate Health Index, PCA3 and genetic risk score （GRS） derived from multiple PCa risk-associated single nucleotide polymorphisms （SNPs） have been shown to provide added value to PSA in discriminating prostate biopsy outcomes. However,

Successful use of closed-loop allostatic neurotechnology for post-traumatic stress symptoms in military personnel： self-reported and autonomic improvements

Background:Military-related post-traumatic stress(PTS)is associated with numerous symptom clusters and diminished autonomic cardiovascular regulation.Highresolution,relational,resonance-based,electroencephalic mirroringis a noninvasive,closed-loop,allostatic,acoustic stimulation neurotechnology that produces realtime translation of dominant brain frequencies into audible tones of variable pitch and timing to support the autocalibration of neural oscillations.We report clinical,autonomic,and functional effects after the use offor symptoms of military-related PTS.Methods:Eighteen service members or recent veterans(15 active-duty,3 veterans,most from special operations,1 female),with a mean age of 40.9(SD=6.9)years and symptoms of PTS lasting from 1 to 25 years,undertook19.5(SD=1.1)sessions over 12 days.Inventories for symptoms of PTS(Posttraumatic Stress Disorder Checklist–Military version,PCL-M),insomnia(Insomnia Severity Index,ISI),depression(Center for Epidemiologic Studies Depression Scale,CES-D),and anxiety(Generalized Anxiety Disorder 7-item scale,GAD-7)were collected before(Visit1,V1),immediately after(Visit2,V2),and at 1 month(Visit3,V3),3(Visit4,V4),and 6(Visit5,V5)months after intervention completion.Other measures only taken at V1 and V2 included blood pressure and heart rate recordings to analyze heart rate variability(HRV)and baroreflex sensitivity(BRS),functional performance(reaction and grip strength)testing,blood and saliva for biomarkers of stress and inflammation,and blood for epigenetic testing.Paired t-tests,Wilcoxon signed-rank tests,and a repeated-measures ANOVA were performed.Results:Clinically relevant,significant reductions in all symptom scores were observed at V2,with durability through V5.There were significant improvements in multiple measures of HRV and BRS[Standard deviation of the normal beat to normal beat interval(SDNN),root mean square of the successive differences(rMSSD),high frequency(HF),low frequency(LF),and total power,HF alpha,sequence all,and systolic,diastolic and mean arterial pressure]as well as reaction testing.Trends were seen for improved grip strength and a reduction in C-Reactive Protein(CRP),Angiotensin II to Angiotensin 1–7 ratio and Interleukin-10,with no change in DNA n-methylation.There were no dropouts or adverse events reported. Conclusion:Service members or veterans showed reductions in symptomatology of PTS,insomnia,depressive mood,and anxiety that were durable through 6 months after the use of a closed-loop allostatic neurotechnology for the autocalibration of neural oscillations.This study is the first to report increased HRV or BRS after the use of an intervention for service members or veterans with PTS.Ongoing investigations are strongly warranted.Trial registration:NCT03230890,retrospectively registered July 25,2017.

Effect of opioid dependence or abuse on opioid utilization after shoulder arthroplasty

AIM To examine whether opioid dependence or abuse has an effect on opioid utilization after anatomic or reverse total shoulder arthroplasty(TSA).METHODS All anatomic TSA(ICD-9 81.80) and reverse shoulder arthroplasty(RSA)(ICD-9 81.88) procedures from 2007 to 2015 were queried from within the Humana claims database utilizing the Pearl Diver supercomputer(Colorado Springs, CO). Study groups were formed based on the presence or absence of a previous history of opioid dependence(ICD-9 304.00 and 304.03) or abuse(ICD-9 305.50 and 305.53). Opioid utilization among the groups was tracked monthly up to 1 year post-operatively utilizing National Drug Codes. A secondary analysis was performed to determine risk factors for pre-operative opioid dependence or abuse.RESULTS Two percent of TSA(157 out of 7838) and 3% of RSA(206 out of 6920) patients had a history of opioid dependence or abuse. For both TSA and RSA, opioid utilization was significantly higher in opioid dependent patients at all post-operative intervals(P < 0.01) although the incidence of opioid use among groups was similar within the first post-operative month. After TSA, opioid dependent patients were over twice as likely to fill opioid prescriptions during the post-operative months 1-12. Following RSA, opioid dependent patients were over 3 times as likely to utilize opioids from months 3-12. Age less than 65 years, history of mood disorder, and history of chronic pain were significant risk factors for pre-operative opioid dependence/abuse in patients who underwent TSA or RSA.CONCLUSION Following shoulder arthroplasty, opioid use between opioid-dependent and non-dependent patients is similar within the first post-operative month but is greater among opioid-dependent patients from months 2-12.

Apical Ballooning Syndrome: Recent Insights from a Consecutive Series of 104 Patients

Apical ballooning syndrome (Takotsubo cardiomyopathy) is an increasingly recognized form of acute systolic dysfunction which is usually reversible. It typically occurs in post-menopausal women following a major psychological stressor. We conducted a single center, retrospective analysis of all hospitalized patients from 2001-2012 and found 104 patients who met the diagnostic criteria for apical ballooning. In this current largest series of its kind, 83% of the patients were women. Among both men and women, an antecedent stressor was not always identified. The exact pathophysiologic mechanism resulting in apical ballooning remains poorly understood. These findings challenge the paradigm that catecholamine cardiotoxicity in the setting of relative estrogen deficiency results in the cardiomyopathy.

Association of low non-invasive near-infrared spectroscopic measurements during initial trauma resuscitation with future development of multiple organ dysfunction

BACKGROUND: Near-infrared spectroscopy(NIRS) non-invasively monitors muscle tissue oxygen saturation(St O2). It may provide a continuous noninvasive measurement to identify occult hypoperfusion, guide resuscitation, and predict the development of multiple organ dysfunction(MOD) after severe trauma. We evaluated the correlation between initial St O2 and the development of MOD in multi-trauma patients.METHODS: Patients presenting to our urban, academic, Level I Trauma Center/Emergency Department and meeting standardized trauma-team activation criteria were enrolled in this prospective trial. NIRS monitoring was initiated immediately on arrival with collection of St O2 at the thenar eminence and continued up to 24 hours for those admitted to the Trauma Intensive Care Unit(TICU). Standardized resuscitation laboratory measures and clinical evaluation tools were collected. The primary outcome was the association between initial St O2 and the development of MOD within the f irst 24 hours based on a MOD score of 6 or greater. Descriptive statistical analyses were performed; numeric means, multivariate regression and rank sum comparisons were utilized. Clinicians were blinded from the StO 2 values.RESULTS: Over a 14 month period, 78 patients were enrolled. Mean age was 40.9 years(SD 18.2), 84.4% were male, 76.9% had a blunt trauma mechanism and mean injury severity score(ISS) was 18.5(SD 12.9). Of the 78 patients, 26(33.3%) developed MOD within the first 24 hours. The MOD patients had mean initial St O2 values of 53.3(SD 10.3), signifi cantly lower than those of nonMOD patients 61.1(SD 10.0); P=0.002. The mean ISS among MOD patients was 29.9(SD 11.5), significantly higher than that of non-MODS patients, 12.1(SD 9.1)(P<0.0001). The mean shock index(SI) among MOD patients was 0.92(SD 0.28), also signifi cantly higher than that of non-MODS patients, 0.73(SD 0.19)(P=0.0007). Lactate values were not signifi cantly different between groups.CONCLUSION: Non-invasive, continuous St O2 near-infrared spectroscopy values during initial trauma resuscitation correlate with the later development of multiple organ dysfunction in this patient population.

Utilization of Hot Spotting to Identify Community Needs and Coordinate Care for High-Cost Patients in Memphis, TN

In 2006, Methodist Le Bonheur Healthcare (MLH) created the Congregational Health Network (CHN, TM pending) which works closely with clergy in the most under-served zip codes of the city to improve access to care and overall health status of the population. To best coordinate CHN resources around high-utilization and address the largest health needs in the community, MLH applied hot spotting and geographic information system (GIS) spatial analysis techniques. These techniques were coupled with the community health needs assessment process at MLH and qualitative, participatory research findings captured in collaboration with church and other community partners. The methodology, which we call “participatory hot spotting,” is based upon the Camden Model, which leverages hot spotting to assess and prioritize community need in the provision of charity care, but adds a participatory, qualitative layer. In this study, spatial analysis was employed to evaluate hospital-based inpatient and outpatient utilization and define costs of charity care for the health system by area of residence. Ten zip codes accounted for 56% of total system charity care costs. Among these, the largest zip code, as defined by a percentage of total charity costs, contributed 18% of the inpatient utilization and 17% of the cost. Further, this zip code (38109) contributed 69% of the inpatient and 76% of the outpatient charity care volume and accounted for 75% of inpatient and 76% of outpatient charity care costs for the system. These findings were combined with grassroots intelligence that enabled a partnership with clergy and community members and Cigna Healthcare to better coordinate care in a place-based population health management strategy. Presentations of the analytics have subsequently been made to HHS and the CDC, referred to by some as the “Memphis Model”.

Effect of aging on cardiovascular responses to cold stress in humans

Cold exposure increases the risk of adverse events related to cardiovascular causes,especially in the elderly.In this review,we focus on recent findings concerning the impact of aging on the regulatory mechanisms of cold-induced cardiovascular responses.In response to cold exposure,the initial physiological thermoregulation in healthy young persons,such as cutaneous vasoconstriction to reduce heat loss,is attenuated in older individuals,resulting in a reduced ability of the older persons to maintain body temperature in cold environment.Impaired sympathetic skin response,reduced noradrenergic neurotransmitter synthesis,insufficient noradrenergic transmitters,and altered downstream signaling pathways inside the vascular smooth muscle may be among the underlying mechanisms for the maladaptive vasoconstrictive response to cold stress in the elderly.The increase in blood pressure during cold exposure in young persons may be further augmented in aging adults,due to greater central arterial stiffness or diminished baroreflex sensitivity with aging.Cold stress raises myocardial oxygen demand caused by increased afterload in both young and old adults.The elderly cannot adjust to meet the increased oxygen demand due to reduced left ventricular compliance and coronary blood flow with advancing age,rendering the elderly more susceptible to hypothermia-induced cardiovascular complications from cold-related diseases.These age-associated thermoregulatory impairments may further worsen patients'health risk with existing cardiovascular diseases such as hypertension,coronary artery disease,and heart failure.We searched PubMed for papers related to cold stress and its relationship with aging,and selected the most relevant publications for discussion.

Impact of MitraClip Program on the Volume and Outcomes of Mitral Valve Surgery:A Single-Center Retrospective Study

Surgical repair has been the standard therapy for severe mitral regurgitation causing symptoms or left ventricular dysfunction.Percutaneous mitral valve repair has become an appealing alternative approach for patients who are not suitable for surgery.However,clinical trial data are not available on the institutional impact of a percutaneous mitral valve repair program on mitral valve surgery.The current study retrospectively evaluated the impact of the MitraClip program on the mitral valve surgery volume and outcomes.Patient data were retrieved from the 2 years before and the 2 years after initiation of the MitraClip program.The volume of MitraClip procedures increased from eight cases in 2015 to 91 cases in 2017.Since the initiation of the MitraClip program in 2015,the volume of both mitral valve replacement and mitral valve repair also increased(43 vs.60 and 110 vs.154,respectively).Importantly,we observed improved surgical outcomes,including fewer perioperative complications and lower operative mortality and in-hospital mortality.Data from our single-institution experience indicate that the introduction of the MitraClip program is associated with increased mitral valve surgery volume and improved outcomes.The establishment of the MitraClip program enables the hospital to provide higher quality of care and potentially become a referring center for structural heart patients.