Perforated peptic ulcer disease in transferred patients is associated with significant increase in length of stay.

BACKGROUND: Perforated peptic ulcer disease (PPUD) has a prevalence of 0.004-0.014% with mortality of 23.5% (Tarasconi et al. in World J Emerg Surg 15(PG-3):3, 2020). In this single center study, we examined the impact associated with patient transfer from outside facilities to our center for definitive surgical intervention (exploratory laparotomy). METHODS: Using EPIC report workbench, we identified 27 patients between 2018 and 2021 undergoing exploratory laparotomy with a concurrent diagnosis of peptic ulcer disease, nine of which were transferred to our institution for care. We queried this population for markers of disease severity including mortality, length of stay, intensive care unit (ICU) length of stay, and readmission rates. Manual chart reviews were performed to examine these outcomes in more detail and identify patients who had been transferred to our facility for surgery from an outside hospital. RESULTS: A total of 27 patients were identified undergoing exploratory laparotomy for definitive treatment of PPUD. The majority of patients queried underwent level A operations, the most urgent level of activation. In our institution, a Level A operation needs to go to the operating room within one hour of arrival to the hospital. Average mortality for this patient population was 14.8%. The readmission rate was 40.1%, and average length of ICU stay post-operatively was 16 days, with 83% of non-transfer patients requiring ICU admission and 100% of transfer patients requiring ICU admission, although this was not found to be statistically significant. Average length of hospital stay was 27 days overall. For non-transfer patients and transfer patients, LOS was 20 days and 41 days, respectively, which was statistically significant by one-sided t-test (p = 0.05). CONCLUSION: Patients transferred for definitive care of PPUD in a population otherwise notable for high mortality and high readmission rates: their average length of stay compared to non-transfer patients was over twice the length, which was statistically significant. Transferred patients also had higher rates of ICU care requirement although this was not statistically significant. Further inquiry to identify modifiable variables to facilitate the care of transferred patients is warranted, especially in the context of improving quality metrics known to enhance patient outcomes, satisfaction, and value.

Comparison of different nonsteroidal anti-inflammatory drugs for cesarean section: a systematic review and network meta-analysis.

BACKGROUND: Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not been elucidated. In this network meta-analysis and systematic review, we compared the influence of control and individual NSAIDs on the indices of analgesia, side effects, and quality of recovery. METHODS: CDSR, CINAHL, CRCT, Embase, LILACS, PubMed, and Web of Science were searched for randomized controlled trials comparing a specific NSAID to either control or another NSAID in elective or emergency cesarean section under general or neuraxial anesthesia. Network plots and league tables were constructed, and the quality of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis. RESULTS: We included 47 trials. Cumulative intravenous morphine equivalent consumption at 24 h, the primary outcome, was examined in 1,228 patients and 18 trials, and control was found to be inferior to diclofenac, indomethacin, ketorolac, and tenoxicam (very low quality evidence owing to serious limitations, imprecision, and publication bias). Indomethacin was superior to celecoxib for pain score at rest at 8-12 h and celecoxib + parecoxib, diclofenac, and ketorolac for pain score on movement at 48 h. In regard to the need for and time to rescue analgesia COX-2 inhibitors such as celecoxib were inferior to other NSAIDs. CONCLUSIONS: Our review suggests the presence of minimal differences among the NSAIDs studied. Nonselective NSAIDs may be more effective than selective NSAIDs, and some NSAIDs such as indomethacin might be preferable to other NSAIDs.

Does increasing insurance improve outcomes for US cancer patients?

BACKGROUND: Although debate continues on US healthcare and insurance reform, data are lacking on the effect of insurance on community-level cancer outcomes. Therefore, the objective of the present study was to examine the association of insurance and cancer outcomes. MATERIALS AND METHODS: The US Census Bureau Current Population Survey, Small Area Health Insurance Estimates (2000) were used for the rates of uninsurance. Counties were divided into tertiles according to the uninsurance rates. The data were compared with the cancer incidence and survival for patients residing in counties captured by the Surveillance, Epidemiology, and End Results database (2000-2006). Aggregate patient data were collected of US adults (aged ≥18 y) diagnosed with the following cancers: pancreatic, esophageal, liver or bile duct, lung or bronchial, ovarian, colorectal, breast, prostate, melanoma, and thyroid. The outcomes included the stage at diagnosis, surgery, and survival. Univariate tests and proportional hazards were calculated. RESULTS: The US uninsurance rate was 14.2%, and the range for the Surveillance, Epidemiology, and End Results counties was 8.3%-24.1%. Overall, patients from lower uninsurance rate counties demonstrated longer median survival. Adjusting for patient characteristics and cancer stage (for each cancer), the patients in the higher uninsurance rate counties demonstrated greater mortality (8%-15% increased risk on proportional hazards). The county uninsurance rate was associated with the stage at diagnosis for all cancers, except pancreatic and esophageal, and was also associated with the likelihood of being recommended for cancer-directed surgery (for all cancers). CONCLUSIONS: Health insurance coverage at a community level appears to influence survival for patients with cancer. Additional investigations are needed to examine whether individual versus community associations exist and how best to surmount barriers to cancer care.

Perioperative mortality after pancreatectomy: a risk score to aid decision-making.

BACKGROUND: Undergoing a pancreatectomy obligates the patient to risks and benefits. For complex operations such as pancreatectomy, the objective assessment of baseline risks may be useful in decision-making. We developed an integer-based risk score estimating in-hospital mortality after pancreatectomy, incorporating institution-specific mortality rates to enhance its use. METHODS: Pancreatic resections were identified from the Nationwide Inpatient Sample (1998-2006), and categorized as proximal, distal, or nonspecified by the International Classification of Diseases, 9th edition. Logistic regression and bootstrap methods were used to estimate in-hospital mortality using demographics, diagnosis, comorbidities (Charlson index), procedure, and hospital volume; 80% of this cohort was selected randomly to create the score and 20% was used for validation. Score assignments were subsequently individually fitted to risk distributions around specific mortality rates. RESULTS: Sixteen thousand one hundred sixteen patient discharges were identified. Nationwide in-hospital mortality was 5.3%. Integers were assigned to predictors (age group, Charlson index, sex, diagnosis, pancreatectomy type, and hospital volume) and applied to an additive score. Three score groups were defined to stratify in-hospital mortality (national mortality, 1.3%, 4.9%, and 14.3%; P < .0001), with sufficient discrimination of derivation and validation sets (C statistics, 0.72 and 0.74). Score groups were shifted algorithmically to calculate risk based on institutional data (eg, with institutional mortality of 2.0%, low-, medium-, and high-risk patient groups had 0.5%, 1.9%, and 5.4% mortality, respectively). A web-based tool was developed and is available online (http://www.umassmed.edu/surgery/panc_mortality_custom.aspx). CONCLUSION: To maximize patient benefit, objective assessment of risk for major procedures is necessary. We developed a Surgical Outcomes Analysis and Research risk score predicting pancreatectomy mortality that combines national and institution-specific data to enhance decision-making. This type of risk stratification tool may identify opportunities to improve care for patients undergoing specific operative procedures.

Update on stem cell therapy for cerebral palsy.

INTRODUCTION: Due to the publicity about stem cell transplantation for the treatment of cerebral palsy, many families seek information on treatment, and many travel overseas for cell transplantation. Even so, there is little scientific confirmation of benefit, and therefore existing knowledge in the field must be summarized. AREAS COVERED: This paper addresses the clinical protocols examining the problem, types of stem cells available for transplant, experimental models used to test the benefit of the cells, possible mechanisms of action, potential complications of cell treatment and what is needed in the field to help accelerate cell-based therapies. EXPERT OPINION: While stem cells may be beneficial in acute injuries of the CNS the biology of stem cells is not well enough understood in chronic injuries or disorders such as cerebral palsy. More work is required at the basic level of stem cell biology, in the development of animal models, and finally in well-conceived clinical trials.

Underutilization of therapy for hepatocellular carcinoma in the medicare population.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is increasing in the United States, and the care of these patients remains highly specialized and complex. Multiple treatment options are available for HCC but their use and effectiveness remain unknown. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data, 8730 patients who were diagnosed with HCC between 1991 and 2005 were identified. Therapy included surgical resection (8.7%), liver transplantation (1.4%), ablation (3.6%), or transarterial chemoembolization (16%). Patients who received no or palliative-only treatment were grouped together (NoTx; 70.3%). Patient, disease, and tumor factors were examined as determinants of therapy. RESULTS: HCC is increasing in the Medicare population. The median age at diagnosis was 75.1 years and 73.6% of patients were coded as white, 17.2% as Asian, 8.3% as black, and 0.9% as other race. The rate of therapy increased over time, but only 29.7% of patients overall underwent therapy. In patients with early stage HCC, only 43.1% underwent therapy. In the NoTx group, 49.4% did not have cirrhosis, 36.0% had tumors that measured <5 cm, and 39.8% were diagnosed with stage I or II disease when variables were complete. The use of therapy for all HCC patients increased over time, correlating with a commensurate increase in median survival. In multivariate regression analysis, patients who received any modality of treatment achieved significant benefit compared with the NoTx group (odds ratio, 0.41; 95% confidence interval, 0.39-0.43). CONCLUSIONS: In the Medicare population, HCC patients who received therapy experienced a substantial survival advantage over their nonoperative peers (NoTx). Despite evidence that many patients had favorable biological characteristics, <30% of patients diagnosed with HCC received any treatment.

Alcohol exposure as a risk factor for adverse outcomes in elective surgery.

BACKGROUND AND AIMS: Alcohol consumption is a well-documented determinant of adverse perioperative outcome. We sought to determine the effect of active alcohol consumption following elective surgery. METHODS: We queried discharge records from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP, 2005-2007) for all elective adult admissions. The 7,631 (2.5%) patients with documented alcohol use (active alcohol use of at least two drinks per day within 2 weeks of surgery; ETOH use) underwent elective surgery; 301,994 (97.5%) patients denied ETOH use. Multivariate analysis was performed with adjustments for demographic and comorbid factors. Primary outcome measures included length of stay (LOS), postoperative complications, and death. RESULTS: ETOH use associated with elective surgery decreased over the course of the study (p < 0.0001). ETOH use was an independent predictor of pneumonia (OR 1.98, 95% CI 1.84-2.13), sepsis (OR 1.19, 95% CI 1.03-1.37), superficial surgical site infection (SSI; OR 1.15, 95% CI 1.02-1.31), wound disruption (OR 1.41, 95% CI 1.11-1.80), and prolonged LOS (OR 1.17, 95% CI 1.08-1.26). Except for SSI, these complications were independent risk factors for postoperative mortality. ETOH use was associated with earlier time to wound disruption (9 vs. 11 days; p = 0.04), longer median hospital stays (5 vs. 3 days; p < 0.0001), and longer LOS after operation (4 vs. 3 days; p < 0.0001). CONCLUSIONS: Active alcohol consumption is a significant determinant of adverse outcomes in elective surgery; patients with ETOH use who are scheduled to undergo elective surgery should be appropriately educated and counseled.

In-hospital mortality after resection of biliary tract cancer in the United States.

OBJECTIVE: To assess perioperative mortality following resection of biliary tract cancer within the U.S. BACKGROUND: Resection remains the only curative treatment for biliary tract cancer. However, current data on operative mortality after surgical resections for biliary tract cancer are limited to small and single-center studies. METHODS: Using the Nationwide Inpatient Sample 1998-2006, a cohort of patient-discharges was assembled with a diagnosis of biliary tract cancer, including intrahepatic bile duct, extrahepatic bile duct, and gall bladder cancers. Patients undergoing resection, including hepatic resection, bile duct resection, pancreaticoduodenectomy, and cholecystectomy, were retained. The primary outcome measure was in-hospital mortality. Categorical variables were analyzed by chi-square. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality following resection. RESULTS: 31 870 patient-discharges occurred for the diagnosis of biliary tract cancer, including 36.2% intrahepatic ductal, 26.7% extrahepatic ductal, and 31.1% gall bladder. Of the total, 18.6% underwent resection: mean age was 69.3 years (median 70.0); 60.8% were female; 73.7% were white. Overall inpatient surgical mortality was 5.6%. Independently predictive factors of mortality included patient age >/=50 (vs. <50; age 50-59 odds ratio [OR] 5.51, 95% confidence interval [CI] 1.70-17.93; age 60-69 OR 7.25, 95% CI 2.29-22.96; age >/= 70 OR 9.03, 95% CI 2.86-28.56), the presence of identified comorbidities (congestive heart failure, OR 3.67, 95% CI 2.61-5.16; renal failure, OR 4.72, 95% CI 2.97-7.49), and admission designated as emergent (vs. elective; OR 1.82, 95% CI 1.39-2.37). CONCLUSION: Increased in-hospital mortality for patients undergoing biliary tract cancer resection corresponded to age, comorbidity, hospital volume, and emergent admission. Further study is warranted to utilize these observations in promoting early detection, diagnosis, and elective resection.

Hospital volume as a surrogate for laparoscopically assisted colectomy.

BACKGROUND: Although laparoscopic colectomy is reported to have favorable outcomes compared with open colectomy, it has yet to gain widespread acceptance in the United States. This study sought to investigate whether hospital volume is a factor determining the use of laparoscopy for colectomy. METHODS: Using the Nationwide Inpatient Sample (NIS, 1998-2006), patients undergoing elective colon resection with and without laparoscopy were identified. Unique hospital identifiers were used to divide hospital volume into equal thirds, with the highest third defined as high volume and the lower two-thirds defined as low volume. The primary end point was the use of laparoscopy after adjustment for patient and hospital covariates. RESULTS: A total of 209,769 colon resections were performed in the study period. Overall, only 8,407 (4%) of these resections were performed with laparoscopy. High-volume centers, which tended to be large, urban teaching hospitals, treated more patients in the highest income bracket and patients with private insurance than low-volume hospitals (p < 0.0001). High-volume hospitals used laparoscopy more often than low-volume hospitals (5.2% vs. 3.4%). After adjustment for covariates using multivariate analysis and propensity scores, analysis showed that patients with private insurance and those in the highest income bracket were more likely to receive laparoscopy (p < 0.0009). High-volume hospitals were more likely to perform laparoscopically assisted colectomy than low-volume hospitals (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.23-1.56). CONCLUSIONS: Socioeconomic differences appear to exist between high- and low-volume hospitals in the use of laparoscopy. High hospital volume is associated with an increased likelihood that colectomy will be performed with laparoscopy.

Adult stem cell therapy for acute brain injury in children.

Adult stem cell therapy has been proposed for brain injury in young children. While there have been no clinical trials in the US, the therapy is widely advertised and anecdotally reported in multiple internet sources, leading families to seek the treatment in uncontrolled circumstances. The purpose of this review is to present a discussion of the various types of stem cell preparations, with emphasis on adult stem cells, the scientific basis of their development, and the available experimental evidence for their utility in childhood brain injury. We will also provide background information on the biologic events occurring in injured immature brain, as they relate to the transplantation of stem cells. We will then review our own data from neonatal rodent studies with experimental hypoxic-ischemic brain injury. We have shown that early intracerebral administration promotes improved behavioral outcome in the animals, the formation of new neurons, and the preservation of intrinsic cells. New experiments demonstrate the equality of intracerebral and intravenous transplantation in acute neonatal hypoxic-ischemic injury in rodent. We will speculate on the possible clinical uses of adult stem cells. Our current impression is that the cells have the greatest potential for success when administered soon after an injury. What needs to be done to further the field? The different types of cell preparations should be tested against each other in experimental situations. A suitable model of chronic brain injury should be utilized for evaluating the benefit of the cells for this purpose. Long term safety of the cells should be confirmed in animal models. Finally, multicenter clinical trials should be conducted in highly controlled protocols.

Intravenous grafts recapitulate the neurorestoration afforded by intracerebrally delivered multipotent adult progenitor cells in neonatal hypoxic-ischemic rats.

Once hypoxic-ischemic (HI) injury ensues in the human neonate at birth, the resulting brain damage lasts throughout the individual's lifetime, as no ameliorative treatments are currently available. We have recently shown that intracerebral transplantation of multipotent adult progenitor cells (MAPCs) results in behavioral improvement and reduction in ischemic cell loss in neonatal rat HI-injury model. In an attempt to advance this cellular therapy to the clinic, we explored the more practical and less invasive intravenous administration of MAPCs. Seven-day-old Sprague-Dawley rats were initially subjected to unilateral HI injury, then 7 days later received intracerebral or intravenous injections of allogeneic rat MAPCs. On post-transplantation days 7 and 14, the animals that received MAPCs via the intracerebral or intravenous route exhibited improved motor and neurologic scores compared with those that received vehicle infusion alone. Immunohistochemical evaluations at day 14 after transplantation revealed that both intracerebrally and intravenously transplanted MAPCs were detected in the ischemic hippocampal area. The degree of hippocampal cell preservation was almost the same in the two treatment groups and greater than that in the vehicle group. These results show that intravenous delivery of MAPCs is a feasible and efficacious cell therapy with potential for clinical use.

Transplantation of cryopreserved human bone marrow-derived multipotent adult progenitor cells for neonatal hypoxic-ischemic injury: targeting the hippocampus.

There is currently no treatment for neonatal hypoxic-ischemic (HI) injury. Although limited clinical trials of stem cell therapy have been initiated in a number of neurological disorders, the preclinical evidence of a cell-based therapy for neonatal HI injury remains in its infancy. Stem cell therapy, via stimulation of endogenous stem cells or transplantation of exogenous stem cells, has targeted neurogenic sites, such as the hippocampus, for brain protection and repair. The hippocampus has also been shown to secrete growth factors, especially during the postnatal period, suggesting that this brain region presents a highly conducive microenvironment for cell survival. Based on its neurogenic and neurotrophic factor-secreting features, the hippocampus stands as an appealing target for stem cell therapy. In the present study, we investigated the efficacy of intrahippocampal transplantation of multipotent adult progenitor cells (MAPCs), which are pluripotent progenitor cells with the ability to differentiate into a neuronal lineage. Seven-day old Sprague-Dawley rats were initially subjected to unilateral HI injury, that involved permanent ligation of the right common carotid artery and subsequent exposure to hypoxic environment. At day 7 after HI

Behavioral and histological characterization of intrahippocampal grafts of human bone marrow-derived multipotent progenitor cells in neonatal rats with hypoxic-ischemic injury.

Children born with hypoxic-ischemic (HI) brain injury account for a significant number of live births wherein no clinical treatment is available. Limited clinical trials of stem cell therapy have been initiated in a number-of neurological disorders, but the preclinical evidence of a cell-based therapy for neonatal HI injury remains in its infancy. One major postulated mechanism underlying therapeutic benefits of stem cell therapy involves stimulation of endogenous neurogenesis via transplantation of exogenous stem cells. To this end, transplantation has targeted neurogenic sites, such as the hippocampus, for brain protection and repair. The hippocampus has been shown to secrete growth factors, especially during the postnatal period, suggesting that this brain region presents as highly conducive microenvironment for cell survival. Based on its neurogenic and neurotrophic factor-secreting features, the hippocampus stands as an appealing target for stem cell therapy. Here, we investigated the efficacy of intrahippocampal transplantation of multipotent progenitor cells (MPCs), which are pluripotent progenitor cells with the ability to differentiate into a neuronal lineage. Seven-day-old Sprague-Dawley rats were initially subjected to unilateral HI injury, which involved permanent ligation of the right common carotid artery and subsequent exposure to hypoxic environment. At day 7 after HI injury, animals received stereotaxic hippocampal injections of vehicle or cryopre-served MPCs (thawed just prior to transplantation) derived either from Sprague-Dawley rats (syngeneic) or Fisher rats (allogeneic). All animals were treated with daily immunosuppression throughout the survival period. Behavioral tests were conducted on posttransplantation days 7 and 14 using the elevated body swing test and the rotarod to reveal general and coordinated motor functions. MPC transplanted animals exhibited reduced motor asymmetry and longer time spent on the rotarod than those that received the vehicle infusion. Both syngeneic and allogeneic MPC transplanted injured animals did not significantly differ in their behavioral improvements at both test periods. Immunohistochemical evaluations of graft survival after behavioral testing at day 14 posttransplantation revealed that syngeneic and allogeneic transplanted MPCs survived in the hippocampal region. These results demonstrate for the first time that transplantation of MPCs ameliorated motor deficits associated with HI injury. In view of comparable behavioral recovery produced by syngeneic and allogeneic MPC grafts, allogeneic transplantation poses as a feasible and efficacious cell replacement strategy with direct clinical application. An equally major finding is the observation lending support to the hippocampus as an excellent target brain region for stem cell therapy in treating HI injury.

The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12) expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury.

BACKGROUND: Stromal cell-derived factor 1 (SDF-1 or CXCL12) is chemotaxic for CXCR4 expressing bone marrow-derived cells. It functions in brain embryonic development and in response to ischemic injury in helping guide neuroblast migration and vasculogenesis. In experimental adult stroke models SDF-1 is expressed perivascularly in the injured region up to 30 days after the injury, suggesting it could be a therapeutic target for tissue repair strategies. We hypothesized that SDF-1 would be expressed in similar temporal and spatial patterns following hypoxic-ischemic (HI) injury in neonatal brain. RESULTS: Twenty-five 7-day-old C57BL/J mice underwent HI injury. SDF-1 expression was up regulated up to 7 days after the injury but not at the later time points. The chief sites of SDF-1 up regulation were astrocytes, their foot processes along blood vessels and endothelial cells. CONCLUSION: The localization of SDF-1 along blood vessels in the HI injury zone suggests that these perivascular areas are where chemotaxic signaling for cellular recruitment originates and that reactive astrocytes are major mediators of this process. The associated endothelium is likely to be the site for vascular attachment and diapedesis of CXCR4 receptor expressing cells to enter the injured tissue. Here we show that, relative to adults, neonates have a significantly smaller window of opportunity for SDF-1 based vascular chemotaxic recruitment of bone marrow-derived cells. Therefore, without modification, following neonatal HI injury there is only a narrow period of time for endogenous SDF-1 mediated chemotaxis and recruitment of reparative cells, including exogenously administered stem/progenitor cells.

SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury.

The chemokine stromal-derived factor-1 (SDF-1, also known as CXCL12) and its receptor CXCR4 have been implicated in homing of stem cells to the bone marrow and the homing of bone marrow-derived cells to sites of injury. Bone marrow cells infiltrate brain and give rise to long-term resident cells following injury. Therefore, SDF-1 and CXCR4 expression patterns in 40 mice were examined relative to the homing of bone marrow-derived cells to sites of ischemic injury using a stroke model. Mice received bone marrow transplants from green fluorescent protein (GFP) transgenic donors and later underwent a temporary middle cerebral artery suture occlusion (MCAo). SDF-1 was associated with blood vessels and cellular profiles by 24 hours through at least 30 days post-MCAo. SDF-1 expression was principally localized to the ischemic penumbra. The majority of SDF-1 expression was associated with reactive astrocytes; much of this was perivascular. GFP+ cells were associated with SDF-1-positive vessels and were also found in the neuropil of regions with increased SDF-1 immunoreactivity. Most vessel-associated GFP+ cells resemble pericytes or perivascular microglia and the majority of the GFP+ cells in the parenchyma displayed characteristics of activated microglial cells. These findings suggest SDF-1 is important in the homing of bone marrow-derived cells, especially monocytes, to areas of ischemic injury.

Stem cell therapy for cerebral palsy.

Cerebral palsy is a group of brain diseases which produce chronic motor disability in children. The causes are quite varied and range from abnormalities of brain development to birth-related injuries to postnatal brain injuries. Due to the increased survival of very premature infants, the incidence of cerebral palsy may be increasing. While premature infants and term infants who have suffered neonatal hypoxic-ischaemic (HI) injury represent only a minority of the total cerebral palsy population, this group demonstrates easily identifiable clinical findings, and much of their injury is to oligodendrocytes and the cerebral white matter. While the use of stem cell therapy is promising, there are no controlled trials in humans with cerebral palsy and only a few trials in patients with other neurologic disorders. However, studies in animals with experimentally induced strokes or traumatic injuries have indicated that benefit is possible. The potential to do these transplants via injection into the vasculature rather than directly into the brain increases the likelihood of timely human studies. As a result, variables appropriate to human experiments with intravascular injection of cells, such as cell type, timing of the transplant and effect on function, need to be systematically performed in animal models with HI injury, with the hope of rapidly translating these experiments to human trials.

Lambert-Eaton Myasthenic syndrome in a child with an autoimmune phenotype.

We report on a child with a family history of autoimmune defects, who presented at the age of 3(1/2) years with alopecia and Graves disease. He subsequently developed vitiligo and psoriasis. At 9(1/2) years, he developed an autoimmune form of Lambert-Eaton Myasthenic syndrome (LEMS) with a significant elevation of glutamic acid decarboxylase (GAD) autoantibodies. Shortly thereafter he developed chronic urticaria. HLA associations were present for Graves disease, vitiligo, psoriasis, and IgA deficiency. There was also evidence of autoimmunity involving the pancreatic islet cells and gastric parietal cells.

Acetoacetate increases expression of intercellular adhesion molecule-1 (ICAM-1) in human brain microvascular endothelial cells.

It has been hypothesized that ketone bodies cause activation of brain endothelial cells and that this is a factor in the intracerebral crises of diabetic ketoacidosis (DKA). In this study we used cultured human brain microvascular endothelial cells (HBMEC) to investigate the effect of beta hydroxybutyrate (BOHB) and acetoacetate (AcAc) on the expression of the adhesion molecule, intercellular adhesion molecule-1 (ICAM-1). Increasing concentrations of AcAc, but not BOHB, caused a significant upregulation of ICAM-1 in comparison to unstimulated cells. Glucose concentrations of 10 and 30 mM, but not 50 mM, also resulted in increased expression of ICAM-1. These results support the hypothesis that activation of HBMEC is involved in the acute complications of DKA, and that ketone bodies and hyperglycemia are factors in the perturbed membrane function.