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The burden of global injury-related deaths predominantly affects developing countries, which have little infrastructure to evaluate these disparities. We describe injury-related mortality patterns in Kampala, Uganda and compare them with data from the United States and San Francisco (SF), California.We created a database in Kampala of deaths recorded by the City Mortuary, the Mulago Hospital Mortuary, and the Uganda Ministry of Health from July to December 2007. We analyzed the rate and odds ratios and compared them to data from the U.S. Centers for Disease Control and Prevention and the California Department of Public Health.In Kampala, 25% of all deaths were due to injuries (812/3303) versus 6% in SF and 7% in the United States. The odds of dying of injury in Kampala were 5.0 times higher than in SF and 4.2 times higher than in the United States. Age-standardized death rates indicate a 93% greater risk of dying from injury in Kampala than in SF. The mean age was lower in Kampala than in SF (29 vs. 44 years). The adult injury death rate (rate ratio, or RR) was higher in Kampala than in SF (2.3) or the United States (1.5). Head/neck injury was reported in 65% of injury deaths in Kampala compared to 34% in SF [odds ratio (OR) 3.7] and 28% in the US (OR 4.8).Urban injury-related mortality is significantly higher in Uganda than in the United States. Injury preferentially affects adults in the prime of their economically productive years. These findings serve as a call for stronger injury prevention and control policies in Uganda.

In the last decade, PET-only systems have been phased out and replaced with PET-CT systems. This merger of a functional and anatomical imaging modality turned out to be extremely useful in clinical practice. Currently, PET-CT is a major diagnostic tool in oncology. At the dawn of the merger of MRI and PET, another breakthrough in clinical imaging is expected. The combination of these imaging modalities is challenging, but has particular features such as imaging biological processes at the same time in specific body locations.

The World Health Organization (WHO) Tool for Situational Analysis to Assess Emergency and Essential Surgical Care (hereafter called the WHO Tool) has been used in more than 25 countries and is the largest effort to assess surgical care in the world. However, it has not yet been independently validated. Test–retest reliability is one way to validate the degree to which tests instruments are free from random error. The aim of the present field study was to determine the test–retest reliability of the WHO Tool.The WHO Tool was mailed to 10 district hospitals in Ghana. Written instructions were provided along with a letter from the Ghana Health Services requesting the hospital administrator to complete the survey tool. After ensuring delivery and completion of the forms, the study team readministered the WHO Tool at the time of an on-site visit less than 1 month later. The results of the two tests were compared to calculate kappa statistics for each of the 152 questions in the WHO Tool. The kappa statistic is a statistical measure of the degree of agreement above what would be expected based on chance alone.Ten hospitals were surveyed twice over a short interval (i.e., less than 1 month). Weighted and unweighted kappa statistics were calculated for 152 questions. The median unweighted kappa for the entire survey was 0.43 (interquartile range 0–0.84). The infrastructure section (24 questions) had a median kappa of 0.81; the human resources section (13 questions) had a median kappa of 0.77; the surgical procedures section (67 questions) had a median kappa of 0.00; and the emergency surgical equipment section (48 questions) had a median kappa of 0.81.Hospital capacity survey questions related to infrastructure characteristics had high reliability. However, questions related to process of care had poor reliability and may benefit from supplemental data gathered by direct observation. Limitations to the study include the small sample size: 10 district hospitals in a single country. Consistent and high correlations calculated from the field testing within the present analysis suggest that the WHO Tool for Situational Analysis is a reliable tool where it measures structure and setting, but it should be revised for measuring process of care.

PDE4 isoenzymes are critical in the control of cAMP signaling in rodent cardiac myocytes. Ablation of PDE4 affects multiple key players in excitation–contraction coupling and predisposes mice to the development of heart failure. As little is known about PDE4 in human heart, we explored to what extent cardiac expression and functions of PDE4 are conserved between rodents and humans. We find considerable similarities including comparable amounts of PDE4 activity expressed, expression of the same PDE4 subtypes and splicing variants, anchoring of PDE4 to the same subcellular compartments and macromolecular signaling complexes, and downregulation of PDE4 activity and protein in heart failure. The major difference between the species is a fivefold higher amount of non-PDE4 activity in human hearts compared to rodents. As a consequence, the effect of PDE4 inactivation is different in rodents and humans. PDE4 inhibition leads to increased phosphorylation of virtually all PKA substrates in mouse cardiomyocytes, but increased phosphorylation of only a restricted number of proteins in human cardiomyocytes. Our findings suggest that PDE4s have a similar role in the local regulation of cAMP signaling in rodent and human heart. However, inhibition of PDE4 has ‘global’ effects on cAMP signaling only in rodent hearts, as PDE4 comprises a large fraction of the total cardiac PDE activity in rodents but not in humans. These differences may explain the distinct pharmacological effects of PDE4 inhibition in rodent and human hearts.

The burden of surgical conditions and diseases is increasing in low-income and middle-income countries, but the capacity to meet the demands they present is not following pace. Ongoing initiatives, such as brief visits by surgeons from advantaged countries, sending surgical residents to spend time in a developing country as part of their training, or ships weighing anchor offshore and offering some limited on-shore or on-board services, have not proven successful. More comprehensive and sustainable solutions include the development of local training programs, better retention of trainees with adequate incentives particularly in rural areas, and engaging government and professional associations, as well as academic institutions, to develop and implement policies to address local training needs.

We report a patient who presented during fetal life with severe aortic stenosis, left-ventricular dysfunction, and endocardial fibroelastosis (evolving hypoplastic left heart syndrome). Management involved in utero and postnatal balloon aortic valvuloplasty for partial relief of obstruction and early postnatal hybrid stage I palliation until recovery of left-ventricular systolic function had occurred. The infant subsequently had successful conversion to a biventricular circulation by combining resection of endocardial fibroelastosis with single-stage Ross-Konno, aortic arch reconstruction, hybrid takedown, and pulmonary artery reconstruction.

By failing to include it under the rubric of the postpartum-onset specifier, Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR has ignored the clinical reality that childbirth is a potent trigger of hypomania. Given the serious and occasionally tragic consequences of misdiagnosis of bipolar II depression as unipolar depression in the postpartum period, it is argued that DSM-V should consider modifying the postpartum-onset specifier to include episodes of hypomania.

Single-port and incisionless surgical approaches hold the promise of fewer complications, reduced pain, faster recovery, and improved cosmesis compared with traditional open or laparoscopic approaches. The ability to select an access approach (i.e., endolumenal, single-port, transvaginal, or transgastric) with one platform may be important to optimization of individual patient results. The authors report their results using these four separate surgical approaches tailored to three different therapeutic procedures, all with the use of a single flexible platform, the Incisionless Operating Platform (IOP).After institutional review board approval, the IOP was used to perform nine cholecystectomies via transvaginal (TV) (n = 4), transgastric (TG) (n = 4), and single-port transumbilical (TU) (n = 1) access. Two appendectomies were performed via TG access. Endolumenal access was used for 18 gastric pouch and stoma reductions after Roux-en-Y gastric bypass. The TG and TV procedures involved the use of one to three trocars. The recorded data included safety, procedural success, operative time, patient pain assessment (on a 0–10 scale) at discharge, and length of hospital stay. Procedural success was achieved for 16 of 18 endolumenal procedures, 1 of 1 single-port procedure, and 10 of 10 NOTES procedures. For 5 of 10 NOTES procedures, only one small trocar was required. The mean operative times were 79 min for pouch with stoma reduction, 171 min for cholecystectomy, and 274 min for appendectomy. Of 29 patients, 27 were discharged in 24 h or less. The average pain scores were 0.44 for pouch with stoma reduction, 1.3 for cholecystectomy, and 2.5 for appendectomy. No significant complications occurred. The ergonomics of IOP allowed the surgeon to interface with the system using an endoscopic or laparoscopic orientation.Availability of a multifunctional, flexible surgery platform provides a choice of a single-port or incisionless surgical approach with the potential to reduce complications, pain, and recovery time while improving cosmesis.

Despite the positive influence of spiritual coping on the acceptance of a cancer diagnosis, higher spirituality is associated with receipt of more high intensity care at the end of life. The purpose of our study was to assess the association between spirituality and type of end-of-life care received by disadvantaged men with prostate cancer.We studied low-income, uninsured men in IMPACT, a state-funded public assistance program, who had died since its inception in 2001. Of the 60 men who died, we included the 35 who completed a spirituality questionnaire at program enrollment. We abstracted sociodemographic and clinical information as well as treatment within IMPACT, including zolendroic acid, chemotherapy, hospice use, and palliative radiation therapy. We measured spirituality with the Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being questionnaire (FACIT-Sp) and compared end-of-life care received between subjects with low and high FACIT-Sp scores using chi-squared analyses.A higher proportion of men with high (33%) versus low (13%) spirituality scores enrolled in hospice, although our analysis was not adequately powered to demonstrate statistical significance. Likewise, we saw a trend toward increased receipt of palliative radiation among those with higher spirituality (37% vs. 25%, P = 0.69). The differences in end-of-life care received among those with low and high spirituality varied little by the FACIT-Sp peace and faith subscales.End-of-life care was similar between men with lower and higher spirituality. Men with higher spirituality trended toward greater hospice use, suggesting that they redirected the focus of their care from curative to palliative goals.

Tyrosine kinases play significant roles in tumor progression and therapy resistance. Inhibitors of tyrosine kinases are on the forefront of targeted therapy. For prostate cancer, tyrosine kinases play an additional role in the development of castration-resistant disease state, the most troubling aspect of prostate cancinogenesis which presently defies any effective treatment. Among the 30 or so tyrosine kinases expressed in a typical prostate cancer cell, nearly one third of them have been implicated in prostate carcinogenesis. Interestingly, most of them channel signals through a trio of non-receptor tyrosine kinases, Src/Etk/FAK, referred here as Src tyrosine kinase complex. This complex has been shown to play a significant role in the aberrant activation of androgen receptor (AR) mediated by growth factors (e.g., epidermal growth factor (EGF)), cytokines (interleukin (IL)-6), chemokines (IL-8), and neurokines (gastrin-releasing peptide). These factors are induced and released from the prostate cancer to the stromal cells upon androgen withdrawal. The Src kinase complex has the ability to phosphorylate androgen receptor, resulting in the nuclear translocation and stabilization of un-liganded androgen receptor. Indeed, tyrosine kinase inhibitors targeting Src can inhibit androgen-independent growth of prostate cancer cells in vitro and in preclinical xenograft model. While effective in inducing growth arrest and inhibiting metastasis of castration-resistant tumors, Src inhibitors rarely induce a significant level of apoptosis. This is also reflected by the general ineffectiveness of tyrosine kinase inhibitors as monotherapy in clinical trials. One of the underlying causes of apoptosis resistance is “autophagy,” which is induced by tyrosine kinase inhibitors and by androgen withdrawal. Autophagy is a self-digesting process to regenerate energy by removal of long-lived proteins and retired organelles to provide a survival mechanism to cells encountering stresses. Excessive autophagy, sometimes, could lead to type II programmed cell death. We demonstrated that autophagy blockade sensitizes prostate cancer cells toward Src tyrosine kinase inhibitor. Thus, a combination therapy based on Src tyrosine kinase inhibitor and autophagy modulator deserves further attention as a potential treatment for relapsed prostate cancer.

Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI.We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relative to AKI diagnosis.We determined the associations among sepsis, clinical characteristics, provision of dialysis, in-hospital mortality, and length of stay (LOS), comparing outcomes among patients according to their sepsis status. Among the 611 patients with data on sepsis status, 174 (28%) had sepsis before AKI, 194 (32%) remained sepsis-free, and 243 (40%) developed sepsis a median of 5 days after AKI. Mortality rates for patients with sepsis developing after AKI were higher than in sepsis-free patients (44 vs. 21%; p

The purpose of this study is to identify risk factors for mesh erosion in women undergoing minimally invasive sacrocolpopexy (MISC). We hypothesize that erosion is higher in subjects undergoing concomitant hysterectomy.This is a retrospective cohort study of women who underwent MISC between November 2004 and January 2009. Demographics, operative techniques, and outcomes were abstracted from medical records. Multivariable regression identified odds of erosion.Of 188 MISC procedures 19(10%) had erosions. Erosion was higher in those with total vaginal hysterectomy (TVH) compared to both post-hysterectomy (23% vs. 5%, p = 0.003) and supracervical hysterectomy (SCH) (23% vs. 5%, p = 0.109) groups. In multivariable regression, the odds of erosion for TVH was 5.67 (95% CI: 1.88–17.10) compared to post-hysterectomy. Smoking, the use of collagen-coated mesh, transvaginal dissection, and mesh attachment transvaginally were no longer significant in the multivariable regression model.Based on this study, surgeons should consider supracervical hysterectomy over total vaginal hysterectomy as the procedure of choice in association with MISC unless removal of the cervix is otherwise indicated.

A close association between pain, depression and disability has been shown. However, the neurometabolic correlates of this association have been barely investigated in disease states. Episodic cluster headache is a severe headache syndrome and represents a suitable disease model for the investigation of episodic pain. The aim of this study was to explore the relationship between depression and disability as well as pain scores and brain metabolism in patients with cluster headache during the disease period with repetitive pain attacks, but outside an acute attack. Thirteen patients with cluster headache underwent 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission (FDG-PET) and completed questionnaires on depression and disability as well as a pain visual analogue rating scale (VAS). A positive correlation between the depression scores and glucose metabolism was observed in the insular cortex. A positive correlation between the pain disability scores and brain metabolism was detected in the amygdala. The same applied to the pain visual analogue rating scores. Our data underline the association between severe episodic pain, depression and disability. In addition to this clinical observation, our results stress the importance of the insula and amygdala in pain processing and suffering.

Metabolic acidosis is common in patients with chronic kidney disease (CKD), particularly once the glomerular filtration rate (GFR) falls below 25 ml/min/1.73 m2. It is usually mild to moderate in magnitude with the serum bicarbonate concentration ([HCO 3 − ]) ranging from 12 to 23 mEq/l. Even so, it can have substantial adverse effects, including development or exacerbation of bone disease, growth retardation in children, increased muscle degradation with muscle wasting, reduced albumin synthesis with a predisposition to hypoalbuminemia, resistance to the effects of insulin with impaired glucose tolerance, acceleration of the progression of CKD, stimulation of inflammation, and augmentation of β2-microglobulin production. Also, its presence is associated with increased mortality. The administration of base to patients prior to or after initiation of dialysis leads to improvement in many of these adverse effects. The present recommendation by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) is to raise serum [HCO 3 − ] to ≥22 mEq/l, whereas Caring for Australians with Renal Impairment (CARI) recommends raising serum [HCO 3 − ] to >22 mEq/l. Base administration can potentially contribute to volume overload and exacerbation of hypertension as well as to metastatic calcium precipitation in tissues. However, sodium retention is less when given as sodium bicarbonate and sodium chloride intake is concomitantly restricted. Results from various studies suggest that enhanced metastatic calcification is unlikely with the pH values achieved during conservative base administration, but the clinician should be careful not to raise serum [HCO 3 − ] to values outside the normal range.

In traumatic brain injury (TBI), severe disruptions occur in the choroid plexus (CP)–cerebrospinal fluid (CSF) nexus that destabilize the nearby hippocampal and subventricular neurogenic regions. Following invasive and non-invasive injuries to cortex, several adverse sequelae harm the brain interior: (i) structural damage to CP epithelium that opens the blood–CSF barrier (BCSFB) to protein, (ii) altered CSF dynamics and intracranial pressure (ICP), (iii) augmentation of leukocyte traffic across CP into the CSF–brain, (iv) reduction in CSF sink action and clearance of debris from ventricles, and (v) less efficient provision of micronutritional and hormonal support for the CNS. However, gradual post-TBI restitution of the injured CP epithelium and ependyma, and CSF homeostatic mechanisms, help to restore subventricular/subgranular neurogenesis and the cognitive abilities diminished by CNS damage. Recovery from TBI is faciltated by upregulated choroidal/ependymal growth factors and neurotrophins, and their secretion into ventricular CSF. There, by an endocrine-like mechanism, CSF bulk flow convects the neuropeptides to target cells in injured cortex for aiding repair processes; and to neurogenic niches for enhancing conversion of stem cells to new neurons. In the recovery from TBI and associated ischemia, the modulating neuropeptides include FGF2, EGF, VEGF, NGF, IGF, GDNF, BDNF, and PACAP. Homeostatic correction of TBI-induced neuropathology can be accelerated or amplified by exogenously boosting the CSF concentration of these growth factors and neurotrophins. Such intraventricular supplementation via the CSF route promotes neural restoration through enhanced neurogenesis, angiogenesis, and neuroprotective effects. CSF translational research presents opportunities that involve CP and ependymal manipulations to expedite recovery from TBI.

While many assume hyperkyphosis reflects underlying spinal osteoporosis and vertebral fractures, our results suggest hyperkyphosis is independently associated with decreased mobility. Hyperyphosis is associated with slower Timed Up and Go performance times and may be a useful clinical marker signaling the need for evaluation of vertebral fracture and falling risk.While multiple studies have demonstrated negative effects of hyperkyphosis on physical function, none have disentangled the relationship between hyperkyphosis, impaired function, and underlying spinal osteoporosis. The purpose of this study is to determine whether kyphosis, independent of spinal osteoporosis, is associated with mobility on the Timed Up and Go, and to quantify effects of other factors contributing to impaired mobility.We used data for 3,108 community-dwelling women aged 55-80 years in the Fracture Intervention Trial. All participants had measurements of kyphosis, mobility time on the Timed Up and Go test, height, weight, total hip bone mineral density (BMD), grip strength, and vertebral fractures at baseline visits in 1993. Demographic characteristics included age and smoking status. We calculated mean Timed Up and Go time by quartile of kyphosis. Using multivariate linear regression, we estimated the independent association of kyphosis with mobility time, and quantified effects of other covariates on mobility.Mean mobility time increased from 9.3 s in the lowest to 10.1 s in the highest quartile of kyphosis. In a multivariate-adjusted model, mobility time increased 0.11 s (p = 0.02) for each standard deviation (11.9°) increase in kyphosis. Longer performance times were significantly associated with increasing age, decreasing grip strength, vertebral fractures, body mass index ≥25, and total hip BMD in the osteoporotic range.Kyphosis angle is independently associated with decreased mobility on the Timed Up and Go, which is in turn correlated with increased fall risk. Hyperkyphosis may be a useful clinical marker signaling the need for evaluation of vertebral fracture and falling risk.

Compliance to oral bisphosphonates is suboptimal, with negative consequences of increased healthcare utilization and less effective fracture risk reduction. Extending dose interval increased adherence only moderately. We used literature derived from multiple chronic conditions to examine the problem of noncompliance with osteoporosis medication. We reviewed the literature on adherence to osteoporosis medication as well as that across multiple chronic conditions to understand what is known about the cause of the poor adherence. Poor compliance to oral medications is due mostly, not to forgetfulness, but to deliberate choice. Gender differences and style of healthcare management also play a role. Preliminary data suggest psychobehavioral interventions may help to improve motivation. We need to understand better reasons for poor compliance before effective interventions can be developed. Forgetfulness is only a small part of poor compliance. Patient preferences must be considered in medication decision making.

A wandering spleen is a rare condition with an unknown incidence. The lack of short gastric vessels and suspensory ligaments is thought to result from a fusion anomaly of the dorsal mesogastrium of the spleen. The major risk in performing a splenectomy for patients with a wandering spleen is overwhelming postsplenectomy infection (OPSI). The incidence of OPSI is 0.13% to 8.1%, with a mortality rate of 30% to 60%. Laparoscopic splenopexy provides the benefits of minimally invasive surgery while avoiding the complications of splenectomy. The reported case presents a patient with a wandering spleen. The patient, an 18-year-old woman, experienced a malarial infection at the age of 5 years and had a computed tomography (CT) scan documenting her spleen in the normal anatomic position. When she was 18 years old, a CT scan showed her spleen located in the right lower quadrant (RLQ). At laparoscopy, the presence of the spleen in the RLQ was confirmed. The spleen could not be easily manipulated with laparoscopic instruments, so a hand port was used to mobilize the spleen to the left upper quadrant (LUQ). No evidence of attenuated suspensory ligaments was seen. The spleen was secured in the left subdiaphragmatic location by the use of a Vicryl mesh bag. An omental sling was used to support the spleen further. A 1-year follow up CT confirmed that the spleen still was located in the correct anatomic position. This is a unique case in that the patient was known to have a normally located spleen at a young age and then found to have a wandering spleen later in life. This could have resulted from a congenital fusion anomaly or attenuation of the patient’s suspensory ligaments caused by her previous malarial infection and splenomegaly.

Facet tropism has been investigated as a predisposing factor for degenerative changes in the lumbar spine; however, no prior study has evaluated the relationship between disc bulge and facet tropism. In this study, we used kinetic magnetic resonance imaging (kMRI) to investigate the association between degree of facet tropism and amount of disc bulge in the lumbar spine in relation to age. kMRIs in the flexion, neutral, and extension positions were performed on 410 consecutive patients with low back pain. T2-weighted midsagittal and axial mid-disc cuts were analyzed to measure disc bulge and facet angle. Facet asymmetry was calculated and classified as: no facet tropism,

Although cyclophilin A (CypA) has been reported to be over-expressed in cancer cells and solid tumors, its expression and role in glioblastomas have not been studied. Herein, we show that expression of CypA in human glioblastoma cell lines and tissues is significantly higher than in normal human astrocytes and normal counterparts of brain tissue. To determine the role of over-expressed CypA in glioblastoma, stable RNA interference (RNAi)-mediated knockdown of CypA (CypA KD) was performed in gliobastoma cell line U87vIII (U87MG · ΔEGFR). CypA KD stable single clones decrease proliferation, infiltration, migration, and anchorage-independent growth in vitro and with slower growth in vivo as xenografts in immunodeficient nude mice. We have also observed that knockdown of CypA inhibits expression of interleukin-8 (IL-8), a tumorigenic and proangiogenic cytokine. Conversely, enforced expression of CypA in the CypA KD cell line, Ud-12, markedly enhanced IL-8 transcripts and restored Ud-12 proliferation, suggesting that CypA-mediated IL-8 production provides a growth advantage to glioblastoma cells. CypA knockdown-mediated inhibition of IL-8 is due to reduced activity of NF-κB, which is one of the major transcription factors regulating IL-8 expression. These results not only establish the relevance of CypA to glioblastoma growth in vitro and in vivo, but also suggest that small interfering RNA-based CypA knockdown could be an effective therapeutic approach against glioblastomas.

A myriad of geopolitical and financial obstacles have kept modern neurosurgery from effectively reaching the citizens of the developing world. Targeted neurosurgical outreach by academic neurosurgeons to equip neurosurgical operating theaters and train local neurosurgeons is one method to efficiently and cost effectively improve sustainable care provided by international charity hospitals. The International Neurosurgical Children’s Association (INCA) effectively improved the available neurosurgical care in the Maria Auxiliadora Hospital of Lima, Peru through the advancement of local specialist education and training.Neurosurgical equipment and training were provided for the local neurosurgeons by a mission team from the University of California at San Diego.At the end of 3 years, with one intensive week trip per year, the host neurosurgeons were proficiently and independently applying microsurgical techniques to previously performed operations, and performing newly learned operations such as neuroendoscopy and minimally invasive neurosurgery.Our experiences may serve as a successful template for the execution of other small scale, sustainable neurosurgery missions worldwide.

Rigorous assessment of medical knowledge and technical skill inspires learning, reinforces confidence, and reassures the public. Identifying curricular effectiveness using objective measures of learning is therefore crucial for competency-oriented program development in a learner-centric educational environment. The aim of this study was to determine whether various measures of learning, including class-average normalized gain, can be used to assess the effectiveness of a one-day introductory bronchoscopy course curriculum.We conducted a quasi-experimental one-group pre-test/post-test study at the University of California, Irvine. The group comprised 24 first-year pulmonary and critical care trainees from eight training institutions in southern California. Class-average normalized gain, single-student normalized gain, absolute gain, and relative gain were used as objective measures of cognitive knowledge and bronchoscopy technical skill learning. A class-average normalized gain of 30% was used to determine curricular effectiveness. Perceived educational value using Likert-scale surveys and post-course questionnaires was determined during and 3 months after course participation.Mean test scores of cognitive knowledge improved significantly from 48 to 66% (p = 0.043). Absolute gain for the class was 18%, relative gain was 37%, class average normalized gain 〈g〉 was 34%, and the average of the single-student normalized gains g(ave) was 29%. Mean test scores of technical skill improved significantly from 43 to 77% (p = 0.017). Absolute gain was 34%, relative gain was 78%, class average normalized gain 〈g〉 was 60%, and the average of the single-student normalized gains g(ave) was 59%. Statistically significant improvements in absolute gain were noted in all five elements of technical skill (p

The PRECISE study used convection enhanced delivery (CED) to infuse IL13-PE38QQR in patients with recurrent glioblastoma multiforme (GBM) and compared survival to Gliadel Wafers (GW). The objectives of this retrospective evaluation were to assess: (1) catheter positioning in relation to imaging features and (2) to examine the potential impact of catheter positioning, overall catheter placement and imaging features on long term clinical outcome in the PRECISE study. Catheter positioning and overall catheter placement were scored and used as a surrogate of adequate placement. Imaging studies obtained on day 43 and day 71 after resection were each retrospectively reviewed. Catheter positioning scores, catheter overall placement scores, local tumor control and imaging change scores were reviewed and correlated using Generalized Linear Mixed Models. Cox PH regression analysis was used to examine whether these imaging based variables predicted overall survival (OS) and progression free survival (PFS) after adjusting for age and KPS. Of 180 patients in the CED group, 20 patients did not undergo gross total resection. Of the remaining 160 patients only 53% of patients had fully conforming catheters in respect to overall placement and 51% had adequate catheter positioning scores. Better catheter positioning scores were not correlated with local tumor control (P = 0.61) or imaging change score (P = 0.86). OS and PFS were not correlated with catheter positioning score (OS: P = 0.53; PFS: P = 0.72 respectively), overall placement score (OS: P = 0.55; PFS: P = 0.35) or imaging changes on day 43 MRI (P = 0.88). Catheter positioning scores and overall catheter placement scores were not associated with clinical outcome in this large prospective trial.

The use of fluorescent proteins to label tumors is revolutionizing cancer research, enabling imaging of both primary and metastatic lesions, which is important for diagnosis, staging, and therapy. This report describes the use of fluorescence laparoscopy to image green fluorescent protein (GFP)-expressing tumors in an orthotopic mouse model of human pancreatic cancer.The orthotopic mouse model of human pancreatic cancer was established by injecting GFP-expressing MiaPaCa-2 human pancreatic cancer cells into the pancreas of 6-week-old female athymic mice. On postoperative day 14, diagnostic laparoscopy using both white and fluorescent light was performed. A standard laparoscopic system was modified by placing a 480-nm short-pass excitation filter between the light cable and the laparoscope in addition to using a 2-mm-thick emission filter. A camera was used that allowed variable exposure time and gain setting. For mouse laparoscopy, a 3-mm 0° laparoscope was used. The mouse’s abdomen was gently insufflated to 2 mm Hg via a 22-gauge angiocatheter. After laparoscopy, the animals were sacrificed, and the tumors were collected and processed for histologic review. The experiments were performed in triplicate.Fluorescence laparoscopy enabled rapid imaging of the brightly fluorescent tumor in the pancreatic body. Use of the proper filters enabled simultaneous visualization of the tumor and the surrounding structures with minimal autofluorescence. Fluorescence laparoscopy thus allowed exact localization of the tumor, eliminating the need to switch back and forth between white and fluorescence lighting, under which the background usually is so darkened that it is difficult to maintain spatial orientation.The use of fluorescence laparoscopy permits the facile, real-time imaging and localization of tumors labeled with fluorescent proteins. The results described in this report should have important clinical potential.