Do Bone Scans Overstage Disease Compared with PSMA PET at Initial Staging? An International Multicenter Retrospective Study with Masked Independent Readers.

Prostate-specific membrane antigen (PSMA) PET has a higher accuracy than CT and bone scans to stage patients with prostate cancer. We do not understand how to apply clinical trial data based on conventional imaging to patients staged using PSMA PET. Therefore, we aimed to evaluate the ability of bone scans to detect osseous metastases using PSMA PET as a reference standard. Methods: In this multicenter retrospective diagnostic study, 167 patients with prostate cancer, who were imaged with bone scans and PSMA PET performed within 100 d, were included for analysis. Each study was interpreted by 3 masked readers, and the results of the PSMA PET were used as the reference standard. Endpoints were positive predictive value (PPV), negative predictive value (NPV), and specificity for bone scans. Additionally, interreader reproducibility, positivity rate, uptake on PSMA PET, and the number of lesions were evaluated. Results: In total, 167 patients were included, with 77 at initial staging, 60 in the biochemical recurrence and castration-sensitive prostate cancer setting, and 30 in the castration-resistant prostate cancer setting. In all patients, the PPV, NPV, and specificity for bone scans were 0.73 (95% CI, 0.61-0.82), 0.82 (95% CI, 0.74-0.88), and 0.82 (95% CI, 0.74-0.88), respectively. In patients at initial staging, the PPV, NPV, and specificity for bone scans were 0.43 (95% CI, 0.26-0.63), 0.94 (95% CI, 0.85-0.98), and 0.80 (95% CI, 0.68-0.88), respectively. Interreader agreement for bone disease was moderate for bone scans (Fleiss κ, 0.51) and substantial for the PSMA PET reference standard (Fleiss κ, 0.80). Conclusion: In this multicenter retrospective study, the PPV of bone scans was low in patients at initial staging, with 57% of positive bone scans being false positives. This suggests that a large proportion of patients considered low-volume metastatic by the bone scan actually had localized disease, which is critical when applying clinical data from trials such as the STAMPEDE M1 radiation therapy trial to patients being staged with PSMA PET.

Association of select psychiatric disorders with incident brain aneurysm and subarachnoid hemorrhage among veterans.

Background: Brain aneurysms represent a significant cause of hemorrhagic stroke. Prior research has demonstrated links between stress and stroke, including brain aneurysms. We aimed to determine relationships between select psychiatric disorders and aneurysms and aneurysmal SAH. Methods: We performed retrospective, case-control study of a National Veterans Affairs population with two experimental groups (aneurysm-only and aneurysmal SAH) and 10-fold controls per group matched by age, date, and clinical data source. The studied the presence of 4 psychiatric disorders: Posttraumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), and other mood disorders. Our main outcomes Unadjusted and multivariable adjusted ORs of PTSD, MDD, GAD, and mood disorders within aneurysm-only and aSAH groups. Results: In 6,320,789 US Veterans who were enrolled for at least 5 years in Medicare and/or the Veterans Health Administration, we identified 35,094 cases of aneurysm without SAH and 5,749 cases of aneurysm with SAH between 1/2005 and 12/2019. In analyses adjusted for sex, hypertension, and tobacco use, patients with aneurysm were more likely than matched controls to have a history of PTSD (OR 1.48), MDD (OR 1.33), GAD (OR 1.26), and other mood disorders (OR 1.34) (all p-values < 0.0001). Similarly, patients with aSAH were more likely than controls to have a history of PTSD (OR 1.35), MDD (OR 1.38), GAD (OR 1.18), and other mood disorders (OR 1.30) (all p-values < 0.0001). Conclusion: The study, the largest of its kind, further suggests links between psychiatric disorders and stroke. This is important as patients with aneurysms are not routinely screened for such psychiatric risk factors. Additional research on this topic could lead to novel strategies to improve stroke prevention.

Presurgical 68Ga-PSMA-11 Positron Emission Tomography for Biochemical Recurrence Risk Assessment: A Follow-up Analysis of a Multicenter Prospective Phase 3 Imaging Trial.

BACKGROUND: In the initial staging of patients with high-risk prostate cancer (PCa), prostate-specific membrane antigen positron emission tomography (PSMA-PET) has been established as a front-line imaging modality. The increasing number of PSMA-PET scans performed in the primary staging setting might be associated with decreases in biochemical recurrence (BCR)-free survival (BCR-FS). OBJECTIVE: To assess the added prognostic value of presurgical PSMA-PET for BCR-FS compared with the presurgical Cancer of the Prostate Risk Assessment (CAPRA) and postsurgical CAPRA-Surgery (CAPRA-S) scores in patients with intermediate- to high-risk PCa treated with radical prostatectomy (RP) and pelvic lymph node dissection. DESIGN, SETTING, AND PARTICIPANTS: This is a follow-up study of the surgical cohort evaluated in the multicenter prospective phase 3 imaging trial (n = 277; NCT03368547, NCT02611882, and NCT02919111). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Each 68Ga-PSMA-11-PET scan was read by three blinded independent readers. PSMA-PET prostate uptake (low vs high), PSMA-PET extraprostatic disease (N1/M1), and CAPRA and CAPRA-S scores were used to assess the risk of BCR. Patients were followed after RP by local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level increasing to ≥0.2 ng/ml after RP or initiation of PCa-specific secondary treatment (>6 mo after surgery). Univariate and multivariable Cox models, and c-statistic index were performed to assess the prognostic value of PSMA-PET and for a comparison with the CAPRA and CAPRA-S scores. RESULTS AND LIMITATIONS: From December 2015 to December 2019, 277 patients underwent surgery after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median follow-up after surgery was 32.4 (interquartile range 23.3-42.9) mo. Of 240 BCR events, 91 (38%) were observed. PSMA-PET N1/M1 was found in 41/240 (17%) patients. PSMA-PET prostate uptake, PSMA-PET N1/M1, and CAPRA and CAPRA-S scores were significant univariate predictors of BCR. The addition of PSMA-PET N1/M1 status to the presurgical CAPRA score improved the risk assessment for BCR significantly in comparison with the presurgical CAPRA score alone (c-statistic 0.70 [0.64-0.75] vs 0.63 [0.57-0.69]; p < 0.001). The C-index of the postsurgical model utilizing the postsurgical CAPRA-S score alone was not significantly different from the presurgical model combining the presurgical CAPRA score and PSMA-PET N1/M1 status (p = 0.19). CONCLUSIONS: Presurgical PSMA-PET was a strong prognostic biomarker improving BCR-FS risk assessment. Its implementation in the presurgical risk assessment with the CAPRA score improved the performance and reduced the difference with the reference standard (postsurgical CAPRA-S score). PATIENT SUMMARY: The use prostate-specific membrane antigen positron emission tomography improved the assessment of biochemical recurrence risk in patients with intermediate- and high-risk prostate cancer who were treated with radical prostatectomy and pelvic lymph node dissection.

Epidemiology and Outcomes of Peripheral and Non-Aortocaval Vascular Trauma in Scotland 2011 - 2018.

OBJECTIVE: This population based study aimed to examine the demographics, mechanisms, and outcomes of patients in Scotland suffering peripheral and non-aortocaval vascular trauma between 2011 and 2018. METHODS: A retrospective observational study was conducted using prospectively collected data derived from the Scottish Trauma Audit Group (STAG) from 1 January 2011 to 31 December 2018. Peripheral and non-aortocaval vascular trauma patients were identified using Abbreviated Injury Severity (AIS) codes. Demographics, mechanisms, types of injury, severity, and outcomes were analysed. RESULTS: Of 30 831 patients admitted with trauma to Scottish hospitals, 569 (1.8%) patients suffered a vascular injury during the eight year study period with 275 (0.9%) patients sustaining a peripheral or non-aortocaval vascular injury. There were 221 (80%) men and 54 (20%) women with a median (range) age of 39 (14 - 88) years. Blunt trauma was responsible for 179 (65%) injuries, of which road traffic accidents were the most common mechanism. A further 67 (24%) injuries were due to penetrating trauma, of which assault was the most common cause. The most common injury was to abdominal arteries (e.g., hepatic, renal, splenic [n = 83]) with an associated mortality rate of 17%. The median (range) Injury Severity Score (ISS) was 16 (4 - 75). Sixteen (6%) patients died in the Emergency Department (ED). Two hundred and twenty-seven (83%) patients were taken to theatre during their admission with a 30 day peri-operative mortality rate of 10%, compared with an overall mortality rate of 16%. Injuries to an abdominal vein (e.g., portal, renal, splenic, superior mesenteric) had the highest number of associated deaths, with 11 (32%) of 34 cases resulting in a fatality. CONCLUSION: There is a low incidence of vascular trauma in Scotland. Blunt force was responsible for more vascular injuries than penetrating trauma. Patients with peripheral and non-aortocaval vascular injuries are likely to be severely injured and suffer a high mortality rate.

Post-operative tension spinal subdural extra-arachnoid hygroma of the lumbar spine: case series, literature review, and recommendations for clinical management.

OBJECTIVE: Case series presentation and literature review of patient group suffering from symptomatic tension subdural extra-arachnoid hygroma following decompressive surgery for degenerative lumbar stenosis or disc disease. The purpose was to better understand this rare post-operative complication with a pathognomic radiological sign to help recommend optimal strategies for clinical management. METHODS: Retrospective case series comprising seven cases from one tertiary Neurosurgical centre spanning a 10-year period from 2011 to 2021. Patients included were those known to have undergone a spinal procedure and subsequently to have developed a symptomatic spinal subdural extra-arachnoid hygroma (SSEH). A literature review was conducted using PubMed, MEDLINE and EMBASE (keywords 'subdural hygroma', 'lumbar CSF hygroma', 'extra arachnoid hygroma', 'extra-arachnoid CSF collection', 'CSF tension hygroma', 'lumbar extra arachnoid hygroma', 'lumbar spinal hygroma', 'post-operating spinal hygroma', 'post-operative spinal CSF collection') and through reading references cited in relevant articles. Articles involving post-operative SSEH following lumbar spinal surgery were included. RESULTS: Rare complication with only five other cases in the literature. Dural breach described intra-operatively in only 5 of 12 total cases from our series and the literature. 5 patients in our series were managed surgically with 2 being managed conservatively. All patients in our series improved symptomatically and radiologically following surgical or conservative management. CONCLUSIONS: This is a rare post-lumbar surgery complication that can cause rapidly deteriorating lower limb and sphincteric function. Surgical management with wide durotomy and arachnoid marsupialisation can lead to reversal of neurological deterioration and excellent clinical results. A delayed presentation with pseudomeningocele formation may be managed conservatively if neurology is stable or improving. It is a condition that it is important for the clinician to recognise in order to instigate appropriate management in a time-dependent fashion.

Paediatric Cavernous Malformation of the Trigeminal Nerve: Case Report and Review of the Literature.

INTRODUCTION: Intradural, extra-axial cerebral cavernous malformations (CCMs) are rare entities and are mostly reported in relation to the optic apparatus or the facial/vestibulocochlear complex. Cranial nerve CCMs tend to follow a clinically aggressive course, with a tendency to progressive neurological dysfunction following intra-lesional haemorrhage or less commonly due to the effects of subarachnoid haemorrhage. CASE PRESENTATION: We report the first case of a trigeminal CCM presenting in a child with otalgia and left-sided headaches. The patient was initially managed with radiological surveillance but required surgical management following deterioration. We describe the successful treatment of the lesion with microsurgical resection. CONCLUSION: A CCM should be considered in the differential diagnosis of mass lesions arising in the region of the trigeminal nerve. Surgical resection is recommended to prevent neurological deterioration and may result in significant symptomatic improvement.

A Review of the Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies.

The B-cell receptor signaling pathway plays an integral role in the proliferation and survival of malignant B cells. Targeting the B-cell receptor pathway via the inhibition of Bruton tyrosine kinase (BTK) has evolved the treatment of a variety of B-cell malignancies, including chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia. Currently, there are three BTK inhibitors approved by the U.S. Food and Drug Administration: ibrutinib, acalabrutinib, and zanubrutinib. This article reviews the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions, and implications for advanced practitioners of BTK inhibitors in the treatment of B-cell malignancies.

Utilization of the iOS Shortcuts App to Generate a Surgical Logbook Tool: Feasibility Study.

BACKGROUND: Surgical audit is an essential aspect of modern reflective surgical practice and is key to improving surgical outcomes. The surgical logbook is an important method of data collection for both personal and unit audits; however, current electronic data collection tools, especially mobile apps, lack the minimum recommended data fields. OBJECTIVE: This feasibility study details the creation of a free, effective surgical logbook tool with the iOS Shortcuts app and investigates the time investment required to maintain a surgical logbook with this tool. In addition, we investigate the potential utility of the Shortcuts app in creating medical data collection tools. METHODS: Using the iOS Shortcuts app, we created a shortcut "Operation Note," which collects surgical logbook data by using the minimum and extended audit data sets recommended by the Royal Australasian College of Surgeons. We practically assessed the feasibility of the tool, assessing the time requirement for entry, accuracy, and completeness of the entered data. RESULTS: The shortcut collected accurate and useful data for a surgical audit. Data entry took on average 65 seconds per case for the minimum data set, and 135 seconds per case for the extended data set, with a mean difference of 68 seconds (P<.001; 95% CI 61.6-77.7). CONCLUSIONS: This feasibility study demonstrates the utility of the iOS Shortcuts app in the creation of a surgical logbook and the time-consuming nature of data collection for surgical audit. Our iOS Operation Note shortcut is a free, rapid, and customizable alternative to currently available logbook apps and offers surgical trainees and consultants a method for recording surgical operations, complications, and demographic data.

Prognostic utility of inflammation-based biomarkers, neutrophil-lymphocyte ratio and change in neutrophil-lymphocyte ratio, in surgically resected lung cancers.

BACKGROUND/OBJECTIVE: Given the poor overall survival (OR) and progression-free survival (PFS) rates for lung cancers managed with surgical resection, there is a need to identify the prognostic markers that would improve the risk stratification of patients with operable lung cancer to inform treatment decisions. We investigate the prognostic utility of two established inflammation-based scores, the neutrophil-lymphocyte ratio (NLR) and the change in neutrophil-lymphocyte ratio (ΔNLR), throughout the operative period in a prospective cohort of patients with lung cancer who underwent surgical resection. METHODS: Demographic, clinical, and treatment details for 345 patients with lung cancer who underwent surgical resection between 2000 and 2019 at multiple centers across Melbourne, Victoria (Australia), were prospectively collected. Preoperative NLR and ΔNLR were calculated after which Cox univariate and multivariate analyses were conducted for OS and PFS against the known prognostic factors. RESULTS: Both univariate and multivariate analyses showed that preoperative NLR >4.54, as well as day 1 and day 2 postoperative NLR (P < 0.01), was associated with increased risk for postoperative mortality (hazard ratio 1.8; P < 0.01) and PFS (P < 0.05), whereas ΔNLR was not a significant predictor of OS or PFS. CONCLUSION: Elevated NLR among patients with lung cancer who underwent surgical resection was prognostic for poor OS and PFS, whereas ΔNLR was not found to be prognostic for either OS or PFS. Further research may yet reveal a prognostic value for ΔNLR when compared across a greater time period.

Accuracy of 18F-Fluorocholine PET for the Detection of Parathyroid Adenomas: Prospective Single-Center Study.

The purpose of this prospective study was to determine the correct localization rate (CLR) of 18F-fluorocholine PET for the detection of parathyroid adenomas in comparison to 99mTc-sestamibi imaging. Methods: This was a single-arm prospective trial. Ninety-eight patients with biochemical evidence of primary hyperparathyroidism were imaged before parathyroidectomy using 18F-fluorocholine PET/MRI. 99mTc-sestamibi imaging performed separately from the study was evaluated for comparison. The primary endpoint of the study was the CLR on a patient level. Each imaging study was interpreted by 3 masked readers on a per-region basis. Lesions were validated by histopathologic analysis of surgical specimens. Results: Of the 98 patients who underwent 18F-fluorocholine PET, 77 subsequently underwent parathyroidectomy and 60 of those had 99mTc-sestamibi imaging. For 18F-fluorocholine PET in patients who underwent parathyroidectomy, the CLR based on the masked reader consensus was 75% (95% CI, 0.63-0.82). In patients who underwent surgery and had an available 99mTc-sestamibi study, the CLR increased from 17% (95% CI, 0.10-0.27) for 99mTc-sestamibi imaging to 70% (95% CI, 0.59-0.79) for 18F-fluorocholine PET. Conclusion: In this prospective study using masked readers, the CLR for 18F-fluorocholine PET was 75%. In patients with a paired 99mTc-sestamibi study, the use of 18F-fluorocholine PET increased the CLR from 17% to 70%. 18F-fluorocholine PET is a superior imaging modality for the localization of parathyroid adenomas.

Evaluation of Montelukast for the Prevention of Infusion-related Reactions With Daratumumab.

BACKGROUND: Daratumumab is an anti-CD38 monoclonal antibody indicated for the treatment of multiple myeloma. Infusion-related reactions (IRRs) are among the most common adverse events associated with daratumumab. IRRs are most common with the first infusion of daratumumab. Recommended premedications to be given prior to the daratumumab dose include acetaminophen, diphenhydramine, and a corticosteroid. There is emerging data to suggest that the addition of montelukast to this premedication regimen can lower the incidence of daratumumab-related IRRs. PATIENTS AND METHODS: This was a single-center, retrospective chart review conducted at a large, multistate health system with several different hematology/oncology practice sites. Eligible patients included those with a primary diagnosis of a plasma cell disorder who received at least 1 dose of daratumumab. The primary outcome was the incidence of IRRs with the first daratumumab infusion. RESULTS: A total of 141 patients receiving daratumumab-based therapy were included in this study. All patients received acetaminophen, diphenhydramine, and a corticosteroid as premedications prior to the first infusion of daratumumab. Overall, 46 (33%) patients experienced an IRR with the first infusion of daratumumab. The incidence of IRR was lower in patients that received montelukast as a premedication compared with those that did not (montelukast, n = 25 [27%]; no montelukast, n = 21 [45%]; P = .0371). Patients in each arm experienced similar rates of overall, composite pulmonary, gastrointestinal, and systemic IRR manifestations. CONCLUSION: The use of montelukast prior to the first daratumumab infusion led to a reduction in the incidence of IRRs in our experience.

Glasdegib: A Novel Hedgehog Pathway Inhibitor for Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive myeloid disorder that is associated with a generally poor prognosis. Effective treatment options have been limited for older patients with AML who are not able to undergo intensive remission induction chemotherapy due to advanced age or comorbidities. New and novel agents are needed to improve treatment outcomes for this patient population. Glasdegib is a novel Hedgehog signaling pathway inhibitor approved by the U.S. Food & Drug Administration for the treatment of patients with newly diagnosed AML who are 75 years of age or older or who have comorbidities that preclude intensive induction chemotherapy. Glasdegib is approved in combination with low-dose cytarabine (LDAC). This approval is based on the results of a multicenter, open-label, randomized trial of glasdegib plus LDAC vs. LDAC monotherapy in which the addition of glasdegib resulted in an improvement in median overall survival.

Encephalitis on deployment in Kenya: think beyond the infections.

A 34-year-old female soldier presented with fever and behavioural changes while deployed in Kenya and was diagnosed with encephalitis. The patient underwent urgent aeromedical evacuation to the Queen Elizabeth Hospital, Birmingham for further management. Microbiology tests excluded common infectious causes that are endemic in the East Africa region. However, an autoantibody screen was positive for antibodies against the N-methyl-D-aspartate receptor (NMDAR). Full body imaging confirmed the presence of limbic encephalitis and an ovarian mass suggestive of a teratoma. The patient was diagnosed with ovarian teratoma-associated anti-NMDAR encephalitis, a potentially fatal disease. The patient underwent surgery to remove the teratoma and commenced immunotherapy with steroids, plasma exchange and rituximab. This case highlights the diagnostic challenges of fever with behavioural changes in military personnel deployed in a tropical environment.

Immunohistochemical assessment of rat nerve isografts and immunosuppressed allografts.

OBJECTIVE: Autologous peripheral nerve grafts are commonly used clinically as a treatment for peripheral nerve injuries. However, in research using an autologous graft is not always feasible due to loss of function, which in many cases is assessed to determine the efficacy of the peripheral nerve graft. In addition, using allografts for research require the use of an immunosuppressant, which creates unwanted side effects and another variable within the experiment that can affect regeneration. The objective of this study was to analyze graft rejection in peripheral nerve grafts and the effects of cyclosporine A (CSA) on axonal regeneration. METHODS: Peripheral nerve grafts in inbred Lewis rats were compared with Sprague-Dawley (SD) rats to assess graft rejection, CSA side effects, immune responses, and regenerative capability. Macrophages and CD8+ cells were labeled to determine graft rejection, and neurofilaments were labeled to determine axonal regeneration. RESULTS: SD rats without CSA had significantly more macrophages and CD8+ cells compared to Lewis autografts, Lewis isografts, and SD allografts treated with CSA. Lewis autografts, Lewis isografts, and SD autografts had significantly more regenerated axons than SD rat allografts. Moreover, allografts in immunosuppressed SD rats had significantly less axons than Lewis rat autograft and isografts. DISCUSSION: Autografts have long been the gold standard for treating major nerve injuries and these data suggest that even though CSA is effective at reducing graft rejection, axon regeneration is still superior in autografts versus immunosuppressed allografts.

Routine but risky: a multi-centre analysis of the outcomes of cranioplasty in the Northeast of England.

BACKGROUND: Cranioplasty is undertaken as a routine secondary operation following craniectomy. At a time when decompressive craniectomy is being evaluated by several large trials, we aimed to evaluate the morbidity associated with cranioplasty and investigate its potential effect on outcome. METHODS: The outcomes of 166 patients undergoing cranioplasty at two centres in the United Kingdom between June 2006 and September 2011 were retrospectively analysed. Outcome measures included mortality, morbidity and functional outcome determined by the modified Rankin score (mRS) at last follow-up. A logistic regression analysis was performed to model and predict determinants related to neurological outcome following cranioplasty. RESULTS: Sixty-seven out of 166 patients (40.4 %) experienced at least one complication during a median follow-up time of 15 months (inter-quartile range 5-38 months). Thirty six patients (21.7 %) developed infection requiring antibiotics, with 27 (16.3 %) requiring removal of the cranioplasty. Nine of 25 patients (36 %) with bi-frontal defects developed an infection whereas 21 of the 153 patients (16.4 %) with a defect other than bi-frontal developed an infection (Chi square p = 0.009). Further surgery in the two groups was required in 16.4 % and 11.7, % respectively. Pseudomeningocoele (9 %), seizures (8.4 %) and poor cosmesis (7.2 %) were also commonly observed. Logistic regression analysis identified initial operation (p < 0.03), mRS at the time of cranioplasty (p < 0.0001) and complications (p < 0.04) as being predictive of neurological outcome at last follow-up. Age at the time of cranioplasty and the timing of cranioplasty were not predictive of last mRS score at follow-up. CONCLUSIONS: Cranioplasty harbours significant morbidity, a risk that appears to be higher with a bifrontal defect. The complications experienced influence subsequent functional outcome. The timing of cranioplasty, early or late, after the initial operation does not impact on the ultimate outcome. These findings should be considered when making decisions relating to craniectomy and cranioplasty.

Polycystic ovary syndrome and chronic inflammation: pharmacotherapeutic implications.

OBJECTIVE: To examine the relationship between polycystic ovary syndrome (PCOS), cardiovascular risk factors, cardiovascular disease (CVD), and chronic inflammation and analyze data regarding pharmacologic therapies that are recommended to reduce CVD risk in PCOS and the impact of those therapies on chronic inflammation. DATA SOURCES: A search of MEDLINE (1950-October 2011) was conducted to identify clinical studies pertaining to the identification and treatment of CVD and chronic low-grade inflammation in PCOS. Search terms included polycystic ovary syndrome, cardiovascular disease, inflammation, metformin, thiazolidinedione, and statin. Bibliographies of these studies and review articles were also examined. STUDY SELECTION AND DATA EXTRACTION: English-language clinical studies evaluating the effect of metformin, thiazolidinediones, and statins on inflammatory markers, endothelial function, adhesion molecules, fibrinolysis, cytokines, and adipokines in PCOS were included. DATA SYNTHESIS: Women with PCOS have an increased prevalence of many cardiovascular risk factors including obesity, android fat distribution, insulin resistance, impaired glucose tolerance, diabetes, dyslipidemia, hypertension, and metabolic syndrome. Markers of chronic low-grade inflammation, which are associated with an increased risk of CVD, are also elevated in PCOS. Clinical guidelines recommend the use of insulin sensitizers and statins to prevent CVD in some patients with PCOS. Current literature indicates that each of these medication classes has beneficial effects on inflammation, as well. Although there are currently no studies to determine whether these treatments decrease CVD in PCOS, it can be hypothesized that drugs impacting chronic inflammation may reduce cardiovascular risk. Some studies show that metformin, thiazolidinediones, and statins have beneficial effects on inflammatory markers in PCOS; however, the data are inconsistent. CONCLUSIONS: There is insufficient information to recommend any pharmacologic therapies for their antiinflammatory effects in PCOS in the absence of other indications such as diabetes and dyslipidemia.

Maternal obesity and risk of infant death based on Florida birth records for 2004.

OBJECTIVE: The purpose of this study was to assess the relationship between pre-pregnancy maternal obesity and risk of infant death. METHODS: In March 2004, maternal height and pre-pregnancy weight were added to the data collected on the Florida birth certificate. Using birth records linked to infant deaths, these data were used to assess the relationship between pre-pregnancy maternal obesity, as measured by body mass index, and infant death. RESULTS: Pre-pregnancy maternal obesity was associated with increased odds of infant death. The increased risk was found with and without adjustments for maternal race, marital status, age, education, trimester prenatal care began, first birth, and tobacco use. CONCLUSION: There is a substantial and significant association between pre-pregnancy maternal obesity and infant death.

Non-invasive automated measurement of cardiac output during stable cardiac surgery using a fully integrated differential CO(2) Fick method.

OBJECTIVES: To re-evaluate the accuracy and precision of a non-invasive method for measurement of cardiac output based on the differential CO(2) Fick approach using an automated change in respiratory rate delivered by a ventilator under control by a prototype measurement system. METHODS: Twenty-four patients during coronary artery bypass surgery, pre- and postcardiopulmonary bypass were recruited. After routine cannulation including pulmonary artery catheter, relaxant general anesthesia was induced. After hemodynamic and ventilatory stability were achieved, simultaneous paired measurements were made by the differential Fick method and by bolus thermodilution. Measurements were generated by inducing a change in respiratory rate by the ventilator under computer control. In Group 1, this involved an increase in respiratory rate from 8 to 12 breaths/min. In Group 2, this involved a decrease from 12 to 6 breaths/min. RESULTS: Nineteen measurements were made in each Group, 12 pre-CPB and 7 post-CPB. In Group 1 mean bias was -0.06 l/min, with a precision of agreement of 0.87 l/min, r = 0.91. In Group 2 (excluding one outlier) mean bias was -0.07 l/min, with a precision of 1.12 l/min, r = 0.71. CONCLUSIONS: Acceptable agreement with thermo- dilution during surgery was found, particularly where the ventilatory change involved an increase in respiratory rate from a lower baseline. This approach has potential to be readily integrated into modern anesthesia delivery platforms, allowing routine non-invasive cardiac output measurement.

Adnexal mass: an unusual presentation of small-bowel adenocarcinoma.

Malignancy of the small bowel presents unique diagnostic and therapeutic challenges resulting in a delayed diagnosis in many cases. Small-bowel tumors respond poorly to most forms of treatment. Metastatic lesions to the ovaries comprise a small percentage of all ovarian malignant neoplasms. Ovarian metastases from primary small-bowel tumors are often difficult to differentiate from primary ovarian tumors. Only few reports have described ovarian metastases from small-bowel sources. A high index of suspicion can lead to an earlier diagnosis and can have an impact on the therapeutic options as well as the survival of the patients. The current report also underscores the importance of careful review of symptoms, investigative studies and pathology.

Preliminary investigation of proton and helium ion radiation effects on fluorescent dyes for use in astrobiology applications.

The Specific Molecular Identification of Life Experiment (SMILE) instrument (Sims et al. Planet. Space Science 2005, 53, 781-791) proposes to use specific molecular receptors for the detection of organic biomarkers on future astrobiology missions (e.g., to Mars). Such receptors will be used in assays with fluorescently labeled assay reagents. A key uncertainty of this approach is whether the fluorescent labels used in the system will survive exposure to levels of solar and galactic particle radiation encountered during a flight to Mars. Therefore, two fluorescent dyes (fluorescein and Alexa Fluor 633) have been exposed to low-energy proton and alpha radiation with total fluences comparable or exceeding that expected during an unshielded cruise to Mars. The results of these initial experiments are presented, which show that both dyes retain their fluorescent properties after irradiation. No significant alteration in the absorption and emission wavelengths or the quantum yields of the dyes with either radiation exposure was found. These results suggest other structurally similar fluorophores will likely retain their fluorescent properties after exposure to similar levels of proton and alpha radiation. However, more extensive radiation fluorophore testing is needed before their suitability for astrobiology missions to Mars can be fully confirmed.