Borrelia burgdorferi CheD Promotes Various Functions in Chemotaxis and the Pathogenic Life Cycle of the Spirochete.

Borrelia burgdorferi possesses a sophisticated chemotaxis signaling system; however, the roles of the majority of the chemotaxis proteins in the infectious life cycle have not yet been demonstrated. Specifically, the role of CheD during host colonization has not been demonstrated in any bacterium. Here, we systematically characterized the B. burgdorferi CheD homolog using genetics and biochemical and mouse-tick-mouse infection cycle studies. Bacillus subtilis CheD plays an important role in chemotaxis by deamidation of methyl-accepting chemotaxis protein receptors (MCPs) and by increasing the receptor kinase activity or enhancing CheC phosphatase activity, thereby regulating the levels of the CheY response regulator. Our biochemical analysis indicates that B. burgdorferi CheD significantly enhances CheX phosphatase activity by specifically interacting with the phosphatase. Moreover, CheD specifically binds two of the six MCPs, indicating that CheD may also modulate the receptor proteins. Although the motility of the cheD mutant cells was indistinguishable from that of the wild-type cells, the mutant did exhibit reduced chemotaxis. Importantly, the mutant showed significantly reduced infectivity in C3H/HeN mice via needle inoculation. Mouse-tick-mouse infection assays indicated that CheD is dispensable for acquisition or transmission of spirochetes; however, the viability of cheD mutants in ticks is marginally reduced compared to that of the wild-type or complemented cheD spirochetes. These data suggest that CheD plays an important role in the chemotaxis and pathogenesis of B. burgdorferi We propose potential connections between CheD, CheX, and MCPs and discuss how these interactions play critical roles during the infectious life cycle of the spirochete.

A retrospective comparison of ring pessary and multicomponent behavioral therapy in managing overactive bladder.

INTRODUCTION AND HYPOTHESIS: Overactive bladder (OAB) is a physically, psychologically, and socially disabling condition that affects millions of women worldwide and is especially prevalent postmenopause. The objective of our study was to compare the cure rates of ring pessary with those of multicomponent behavioral therapy in managing overactive bladder. METHODS: We performed a comparative retrospective parallel cohort study of all women whose overactive bladder was treated with multicomponent behavioral therapy or ring pessary over a 42-month period. At the end of the 6-month treatment period, cure was defined as the subjective (self-reported) absence of urinary urgency, frequency, nocturia, and urge incontinence in the preceding 30 days; the objective absence of these symptoms in a 7-day voiding diary; and a Patient Global Impression of Improvement response of "much better" or "very much better." RESULTS: Ring pessary and multicomponent behavioral therapy had similar cure rates (29 out of 150 [19 %] vs 46 out of 231 [20 %] respectively, P = 0.889; OR of 1.04, 95 % confidence interval 0.618-1.742, P = 0.887). They also produced comparable cure rates in premenopausal (4 out of 31 [13 %] vs 14 out of 68 [21 %], P = 0.358) and postmenopausal subjects (25/ out of 19 [21 %] vs 32 out of 163 [20 %], P = 0.776), and in women who had undergone previous treatment (21 out of 108 [19 %] vs 31 out of 176 [18 %], P = 0.699) and those who had not (8 out of 42 [19 %] vs 15 out of 55 [27 %], P = 0.345). Logistic regression showed that neither treatment outcome is significantly associated with demographic characteristics; Pelvic Organ Prolapse Quantification at the anterior and posterior vaginal walls and at the vaginal cuff; previous treatment; overactive bladder symptoms; pad usage; or any combination thereof. CONCLUSIONS: Ring pessary has a cure rate similar to that of multicomponent behavioral therapy in managing overactive bladder.

A cross-sectional survey of the relationship between fecal incontinence and constipation.

INTRODUCTION AND HYPOTHESIS: We compared the prevalence of fecal incontinence between constipated and nonconstipated women and correlated its prevalence with the number of Rome III constipation symptoms. METHODS: We performed a cross-sectional survey to evaluate the prevalence of fecal incontinence and constipation among women who presented to two gynecologic clinics for routine care over a 24-month period. Fecal incontinence was defined as loss of well-formed and/or loose stool beyond the patient's control that occurred at least once in the last 4 weeks, was bothersome, had been present for the past 3 or more months, and had affected the person's activities, relationships, or feelings. Constipation was diagnosed using the Rome III criteria. Our study was exempt from institutional review board approval because it was a survey and did not ask for information that could be used to identify the participant. RESULTS: Mean age of the 2,319 participants was 50.1 ± 15 years and mean body mass index (BMI) was 28.7 ± 7. Seven hundred and twenty-five (31 %) women had constipation, and 233 (10 %) had fecal incontinence. One hundred and one (43 %) incontinent women had coexisting constipation. Logistic regression analysis identified white race (p = .013), menopause (p = .010), and constipation (p = .004) as risk factors for fecal incontinence. After controlling for these risk factors, constipated women were more likely to have fecal incontinence than nonconstipated women [relative risk (RR) 1.60, 95 % confidence interval (CI) 1.26-2.05]. In addition, the prevalence of fecal incontinence was strongly associated with the number of Rome III constipation symptoms (p < .001). CONCLUSION: Constipation is an important risk factor for fecal incontinence.

Identification of a novel marker associated with risk for delayed chemotherapy-induced vomiting.

PURPOSE: Besides chemotherapy drugs, a number of patient-related factors (i.e., gender, age, history of alcohol consumption, and/or motion sickness) may be used to calculate the risk for chemotherapy-induced vomiting. We evaluated data with the intent of identifying a unique variable associated with delayed vomiting in patients receiving moderately emetogenic chemotherapy (MEC). METHODS: From an ongoing research study, the serotonin metabolite, 5-hydroxyindole acetic acid (5-HIAA), creatinine, and substance P were measured over a 72-h period in 25 patients receiving MEC. All patients were treated with a 5-hydroxytryptamine-3 receptor antagonist plus dexamethasone according to published guidelines; none received aprepitant prophylactically. Urine 5-HIAA/creatinine and serum substance P values were grouped according to the development (+) or absence (-) of delayed emesis. Baseline mean values associated with the two neurotransmitters were analyzed by analysis of variance. RESULTS: Eleven patients developed moderate to severe delayed vomiting; the other 14 were symptom-free. The pretreatment log (mean 5-HIAA/creatinine) was 1.22 and 1.81 in the (+) and (-) emesis groups, respectively, p = 0.0049; the pretreatment log (mean substance P) for the same respective groups was 5.33 and 4.09 pg/mL, p > 0.05. The log (mean ratio of substance P to 5-HIAA/creatinine) between-group difference in those with and without emesis was 4.53 and 2.52, respectively, p = 0.0002. The 5-HIAA/creatinine and ratio of substance P to 5-HIAA/creatinine data were also used to determine cutoff points which resulted in the optimal predictive accuracy. CONCLUSIONS: These preliminary findings suggest that an elevated pretreatment ratio of substance P to 5-HIAA/creatinine >70 is associated with the development of delayed vomiting induced by MEC.

A retrospective cohort study of perioperative management on the morbidity of urogynecologic surgery.

INTRODUCTION AND HYPOTHESIS: To determine whether premenopausal and early (<70) and late postmenopausal women whose comorbidities were screened and managed using a standardized protocol experienced comparable perioperative complications after urogynecologic surgery. METHODS: We retrospectively reviewed the charts of all women who presented for surgical management of their pelvic floor disorders over 4.5 years for any complications, which occurred intraoperatively to 6 weeks postoperatively. RESULTS: Late postmenopausal women underwent more vaginal (100/124, 159/246, and 226/288, p < 0.001) and obliterative (15/124, 0/246, and 4/288, p < 0.001), and fewer abdominal (9/124, 87/246, and 58/288, p < 0.001) procedures and had lower body mass index (27.1, 31.4, and 29.4, P < 0.001) and fewer smokers (4/124, 86/246, and 52/288, p < 0.001) than premenopausal and early postmenopausal subjects. After adjusting for these differences, the proportions that experienced perioperative complications were similar among the three groups (P = 0.789). CONCLUSIONS: With standardized screening and management, our premenopausal and early and late postmenopausal women experienced similar perioperative complications.

Sex Disparities in the Presentation of Gallbladder Disease.

INTRODUCTION: Although gallbladder disease is more common in women, there is a trend toward more complicated cases in male patients. METHODS: All cholecystectomies captured by the National Surgical Quality Improvement Program database for the year 2016 were reviewed. This encompassed 38 736 records. Records were reviewed for age, sex, procedure performed, operative time, postoperative diagnosis, functional status, American Society of Anesthesiologists (ASA) class, preoperative lab values (total bilirubin, alkaline phosphatase, white blood cell count, and aspartate aminotransferase. Descriptive and inferential statistical analyses were conducted. RESULTS: Male patients are more likely to undergo cholecystectomy for a diagnosis of cholecystitis, gallstone pancreatitis, or cholangitis than women who are more likely to carry a diagnosis of biliary dyskinesia. The average operative time increases for both sexes as the patients become older. The average operative time is higher for men than women in all age groups and the variance becomes greater as the patients become older. Age, sex, postoperative diagnosis, ASA class, and functional status were all independently significant in predicting operative time. There was no difference in need for cholangiogram between the sexes. Female patients were more likely to have their cholecystectomy completed laparoscopically and they were more likely to have their surgery performed as an outpatient. CONCLUSION: These data show that women were more likely to present with uncomplicated gallbladder disease, while men were more likely to present with complicated gallbladder disease. This suggests that male patients present at a more advanced stage of disease.

Assessing Loneliness among Adults Receiving Outpatient Treatment with Medication for Opioid Use Disorder (MOUD).

Loneliness is a significant risk factor for substance use, however, impacts of treatments on loneliness are relatively unexplored. Living in a rural location is a greater risk factor for loneliness. This study examined data from a quasi-experimental study in rural Appalachia, comparing the effectiveness of Mindfulness-Based Relapse Prevention (MBRP) versus Treatment as Usual (TAU) among adults receiving MOUD in outpatient therapy. Our objective was to determine whether observed reductions in self-reported craving, anxiety, depression, and increased perceived mindfulness would also improve loneliness reports. Eighty participants (n = 35 MBRP; n = 45 TAU) were included in the analysis from a group-based Comprehensive Opioid Addiction Treatment program. Outcomes tracked included craving, anxiety, depression, mindfulness, and loneliness as measured by the Revised UCLA Loneliness Scale (R-UCLA). A linear mixed model ANOVA determined the significance of the treatments on changes in loneliness scores at baseline, 12 weeks, 24 weeks, and 36 weeks post-recruitment. Both groups reported significantly reduced loneliness over the course of the study (F = 16.07, p < 0.01), however there were no significant differences between groups. Loneliness was also significantly positively (p < 0.01) correlated with anxiety (0.66), depression (0.59), and craving (0.38), and significantly (p < 0.01) inversely correlated (-0.52) with mindfulness. Results suggest that participation in MOUD group-based outpatient therapy has the potential to diminish loneliness and associated poor psychological outcomes. Thus, it is possible that a more targeted intervention for loneliness would further diminish loneliness, which is important as loneliness is linked to risk for relapse.

Analysis of the Borrelia burgdorferi cyclic-di-GMP-binding protein PlzA reveals a role in motility and virulence.

The cyclic-dimeric-GMP (c-di-GMP)-binding protein PilZ has been implicated in bacterial motility and pathogenesis. Although BB0733 (PlzA), the only PilZ domain-containing protein in Borrelia burgdorferi, was reported to bind c-di-GMP, neither its role in motility or virulence nor it's affinity for c-di-GMP has been reported. We determined that PlzA specifically binds c-di-GMP with high affinity (dissociation constant [K(d)], 1.25 µM), consistent with K(d) values reported for c-di-GMP-binding proteins from other bacteria. Inactivation of the monocistronically transcribed plzA resulted in an opaque/solid colony morphology, whereas the wild-type colonies were translucent. While the swimming pattern of mutant cells appeared normal, on swarm plates, mutant cells exhibited a significantly reduced swarm diameter, demonstrating a role of plzA in motility. Furthermore, the plzA mutant cells were significantly less infectious in experimental mice (as determined by 50% infectious dose [ID(50)]) relative to wild-type spirochetes. The mutant also had survival rates in fed ticks lower than those of the wild type. Consequently, plzA mutant cells failed to complete the mouse-tick-mouse infection cycle, indicating plzA is essential for the enzootic life cycle of B. burgdorferi. All of these defects were corrected when the mutant was complemented in cis. We propose that failure of plzA mutant cells to infect mice was due to altered motility; however, the possibility that an unidentified factor(s) contributed to interruption of the B. burgdorferi enzootic life cycle cannot yet be excluded.

Analysis of the HD-GYP domain cyclic dimeric GMP phosphodiesterase reveals a role in motility and the enzootic life cycle of Borrelia burgdorferi.

HD-GYP domain cyclic dimeric GMP (c-di-GMP) phosphodiesterases are implicated in motility and virulence in bacteria. Borrelia burgdorferi possesses a single set of c-di-GMP-metabolizing enzymes, including a putative HD-GYP domain protein, BB0374. Recently, we characterized the EAL domain phosphodiesterase PdeA. A mutation in pdeA resulted in cells that were defective in motility and virulence. Here we demonstrate that BB0374/PdeB specifically hydrolyzed c-di-GMP with a K(m) of 2.9 nM, confirming that it is a functional phosphodiesterase. Furthermore, by measuring phosphodiesterase enzyme activity in extracts from cells containing the pdeA pdeB double mutant, we demonstrate that no additional phosphodiesterases are present in B. burgdorferi. pdeB single mutant cells exhibit significantly increased flexing, indicating a role for c-di-GMP in motility. Constructing and analyzing a pilZ pdeB double mutant suggests that PilZ likely interacts with chemotaxis signaling. While virulence in needle-inoculated C3H/HeN mice did not appear to be altered significantly in pdeB mutant cells, these cells exhibited a reduced ability to survive in Ixodes scapularis ticks. Consequently, those ticks were unable to transmit the infection to naïve mice. All of these phenotypes were restored when the mutant was complemented. Identification of this role of pdeB increases our understanding of the c-di-GMP signaling network in motility regulation and the life cycle of B. burgdorferi.

Testicular torsion: a case study and evaluation of young men's knowledge about testicular pain.

PURPOSE: This study examines an illustrative case, and investigates the knowledge of 267 freshman males regarding testicular torsion (TT). In addition, we discuss the predisposing factors and common presentations of TT, and highlight the importance of seeking immediate care for testicular pain. METHODS: A case is presented and a study was done in which participants were asked to complete the anonymous "Men's Health Questionnaire" as they entered one of three university dining halls. RESULTS: Many, 48%, chose the correct response to sudden, severe testicular pain, however 39% chose to delay care. Most were never taught the significance of testicular pain or about TT. Our case report illustrates testicular loss as an end result of delayed presentation. CONCLUSIONS: Education of young men regarding TT is needed. This could lead to a decrease in delayed care seeking, and thus reduced testicular loss due to torsion.

Testing Mindfulness-Based Relapse Prevention with Medications for Opioid Use Disorder Among Adults in Outpatient Therapy: a Quasi-experimental Study.

OBJECTIVES: This study aimed to explore the effectiveness of mindfulness-based relapse prevention (MBRP) with individuals receiving medication for opioid use disorder (MOUD) in a naturalistic, open-ended outpatient group treatment setting. METHODS: Eighty participants (mean age 36.3) who had at least 90 consecutive days substance free self-selected into treatment (MBRP, n = 35) or comparison groups (treatment as usual, TAU, n = 45). Outcomes tracked included treatment retention and relapse, and self-reported craving, anxiety, depression, and mindfulness at baseline, 12 weeks, 24 weeks, and 36 weeks post-recruitment. MBRP group participants attended biweekly 60-min sessions for 24 weeks. A linear mixed model analysis of variance determined the significance of the MBRP intervention on changes in craving, anxiety, depression, and mindfulness. RESULTS: No significant differences in sex, education level, insurance status, relationship status, or employment status were detected at baseline between groups. The 36-week retention (74%, MBRP/MOUD; 71%, TAU/MOUD) and relapse rates (43%, MBRP/MOUD; 47%, TAU/MOUD) were similar for the groups. There were only four relapses on opioids. Significant reductions (p < .05) were observed in the MBRP/MOUD group for craving, anxiety, and depression in addition to significant increases in mindfulness compared to those in TAU/MOUD. CONCLUSIONS: Although state and federal resources are available to expand MOUD, no standard of behavioral therapy has been established as most complimentary to MOUD. The current study results suggest MBRP can be implemented as an outpatient therapy for individuals in MOUD.

Suicide and unintentional poisoning mortality trends in the United States, 1987-2006: two unrelated phenomena?

BACKGROUND: Two counter trends in injury mortality have been separately reported in the US in recent times - a declining suicide rate and a rapidly rising unintentional poisoning mortality rate. Poisoning suicides are especially difficult to detect, and injury of undetermined intent is the underlying cause-of-death category most likely to reflect this difficulty. We compare suicide and poisoning mortality trends over two decades in a preliminary assessment of their independence and implications for suicide misclassification. METHODS: Description of overall and gender- and age-specific trends using national mortality data from WISQARS, the Web-based Injury Statistics Query and Reporting System, maintained by the Centers for Disease Control and Prevention (CDC). Subjects were the 936,633 residents dying in the 50 states and the District of Columbia between 1987 and 2006 whose underlying cause of death was classified as suicide, unintentional poisoning, or injury mortality of undetermined intent. RESULTS: The official US suicide rate declined 18% between 1987 and 2000, from 12.71 to 10.43 deaths per 100,000 population. It then increased to 11.15 deaths per 100,000 by 2006, a 7% rise. By contrast to these much smaller rate changes for suicide, the unintentional poisoning mortality rate rose more than fourfold between 1987 and 2006, from 2.19 to 9.22 deaths per 100,000. Only the population aged 65 years and older showed a sustained decline in the suicide rate over the entire observation period. Consistently highest in gender-age comparisons, the elderly male rate declined by 35%. The elderly female rate declined by 43%. Unlike rate trends for the non-elderly, both declines appeared independent of corresponding mortality trends for unintentional poisoning and poisoning of undetermined intent. The elderly also deviated from younger counterparts by having a smaller proportion of their injury deaths of undetermined intent classified as poisoning. Poisoning manifested as a less common method of suicide for this group than other decedents, except for those aged 15-24 years. Although remaining low, the undetermined poisoning mortality rate increased over the observation period. CONCLUSIONS: The official decline in the suicide rate between 1987 and 2000 may have been a partial artifact of misclassification of non-elderly suicides within unintentional poisoning mortality. We recommend in-depth national, regional, and local population-based research investigations of the poisoning-suicide nexus, and endorse calls for widening the scope of the definition of suicide and evaluation of its risk factors.

p38 MAP kinase inhibitor reverses stress-induced myocardial dysfunction in vivo.

Recent clinical reports strongly support the intriguing possibility that emotional stress alone is sufficient to cause reversible myocardial dysfunction in patients. We previously reported that a combination of prenatal stress followed by restraint stress (PS+R) results in echocardiographic evidence of myocardial dysfunction in anesthetized rats compared with control rats subjected to the same restraint stress (Control+R). We now report results of our catheter-based hemodynamic studies in both anesthetized and freely ambulatory awake rats, comparing PS+R vs. Control+R. Systolic function [positive rate of change in left ventricular pressure over time (+dP/dt)] was significantly depressed (P < 0.01) in PS+R vs. Control+R both under anesthesia (6,287 +/- 252 vs. 7,837 +/- 453 mmHg/s) and awake (10,438 +/- 741 vs. 12,111 +/- 652 mmHg/s). Diastolic function (-dP/dt) was also significantly depressed (P < 0.05) in PS+R vs. Control+R both under anesthesia (-5,686 +/- 340 vs. -7,058 +/- 458 mmHg/s) and awake (-8,287 +/- 444 vs. 10,440 +/- 364 mmHg/s). PS+R also demonstrated a significantly attenuated (P < 0.05) hemodynamic response to increasing doses of the beta-adrenergic agonist isoproterenol. Intraperitoneal injection of the p38 MAP kinase inhibitor SB-203580 reversed the baseline reduction in +dP/dt and -dP/dt as well as the blunted isoproterenol response. Intraperitoneal injection of SB-203580 also reversed p38 MAP kinase and troponin I phosphorylation in cardiac myocytes isolated from PS+R. Thus the combination of prenatal stress followed by restraint stress results in reversible depression in both systolic and diastolic function as well as defective beta-adrenergic receptor signaling. Future studies in this animal model may provide insights into the basic mechanisms contributing to reversible myocardial dysfunction in patients with ischemic and nonischemic cardiomyopathies.

Concordance between substance P levels and antiemetic guidelines.

Practice guidelines now include an antagonist of the substance P/NK1 (neurokinin 1) receptor pathway as part of the standard antiemetic regimen for patients receiving highly, as well as certain moderately, emetogenic chemotherapy regimens. Accumulated laboratory data were used to determine the degree of concordance between substance P levels and the current antiemetic guidelines. Five blood samples were collected over 72 hours from 22 adult patients treated with cisplatin-containing chemotherapy regimens. Overall, the mean baseline substance P level was 318 pg/mL. Although increases in substance P were observed during both phases of the emetic response, analysis by least squares means grouped by cisplatin dosage and vomiting phase was significantly different (P< 0.0001). Preliminary analysis of substance P levels appears to provide additional justification for including the NK1 receptor antagonist in the current antiemetic practice guidelines. In addition, these data provide biochemical justification for the cisplatin dosage criterion used in clinical trials.

Efficacy of methylcellulose and loperamide in managing fecal incontinence.

OBJECTIVE: To evaluate the efficacy of methylcellulose (Citrucel) and loperamide (Imodium) in managing fecal incontinence by comparing cure rates with expectant management. DESIGN: Prospective controlled study. SETTING: Urogynecology clinic in a university hospital. POPULATION: Sixty-nine women with fecal incontinence. METHODS: All incontinent women received one heaping tablespoon of methylcellulose twice a day, which was increased to two heaping tablespoons twice a day as needed. If the incontinence persisted after taking the maximum dose of methylcellulose for two weeks, loperamide, one capsule twice a day was added, which was increased to two capsules three times a day as needed. If both fecal urgency and incontinence resolved, the therapy was continued for a three-month treatment period. Women, who declined the proposed treatment and did not undergo any other therapy during the subsequent eight weeks, served as controls. A subject or control was considered cured if she stated that her incontinence was cured, had zero Pescatori incontinence point, resolution of fecal urgency, and her incontinence did not affect her emotional, social, occupational, and physical functions during the three-month treatment or eight-week observation period. MAIN OUTCOME MEASURES: Difference in the cure rate between subjects and controls. Results. Fifty-nine subjects were treated with methylcellulose. Forty (68%) also required loperamide. Ten women served as controls. Women treated with methylcellulose and loperamide had a higher cure rate than those managed expectantly (46% vs. 0%, p<0.01). CONCLUSION: Methylcellulose and loperamide are an effective treatment for fecal incontinence, at least on a short-term basis.

Relation between vaginal birth and pelvic organ prolapse.

OBJECTIVE: To evaluate the relation between vaginal birth and pelvic organ prolapse quantification (POPQ) stages III and IV prolapse and whether each additional vaginal birth is associated with an increase in pelvic support defects. DESIGN: Prospective cross-sectional study. SETTING: Gynecology clinic in a University Hospital. POPULATION: Four hundred and fifty-eight nulliparas and 892 multiparas, including 272 with one, 299 with two and 321 with at least three term vaginal deliveries. METHODS: In a Human Investigation Committee approved-study, the pelvic support of nulliparas and multiparas who only had term vaginal deliveries was evaluated for prolapse using the POPQ system. MAIN OUTCOME MEASURE: 1. Difference in POPQ stages III and IV prolapse between nulliparas and multiparas. 2. Difference in POPQ stage distribution among nulliparas and multiparas who had one, two, and at least three term vaginal deliveries. RESULTS: Compared with nulliparas, the odds ratios of having POPQ stage II defect and stage III or IV prolapse associated with multiparas was 2.95 (95% CI: 2.06-4.24) and 1.01 (95% CI: 0.40-2.79), respectively. The prevalence of POPQ stage II defect among nulliparas and multiparas that had one, two, and at least three term vaginal deliveries was 25% (119/458), 50% (137/272), 66% (198/299), and 69% (220/321), respectively (p<0.001), while 1% (6/458), 1% (4/272), 2% (7/299), and 2% (8/321), respectively, had POPQ stage III or IV prolapse (p=0.618). CONCLUSIONS: Vaginal birth is not associated with POPQ stages III and IV prolapse, but it is associated with an increase in POPQ stage II defect.

Gender Disparities in the Presentation of Gallbladder Disease.

Although gallbladder disease (GBD) is more common in females, we have noticed a trend toward more complicated cases in male patients. We reviewed all cholecystectomies performed at our institution over the last five years. After eliminating cases with confounding variables, we identified 1529 records. Charts were reviewed for age, gender, BMI, procedure performed, operative time, length of stay, and preoperative diagnosis. Descriptive and inferential statistical analyses were conducted along with linear regression. There were 1444 laparoscopic, 64 laparoscopic converted to open, and 21 primary open cases. Patients were 1008 (66%) females and 521 (34%) males. Average operative time was 89.8 minutes. Cholecystectomy averaged 17.7 minutes longer in males (P = 0.0046). Two per cent of female patients and 7.9 per cent male patient converted to open. Males were more likely to have complicated GBD, whereas women had uncomplicated disease. Average age was 51.9 years for males versus 42.7 years for females. Age, gender, BMI, length of stay, and preoperative diagnosis were all independently significant in predicting operative time. In our study, women presented with uncomplicated GBD, whereas men presented with complicated GBD. This suggests that male patients present at a later stage of disease.

Correlation among [18F]fluorodeoxyglucose positron emission tomography/computed tomography, cancer antigen 27.29, and circulating tumor cell testing in metastatic breast cancer.

BACKGROUND: Tumor marker cancer antigen (CA) 27.29 and combined [18F]-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) scans are used to follow up response to treatment and disease progression in patients with metastatic breast cancer (MBC). Recently, circulating tumor cell testing (CTC) has been used in this context. It is not known if 1 of the 3 tests can be a surrogate for another. PATIENTS AND METHODS: We analyzed a database of 35 patients with MBC. There were 173 time points (> or = 6 weeks apart) when > or = 2 of these tests were performed. Correlation among all the 3 tests was statistically analyzed. RESULTS: Results of PET/CT scans were compared with CA 27.29 at 163 time points. There was a statistically significant correlation between both groups (P = .02); however, sensitivity of CA 27.29 to detect metastatic disease observed on PET/CT scan was 59%. The results of PET/CT scans were compared with CTC at 93 events, where there was a statistically significant correlation between both groups (P = .0002); however, sensitivity of CTC to detect metastatic disease shown on PET/CT scans was 55%. Cancer antigen 27.29 results were also compared to CTC at 100 events, where there was a statistically significant correlation between both groups (P = .0002). However, only 64% of patients with high CA 27.29 had abnormal CTC. CONCLUSION: Our data shows correlation among PET/CT scan, CA 27.29, and CTC. However, both CA 27.29 and CTC had poor sensitivity and negative predictive value to detect metastatic disease observed on PET/CT scan. Normal CA 27.29 testing or CTC has to be interpreted cautiously in patients with MBC.

Inferior vena cava filter placement in late-stage cancer.

Inferior vena cava (IVC) filters are increasingly used in patients with advanced-stage cancer for prophylaxis of pulmonary embolus. We evaluated the survival benefit of placing IVC filters in patients with late-stage malignancy and assessed their effectiveness in preventing pulmonary embolism. Between 1998 and 2003, 5,970 patients were treated with a primary diagnosis of malignancy at a tertiary care facility. Retrospective analysis identified 55 consecutive patients with stage III or IV malignant disease and venous thromboembolism (VTE) who received IVC filters. Retrospective review of electronic hospital charts identified subsequent pulmonary emboli, procedure-related complications, and survival. In a case control study, 16 patients with VTE but without IVC filter were matched for age, sex, type of malignancy, and stage of disease. IVC filter placement effectively prevented computed tomography (CT) scan or ventilation/perfusion ratio (V/Q) scan-proven pulmonary embolus in 52/55 (94.5%) patients. Complications developed in 4/55 or 7.3% of patients; 13/55 (23.6%) patients with late-stage cancer survived less than 30 days following placement of the filter. Another 23.6% of this group survived longer than 1 year. Ambulatory status differed significantly (p = 0.01) between these 2 subgroups. In the case control study, IVC filter placement conferred no survival benefit compared to the control group. One recurrent pulmonary embolism was observed in both the filter group and the control group. No deaths due to thromboembolic complications were observed in either group. In late-stage cancer, patient survival is limited primarily by the malignant process. While IVC filter placement is effective in preventing pulmonary emboli, there may be limited survival benefit in this particular patient population. However, there exists a subset of this population whose functional status predicts longer survival times after filter placement.

Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers.

STUDY OBJECTIVE: To determine whether daily high-dose vitamin C alters the steady-state pharmacokinetics of indinavir, a protease inhibitor indicated for treatment of the human immunodeficiency virus type 1. DESIGN: Prospective, open-label, longitudinal, two-period time series. SETTING: University medical center. SUBJECTS: Seven healthy volunteers. INTERVENTION: Indinavir 800 mg every 8 hours was given to subjects for four doses on days 1 and 2. Plasma samples were then collected for indinavir pharmacokinetic determination. After a 7-day washout period, subjects were given vitamin C 1000 mg/day for 7 days. Beginning on day 6 of vitamin C administration, indinavir 800 mg every 8 hours was restarted for four doses. Plasma was then collected from subjects to determine indinavir pharmacokinetics. All subjects were given a vitamin C content-controlled diet for 1 week before the study began and throughout the study period. MEASUREMENTS AND MAIN RESULTS: Steady-state plasma samples were collected before dosing (0 hr) and 0.5, 1, 2, 3, 4, and 5 hours after dosing to determine indinavir pharmacokinetics. Parameters of interest were maximum plasma concentration (C max ), time to C max , area under the plasma concentration-time curve from 0-5 hours after the dose (AUC 0-5 ), an extrapolated 8-hour AUC (AUC 0-8 ), trough (minimum) plasma concentration (C min ), and oral clearance. Mean steady-state indinavir C max was significantly reduced (20%) after 7 days of vitamin C administration (10.3 +/- 1.5 vs 8.2 +/- 2.9 microg/ml, p=0.04). The corresponding mean AUC 0-8 was also significantly decreased (14%; 26.4 +/- 7.2 vs 22.7 +/- 8.1 microg*hr/ml, p=0.05). Although not statistically significant, the mean indinavir C min was 32% lower in the presence of vitamin C (0.27 +/- 0.17 C vs 0.18 +/- 0.08 microg/ml, p=0.09). Indinavir oral clearance and half-life were not significantly different. CONCLUSION: Concomitant administration of high doses of vitamin C can reduce steady-state indinavir plasma concentrations. Subtherapeutic concentrations of antiretroviral agents have been associated with viral resistance and regimen failure, but the clinical significance of our findings remains to be established.