Antibiotic prophylaxis in colorectal surgery: are oral, intravenous or both best and is mechanical bowel preparation necessary?

BACKGROUND: The benefit of adding oral antibiotic prophylaxis (OA) to intravenous prophylaxis (IV) in elective colorectal surgery to prevent surgical site infection (SSI) and whether the benefit of OA requires a mechanical bowel cleansing (MBP) are assessed in a systematic review. Meta-analyses compare randomized trials of IV versus IV plus OA, both with MBP; OA versus IV plus OA, both again with MBP; OA plus IV in studies randomizing patients to MBP or no MBP; and IV versus IV plus OA in patients with no MBP. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched for eligible studies from 1965 to April 1, 2020. The outcome assessed was SSI, superficial and deep, but not organ space. For each included study, risk of bias was assessed using the Cochrane Risk of Bias tool version 1. For each comparison, meta-analysis was performed from data from eligible studies to obtain a summary effect and heterogeneity using RevMan. Sensitivity analyses were performed excluding studies of poor quality. Certainty of evidence was assessed using GRADE for each comparison. RESULTS: Sixty-one studies published in 1971-2020 from 55 publications reporting 12,297 patients were eligible for inclusion. A total of 36 studies compared IV to OA plus IV with MBP. The risk ratio (RR) and 95% confidence interval (CI) for SSI with oral and IV vs. IV alone are 0.47, 0.40-0.56. The RR in 19 studies for IV plus OA versus OA alone is 0.48, 0.38-0.62. The RR for OA plus IV with MBP versus without MBP in 5 studies is 1.17, 0.84-1.64. The RR for OA plus IV versus IV alone when no bowel prep was used in two studies is 0.36, 0.18-0.72. RRs were similar in sensitivity analyses. The GRADE is high for the first two comparisons, moderate for the 3rd, and low for the 4th due to imprecision and heterogeneity. CONCLUSIONS: Combined OA and IV is superior to either alone in preventing SSI. The certainty of evidence is such that further research is unlikely to alter this relationship when MBP is used. In randomized trials of MBP, OA plus IV shows no benefit from MBP versus no MBP. The last comparison shows in just two studies that as in the first meta-analysis, but in the absence of MBP, combined OA plus IV is also superior to IV alone.

Hormone levels in vegetarian and nonvegetarian teenage girls: potential implications for breast cancer risk.

Between September 1984 and June 1985, a total of 75 adolescent girls, 35 vegetarians residing in a Seventh-Day Adventist school and 40 nonvegetarians residing in a private non-Adventist boarding school, underwent measurement of their plasma hormone levels in the follicular and luteal phase of their menstrual cycles as well as dietary intake measured by 3-day food records, medical history, height, and weight. There were no significant differences between vegetarians and nonvegetarians in average age of the girls, weight, body mass index, age at menarche, years since the onset of menstruation, or percentage of girls with ovulatory cycles. Vegetarian girls had significantly higher levels of log follicular estradiol [2.00 +/- 0.27 (SD) versus 1.85 +/- 0.27 pg/ml, P less than or equal to 0.05] and luteal dehydroepiandrosterone sulfate (DHS) (1.88 +/- 0.71 versus 1.45 +/- 0.80 microgram/ml, P less than or equal to 0.05) than nonvegetarian girls. Follicular DHS was higher in vegetarians than in nonvegetarians (1.72 +/- 0.79 versus 1.45 +/- 0.95 microgram/ml), but the difference was not significant. The differences in follicular and luteal DHS, but not the difference in log estradiol, were significant (P less than or equal to 0.05) after controlling for ovulation, smoking, and alcohol intake with multivariable regression analysis. There were no significant differences in testosterone or in percentage free estradiol levels between vegetarians and nonvegetarians. Smoking was significantly associated with follicular and luteal DHS and with percentage free follicular estradiol, while alcohol use was significantly and inversely associated with percentage free follicular estradiol after controlling for other variables. The implications for breast cancer risk are discussed.

Hepatitis C Virus Infection of Cultured Human Hepatoma Cells Causes Apoptosis and Pyroptosis in Both Infected and Bystander Cells.

Individuals infected with hepatitis C virus (HCV) are at high risk of developing progressive liver disease, including cirrhosis and hepatocellular carcinoma (HCC). How HCV infection causes liver destruction has been of significant interest for many years, and apoptosis has been proposed as one operative mechanism. In this study, we employed a tissue culture-adapted strain of HCV (JFH1T) to test effects of HCV infection on induction of programmed cell death (PCD) in Huh-7.5 cells. We found that HCV infection reduced the proliferation rate and induced caspase-3-mediated apoptosis in the infected cell population. However, in addition to apoptosis, we also observed infected cells undergoing caspase-1-mediated pyroptosis, which was induced by NLRP3 inflammasome activation. By co-culturing HCV-infected Huh-7.5 cells with an HCV-non-permissive cell line, we also demonstrated induction of both apoptosis and pyroptosis in uninfected cells. Bystander apoptosis, but not bystander pyroptosis, required cell-cell contact between infected and bystander cells. In summary, these findings provide new information on mechanisms of cell death in response to HCV infection. The observation that both apoptosis and pyroptosis can be induced in bystander cells extends our understanding of HCV-induced pathogenesis in the liver.

The influence of lymphocyte counts and disease progression on circulating and inducible anti-HIV-1 cytotoxic T-cell activity in HIV-1-infected subjects.

OBJECTIVE: To evaluate specific anti-HIV cytotoxic T-lymphocyte (CTL) activity in relation to basic clinical and laboratory parameters used to follow HIV infection. METHODS: Lymphocytes from HIV-1-infected subjects with different clinical and immunologic features of HIV infection were tested for circulating and inducible anti-HIV CTL activity using autologous B-lymphoblastoid cells infected with recombinant vaccinia viruses expressing the HIV gag, pol and env genes as targets. Anti-HIV CTL were induced by stimulation with HIV-infected autologous lymphoblasts in vitro. RESULTS: We detected circulating anti-HIV CTL in asymptomatic subjects exclusively and found a significant association (P < 0.01) between CD8+ lymphocyte counts > or = 900/microliters blood and detectable levels of circulating anti-HIV CTL. Subjects with circulating anti-HIV CTL also had a higher mean CD8+ lymphocyte count than those without detectable circulating activity (P < 0.001), but there was no significant difference in mean CD4+ lymphocyte count. CD8+ human histocompatibility leukocyte antigen (HLA) class I-restricted anti-HIV CTL were induced in all HIV-infected subjects tested following stimulation with HIV-infected autologous lymphoblasts in vitro. In subjects without detectable circulating anti-HIV CTL, circulating HLA-DR+ cells contributed to anti-HIV CTL activity induced by stimulation with HIV or concanavalin A in vitro. CONCLUSIONS: Circulating anti-HIV CTL activity is associated with CD8+ lymphocyte counts > or = 900/microliters. Anti-HIV CTL retain proliferative and functional capacity following in vitro stimulation with HIV and interleukin-2 through all stages of HIV infection. Persistent inducible anti-HIV CTL activity in subjects with advanced HIV disease and without circulating CTL suggests impaired activation and/or proliferation of the CTL in vivo.

Functional and genetic integrity of the CD8 T-cell repertoire in advanced HIV infection.

BACKGROUND: HIV-specific cytotoxic T lymphocytes (CTL) can restrict HIV replication in acute and chronic infection, but disease progression occurs in parallel with declining CTL activity. An understanding of why CTL fail to control HIV replication might reveal important mechanisms of disease progression and enhance prospects for developing effective CTL-based immunotherapies. OBJECTIVES: To investigate the functional integrity, T-cell repertoire diversity, and HIV reactivity of CD8 T lymphocytes in individuals with advanced HIV infection. METHODS: Individuals were considered to have progressed to advanced HIV infection if their total T-cell count was < 500 x 10(6) cells/(l) on at least two successive clinic visits. CD8 T cells from these individuals were analyzed for CTL function, HIV reactivity and T-cell receptor (TCR) diversity by chromium release assays and reverse transcriptase polymerase chain reaction. RESULTS: CD8 T cells from all individuals with advanced HIV infection proliferated and differentiated into functional CTL in vitro. Despite extremely low T-cell counts and previous AIDS-defining illnesses, six individuals had inducible anti-HIV CTL responses. In two additional cases, HIV-specific CTL activity became detectable following significant treatment-associated remission of T-cell lymphopenia. Assessment of TCRbetaV gene family representation and betaV gene intrafamily diversity indicated CD8 T-cell repertoire diversity is maintained through advanced HIV infection. CONCLUSIONS: These data suggest that HIV-specific CTL activity can be selectively compromised while the functional and genetic integrity of the CD8 population as a whole remains intact. A substantial fraction of individuals retain inducible anti-HIV CTL activity through advanced HIV infection and, in at least some cases, effective treatment can restore HIV-specific CTL responses even at this late stage of disease.

Cytotoxic T-lymphocytes that kill autologous CD4+ lymphocytes are associated with CD4+ lymphocyte depletion in HIV-1 infection.

Human immunodeficiency virus type 1 (HIV-1)-infected individuals, but not HIV-seronegative controls, have non-HLA-restricted T-cell receptor alpha beta+ CD8+ cytotoxic T-lymphocytes (CTL) that kill activated uninfected CD4+ lymphocytes. In vitro stimulation of peripheral blood mononuclear cells from HIV-1-infected individuals with concanavalin A (Con A) or by coculture with phytohemagglutinin-activated autologous lymphoblasts induced CTL that killed autologous and heterologous CD4+ lymphocytes, but not Con A-activated CD8+ lymphocytes or Epstein-Barr virus (EBV)-transformed B lymphocytes. EBV did not stimulate such CTL in two subjects tested, although stimulation with Con A or autologous lymphoblasts induced CTL activity against CD4+ lymphocytes in both subjects. CTL activity against autologous CD4+ lymphocytes varied over time; killing of heterologous CD4+ lymphocytes was often higher than that of autologous CD4+ lymphocytes. HIV-infected individuals with Con A-inducible CTL against autologous CD4+ lymphocytes lost more CD4+ lymphocytes within 6 months of testing than HIV-infected individuals with no such CTL (p < .01). The mean (+/- SD) decrease in CD4+ lymphocyte counts in a group of HIV-infected individuals with CTL activity against autologous CD4+ lymphocytes was 121 +/- 84, or 36%, of total CD4+ lymphocytes over 6 months. In contrast, there was no significant change in mean CD4+ lymphocyte count over 6 months in a group of HIV-infected individuals without CTL activity against autologous CD4+ lymphocytes. In some HIV-infected individuals, CTL activity against autologous CD4+ lymphocytes fell coincident with a drop in CD4+ lymphocyte number in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in the cytotoxic T-cell repertoire of HIV-1-infected individuals: relationship to disease progression.

The repertoire of antigen-specific receptors expressed on T lymphocytes is shaped by fixed genetic and variable environmental selective pressures. Recent technological advances have enabled the analysis of T-cell receptor (TCR) expression in the context of selective pressures arising through normal immune system development and also through pathological features of disease. The pathological features of acquired immune deficiency syndrome (AIDS) are reflected by selective depletion of particular T lymphocyte subsets and expansion of others. An important question concerning the immunopathogenesis of AIDS is whether or not the perturbation of the CD4+ and CD8+ T-cell subsets following infection with human immunodeficiency virus (HIV) is selective based on TCR variable (V) region gene expression. To address this question, we have functionally analyzed TCR V gene expression on CD8+ cytotoxic T lymphocytes from HIV-1-infected individuals. This was done using monoclonal antibodies against individual TCR V regions to trigger redirected cytolysis in 51Cr release assays. The percent specific lysis induced by each antibody functionally measures the representation of the TCR V region gene product it is specific for. Relative to non-HIV-infected controls and asymptomatic HIV-infected individuals with only moderate CD4 lymphocyte depletion, HIV-infected individuals with low CD4 lymphocyte counts exhibited skewed patterns of TCR V region representation. Therefore, the perturbation within the CD8+ cytotoxic T lymphocyte repertoire in HIV infection appears to be selective based on TCR V region usage, increasingly so as disease progresses. The TCR V genes affected varied between different HIV-infected individuals and skewing detected in functional assays was not always apparent by flow cytometric analysis. These results suggest that HIV infection causes generalized effects on the T-cell repertoire, which are reflected in the relative TCR V gene representation of the CD8+ cytotoxic T lymphocyte population in peripheral blood.

HIV-1 DNA burden in peripheral blood CD4+ cells influences disease progression, antiretroviral efficacy, and CD4+ T-cell restoration.

Integration of human immunodeficiency virus type-1 (HIV-1) proviral DNA into host cell genomic DNA ensures viral persistence despite suppression of active replication. Because HIV RNA originates from integrated HIV DNA, HIV RNA and DNA loads should interrelate when suppression of viral replication is incomplete. In addition, the link between proviral DNA formation and generation of HIV-1 genetic diversity suggests that the ease with which HIV escapes immune or drug-based suppression should vary with proviral load. Thus, HIV proviral load should have unique prognostic significance independent of the highly labile plasma HIV RNA levels commonly used to monitor patient status. To test this possibility, we developed a simple standardized research assay estimating the proportion of CD4+ peripheral blood mononuclear cells (PBMC) carrying HIV-1 DNA and investigated associations between this parameter, plasma virus load, long-term efficacy of antiretroviral therapy and restoration of CD4+ T cells. Lower proportions of CD4+ PBMC carrying HIV-1 DNA were associated with lower peak plasma HIV RNA levels and with more favorable long-term responses to antiretroviral therapy. These results suggest that HIV proviral load affects both disease progression and responsiveness to antiretroviral therapy. Therefore, new anti-HIV therapies addressing the stable pool of HIV proviral DNA should be developed to improve long-term prospects for suppression of HIV replication.

Differences in locomotor activity across the lifespan of Drosophila melanogaster.

The identification of differential patterns of change across the lifespan in quantitative traits is of abiding interest in the biological and gerontological research communities. These differential phenotypic patterns in complex systems illuminate developmental processes and form the foundation for the identification of putative biomarkers of aging. The goal of the present study was to explore changes in locomotor activity through the lifespan of Drosophila melanogaster. A replicated serial cross-sectional sampling design was used to test activity in five genetically independent inbred strains at 7, 14, 21, 28, 35, and 42 days of age. Differences were observed in activity level across ages and strains, suggesting that patterns of activity throughout the lifespan of D. melanogaster are influenced by genetic factors. Observed sex differences in change in activity level indicate that the aging processes may proceed differently in males and females.

Self-reported health and survival in the Longitudinal Study of Aging, 1984-1986.

Changing and often declining health among elderly individuals makes interpreting the long-standing association between self-reported health (SRH) and mortality potentially problematic. This analysis of the Longitudinal Study of Aging from 1984 through 1986 explores changes over time in the association between a single self-report of health and survival among 4380 noninstitutionalized individuals aged 70 and older. Health was reported as excellent or very good (excellent/very good), good, fair or poor. The association between SRH and survival was modeled controlling for age, race, education, marital status, body mass index, difficulty performing activities of daily living, social contacts, self-reported stroke, heart disease, cancer, diabetes and recent hospitalization. Among women, SRH and survival were associated in a nonproportional model, with relative hazard declining over time. Women with poor vs excellent/very good SRH had adjusted relative hazards at 5, 14, 23 and 32 months of 3.8 [95% confidence interval (CI) 2.0-7.1], 2.7 (95% CI: 1.8-4.1), 2.0 (95% CI: 1.3-3.0), and 1.4 (95% CI: 0.7-2.7). The declining relative hazard was due to an increasing mortality rate over time among women initially reporting excellent/very good health. SRH was associated with survival among men in a proportional model (constant relative hazard over time). Men with poor vs excellent/very good SRH had an adjusted relative hazard of 1.7 (95% CI: 1.1-2.6) over the entire follow-up. The relative hazard of lesser magnitude among men reflects the weaker SRH-survival association, possibly too weak for any interaction with time to be detected. The constant relative hazard is also consistent with a rapid decline in health before death among men. The diminishing SRH-survival association among women is consistent with their longer period of declining health before death.

Declining cholesterol and mortality in a sample of older nursing home residents.

OBJECTIVE: To examine the association between declining serum cholesterol and mortality in a sample of older nursing home residents. DESIGN: A retrospective cohort study. SETTING: A 203-bed nursing home. PARTICIPANTS: Persons aged 65 and older, resident in the nursing home on January 1, 1988, or admitted through December 31, 1989, were eligible (n = 185) for the study. Follow-up for mortality was conducted until June 30, 1991. Fifty-five survivors with two or more cholesterol levels recorded before January 1, 1990, and the 76 decedents with two or more recorded cholesterol levels constituted the analytic sample (71% of eligible subjects). OUTCOME MEASURE: Mortality of the nursing home residents. RESULTS: Cholesterol declined 31.1 mg/dL/yr (95% confidence interval [CI], 19.7 to 42.6) among decedents, versus 4.2 mg/dL/yr (95% CI, -4.9 to 13.2) among survivors. The association between cholesterol decline (absolute or relative rates) and mortality was examined using logistic regression controlling for age, sex, and tube feeding. Compared with a referrent group with no change or increase, declining cholesterol greater than 45 mg/dL/yr was accompanied by an adjusted relative odds for death of 6.2 (95% CI, 2.1 to 18.4); declining cholesterol greater than 20% per year was accompanied by an adjusted relative odds for death of 7.3 (95% CI; 2.4 to 22.2). Extreme declines greater than 20% per year occurred in 47% of decedents but in only 15% of survivors. CONCLUSION: Precipitously declining cholesterol appeared to be a marker for mortality in the sample and may help explain the low cholesterol-mortality association in older nursing home residents.

Male inflammatory breast cancer.

A case of a 48-year-old male with an inflammatory breast cancer is used to illustrate this uncommon malignancy. The physical examination of thickening and erythema made the clinical diagnosis. Mammographic findings of increased density in the right breast with coarsened stroma and an underlying mass confirmed the clinical findings. The sonographic evaluation revealed a 2-cm ill-defined hypoechoic mass. The pathologic examination of the mastectomy specimen showed an infiltrating duct cell carcinoma with lobular features. Male breast cancer afflicts 1500 men each year. Clinically it must be differentiated from gynecomastia, a much more common and benign condition.

Effectiveness of feeding tubes in nursing home residents with swallowing disorders.

BACKGROUND: Among nursing home residents who stop eating, a common decision for residents, caregivers, and families is the decision to begin tube feeding. This study examines the effectiveness of feeding tubes at reducing mortality among nursing home residents with swallowing disorders and feeding disabilities. METHODS: Data from a version of the Minimum Data Set+ (MDS +) encompassing three different states from calendar years 1993 and 1994 were analyzed. Residents were included in the study if they were not totally dependent on staff for eating upon their first assessment but became totally dependent on staff for eating and had a swallowing disorder at some point during their nursing home stay. We used a proportional hazard regression to examine the relationship of feeding tubes with mortality after total eating dependence occurred. RESULTS: Unadjusted Kaplan-Meier curves found that those with feeding tubes were less likely to die than comparable residents without feeding tubes (p < .001). Estimated survival at 1 year was 39% for those without feeding tubes and 50% for those with feeding tubes. The multivariate results indicated that feeding tubes were associated with a reduced risk of death (risk ratio, 0.71; 95% confidence interval, 0.59, 0.86). CONCLUSIONS: This study provides evidence that tube feeding can be life-prolonging, even if the gain in life is not substantial. Such information can be useful to nursing home staff, residents, and families when trying to decide whether to place a feeding tube in a resident with swallowing disorders and eating disabilities.

Case report: splenectomy in patients with Hodgkin's disease and marrow hypoplasia.

Two patients with Hodgkin's disease and hypoplastic bone marrow underwent splenectomy in an attempt to reverse pancytopenia and to improve chemotherapeutic tolerance. Although the peripheral blood counts were improved, the clinical course was not significantly affected. Infectious complications occurred. This suggests that the peripheral hematologic improvement following splenectomy may not reflect a true improvement in marrow tolerance.

Natural rates of teacher approval and disapproval in grade-7 classrooms.

The natural rates of teacher verbal approval and disapproval in ten grade-seven classrooms were determined and compared with those described by White (1975). Although there were differences in the observation techniques used and the behavioral, cultural, and ethnic groups sampled, the results were similar. The majority of the teachers displayed individual rates of disapproval that were higher than their individual approval rates. The correlations between levels of on-task behavior and approval and disapproval rates were low. The issues raised by these findings are discussed in terms of directions for further research.

A multivariate twin study of hippocampal volume, self-esteem and well-being in middle-aged men.

Self-esteem and well-being are important for successful aging, and some evidence suggests that self-esteem and well-being are associated with hippocampal volume, cognition and stress responsivity. Whereas most of this evidence is based on studies on older adults, we investigated self-esteem, well-being and hippocampal volume in 474 male middle-aged twins. Self-esteem was significantly positively correlated with hippocampal volume (0.09, P = 0.03 for left hippocampus, 0.10, P = 0.04 for right). Correlations for well-being were not significant (Ps > 0.05). There were strong phenotypic correlations between self-esteem and well-being (0.72, P < 0.001) and between left and right hippocampal volume (0.72, P < 0.001). In multivariate genetic analyses, a two-factor additive genetic and unique environmental (AE) model with well-being and self-esteem on one factor and left and right hippocampal volumes on the other factor fits the data better than Cholesky, independent pathway or common pathway models. The correlation between the two genetic factors was 0.12 (P = 0.03); the correlation between the environmental factors was 0.09 (P > 0.05). Our results indicate that largely different genetic and environmental factors underlie self-esteem and well-being on one hand and hippocampal volume on the other.

Testosterone modifies the effect of APOE genotype on hippocampal volume in middle-aged men.

BACKGROUND: The APOE epsilon4 allele is an established risk factor for Alzheimer disease (AD), yet findings are mixed for how early its effects are manifest. One reason for the mixed results could be the presence of interaction effects with other AD risk factors. Increasing evidence indicates that testosterone may play a significant role in the development of AD. The aim of the present study was to examine the potential interaction of testosterone and APOE genotype with respect to hippocampal volume in middle age. METHODS: Participants were men from the Vietnam Era Twin Study of Aging (n = 375). The mean age was 55.9 years (range 51-59). Between-group comparisons were performed utilizing a hierarchical linear mixed model that adjusted for the nonindependence of twin data. RESULTS: A significant interaction was observed between testosterone and APOE genotype (epsilon4-negative vs epsilon4-positive). Those with both low testosterone (> or =1 SD below the mean) and an epsilon4-positive status had the smallest hippocampal volumes, although comparisons with normal testosterone groups were not significant. However, individuals with low testosterone and epsilon4-negative status had significantly larger hippocampal volumes relative to all other groups. A main effect of APOE genotype on hippocampal volume was observed, but only when the APOE-by-testosterone interaction was present. CONCLUSIONS: These findings demonstrate an interaction effect between testosterone and the APOE epsilon4 allele on hippocampal volume in middle-aged men, and they may suggest 2 low testosterone subgroups. Furthermore, these results allude to potential gene-gene interactions between APOE and either androgen receptor polymorphisms or genes associated with testosterone production.