Laparoscopic lavage for perforated diverticulitis in the LapLav study: population-based registry study.

BACKGROUND: The standard treatment for Hinchey III perforated diverticulitis with peritonitis was resection with or without a stoma, but recent trials have shown that laparoscopic lavage is a reasonable alternative. This registry-based Swedish study investigated results at a national level to assess safety in real-world scenarios. METHODS: Patients in Sweden who underwent emergency surgery for perforated diverticulitis between 2016 and 2018 were studied. Inverse probability weighting by propensity score was used to adjust for confounding factors. RESULTS: A total of 499 patients were included in this study. Laparoscopic lavage was associated with a significantly lower 90-day Comprehensive Complication Index (20.9 versus 32.0; odds ratio 0.77, 95 per cent compatibility interval (c.i.) 0.61 to 0.97) and overall duration of hospital stay (9 versus 15 days; ratio of means 0.84, 95 per cent c.i. 0.74 to 0.96) compared with resection. Patients had 82 (95 per cent c.i. 39 to 140) per cent more readmissions following lavage than resection (27.2 versus 21.0 per cent), but similar reoperation rates. More co-morbidity was noted among patients who underwent resection than those who had laparoscopic lavage. CONCLUSION: Laparoscopic lavage is safe in routine care beyond trial evaluations.

Diverticulitis comprises inflammation in pouches (diverticula) of the large intestine. In the most severe instances, this inflammation can cause perforation of the bowel with purulent or faecal peritonitis. If this happens, surgery is needed. The traditional method has been resection of the inflamed bowel with a stoma. A new technique has been proposed whereby the abdomen is rinsed with saline laparoscopically and a drain is placed (laparoscopic lavage). This study aimed to compare these two methods in terms of clinical short-term outcomes, with a focus on complications. It was found that laparoscopic lavage had fewer complications than resectional surgery and a shorter hospital stay. The new method was safe when used in Swedish routine care.

European Society of Coloproctology: guidelines for the management of diverticular disease of the colon.

AIM: The goal of this European Society of Coloproctology (ESCP) guideline project is to give an overview of the existing evidence on the management of diverticular disease, primarily as a guidance to surgeons. METHODS: The guideline was developed during several working phases including three voting rounds and one consensus meeting. The two project leads (JKS and EA) appointed by the ESCP guideline committee together with one member of the guideline committee (WB) agreed on the methodology, decided on six themes for working groups (WGs) and drafted a list of research questions. Senior WG members, mostly colorectal surgeons within the ESCP, were invited based on publication records and geographical aspects. Other specialties were included in the WGs where relevant. In addition, one trainee or PhD fellow was invited in each WG. All six WGs revised the research questions if necessary, did a literature search, created evidence tables where feasible, and drafted supporting text to each research question and statement. The text and statement proposals from each WG were arranged as one document by the first and last authors before online voting by all authors in two rounds. For the second voting ESCP national representatives were also invited. More than 90% agreement was considered a consensus. The final phrasing of the statements with < 90% agreement was discussed in a consensus meeting at the ESCP annual meeting in Vienna in September 2019. Thereafter, the first and the last author drafted the final text of the guideline and circulated it for final approval and for a third and final online voting of rephrased statements. RESULTS: This guideline contains 38 evidence based consensus statements on the management of diverticular disease. CONCLUSION: This international, multidisciplinary guideline provides an up to date summary of the current knowledge of the management of diverticular disease as a guidance for clinicians and patients.

Comparison of number of airborne bacteria in operating rooms with turbulent mixing ventilation and unidirectional airflow when using reusable scrub suits and single-use scrub suits.

INTRODUCTION: A low count of airborne bacteria in the operating room is a means to prevent surgical site infection. AIM: To investigate levels of airborne bacteria during surgical procedures in two operating rooms with turbulent mixing ventilation (TMV) and unidirectional airflow (UDAF), both with an air supply of 2600 L/s, when staff used either reusable scrub suits made from a mixed material (dry penetration ≤300 cfu) or single-use scrub suits made from polypropylene (dry penetration ≤100 cfu). MATERIAL AND METHODS: In the TMV-room cfu/m3 air was measured during eight procedures with staff wearing reusable scrub suits and seven procedures with single-use scrub. In the UDAF-room cfu/m3 air was measured during seven procedures with staff wearing reusable scrub suits. FINDINGS: Mean values of cfu/m3 air were 1.3-10.8 in the TMV-room with staff dressed in reusable scrub suits and 0.8-4.0 with staff dressed in single-use scrub suits (P<0.01). Mean values of cfu/m3 air were 0.2-4.5 in the UDAF-room with staff dressed in reusable scrub suits. The difference obtained with reusable scrub suits in the two rooms was significant (P<0.01). CONCLUSIONS: The mode of ventilation affects the cfu levels when staff are dressed in less occlusive scrub suits despite a high air supply. It is possible to decrease the cfu levels in a TMV-room by using scrub suits made from a tight material, thus reaching the same levels that are achieved by less protective scrub suits in a UDAF-room.

Urea clearance: a new technique based on microdialysis to assess liver blood flow studied in a pig model of ischemia/reperfusion.

Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.

Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor.

The molecular basis for the anti-inflammatory property of intravenous gamma globulin (IVIG) was investigated in a murine model of immune thrombocytopenia. Administration of clinically protective doses of intact antibody or monomeric Fc fragments to wild-type or Fcgamma receptor-humanized mice prevented platelet consumption triggered by a pathogenic autoantibody. The inhibitory Fc receptor, FcgammaRIIB, was required for protection, because disruption either by genetic deletion or with a blocking monoclonal antibody reversed the therapeutic effect of IVIG. Protection was associated with the ability of IVIG administration to induce surface expression of FcgammaRIIB on splenic macrophages. Modulation of inhibitory signaling is thus a potent therapeutic strategy for attenuating autoantibody-triggered inflammatory diseases.

Photoperiod alters hypothalamic cytokine gene expression and sickness responses following immune challenge in female Siberian hamsters (Phodopus sungorus).

Rodents that live in changing environments display different immune responses mediated in part by photoperiod (day length) cues. Siberian hamsters maintained in winter-like (short) photoperiods display smaller physiological and behavioral responses to immune challenges as compared with hamsters housed in summer-like (long) photoperiods. We hypothesized that these different response patterns are attributable to altered cytokine production in the hypothalamus in response to photoperiod changes. Female hamsters were housed in long or short days for 10 weeks to induce photoperiodic alterations, then injected with either LPS (a bacterial endotoxin) or saline. Fever and food intake were assessed 3 h post-injection; hypothalami and blood were collected 3, 6, and 12 h post-injection. LPS induced lower fever and reduction in food intake responses in short-day hamsters as compared with long-day hamsters. Additionally, short-day hamsters reduced IL-1beta and Tnfalpha expression in the hypothalamus 6 h after LPS injection, as measured by quantitative RT-PCR. Plasma estradiol concentrations did not differ between long- and short-day hamsters. These data suggest that differences in cytokine production in the hypothalamus may underlie the photoperiod-induced differences in sickness responses, and that these changes are not mediated by estradiol.

Serum homocysteine concentration as an indicator of survival in patients with acute coronary syndromes.

BACKGROUND: Circulating homocysteine levels are predictive of survival in patients with stable coronary artery disease. The prognostic value of serum homocysteine levels, obtained in the acute phase in patients with myocardial infarction or unstable angina, is unknown. OBJECTIVES: To test the hypothesis that circulating homocysteine levels, obtained during the first 24 hours following hospital admission in patients with acute coronary syndromes, are predictive of long-term mortality. METHODS: To test this hypothesis we performed a prospective inception cohort study at a teaching hospital in Gothenburg, Sweden. A total of 579 patients (179 women and 400 men; median age, 67 years) were included (Q-wave myocardial infarction in 163 patients, non-Q-wave myocardial infarction in 210 patients, unstable angina pectoris in 206 patients). MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: During a median follow-up of 628 days, 65 patients died. The serum homocysteine level (mean [SD]) was significantly lower in long-term survivors (n = 514) than in nonsurvivors (n=65) (12.3 [7.0] vs 14.3 [5.9] pmol/L; P=.003). The relative risk (all-cause mortality) for patients with homocysteine levels in the upper quartile was 2.4 (95% confidence interval, 1.5-4.0) compared with that of patients in the 3 lower quartiles. After adjustment for relevant confounders, the relative risk estimate remained significant (relative risk= 1.69; 95% confidence interval, 1.02-2.80). In a stepwise model the homocysteine level provided prognostic information additional to that of patient age, diabetes mellitus, and diuretic usage prior to hospital admission (P=.03). CONCLUSION: The serum homocysteine level on hospital admission is an independent predictor of long-term survival in patients with acute coronary syndromes.

The lymphoid-specific cofactor OBF-1 is essential for the expression of a V(H) promoter/HS1,2 enhancer-linked transgene in late B cell development.

Mice deficient for the lymphoid-specific cofactor OBF-1 display reduced levels of IgG, IgA and IgE. To examine whether the lowered immunoglobulin expression is linked to reduced activity of IgH cis-regulatory elements, OBF-1(-/-) mice were crossed with mice expressing transgenes driven by a V(H) or beta-globin promoter linked to the HS1,2 enhancer. Here we show that OBF-1 is essential for the induced expression of a V(H) promoter-linked transgene, in contrast to a beta-globin promoter-dependent transgene, in LPS/IL-4 or CD40-stimulated splenic B cells. Furthermore, impaired transgene expression is observed in OBF-1(-/-) peritoneal B cells. This deficiency may be linked to OBF-1, as peritoneal cells from normal mice express OBF-1 protein constitutively. Our data link OBF-1 to IgH gene expression in late B lymphoid development.

Identification of four antibody-binding sites in the envelope proteins of simian immunodeficiency virus, SIVsm.

OBJECTIVE: To identify antigenic regions in the envelope glycoproteins of the simian immunodeficiency virus isolate, SIVsm. METHODS: Thirty-eight peptides were synthesized and used in site-directed enzyme-linked immunosorbent assays with sera from experimentally infected macaques. RESULTS: Four antibody-binding regions were identified, corresponding to the second variable region [V2; amino acids (aa) 170-196], the region homologous to V3 in HIV-1 (aa 313-346), the carboxy terminus of gp120 (aa 514-537) and the amino terminus of the transmembrane protein (aa 608-638). Serum reactivity to the V2 region was higher in surviving monkeys than in animals with an early development of simian AIDS. The antigenicity of the peptide appears to be conformationally dependent. CONCLUSIONS: The majority of antigenic sites identified in the envelope proteins of SIV correspond to sites identified in HIV-1 and HIV-2, which further supports the use of the simian model in vaccine development. The pattern of reactivity to the V2 region suggests that absence of antibodies directed to this site might correlate with disease progression.

Soft tissue sarcoma after treatment for breast cancer--a Swedish population-based study.

The aim was to quantify the risk of post-treatment sarcoma in breast cancer patients. All 122,991 women with a breast cancer from 1958 to 1992 in the Swedish Cancer Register were followed up for soft tissue sarcomas and 116 were found, giving a standardised incidence ratio of 1.9 (95% CI 1.5-2.2). The absolute risk was 1.3 per 10(4) person-years. The sarcomas were located in the breast region or on the ipsilateral arm in 63% (67/106). There were 40 angiosarcomas and 76 sarcomas of other types. In a case-control study, angiosarcoma correlated significantly with lymphoedema of the arm, odds ratio (OR) 9.5 (95% CI 3.2-28.0), but no correlation with radiotherapy was observed. For other types of sarcoma there was a correlation with the integral dose. The dose-response relationship indicated that the risk increased linearly with the integral dose to 150-200 J and stabilised at higher energies. The OR was 2.4 (95% CI 1.4-4.2) for an energy of 50 J, approximately corresponding to the radiation of the breast after breast-conserving surgery. Thus, only oedema of the arm correlated with angiosarcoma, but for other types of sarcoma the integral dose of radiotherapy was a predictor of the risk.

Blood pressure, cardiac structure and severity of obstructive sleep apnea in a sleep clinic population.

OBJECTIVES: We investigated whether the severity of obstructive sleep apnea (OSA) predicts blood pressure or cardiac left ventricular thickness in a clinical population of OSA patients, if adjustments are made for age, gender, use of antihypertensive agents, smoking, body mass index, history of coronary artery disease, hypercholesterolemia and circulating C-peptide concentrations. DESIGN: Relationships in this cross-sectional study were investigated with correlation analysis and multiple regression procedures. PATIENTS AND METHODS: Apnea-hypopnea index (AHI, polysomnography) and office systolic and diastolic blood pressures (SBP and DBP) were measured in 81 subjects referred to a university hospital sleep laboratory. Ambulatory blood pressures were recorded during one 24 h cycle. Left ventricular (LV) muscle size was quantified as two-dimensionally directed M-mode-derived end-diastolic thickness of interventricular septum and posterior chamber wall. RESULTS: After adjustment for separate or the entire set of covariates, AHI predicted office SBP and DBP as well as daytime ambulatory DBP and night-time ambulatory SBP and DBP, but not daytime ambulatory SBP. In contrast, associations between AHI and LV muscle thickness reflected complex inter-relationships with confounding variables. Smoking and age suppressed, whereas body mass index (BMI) and hypertension inflated the relationship between OSA severity and LV muscle thickness in this study. CONCLUSIONS: AHI is an independent predictor of several measures of blood pressure. OSA severity and LV muscle thickness appear to be primarily linked via increased blood pressure.

Progressive B cell apoptosis and expression of Fas ligand during human immunodeficiency virus type 1 infection.

HIV-1 infection causes functional defects in T cells. It also leads to a progressive reduction in numbers of such cells and both CD4+ and CD8+ cells have been reported to undergo apoptosis in culture. A corresponding reduction in B cells has not been described, but these cells are also functionally altered, with reports of polyclonal activation and hyporesponsiveness to antigenic and mitogenic stimuli. Here we investigated B cells from HIV-1-seropositive individuals and found that these cells, which are not the target for virus infection, died of apoptosis on culturing. We could also confirm previous findings that CD4+ cells from HIV-1-infected individuals undergo apoptosis in culture. Apoptosis of both B cells and CD4+ cells correlated inversely with CD4 cell counts. B cells from HIV-1-infected individuals were found to express Fas ligand, and the expression of this protein correlated with the levels of apoptosis in the same cells. Non-B cells, on the other hand, expressed increased levels of Fas but low levels of Fas ligand. These results are in line with suggestions that the Fas/Fas ligand pathway may trigger the increased levels of apoptosis observed in cells from HIV-1-infected individuals.

Impairment of vascular endothelial function and left ventricular filling : association with the severity of apnea-induced hypoxemia during sleep.

STUDY OBJECTIVE: To investigate whether a dose-effect relationship exists between the severity of obstructive sleep apnea (OSA) and subclinical indicators of myocardial or vascular dysfunction. DESIGN: Cross-sectional study using correlation analysis. PARTICIPANTS: Twenty subjects referred to our sleep laboratory for screening or therapy of OSA but without regular medication and without known cardiovascular disease. MEASUREMENTS: Severity of OSA was quantified by polysomnography. Moreover, nocturnal excretion of norepinephrine was determined. Left ventricular (LV) myocardial function was assessed with Doppler echocardiography. Using ultrasonographic measurements, endothelium-dependent and endothelium-independent conduit artery dilation were measured as flow-mediated and glyceryltrinitrate-induced changes in brachial artery diameter. RESULTS: Worsening nocturnal hypoxemia, measured as nocturnal oxygen saturation nadir or percentage of sleep time spent in hypoxemia (< 90% hemoglobin oxygen saturation), predicted increased interventricular septum thickness (corrected for age and body mass index), prolonged isovolumetric relaxation time, decreased ratio between peak early and late mitral flow velocities, as well as reduced endothelium-dependent dilatory capacity of the brachial artery (all relationships corrected for cofactor age and with p < 0.05) were observed. Associations between these cardiovascular function markers and nocturnal excretion of norepinephrine followed the same trend, but relations with interventricular septum thickness and flow-mediated artery dilation missed significance (p = 0.064 and p = 0.061, respectively). LV posterior wall thickness, measures of LV systolic function, early mitral flow deceleration time, and endothelium-independent artery dilation were not significantly related to the degree of nocturnal hypoxemia or norepinephrine excretion. None of the correlations with apnea-hypopnea index were statistically significant. CONCLUSIONS: The severity of apnea-related hypoxemia is associated with a gradual deterioration of LV diastolic function as well as large-artery endothelial function.

Nosocomial calicivirus gastroenteritis in a pediatric hospital.

At St. Göran's Children's Hospital (a tertiary center), we perform electron microscopy of feces in most cases of nosocomial gastroenteritis. From September 1987 through April 1992 we identified 32 episodes of calicivirus infection, 25 of which were nosocomial and, except for one outbreak, sporadic. Systematic study of the nosocomial outbreak of calicivirus gastroenteritis from November 1991 to January 1992, revealed calicivirus in the stools of 8 of 23 children with diarrhea and 0 of 10 without diarrhea. In 3 of 7 sampled after cessation of diarrhea, calicivirus excretion continued for 3 to 6 days. We found no calicivirus in 42 staff members or 9 members of infected patients' families. Nosocomial transmission of calicivirus can occur among infants.

Successful pregnancy in a 28-year-old patient autografted for acute lymphoblastic leukemia following myeloablative treatment including total body irradiation.

We report a successful pregnancy in a woman who at the age of 28 years received total body irradiation (TBI; 7.5 Gy) and high-dose chemotherapy prior to autografting of purged bone marrow for acute lymphoblastic leukemia. Four years after transplantation she delivered a healthy girl. Only five previous cases of successful pregnancies are described in the literature after conditioning regimens including TBI. This case shows that restored ovarian function is possible after TBI in spite of prolonged exposure to chemotherapeutic agents during induction and consolidation therapy and relatively high age at the time of transplantation.

Intrathecal antibody production against viruses of the herpesvirus family in acute retinal necrosis syndrome.

Viruses of the herpesvirus family cause acute retinal necrosis syndrome, a devastating necrotic retinitis in immunocompetent individuals. Direct proof of the viral origin of this disease may be obtained by demonstration of the virus, viral antigens, or viral DNA in biopsy specimens of retinas. In search of alternative diagnostic methods, we analyzed cerebrospinal fluid and serum with enzyme-linked immunosorbent assays for virus-specific antibody activity. Intrathecally produced viral antibodies were found in three consecutive patients with acute retinal necrosis syndrome: herpes simplex type 2 in a 30-year-old woman with a history of suspected neonatal herpes encephalitis, herpes simplex type 1 in a 35-year-old man, and varicella-zoster virus activity in a 62-year-old woman. None of the patients had clinical signs indicating an acute disorder in the central nervous system. This serologic approach seems to be of value for the diagnosis of an associated intracerebral viral infection in cases of acute retinal necrosis syndrome.

Clustering of enterococcal infections in a general intensive care unit.

This is a retrospective study comparing patients' characteristics, antibiotic consumption and environmental contamination before the impact of a new regimen of intensified infection control measures in a general intensive care unit (ICU) at a university-affiliated tertiary-care teaching hospital. The new regimen consisted of (1) reorganization of patient rooms (2) improved hygienic measures including strict hygiene barrier nursing (3) more isolated patient care and (4) more restrictive use of antibiotics. The regimen was introduced after a cluster of enterococcal infections. All patients admitted to the ICU from 1 March 1995 to 28 february 1997 were included. A study period of 12 months after reorganization of the ward was compared with the 12 months immediately before it. The antibiotic consumption, the individual patient's severity of disease (APACHE score), and the extent of therapeutic interventions (TISS score) were recorded. Enterococci were typed biochemically, antibiograms were established and the relation between the isolates was investigated with pulsed-field gel electrophoresis. The bacteriological results and the patient data suggested a hospital-acquired spread as the cause of the ICU enterococcal outbreak. After implementation of the new regimen, we observed a reduction in the rate of enterococcal bloodstream infections from 3.1 to 1.8%. The consumption of antibiotics fell from 6.11 to 4.24 defined daily doses per patient. The introduction of strict hygiene and barrier nursing, more restrictive use of antibiotics, isolation of infected patients, thorough cleaning and disinfection of the unit was followed by an absence of enterococcal infection clustering and reduction in incidence of enterococcal bacteraemia. We were not able to determine whether the reduction in antibiotic consumption was due to the intervention programme.

Gene expression of cyclooxygenase-2, group II and cytosolic phospholipase A2 in human colorectal cancer.

The development of intestinal tumours in the Min mouse is influenced by Moml locus, where the group II phospholipase A2 (PLA2-II) gene has been suggested as the candidate gene. Since no causative genetic alterations have been identified in PLA2-II in human colorectal tumours, we tested whether PLA2-II or the cytosolic isoform cPLA2, are dysregulated in human colorectal carcinogenesis. By means of RT-PCR, the expression of these genes and cyclooxygenase-2 (COX-2), which is upregulated in colorectal tumours, were examined. No changes in gene expression of PLA2-II were found in 44 tumours compared to normal mucosa. cPLA2 and COX-2 were upregulated; however, no correlation in expression was found between these genes. Thus, the supply of arachidonic acid provided by PLA2-II/cPLA2 seems not to be the rate limiting step in PGE2 (a prostaglandin/mitogen) formation via COX-2 and PLA2-II plays a minor or no role in human colorectal carcinogenesis.

Dose accuracy check of the 3D electron beam algorithm in a treatment planning system.

The accuracy of the recently implemented three-dimensional electron beam dose calculating algorithm in CADPLAN version 2.62 manufactured by Varian Dosetek was investigated. The algorithm uses a generalized Gaussian pencil beam model and the dose distributions are calculated as the sum of three weighted Gaussians. To use the calculating program in an optimum way, one needs to know the dose calculation accuracy of the algorithm as well as its limitations. This investigation includes comparisons of measured relative dose distributions with calculated dose distributions and also comparisons of measured and calculated monitor units. The geometries tested were quadratic fields, irregularly shaped fields, oblique fields, irregularly shaped phantom surfaces and internal heterogeneities and were most often irradiated with 8 and 20 MeV electrons. The results indicate that the algorithm is well suited for clinical three-dimensional dose planning. Some deviations occurred but they were most often within the limits of international criteria of acceptability.