A clinical and radiological comparison of sigmoid diverticulitis episodes 1 and 2

Aim After an initial uncomplicated attack, sigmoid diverticulitis may recur, but the morphological characteristics of recurrent diverticulitis have not been investigated. We compared the clinical and radiological severity, the respective location and clinical outcome of the first two episodes of sigmoid diverticulitis. Method We reviewed the charts of 60 patients [median age 61 (range 31–90) years] who were admitted initially for a first episode of uncomplicated left colonic diverticulitis, and who were eventually readmitted for a second episode, both being documented by abdominal computed tomography (CT) scan. Results The median delay between the two episodes was 19 (3–97) months. Six (10%) patients developed a second complicated episode of diverticulitis [Hinchey II (n = 2), CT‐guided percutaneous drainage; Hinchey III (n = 3), emergency Hartmann’s operation; colovesical fistula (n = 1), elective sigmoid resection]. Fifty‐four (90%) patients were admitted for a second episode of uncomplicated diverticulitis. In this group, the duration of hospital stay [11 (4–22) vs 10 (1–39) days, P = 0.28], serum levels of C‐reactive protein [131 (31–350) vs 112 (22–333) mm , P = 0.62] and CT scan‐based severity score [3 (1–6) vs 3 (0–7) points, P = 0.07] were similar between the two episodes. In 19 out of 54 (35%) patients with simple recurrent diverticulitis, although disease severity was similar, the disease topography differed and recurrence involved another segment of the left colon. Conclusion The majority of patients who develop recurrence do so in a similar mode and location. However, 10% develop complicated diverticulitis and in 35% of patients recurrent diverticulitis occurs at a different location.     

Cytoreductive nephrectomy in the elderly: a population-based cohort from the USA

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? While cytoreductive nephrectomy is associated with a survival benefit in the context of metastatic renal cell carcinoma, the rates of morbidity and perioperative mortality remain non‐negligible. For example, perioperative mortality may be as high as 21% in elderly patients. The study shows that perioperative death amongst the elderly was substantially lower than what was previously reported from a single institutional report. Nonetheless, postoperative adverse outcomes were non‐negligible in elderly patients relative to their younger counterparts. In consequence, these rates should be discussed at informed consent and a rigorous patient selection remains essential.

OBJECTIVE

• ? To examine the rate of perioperative mortality (PM), and other adverse outcomes in ‘elderly’ patients treated with cytoreductive nephrectomy (CNT).

MATERIAL AND METHODS

• ? Patients who underwent CNT for metastatic renal cell carcinoma were abstracted from the Nationwide Inpatient Sample (1998–2007). ‘Elderly’ was defined as ≥75 years, according to previous definition.
• ? Endpoints consisted of PM, intraoperative and postoperative complications, blood transfusions and length of stay.
• ? We adjusted for the effect of elderly status within five separate logistic regression models. Covariates consisted of comorbidity, race, gender, year of surgery and hospital region.

RESULTS

• ? Overall, CNT was performed in 504 (15.3%) elderly patients and in 2796 (84.7%) ‘younger’ patients (<75 years).
• ? The rate of PM was 4.8% in elderly patients vs 1.9% in the younger patients (P < 0.001). Similarly, the rates of blood transfusions (29.8 vs 21.5%), postoperative complications (27.8 vs 22.8%), and prolonged length of stay (≥8 days) were higher in the elderly (45.0 vs 32.0%; all P < 0.001).
• ? In multivariable analyses, elderly patients were 2.2‐, 1.5‐, and 1.6fold more likely to experience PM, to receive a blood transfusion and to be hospitalized ≥8 days than the younger patients.

CONCLUSIONS

• ? Although the rate of PM was substantially lower than 21%, elderly patients are significantly more likely to die after this type of surgery, to receive a transfusion, and to experience a prolonged length of stay.
• ? These facts and figures should be discussed at informed consent and a rigorous patient selection is essential.

     

Comparative genome analysis of two Cryptosporidium parvum isolates with different host range

Parasites of the genus Cryptosporidium infect the intestinal and gastric epithelium of different vertebrate species. Some of the many Cryptosporidium species described to date differ with respect to host range; whereas some species' host range appears to be narrow, others have been isolated from taxonomically unrelated vertebrates. To begin to investigate the genetic basis of Cryptosporidium host specificity, the genome of a Cryptosporidium parvum isolate belonging to a sub-specific group found exclusively in humans was sequenced and compared to the reference C. parvum genome representative of the zoonotic group. Over 12,000 single-nucleotide polymorphisms (SNPs), or 1.4 SNP per kilobase, were identified. The genome distribution of SNPs was highly heterogeneous, but non-synonymous and silent SNPs were similarly distributed. On many chromosomes, the most highly divergent regions were located near the ends. Genes in the most diverged regions were almost twice as large as the genome-wide average. Transporters, and ABC transporters in particular, were over-represented among these genes, as were proteins with predicted signal peptide. Possibly reflecting the presence of regulatory sequences, the distribution of intergenic SNPs differed according to the function of the downstream open reading frame. A 3-way comparison of the newly sequenced anthroponotic C. parvum, the reference zoonotic C. parvum and the human parasite Cryptosporidium hominis identified genetic loci where the anthroponotic C. parvum sequence is more similar to C. hominis than to the zoonotic C. parvum reference. Because C. hominis and anthroponotic C. parvum share a similar host range, this unexpected observation suggests that proteins encoded by these genes may influence the host range.     

The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome

OBJECTIVES: To determine the concentrations of proinflammatory mediators, collagenases, and procollagen type III peptides in undiluted pulmonary edema fluids and in plasma obtained in patients with early acute respiratory distress syndrome (ARDS) and in control patients with hydrostatic lung edema; and to assess the relationship between these inflammatory and profibrotic markers. DESIGN: A prospective, clinical study with measurements of inflammatory markers in pulmonary edema fluids and in paired plasma samples. SETTING: A medical intensive care unit. PATIENTS: Patients intubated with lung permeability (n = 23) and hydrostatic (n = 8) pulmonary edema were prospectively enrolled in the study. The severity of the disease at the time of intubation was assessed, using the Simplified Acute Physiological Score (SAPS) II and the Lung Injury Score (LIS). INTERVENTIONS: Plasma and undiluted edema fluids were obtained at the time of intubation with pulmonary edema requiring mechanical ventilation; and in some patients, a second edema fluid sample was collected a few hours later. MEASUREMENTS AND MAIN RESULTS: Proinflammatory activity, dependent on the presence of bioactive proinflammatory cytokines, interleukin (IL)-8, and neutrophil matrix metalloproteinase (MMP)-9 were significantly increased in ARDS fluids compared with plasma or control fluids from patients with congestive heart failure. In contrast, MMP-2, originating from lung cells other than phagocytes, was slightly increased in ARDS edema fluids compared with plasma, but similar to levels found in hydrostatic edema fluids. Proinflammatory activity was undetectable in plasma from ARDS patients. Levels of procollagen peptide III, a marker of collagen synthesis, were increased in permeability edema fluids compared with hydrostatic edema fluids or plasma, confirming that alveolar collagen synthesis begins very early and in parallel with acute inflammation in ARDS. Control patients with hydrostatic edema had similar SAPS II and LIS scores compared with ARDS patients. CONCLUSIONS: These results strongly support the conclusion that during the early phase of ARDS, the lung is the site of an intense inflammatory process with sequential activation of cytokines, chemokines, and secretion of proteases, as well as concomitant collagen synthesis. The inflammation is mostly limited to the lung, with low levels of inflammatory mediators in the systemic circulation. Unlike clinical scoring systems (SAPS II and LIS), inflammatory markers differentiate patients with permeability and hydrostatic pulmonary edema.     

Distribution of Legionella species and serogroups isolated by culture in patients with sporadic community-acquired legionellosis: an international collaborative survey

This international collaborative survey identified culture-confirmed legionellosis in 508 patients with sporadic community-acquired legionellosis. Legionella pneumophila constituted 91.5% of the isolates. Serogroup 1 was the predominant serogroup (84.2%), and serogroups 2-13 (7.4%) accounted for the remaining serogroups. The Legionella species most commonly isolated were L. longbeachae (3.9%) and L. bozemanii (2.4%), followed by L. micdadei, L. dumoffii, L. feeleii, L. wadsworthii, and L. anisa (2.2% combined). L. longbeachae constituted 30.4% of the community-acquired Legionella isolates in Australia and New Zealand.     

PIERS Proteinuria: Relationship With Adverse Maternal and Perinatal Outcome

ObjectiveTo examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes.MethodsWe performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women (“ALL measures”) who had all three proteinuria assessments.ResultsMore women were proteinuric by urinary dipstick (≥ 2 +, 61.4%) than by spot urine Pr/Cr (≥ 30g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome.ConclusionThe measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.     

Identification of growth inhibiting compounds in a Giardia lamblia high-throughput screen

Giardia lamblia is one of the most common eukaryotic pathogens and is classified by the CDC as a category B agent of bioterrorism. In a departure from more traditional research focused on specific pathways or molecules, we have developed a high-throughput assay for screening libraries of small compounds for inhibitors and enhancers of trophozoite multiplication. Following a 24-h period of culture in 384-well plates in the presence of compounds, trophozoites were fixed, stained and enumerated. Quadruplicate screening of 1520 compounds from two libraries of known bioactives detected numerous inhibitory compounds. Based on a stringent cut-off of 5 standard deviations from the plate mean, 50 compounds (3.3%) were inhibitory. The activity of 3 compounds was confirmed in conventional culture. Although not meeting the threshold, one compound (indirubin) was identified as an agonist of trophozoite proliferation. Demonstrating the potential of high-throughput screening for rapidly finding new compounds which perturb G. lamblia multiplication, most of the hits identified by high-throughput screening do not appear to have been tested previously for their ability to affect G. lamblia trophozoites. High-throughput screening of bioactive compounds will open new avenues to a system-wide analysis of pathways affecting G. lamblia proliferation, and eventually to other phases of the life cycle.     

Distribution of postpartum blood loss: modeling,estimation and application to clinical trials

Background

The loss of large amounts of blood postpartum can lead to severe maternal morbidity and mortality. Understanding the nature of postpartum blood loss distribution is critical for the development of efficient analysis techniques when comparing treatments to prevent this event. When blood loss is measured, resulting in a continuous volume measure, often this variable is categorized in classes, and reduced to an indicator of volume greater than a cutoff point. This reduction of volume to classes entails a substantial loss of information. As a consequence, very large trials are needed to assess clinically important differences between treatments to prevent postpartum haemorrhage.

Methods

The authors explore the nature of postpartum blood loss distribution, assuming that the physical properties of blood loss lead to a lognormal distribution. Data from four clinical trials and one observational study are used to confirm this empirically. Estimates of probabilities of postpartum haemorrhage events ‘blood loss greater than a cutoff point’ and relative risks are obtained from the fitted lognormal distributions. Confidence intervals for relative risk are obtained by bootstrap techniques.

Results

A variant of the lognormal distribution, the three-parameter lognormal distribution, showed an excellent fit to postpartum blood loss data of the four trials and the observational study. A measurement quality assessment showed that problems of digit preference and lower limit of detection were well handled by the lognormal fit. The analysis of postpartum haemorrhage events based on a lognormal distribution improved the efficiency of the estimates. Sample size calculation for a hypothetical future trial showed that the application of this procedure permits a reduction of sample size for treatment comparison.

Conclusion

A variant of the lognormal distribution fitted very well postpartum blood loss data from different geographical areas, suggesting that the lognormal distribution might fit postpartum blood loss universally. An approach of analysis of postpartum haemorrhage events based on the lognormal distribution improves efficiency of estimates of probabilities and relative risk, and permits a reduction of sample size for treatment comparison.

Trial registration

This paper reports secondary analyses for trials registered at Australian New Zealand Clinical Trials Registry (ACTRN 12608000434392 and ACTRN12614000870651); and at clinicaltrials.gov (NCT00781066).

     

Is the Incidence of Anaerobic Bacteremia Decreasing? Analysis of 114,000 Blood Cultures over a Ten-Year Period

The number of positive anaerobic blood culture results per 1,000 blood cultures performed decreased from 12.6 in the period from 1997 to 2001 to 7.0 in the period from 2002 to 2006 (P < 0.001), as did the proportion of isolated anaerobic organisms compared to the number of all organisms isolated from blood cultures (7.6% to 4.3% [P < 0.001]), while positive aerobic cultures remained stable. In contrast, the proportion of Bacteroides fragilis group members and gram-positive cocci within the anaerobic group increased (26.8% to 36.7% [P = 0.004] and 5.4% to 12% [P < 0.001], respectively). The number of patients with anaerobic bacteremia decreased from 122 patients in 1997 to 69 in 2006.