Synchronous colorectal cancer using CT colonography vs. other means: a systematic review and meta-analysis

Objectives

The objective of our study was to systematically review the evidence about synchronous colorectal cancer diagnosed with or without computed tomography colonography (CTC).

Materials and methods

Two systematic searches were performed (PubMed and EMBASE) for studies reporting the prevalence of synchronous colorectal cancer (CRC): one considering patients who underwent CTC and the another one considering patients who did not undergo CTC. A three-level analysis was performed to determine the prevalence of patients with synchronous CRC in both groups of studies. Heterogeneity was explored for multiple variables. Pooled prevalence and 95% confidence interval (CI) were calculated. A quality assessment (STROBE) was done for the studies.

Results

For CTC studies, among 2645 articles initially found, 21 including 1673 patients, published from 1997 to 2018, met the inclusion criteria. For non-CTC studies, among 6192 articles initially found, 27 including 111,873 patients published from 1974 to 2015 met the inclusion criteria. The pooled synchronous CRC prevalence was 5.7% (95% CI 4.7%–7.1%) for CTC studies, and 3.9% (95% CI 3.3%–4.4%) for non-CTC studies, with a significant difference (p = 0.004). A low heterogeneity was found for the CTC group (I² = 10.3%), whereas a high heterogeneity was found in the non-CTC group of studies (I² = 93.5%), and no significant explanatory variables were found. Of the 22 STROBE items, a mean of 18 (82%) was fulfilled by CTC studies, and a mean of 16 (73%) by non-CTC studies.

Conclusions

The prevalence of synchronous CRC was about 4–6%. The introduction of CTC is associated with a significant increase of the prevalence of synchronous CRCs.

     

The Growing Demand for Hospice and Palliative Medicine Physicians: Will the Supply Keep Up?

Context

The need for hospice and palliative care is growing rapidly as the population increases and ages and as both hospice and palliative care become more accepted. Hospice and palliative medicine (HPM) is a relatively new physician specialty, currently training 325 new fellows annually. Given the time needed to increase the supply of specialty-trained physicians, it is important to assess future needs to guide planning for future training capacity.

Kinetics of Serologic Responses to MERS Coronavirus Infection in Humans,South Korea

We investigated the kinetics of serologic responses to Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using virus neutralization and MERS-CoV S1 IgG ELISA tests. In most patients, robust antibody responses developed by the third week of illness. Delayed antibody responses with the neutralization test were associated with more severe disease.     

Rifabutin as salvage therapy for Helicobacter pylori eradication: Cornerstones and novelties

When several Helicobacter pylori eradication treatments fail, guidelines recommend a cultured guided approach; however, culture is not widely available. Therefore, a rifabutin based regimen could be the best solution. Rifabutin indeed shows a low rate of antibiotic resistance. Rifabutin is generally used in combination with amoxicillin in a triple therapy, with eradication rates about 80% in third-line regimens. The ideal duration of this therapy should range between 10 and 12 d. Combinations with antibiotics other than amoxicillin have demonstrated even better results, such as vonoprazan, which is a type of novel acid suppressor drug. Finally, a new formulation of triple therapy in a single capsule is under investigation, which is a field that deserves further investigation. Some notes of caution about rifabutin should be mentioned. This drug is used to treat tuberculosis or atypical mycobacteria; therefore, before starting a rifabutin-based eradication regimen, Mycobacterium tuberculosis infection should be thoroughly tested, since its use could promote the development of antibiotic resistance, thus affecting its effectiveness against Koch’s bacillus. Additionally, some serious side effects must be evaluated before starting any rifabutin-based therapy. Adverse effects include fever, nausea, vomiting and bone marrow suppression. For this reason, full blood count surveillance is required.     

Role of bile acids and metabolic activity of colonic bacteria in increased risk of colon cancer after cholecystectomy

Since the metabolic activity of the colonic flora plays a definite role in colon cancer and an increased incidence of this disease is reported after cholecystectomy, we studied the metabolic activity of the colonic flora in a group of postcholecystectomy patients and matched controls by measuring, as representative end products of the bacterial metabolism, their fecal bile acids (BA), fecal 3-methylindole (SK) and indole (IN), and respiratory methane and hydrogen. Patients had significantly higher SK and lower IN, and, among BA, higher lithocholic (LCA) and chenodeoxycholic acid concentrations and LCA/deoxycholic acid ratio in the stools than controls. Similar differences from controls were reported for colon cancer. Comparable bacterial metabolic activities are thus operative in the large bowel of postcholecystectomized and colon cancer patients. This supports the biological plausibility of the association of cholecystectomy and colon cancer.     

A human antibody that inhibits factor IX/IXa function potently inhibits arterial thrombosis without increasing bleeding

10C12, a human antibody F(ab')2, which specifically binds to the gamma-carboxyglutamic acid domain of factor IX/factor IXa (F.IX/IXa), interferes with all known coagulation processes in which F.IX/IXa is involved. In a rabbit model of carotid artery injury, intravenous administration of 10C12 or heparin decreased thrombosis dose dependently. The dose that resulted in a 90% reduction of thrombus mass (ED90) was a 30-microg/kg bolus of 10C12 or a 100-U/kg bolus plus 1.0 U x kg(-1) x min(-1) infusion of heparin. Heparin, at and below the ED90, significantly prolonged coagulation times and cuticle bleeding times. In contrast, 10C12 had no effect on coagulation or bleeding times at doses up to 4 times the ED90. To further evaluate the effect of 10C12 on bleeding, it was compared with heparin in a novel model of blood loss. At the ED90 of heparin, blood loss induced by a standardized injury to the vasculature of the rabbit tibia increased to more than 2 times that of saline controls. In contrast, the dose of 10C12 required to produce a similar increase in blood loss was more than 30 times the ED90. The antithrombotic potency and relative safety of this fully human antibody suggests that it may have therapeutic value for treatment of thrombotic disorders.     

Glucocorticoid and mineralocorticoid cross-talk with progesterone receptor to induce focal adhesion and growth inhibition in breast cancer cells

Progesterone receptor (PR), glucocorticoid receptor, and mineralocorticoid receptor belong to a subfamily of nuclear receptor superfamily with similar sequence and structural characteristics. Many reports have documented glucocorticoid-like effects of progesterone in various tissues. This study addresses the issue of cross-talk between corticosteroids and PR using PR-transfected MDA-MB-231 cells ABC28 and vector-transfected control cells CTC15. At physiological concentrations, dexamethasone, cortisol, and aldosterone mimic the effects of progesterone by inducing significant growth inhibition, cell spreading, and focal adhesions in PR-positive ABC28 cells. These hormones also induce progesterone-like effects in increasing the expression of p21(CIP1/WAF1) protein and decreasing the level of phospho-p42/p44 mAPK. Two lines of evidence suggest that these effects are mediated by cross-talk with PR. First, these compounds do not exhibit the same progesterone-like effects in PR-negative CTC15 cells. Second, PR blocker ZK98299 abolishes their effect on cell spreading and focal adhesion in ABC28 cells. The cross-talk is corticosteroid specific because estradiol and thyroid hormone triiodothyronine have no effect on PR-transfected cells ABC28. It is also interesting to note that dexamethasone induces a small but detectable increase of focal adhesions and limited growth stimulation in vector-transfected cells CTC15. In contrast, progesterone exhibits no detectable effect on CTC15 cells. This study provides evidence that glucocorticoid and mineralocorticoid cross-talk with PR to produce progesterone-like effects in breast cancer cells. Glucocorticoid receptor and PR share some overlapping activity in mediating focal adhesion but not in regulating cell proliferation.     

Early selective neuroretinal disorder in prepubertal type 1 (insulin-dependent) diabetic children without microvascular abnormalities

The duration of diabetes before puberty is not considered relevant to the future development of complications. To evaluate the effects of diabetes on the neural retina, we analysed macular function by steady-state focal electroretinography in 20 prepubescent diabetic children without vascular retinopathy and in 39 sex- and age-matched normal children. The mean (±SD) response related to retinal cellular elements between the photoreceptors and ganglion cells was significantly lower in diabetic children than in the control group (0.38±0.12 vs. 0.51±0.13 V; unpairedt-test=3;P=0.005). Similarly, ganglion cell function showed a significant impairment in diabetic children with respect to the control group (0.4±0.13 vs. 0.53±0.09 V; unpairedt-test=5.4;P=0.0001), whereas the photoreceptors appeared unaffected. Metabolic control and disease duration were not correlated with functional deficits. Our results suggest that before puberty, early diabetes may have a selective effect on the neural retina prior to the appearance of microvascular changes. A focal electroretinogram could identify diabetic children with neurosensory disorders who may have a higher risk of developing microvascular retinopathy.     

Intracoronary streptokinase in unstable angina: a prospective randomised study.

Results of our prospective, randomised pilot trial to evaluate the clinical effects and the angiographic correlates of early thrombolysis in patients with unstable angina are reported. Sixty-seven patients had coronary angiography 10 +/- 8 (median 7) hours after an episode of transient chest pain at rest with reversible ischaemic changes on the electrocardiogram. Patients with left main disease (4), or diffuse coronary disease and unidentified ischemia-producing lesions (13) were excluded, as were those without severe (greater than or equal to 70%) stenosis (10). Intracoronary thrombus was identified at angiography in 7 patients (17%) and complex coronary lesions in 5 (12%) of the remaining 40 patients who were randomised to either intracoronary streptokinase 250,000 IU followed by intravenous heparin along with conventional treatment (20 patients), or to conventional treatment alone (20 patients). All patients received Aspirin. No differences between the streptokinase and the conventional treatment groups were observed with respect to demographic and clinical characteristics at admission to the study. During observation in the intensive care unit for 3 +/- 1 days, 8 patients (40%) with streptokinase and 10 (50%) with conventional treatment were free from angina and infarction (p = 0.75; 95% confidence interval for the difference in response rates = -20 to 40%). There were no bleeding complications and no patient died. Patients enrolled in our study had fewer coronary thrombi at angiography than currently reported. Our data did not show that adjunct treatment with streptokinase and heparin is superior to conventional treatment alone in these patients.