Mortality risk associated with venous thromboembolism: a systematic review and Bayesian meta-analysis.

BACKGROUND: Venous thromboembolism is associated with increased mortality risk in some populations, but how frequently it is a direct cause of death is unclear. We used data from venous thromboembolism prevention trials to evaluate the causal effect of venous thromboembolism reduction on mortality. METHODS: We did a systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating venous thromboembolism prevention. We searched MEDLINE, Embase, PubMed, and Web of Science starting from Jan 1, 1993, to March 19, 2018. We included studies of patients who were at elevated risk of venous thromboembolism and were randomly assigned to either anticoagulant or antiplatelet therapy versus placebo or no treatment. We excluded studies with an active control agent (which might mitigate the lethality of venous thromboembolism) and those for which mortality data were unavailable. We modelled heterogeneity in a Bayesian framework, taking overall mortality as a primary endpoint, and pulmonary embolism, fatal pulmonary embolism, and major bleeding as secondary endpoints. We focused our analyses on studies reporting statistically significant effects of prevention on venous thromboembolism endpoints. We report treatment effects as median risk ratios (RRs), wherein a null effect equals 1, with 95% credible intervals (CrIs). This meta-analysis was registered with PROSPERO, CRD42018089697. FINDINGS: From 4229 studies screened, we identified 86 eligible RCTs; 52, with data from over 70 000 patients, were positive, with significantly increased venous thromboembolism risk in patients in control groups versus treatment groups (RR 2·74, 95% CrI 2·32-3·31, p<0·0001). The meta-analysis established that the causal effect of venous thromboembolism prevention on mortality was null (control group mortality was 3391 [9·8%] of 34 537 patients; treatment group mortality was 3498 [9·8%] of 35 795 patients [RR 1·01, 95% CrI 0·97-1·06; p=0·58]) with low heterogeneity (τ 0·02, 95% CrI 0·00-0·07, p=0·89). Patients in control groups had more pulmonary embolism (RR 2·22, 95% CrI 1·78-2·89, p<0·0001) and fatal pulmonary embolism (1·58, 1·14-2·19, p=0·01), but less major bleeding (0·60, 0·47-0·75, p<0·0001) than those in treatment groups. A meta-analysis with the additional 34 negative studies yielded similar results for all endpoints except fatal pulmonary embolism, where evidence of an effect was weaker (1·42, 1·05-1·91, p=0·02). INTERPRETATION: The perception that venous thromboembolism is a common cause of mortality should be revised considering the null effect of venous thromboembolism prevention on mortality. Our findings call into question the use of composite endpoints in venous thromboembolism-prevention trials and provide rationale for de-escalation trials. FUNDING: None.

Adjuvant Gemcitabine and Gemcitabine-based Chemoradiotherapy Versus Gemcitabine Alone After Pancreatic Cancer Resection: The Indiana University Experience.

OBJECTIVES: Adjuvant therapy after surgical resection is the current standard for pancreatic adenocarcinoma; however, the role of chemoradiotherapy (CRT) remains unclear. This study was conducted to compare the efficacy outcomes with adjuvant gemcitabine and gemcitabine-based CRT (CT-CRT) versus gemcitabine chemotherapy (CT) alone after pancreaticoduodenectomy. METHODS: Among 165 patients who underwent surgical resection for pancreatic cancer at Indiana University Medical Center between 2004 and 2008, we retrospectively identified 53 consecutive patients who received adjuvant therapy (CT-CRT=34 patients; CT=19 patients) and had adequate follow-up medical records. The median follow-up was 19.1 months. Median disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier method, and a Cox-regression model was used to compare survival outcomes after adjusting for age, status of resection margins, and lymph node involvement. RESULTS: The OS for the CT-CRT group was significantly higher compared with the CT group (median, 20.4 vs. 16.6 mo; hazard ratio, 2.42; 95% CI, 1.17-5.01). The median DFS for the CT-CRT group was 13.7 versus 11.1 months for the CT group (hazard ratio, 2.88; 95% CI, 1.37-6.06). On subgroup analyses, significantly superior OS and DFS were observed among patients younger than 65 years, T3/T4 tumor stage, negative resection margins, and positive lymph node involvement. CONCLUSION: Gemcitabine plus gemcitabine-based CRT compared with gemcitabine alone leads to superior DFS and OS for patients with resected pancreatic cancer.

Pericecal hernia: a rare form of internal hernias.

We report a rare and interesting case of a pericecal hernia. A 34-year-old male presented to the emergency department with severe periumbilical pain, emesis and a prior syncopal episode. He noted a 3-month history of intermittent, colicky periumbilical pain. His abdominal examination demonstrated a palpable mass in the right lower quadrant, involuntary guarding and rebound tenderness. CT demonstrated dilated small-bowel loops and findings suggestive of ischemia. The patient was immediately taken to the operating room where a diagnosis of pericecal hernia was made. The patient underwent a reduction of the hernia and a repair of the mesenteric defect.

Ileal diverticulitis: an uncommon diagnosis for right lower quadrant pain.

We report an interesting case of ileal diverticulitis which posed a diagnostic challenge. A 75-year-old female presented to the emergency department with severe right lower quadrant pain for 3 days. The clinical history, examination and imaging suggested a diagnosis of acute appendicitis. The patient was taken to the operating room for an open appendectomy. The intra-operative findings demonstrated a large mass at the ileocecal junction involving the appendix as well as multiple nodular masses in the ileum and cecum. The patient underwent a right hemicolectomy with ileocecal anastomosis. The pathology result revealed Ileal diverticulitis. Ileal diverticulitis is a rare form of diverticulitis. It can often mimic other processes such as acute appendicitis. Once ileal diverticulitis is diagnosed, it should be treated with the same principles as for sigmoid diverticulitis. Though rare, ileal diverticulitis should be considered in the differential diagnosis of a patient who presents with right lower quadrant pain, and a computed tomography scan that shows an inflammatory process in the right lower quadrant, in the setting of a normal appendix.