Coffee intake protects against symptomatic gallstone disease in the general population: a Mendelian randomization study.

BACKGROUND AND OBJECTIVES: Coffee intake is associated with low risk of symptomatic gallstone disease (GSD). We tested the hypothesis that high coffee intake causally protects against symptomatic GSD using a Mendelian randomization design. METHODS: First, we tested whether high coffee intake was associated with low risk of GSD in 104 493 individuals from the general population. Mean follow-up was 8 years (range: <1-13 years). Secondly, we tested whether two genetic variants near CYP1A1/A2 (rs2472297) and AHR (rs4410790), combined as an allele score, were associated with higher coffee intake measured as a continuous variable. Thirdly, we tested whether the allele score was associated with lower risk of GSD in 114 220 individuals including 7294 gallstone events. Mean follow-up was 38 years (range: <1-40 years). RESULTS: In observational analysis, those with coffee intake of >6 cups daily had 23% lower risk of GSD compared to individuals without coffee intake [hazard ratio (HR) = 0.77 (95% confidence interval: 0.61-0.94)]. In genetic analysis, there was a stepwise higher coffee intake of up to 41% (caffeine per day) in individuals with 4 (highest) versus 0 (lowest) coffee intake alleles (P for trend = 3 x 10-178 ) and a corresponding stepwise lower risk of GSD up to 19%[HR = 0.81 (0.69-0.96)]. The estimated observational odds ratio for GSD for a one cup per day higher coffee intake was 0.97 (0.96-0.98), equal to 3% lower risk. The corresponding genetic odds ratio was 0.89 (0.83-0.95), equal to 11% lower risk. CONCLUSION: High coffee intake is associated observationally with low risk of GSD, and with genetic evidence to support a causal relationship.

Red blood cell transfusion in surgery: an observational study of the trends in the USA from 2011 to 2016.

Guidelines recommend restrictive red blood cell transfusion strategies. We conducted an observational study to examine whether the rate of peri-operative red blood cell transfusion in the USA had declined during the period from 01 January 2011 to 31 December 2016. We included 4,273,168 patients from all surgical subspecialties. We examined parallel trends in rates of the following: pre-operative transfusion; prevalence of bleeding disorders and coagulopathy; and minimally invasive procedures. To account for changes in population and procedure characteristics, we performed multivariable logistic regression to assess whether the risk of receiving a transfusion had declined over the study period. Clinical outcomes included peri-operative myocardial infarction, stroke and all-cause mortality at 30 days. Peri-operative red blood cell transfusion rates declined from 37,040/441,255 (8.4%) in 2011 to 46,845/1,000,195 (4.6%) in 2016 (p < 0.001) across all subspecialties. Compared with 2011, the corresponding adjusted OR (95%CI) for red blood cell transfusion decreased gradually from 0.88 (0.86-0.90) in 2012 to 0.51 (0.50-0.51) in 2016 (p < 0.001). Pre-operative red blood cell transfusion rates and the prevalence of bleeding disorders decreased, whereas haematocrit levels and the proportion of minimally invasive procedures increased. Compared with 2011, the adjusted hazard ratios (95%CI) in 2012 and 2016 were 0.96 (0.90-1.02) and 1.05 (0.99-1.11) for myocardial infarction, 0.91 (0.83-0.99) and 0.99 (0.92-1.07) for stroke and 0.98 (0.94-1.02) and 0.99 (0.96-1.03) for all-cause mortality. Use of peri-operative red blood cell transfusion declined from 2011 to 2016. This was not associated with an increase in adverse clinical outcomes.

Major vascular injuries during laparoscopic procedures.

BACKGROUND: Major vascular complications following laparoscopic procedures are rare, with only 20 cases reported in the literature. PATIENTS AND METHODS: The cases of 4 patients who sustained 5 vascular injuries during laparoscopic procedures between June 1991 and May 1994 are presented, and previously reported cases in the literature are reviewed. RESULTS: All injuries occurred during pelvic laparoscopy (2 diagnostic procedures, 1 tubal ligation, and 1 hernia repair). The vascular injury was recognized during laparoscopy in 3 patients. In only 1 patient was immediate vascular surgery consultation requested. The iliac artery was injured in 3 patients, the iliac vein in 1, and the inferior epigastric artery in 1. The mechanism of injury was by the trocar in 2 patients and by sharp dissection in 2 patients. Arterial repair was accomplished by polytetrafluoroethylene (PTFE) interposition, PTFE patch angioplasty, resection and primary anastomosis, and ligation in 1 patient each. The venous injury was repaired by lateral venorrhaphy. Three patients recovered without sequelae, and 1 patient had a stroke. A review of the literature revealed only 20 reported cases of major vascular injuries as a result of the pneumoperitoneum needle or trocar insertion. Characteristically, the terminal aorta, cava, iliac arteries, and veins were injured. Most injuries were treated by direct suture repair. With immediate recognition, recovery was the rule; however, 3 of the 8 patients with delayed recognition died. CONCLUSION: Laparoscopists must be aware of this rare, serious, and potentially lethal complication. Once recognized, immediate conversion to an open procedure and application of appropriate vascular surgical techniques are required to reestablish arterial and venous continuity and minimize morbidity and mortality.

[High mortality from both natural and unnatural causes. A 10-year follow-up of patients admitted to a center for poisoning treatment after attempted suicide]. / Høj dødelighed af naturlige og unaturlige årsager. En tiårs-opfølgningsundersøgelse af patienter indlagt på en forgiftningscentral efter selvmordsforsøg.

While it is well known that suicide rates for suicide attempters are high, mortality rates for all causes needed to be more thoroughly investigated. A Danish 10-year follow-up study of patients who in 1980 were admitted to a poisoning treatment centre after attempted suicide was carried out with the purpose of describing mortality by suicide and other causes of death, and to identify predictive factors. A total of 974 patients aged 15 and over referred to a poisoning treatment centre after deliberate self-poisoning were included in the study. Death by different causes registered in the Danish Death Cause Register was the outcome measure. Over a 10-year follow-up period 306 patients had died; 103 by suicide, 131 from natural causes, 31 by accidents, five were murdered and in 36 cases the cause of death was uncertain. The Standard Mortality Rate (SMR) was 550. The cause-specific SMRs were for suicide 2960, for natural causes 236, for accidents 1256 and for uncertain causes 5459. In Cox-regression analysis high-risk factors for later suicide were more than one previous suicide attempt (relative risk (RR) 2.25), living alone (RR 2.28) and age (RR 1.03 per year). Predictors of death by natural causes were pension (RR 1.69), drug abuse (RR 2.72), more than one previous suicide attempt (RR 2.25), age (RR 1.06 per year) and male sex (RR 2.49). The group of patients fulfilling at least one high-risk criteria for later suicide differed significantly from the rest of the patient group regarding frequency of suicide, but both sensitivity and specificity remain low.(ABSTRACT TRUNCATED AT 250 WORDS)

High mortality by natural and unnatural causes: a 10 year follow up study of patients admitted to a poisoning treatment centre after suicide attempts.

OBJECTIVE: To describe mortality by suicide and other causes of death in a group of patients who attempted suicide, and to identify predictive factors. DESIGN: 10 year follow up study based on records of suicide attempters in 1980. SETTING: Poisoning treatment centre at a general hospital. SUBJECTS: 974 patients aged 15 and over referred to the poisoning treatment centre after deliberate self poisoning. MAIN OUTCOME MEASURES: Death by different causes registered in the Danish death cause register. RESULTS: In 10 years of follow up 306 patients died: 103 by suicide, 131 from natural causes, and 31 by accident; five were murdered, and in 36 cases the cause of death was uncertain. The standard mortality ratio was 550. Cause specific standardised mortality rates were 2960 for suicide, 236 for natural causes, 1256 for accidents, and 5459 for uncertain causes. In a Cox regression analysis, high risk factors for subsequent suicide were: more than one previous suicide attempt (relative risk 2.25), living alone (2.28), and age (1.03 per year). Predictors of death by natural causes were receiving a pension (1.69), drug misuse (2.72), more than one previous suicide attempt (2.25), age (1.06 per year), and male sex (2.49). The group of patients fulfilling at least one high risk criterion for later suicide differed significantly from the rest of the patient group in incidence of suicide, but both sensitivity and specificity were low. CONCLUSIONS: Most patients who attempted suicide were at high risk of succeeding because the risk factors, though significant, are not very specific. A strategy to prevent suicide must be directed toward the majority of those who attempt suicide.

Omphalocaval shunt: an alternative procedure for portal decompression.

We report a case in which umbilical vein was used to construct an omphalocaval shunt in a patient with a long history of alcoholic liver disease and recurrent esophageal and gastric variceal bleeding episodes. The indication for the choice of this procedure included the presence of dense adhesions in the porta hepatis, arteriographic documentation of continuity with the portal venous system, and an umbilical vein 12 mm in internal diameter. The hypertensive portal system was successfully decompressed and proved patent 6 months postoperatively.

Contemporary management of amebic liver abscess.

In a retrospective review covering 16 years divided into two time periods, 133 patients with amebic liver abscess were evaluated. Most of the patients were young, Hispanic men, and one-third had coexistent disease. A reliable diagnosis can be established in 24 hours using ultrasound or computed tomography scans. Over the entire time period, antiparasitic therapy was evolved to occupy a primary role and surgery was reserved for management of abscess complications.

High grade occlusion of the iliac vein by a traumatic pelvic hematoma without fracture.

A case of a man with a massive pelvic hematoma from blunt trauma without bony fracture is presented. The pressure of the hematoma on the iliac vein prevented fluid resuscitation using this route. A pelvic hematoma should be suspected in patients with iliac vein obstruction after blunt pelvic trauma even in the absence of fractures.

Effect of Aspirin and Dipyridamole on Sequential Graft Platelet Accumulation after Implantation of Small Diameter PTFE Prosthesis.

The optimal duration of antiplatelet therapy was evaluated by sequential measurement of platelet accumulation on polytetrafluoroethylene (PTFE) grafts. Sixty four New Zealand white rabbits received aspirin (ASA, 10 mg/kg/day) and dipyridamole (DPM, 10 mg/kg/day) (n = 34), or placebo (n = 30), beginning 3 days prior to insertion of a 10 mm x 3 mm PTFE interposition aortic graft. Using autologous In-111 labelled platelets, a graft platelet accumulation index (GPAI) was calculated as the grafttreference aorta ratio of activity of In-111. ASA/DPM significantly reduced mean GPAI from grafts and reference aorta removed 48 h after graft insertion from 217 ± 74 (mean ± SEM) on placebo (n = 8) to 43 ± 3 (n = 9), (p<0.05). Mean GPAI at 4 weeks were 55 ± 28 (n = 5) and 28 ± 6 (n = 5), (not significant), at 8 weeks 64 ± 17 (n = 5) and 49 ± 9 (n = 5) (not significant) and at 12 weeks 11 ± 4 (n = 4) and 25 ± 10 (n = 5), (not significant) for the control and ASA/DPM groups, respectively. We conclude that ASA/DPM significantly reduce early platelet deposition on PTFE grafts. These data support the use of antiplatelet therapy after vascular bypass procedures in man and further suggest that only a few months of antiplatelet therapy may be beneficial in man.

Hepatic artery versus portal vein and systemic infusion of fluorodeoxyuridine of rabbit VX-2 hepatic implants.

To compare the efficacy of regional and systemic infusions of hepatic tumors, and to correlate this with tumor perfusion, 29 New Zealand white rabbits underwent perfusion of VX-2 hepatic implants. Tritium-labeled fluorodeoxyuridine (H3-FUDR) and technetium-99m-labeled macroaggregated albumin (Tc 99m-MAA) were infused through the hepatic artery, portal vein, and peripheral vein. Hepatic artery infusion resulted in a significantly improved tumor-to-liver ratio of FUDR uptake (p less than 0.001). The increased tumor uptake correlated with a two-fold increase in tumor arterial blood flow as compared with normal liver demonstrated by the MAA infusion. We conclude that infusional therapy is superior to both portal vein and systemic infusions. Portal vein infusion results in no uptake of drug by the tumor. Hepatic artery scintigraphy with MAA may be useful in selecting appropriate patients for this type of therapy.

Perioperative suppression of platelet adherence to small-diameter polytetrafluoroethylene (PTFE) grafts.

The perioperative effect of platelet antagonists on small-diameter polytetrafluoroethylene (PTFE) grafts was evaluated in forty-six New Zealand white male rabbits receiving either dipyridamole (DPM) 100 mg/kg/day (n = 10; group 1), aspirin (ASA) 10 mg/kg/day (n = 10; group 2), a combination of ASA 10 mg/kg/day and DPM 10 mg/kg/day (n = 9; group 3) or 100 mg/kg/day (n = 10; group 4), or placebo (n = 7) as single daily doses. All regimens began 72 hr prior to insertion of a 20 x 3-mm internal diameter PTFE interposition aortic graft. Autologous indium-111 labeled platelets were injected immediately after implantation. Graft and an equivalent segment of aorta were harvested after 48 hr. Graft platelet adherence index (GPAI) was calculated as the graft:reference aorta ratio of emissions. The GPAI in the control group was 238 +/- 46 (mean +/- SD). Single regimen antiplatelet agents in groups 1 and 2 reduced mean GPAI to 47 +/- 38 and 40 +/- 12, respectively. The combination regimen in group 3 lowered mean GPAI to 43 +/- 8 and in group 4 to 21 +/- 7. Platelet uptake in PTFE grafts at 48 hr is significantly lowered to 8.8 to 19.7% of control by perioperative antiplatelet agents given as a single daily oral dose (P less than 0.001). ASA alone and DPM alone provided similar suppression of platelet uptake, but combination ASA + low dose or high dose DPM gave significantly greater (P less than 0.001) suppression of early platelet deposition than the single agent regimens. These results support perioperative administration of combination oral antiplatelet agents as adjunctive therapy in small diameter prosthetic graft implantation.

Neoendothelialization of small-diameter polytetrafluoroethylene arterial grafts is not delayed by aspirin and dipyridamole.

The effect of aspirin and dipyridamole on neoendothelialization of polytetrafluoroethylene (PTFE) was studied in the rabbit aortic graft model. Forty-three New Zealand white rabbits were allocated to receive a combination of aspirin 10 mg/kg/day and dipyridamole 10 mg/kg/day (n = 23) or placebo (n = 20). Both regimens began 3 days before insertion of PTFE aortic grafts (10 mm long and 3 mm internal diameter). Serum thromboxane B2 concentration in the control group averaged 254 +/- 22 ng/ml (+/- standard error of the mean) and 40 +/- 23 ng/ml in the treatment group (p less than 0.001). Grafts and adjacent aorta were harvested at 2 weeks (n = 4), 4 weeks (n = 9), 8 weeks (n = 13), and 12 weeks (n = 17) after implantation. Morphologic techniques, including conventional light microscopy, immunoperoxidase staining for endothelial factor VIII-related antigen, and scanning electron microscopy (SEM) demonstrated that neointima was composed of endothelial cells arising by ingrowth at anastomotic site and as islands in the center of the graft. The percentage of graft neoendothelialization was measured by SEM. At 2 weeks 18% +/- 2% of the PTFE surface was covered with endothelium in the aspirin/dipyridamole group. The percentages of graft neoendothelialization for the treatment and control groups at 4 weeks were 44% +/- 13% (n = 5) and 46% +/- 10% (n = 4) (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of serum amylase levels with pancreatic pathology and pancreatitis etiology.

Fifty-one patients, 35 men and 16 women, with acute pancreatitis were studied prospectively with early computed tomography (CT). Etiological factors for acute pancreatitis were alcohol abuse (n = 28), gallstones (n = 14), pancreas cancer (n = 3) and miscellaneous (n = 6). Admission serum amylase levels ranged between 68-5,856 U/L with a mean of 1,090 +/- 1,369 U/L. The mean serum amylase level was significantly different between patients with alcoholic pancreatitis (439 +/- 302 U/L) and gallstone pancreatitis (2,480 +/- 1,575) (p less than 0.001). The initial pancreatic CT findings and corresponding mean serum amylase levels were in CT grade A (pancreas normal) 1,499 +/- 1,569 U/L (n = 11), in CT grade B (pancreatic enlargement with inflammation confined to pancreas) 1,144 +/- 1,542 U/L (n = 18), in CT grade C (inflammatory extension into one peripancreatic space) 722 +/- 962 U/L (n = 13) and in CT grade D (inflammatory extension into two or more peripancreatic spaces) 590 +/- 369 U/L (n = 9). However, on separating the etiology subgroups, there was no increase or decrease in the serum amylase level with increasing pancreatic inflammatory involvement. Pancreatic complications (pseudocyst, abscess, necrosis) requiring surgical intervention developed only in patients with CT grades C and D. We conclude that within the etiologic subgroups there is no correlation between the initial serum amylase level and the extent of pancreatic involvement visualized by CT. These findings provide a pathological basis for the clinical observation that the initial serum amylase level cannot predict the outcome in acute pancreatitis.

Radionuclide study of platelets and prosthetic interactions: external versus specimen quantitation.

UNLABELLED: Twenty-nine New Zealand white rabbits were allocated to undergo insertion of either polytetrafluoroethylene (PTFE) (n = 22) or microporous silicone rubber (SR) (n = 7), 3-mm diameter, 10-mm long aortic grafts. Animals with PTFE grafts received aspirin (ASA) 10 mg/kg/d and dipyridamole (DPM) 10 mg/kg/d (n = 11) or placebo (n = 11). Autologous In-111-oxine-labeled platelets were reinfused on reestablishment of blood flow through the graft. Using gamma camera images, an external graft platelet accumulation index (E-GPAI) was calculated as the In-111 activity in the graft area to the reference aorta at 24, 48, and 72 hours post implantation. Mean E-GPAI +/- SEM values for the ASA/DPM (n = 4) and control groups (n = 7) were 1.13 +/- 0.16 and 1.34 +/- 0.05 (NS) at 24 hours, 1.20 +/- 0.16 and 1.33 +/- 0.07 (NS) at 48 hours, and 1.38 +/- 0.07 and 1.35 +/- 0.10 (NS) at 72 hours, respectively. A similar internal graft platelet accumulation index (I-GPAI) was constructed based on In-111 activity in excised grafts and reference aorta measured in a scintillation counter. Mean I-GPAI +/- SEM values for the PTFE ASA/DPM (n = 9) and control groups (n = 8) at 48 hours post implantation were 43.1 +/- 2.7 and 216.8 +/- 73.9 (P = 0.05), respectively. I-GPAI values for the SR grafts were 192.5 +/- 43.1. CONCLUSION: The E-GPAI was not sensitive enough to demonstrate the effect of antiplatelet medication on platelet accumulation on the PTFE grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Blunt traumatic dissection of the internal carotid artery treated by balloon occlusion.

An extensive traumatic intimal dissection of the internal carotid artery was successfully managed by permanent occlusion of the vessel with percutaneously-placed, inflatable balloons in a young patient who had suffered transient ischemic neurological attacks despite anticoagulation. This technique has not been previously reported for treatment of dissection. Review of 34 published reports of symptomatic intimal dissection associated with non-penetrating trauma to the head and neck revealed that most did not have a direct injury to the carotid region and that development of symptoms was often delayed. Only 50% of these patients had onset of neurological symptoms within six hours of the episode of trauma, while 33% remained asymptomatic for more than one week before complications occurred. In 15 patients who were treated surgically, only nine (60%) achieved full recovery. Operative repair was considered unduly hazardous in our patient because of extension of the spiral dissection to the base of the skull. Successful use of percutaneous balloon occlusion of the carotid in this patient suggests that this technique should be considered a worthy alternative for management of selected cases.

Platelet antagonists eliminate thromboembolic complications of small-diameter arterial prostheses.

An animal model suitable for study of the origin and method of prevention of thromboembolic complications of arterial prostheses has been developed in the rabbit. In phase I of the experiments 42 New Zealand white rabbits underwent insertion of polytetrafluoroethylene (PTFE) aortic grafts, 10 mm in length and of 2 mm internal diameter (I.D.) (n = 17) and 3 mm I.D. (n = 25). The patency rate at 3 months was 24% and 82%, respectively. Unexpected ischemic hind limb ulcers occurred in nine (38%) of the long-term survivors. Arteriograms in these animals showed a typical embolic occlusion of a distal artery, suggesting that the ulcers were due to embolization of loose mural thrombus, which was present in 50% of the grafts when removed. In phase II experiments 54 rabbits were randomly allocated to receive aspirin (ASA) 10 mg/kg/day and dipyridamole (DPM) 10 mg/kg/day (n = 25) or placebo (n = 29). Both regimens began 3 days before insertion of PTFE aortic grafts (10 mm long and 3 mm I.D.). Serum thromboxane B2 concentrations in the control group averaged 300.4 +/- 147.4 ng/ml and 43.2 +/- 58.6 ng/ml in the ASA/DPM group (p less than 0.0005). With the use of autologous indium 111 oxine-labeled platelets, a graft platelet accumulation index (GPAI) was calculated as the graft: reference ratio of emissions. ASA/DPM significantly reduced the mean GPAI calculated from grafts and reference aorta removed 48 hours after graft insertion from 69.3 +/- 4.0 on placebo (n = 4) to 34.3 +/- 2.9 (n = 4) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A laboratory model for the evaluation of thromboembolic complications of small diameter vascular prostheses.

Seventeen 2 mm and twenty-five 3 mm internal diameter petrafluoroethylene (PTFE) vascular prostheses were inserted as aortic interposition grafts in 42 rabbits. The 3 month patency with 2 mm grafts was disappointingly low at 24% whereas patency with 3 mm grafts was 82%, comparable to other studies of small diameter prostheses. Hind limb paralysis occurred in 18 animals and proved a reliable indicator of graft thrombosis. Unexpected and previously unreported lower limb ulceration occurred in nine of the 23 long term survivors. Angiographic studies indicated that these ulcers were due to distal embolization of loosely attached mural thrombi. These were found in four of eight patent grafts removed from animals with leg ulcers. Aortic grafting in the rabbit is an economic model for the study of thromboembolic phenomena in small diameter vascular prostheses and their modification by pharmacological agents.

Early computerized tomography as a predictor of outcome in acute pancreatitis.

Fifty-one patients with the clinical diagnosis of acute pancreatitis were studied prospectively with early computerized tomography. It was found to be superior to ultrasonography for detecting acute pancreatitis and defining its extent. Grading of the initial computerized tomographic findings according to the extent of pancreatic inflammatory reaction identified patients with a high risk of local complications after onset of acute pancreatitis. Extension of the pancreatic inflammatory reaction into one or more peripancreatic areas with the simultaneous finding of pancreatic or extrapancreatic fluid collection or both was associated with a high frequency of pancreatic complications requiring surgical intervention and death. We believe that the severity of pancreatitis as shown by initial computerized tomographic scan is a more accurate predictor of clinical outcome than Ranson's criteria.