Citations

A woman with no significant personal or family history of thrombosis asked her internist to obtain a thrombophilia work-up prior to starting the combined oral contraceptive for dysmenorrhoea, after another physician advised her to have the test. The case was sent to an international email discussion group where the consensus was that testing should not be done. The responses of the group and review of this controversial topic are presented.

Anaerobic gram-positive bacilli can occasionally be implicated in infections but are difficult to identify in culture by conventional biochemical methods. We report a case of liver abscesses caused byEggerthella lenta, identified via 16S rRNA sequencing in a previously healthy patient, successfully treated with percutaneous drainage and ertapenem.

Background— Mitral regurgitation (MR) of mitral valve prolapse predominates in late systole but may be holosystolic or purely mid-late systolic, but the impact of MR timing on MR left ventricular and left atrial consequences and outcome is unknown. Whether effective regurgitant orifice (ERO) by the flow convergence method is similarly linked to outcome in mid-late systolic MR and holosystolic MR is uncertain. Methods and Results— We comprehensively and prospectively quantified MR in 111 patients with mitral valve prolapse and mid-late systolic MR and matched them to 90 patients with mitral valve prolapse and holosystolic MR for age, gender, atrial fibrillation, ejection fraction, and ERO (flow convergence). Mid-late systolic MR versus holosystolic MR groups were well matched, including for comorbidity, blood pressure, and heart rate (all P >0.10). Mid-late systolic MR versus holosystolic MR caused similar color jet area, midsystolic regurgitant flow, and peak velocity ( P >0.40). Despite identical ERO (0.25±0.15 versus 0.25±0.15 cm 2 ; P =0.53), the shorter duration of mid-late systolic MR (233±56 versus 426±50 ms; P <0.0001) yielded lower regurgitant volume (24.8±13.4 versus 48.6±25.6 mL; P <0.0001). MR consequences, systolic pulmonary pressure, and left ventricular and left atrial volume index (all P <0.001) were more benign in mid-late systolic MR versus holosystolic MR. Under medical management, fewer cardiac events (5 years: 15.8±4.6% versus 40.4±6.1%; P <0.0001) occurred in mid-late systolic MR versus holosystolic MR, requiring less mitral surgery. Multivariable analysis confirmed the independent association of mid-late systolic MR with benign consequences and outcomes (all P <0.01). Absolute ERO was not linked to outcome, in contrast to regurgitant volume. Conclusions— MR of mitral valve prolapse that is purely mid-late systolic causes more benign consequences and outcomes than holosystolic MR. Assessment may be misleading because jet area and ERO by flow convergence appear similar to those of holosystolic MR. However, shorter MR yields lower regurgitant volume, consequences, and benign outcomes. Instantaneous ERO by flow convergence should be interpreted in context, and in mid-late systolic MR, regurgitant volume provides information more reflective of MR severity. Therefore, for clinical management and surgical referral, clinicians should carefully take into account the timing and consequences of MR.

Objective— Transition from obesity to metabolic-syndrome (MetS) promotes cardiovascular diseases, but the underlying cardiac pathophysiological mechanisms are incompletely understood. We tested the hypothesis that development of insulin resistance and MetS is associated with impaired myocardial cellular turnover. Methods and Results— MetS-prone Ossabaw pigs were randomized to 10 weeks of standard chow (lean) or to 10 (obese) or 14 (MetS) weeks of atherogenic diet (n=6 each). Cardiac structure, function, and myocardial oxygenation were assessed by multidetector computed-tomography and Blood Oxygen Level-Dependent–MRI, the microcirculation with microcomputed-tomography, and injury mechanisms by immunoblotting and histology. Both obese and MetS showed obesity and dyslipidemia, whereas only MetS showed insulin resistance. Cardiac output and myocardial perfusion increased only in MetS, yet Blood Oxygen Level-Dependent–MRI showed hypoxia. Inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis also increased in both obese and MetS, but more pronouncedly in MetS. Furthermore, autophagy in MetS was decreased and accompanied by marked apoptosis. Conclusion— Development of insulin resistance characterizing a transition from obesity to MetS is associated with progressive changes of myocardial autophagy, apoptosis, inflammation, mitochondrial dysfunction, and fibrosis. Restoring myocardial cellular turnover may represent a novel therapeutic target for preserving myocardial structure and function in obesity and MetS.

SummaryBackgroundIt remains unclear whether a long‐acting preparation of octreotide (Sandostatin LAR) can be safely used for portal hypertension in patients with compensated cirrhosis.AimTo determine the safety and efficacy of LAR among patients with Child Pugh Class A or B cirrhosis and small oesophageal varices.MethodsA randomised, double‐blind, placebo‐controlled study was conducted in 39 patients with cirrhosis and small oesophageal varices. Safety was based on frequency and severity of adverse events. Efficacy was determined by hepatic vein pressure gradient (HVPG) measured at baseline and day 84 following administration of LAR 10 mg (n = 15), 30 mg (n = 10) or saline (n = 14). Fasting and postprandial portal blood flow (PBF), superior mesenteric artery pulsatility index (SMA‐PI), glucagon and octreotide levels were measured. An intention‐to‐treat analysis was performed.ResultsFour patients in the LAR 30 group (40%) withdrew from the study due to serious adverse events. No patient in the LAR 10 or control group had serious adverse events. There was no statistically significant decrease between HVPG at day 84 and baseline with LAR 30 mg (11.8 ± 2.3 mmHg vs. 14.1 ± 3.2), LAR 10 mg (15.3 ± 4.8 mmHg vs. 15.1 ± 3.8), or saline (13.3 ± 3.8 mmHg vs. 15.1 ± 4.3) (P = 0.26). Neither PBF, SMA‐PI nor plasma glucagon levels were significantly decreased from baseline (P = 0.56).ConclusionsThe absence of significant haemodynamic benefit, as well as the high frequency of severe adverse events associated with use of LAR, do not support the use of this agent in the treatment of portal hypertension.

AbstractBackgroundMany serologic and radiographic modalities are used for monitoring multiple endocrine neoplasia type 1 (MEN 1) patients for pancreaticoduodenal neuroendocrine tumors (PNETs). We compared serum markers and imaging studies obtained preoperatively with the gross pathology and immunohistochemical findings and correlated preoperative testing with postoperative outcome.MethodsFrom 2000 to 2008, 52 MEN 1 patients [32 (62%) female; median age = 43 years, range 19–74 years] underwent 56 pancreatic operations [49 (88%) distal pancreatectomies] for suspected PNETs. Preoperative serum markers [human pancreatic polypeptide (HPP), gastrin, and glucagon] and imaging [CT, 111In pentetreotide scintigraphy, and endoscopic ultrasound (EUS)] were compared to the pathologic findings. Postoperative serum markers and survival were followed.ResultsHuman pancreatic polypeptide had the highest agreement between an elevated serum level and positive tumor immunostaining (83% vs. 50% agreement for gastrin vs. 67% agreement for glucagon). Preoperative CT had 81% sensitivity and positive predictive value (PPV) of 97% for PNETs. 111In pentetreotide scintigraphy had 84% sensitivity and PPV of 96%. Preoperative endoscopic ultrasonography (EUS) had 100% sensitivity and PPV, with close correlation (rs = 0.93) between the largest lesion seen on EUS and pathology. Median follow‐up was 4.3 years (range = 0.1–10.9 years). Overall survival was 89% at 5‐year follow‐up.ConclusionsOur study substantiates EUS as providing the highest preoperative sensitivity and PPV in assessing the presence of PNETs in MEN 1 patients. CT and octreotide scintigraphy can yield both false‐positive and false‐negative results. HPP, gastrin, and glucagon were the most commonly measured tumor markers in our series but did not always correlate with immunostaining. With an aggressive surgical approach, satisfactory rates of biochemical improvement and long‐term survival were observed.