Citations

Abstract The frequent von Willebrand factor (VWF) variant p.Phe2561Tyr is located within the C4 domain, which also harbors the platelet GPIIb/IIIa-binding RGD sequence. To investigate its potential effect on hemostasis, we genotyped 865 patients with coronary artery disease (CAD), 915 with myocardial infarction (MI), and 417 control patients (Ludwigshafen Risk and Cardiovascular Health Study) and performed functional studies of this variant. A univariate analysis of male and female carriers of the Tyr2561 allele aged 55 years or younger revealed an elevated risk for repeated MI (odds ratio, 2.53; 95% confidence interval [CI], 1.07-5.98). The odds ratio was even higher in females aged 55 years or younger, at a value of 5.93 (95% CI, 1.12-31.24). Cone and plate aggregometry showed that compared with Phe2561, Tyr2561 was associated with increased platelet aggregate size both in probands’ blood and with the recombinant variants. Microfluidic assays revealed that the critical shear rate for inducing aggregate formation was decreased to 50% by Tyr2561 compared with Phe2561. Differences in C-domain circular dichroism spectra resulting from Tyr2561 suggest an increased shear sensitivity of VWF as a result of altered association of the C domains that disrupts the normal dimer interface. In summary, our data emphasize the functional effect of the VWF C4 domain for VWF-mediated platelet aggregation in a shear-dependent manner and provide the first evidence that a functional variant of VWF plays a role in arterial thromboembolism.

Hillebrandt, David, Anil Gurtoo, Thomas Kupper, Paul Richards, Volker Schöffl, Pankaj Shah, Rianne van der Spek, Nikki Wallis, and Jim Milledge. UIAA Medical Commission recommendations for mountaineers, hillwalkers, trekkers, and rock and ice climbers with diabetes. High Alt Med Biol . 24: 110–126.—The object of this advice article is not only to give the diabetic mountaineer general guidance but also to inform his or her medical team of practical aspects of care that may not be standard for nonmountaineers. The guidelines are produced in seven sections. The first is an introduction to the guidelines, and the second is an introduction to this medical problem and is designed to be read and understood by diabetic patients and their companions. The third section is for use in an emergency in mountains. The fourth is for rock, ice, and competition climbers operating in a less remote environment. These initial sections are deliberately written in simple language. The fifth and sixth sections are written for clinicians and those with skills to read more technical information, and the seventh looks at modern technology and its pros and cons in diabetes management in a remote area. Sections One and Two could be laminated and carried when in the mountains, giving practical advice.

Abstract Objectives Working Group 2 was convened to address topics relevant to prosthodontics and dental implants. Systematic reviews were developed according to focused questions addressing (a) the number of implants required to support fixed full‐arch restorations, (b) the influence of intentionally tilted implants compared to axial positioned implants when supporting fixed dental prostheses ( FDP s), (c) implant placement and loading protocols, (d) zirconia dental implants, (e) zirconia and metal ceramic implant supported single crowns and (f) zirconia and metal ceramic implant supported FDP s. Materials and methods Group 2 considered and discussed information gathered in six systematic reviews. Group participants discussed statements developed by the authors and developed consensus. The group developed and found consensus for clinical recommendations based on both the statements and the experience of the group. The consensus statements and clinical recommendations were presented to the plenary (gathering of all conference attendees) and discussed. Final versions were developed after consensus was reached. Results A total of 27 consensus statements were developed from the systematic reviews. Additionally, the group developed 24 clinical recommendations based on the combined expertise of the participants and the developed consensus statements. Conclusions The literature supports the use of various implant numbers to support full‐arch fixed prostheses. The use of intentionally tilted dental implants is indicated when appropriate conditions exist. Implant placement and loading protocols should be considered together when planning and treating patients. One‐piece zirconia dental implants can be recommended when appropriate clinical conditions exist although two‐piece zirconia implants should be used with caution as a result of insufficient data. Clinical performance of zirconia and metal ceramic single implant supported crowns is similar and each demonstrates significant, though different, complications. Zirconia ceramic FDP s are less reliable than metal ceramic. Implant supported monolithic zirconia prostheses may be a future option with more supporting evidence.

Background: There is controversy regarding the effectiveness of brachial plexus reconstruction for elbow function in older patients, as reported outcomes are generally poor. The purpose of this study was to evaluate elbow function outcomes in patients older than 50. Methods: Fifty-eight patients older than 50 years underwent nerve grafting, transfers, or free functioning muscle transfer to improve elbow function after traumatic brachial plexus injury. Patients were evaluated preoperatively and postoperatively for elbow flexion strength and range of motion; Disabilities of the Arm, Shoulder and Hand scores; pain; concomitant trauma; severity of trauma; and type of reconstruction. Results: The average age of the patients was 57.8 years, and the average follow-up was 24.0 months. The average modified British Medical Research Council elbow flexion grade improved significantly from 0.26 to 2.63. Thirty-three patients (60 percent) achieved functional flexion greater than or equal to M3 postoperatively, compared to zero patients preoperatively. There was no correlation between age and modified British Medical Research Council grade. Active elbow range of motion improved significantly postoperatively, with no effect of age on flexion motion. More patients achieved greater than or equal to M3 flexion with nerve transfers (69 percent) compared to free functioning muscle transfer (43 percent). Patients had worse outcomes with high-energy injuries. The mean Disabilities of the Arm, Shoulder and Hand score decreased from 51.5 to 49.6 postoperatively, and the average pain score decreased from 5.0 to 4.3. Conclusion: Brachial plexus reconstruction for elbow function in patients older than 50 can yield useful flexion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Background The utility of early postoperative ultrasound measurements in predicting arteriovenous fistula (AVF) clinical maturation is uncertain. Methods We investigated the relationships of ultrasound parameters with AVF clinical maturation in newly created AVF, measured at 1 day and 2 and 6 weeks, in 602 participants of a multicenter, observational cohort study. A backward elimination algorithm identified ultrasound measurements that independently predicted unassisted and overall AVF maturation. Candidate variables included AVF blood flow, diameter, and depth, upper arm arterial diameter, presence of stenosis, presence of accessory veins, seven case-mix factors (age, sex, black race, AVF location, diabetes, dialysis status, and body mass index), and clinical center. We evaluated the accuracy of the resulting models for clinical prediction. Results At each ultrasound measurement time, AVF blood flow, diameter, and depth each predicted in a statistically significant manner both unassisted and overall clinical maturation. Moreover, neither the remaining ultrasound parameters nor case-mix factors were associated with clinical AVF maturation after accounting for blood flow, diameter, and depth, although maturation probabilities differed among clinical centers before and after accounting for these parameters. The crossvalidated area under the receiver operating characteristic curve for models constructed using these three ultrasound parameters was 0.69, 0.74, and 0.79 at 1 day and 2 and 6 weeks, respectively, for unassisted AVF clinical maturation and 0.69, 0.71, and 0.76, respectively, for overall AVF maturation. Conclusions AVF blood flow, diameter, and depth moderately predicted unassisted and overall AVF clinical maturation. The other factors considered did not further improve AVF maturation prediction.

Background: Establishing continuity of the cutaneous roll is critical to cleft lip repair. Unfortunately, this landmark can be difficult to appreciate depending on the patient’s skin tone, surgical lighting, or preexisting scar. Solution: When applied to the lip, dilute povidone-iodine solution beads off the cutaneous roll and dry vermilion, clearly defining these structures. What We Do: We use dilute povidone-iodine solution not only to prep the lip but to delineate landmarks critical to cleft lip repair.

Summary Background Irritable bowel syndrome ( IBS ) is a chronic functional bowel disorder. Disturbances in the gastrointestinal microbiome may be involved in its aetiology. Aim To perform a systematic review and meta‐analysis to examine the efficacy of prebiotics, probiotics, synbiotics and antibiotics in IBS . Methods MEDLINE , EMBASE , and the Cochrane Controlled Trials Register were searched (up to July 2017). Randomised controlled trials ( RCT s) recruiting adults with IBS , comparing prebiotics, probiotics, synbiotics or antibiotics with placebo or no therapy were eligible. Dichotomous symptom data were pooled to obtain a relative risk ( RR ) of remaining symptomatic after therapy, with a 95% confidence interval ( CI ). Continuous data were pooled using a standardised mean difference with a 95% CI . Results The search identified 4017 citations. Data for prebiotics and synbiotics were sparse. Fifty‐three RCT s of probiotics, involving 5545 patients, were eligible. Particular combinations of probiotics, or specific species and strains, appeared to have beneficial effects on global IBS symptoms and abdominal pain, but it was not possible to draw definitive conclusions about their efficacy. There were five trials of similar design that used rifaximin in non‐constipated IBS patients, which was more effective than placebo ( RR of symptoms persisting = 0.84; 95% CI 0.79‐0.90). Adverse events were no more common with probiotics or antibiotics. Conclusions Which particular combination, species or strains of probiotics are effective for IBS remains, for the most part, unclear. Rifaximin has modest efficacy in improving symptoms in non‐constipated IBS .

Arthroscopic dorsal wrist ganglionectomy is demonstrably a safe procedure with recurrence rates comparable to open surgery. We present a patient with wrist pain following arthroscopic ganglion excision. MRI and arthroscopic findings showed a large dorsal capsular defect, synovial fistula to the fourth extensor compartment, and dorsal radiocarpal ligament resection. Ligament reconstruction and capsular imbrication resolved her symptoms. We postulate that this complication resulted from a large capsular resection. Because we feel that it can be difficult to judge the size of the debridement through an arthroscope, the need for adequate capsular resection in dorsal wrist ganglionectomy needs to be balanced by consideration of potential complications from more aggressive capsular debridement, and thus we feel that capsular resection should be limited to no more than 1 cm2.