Perioperative Management of Traditional and Direct Oral Anticoagulants in Hip Fracture Patients.

Hip fractures are an increasingly common injury in the senior population and almost always require surgical fixation or prosthetic replacement. These surgeries, according to the American Academy of Orthopaedic Surgeons, are considered high-risk for bleeding, especially in a population fraught with comorbidities and often presenting on anticoagulation medications. Direct oral anticoagulants represent a class of drugs that have been becoming more popular in use in this population, with many benefits over the historically used Warfarin. There are recommendations for preoperative discontinuation and postoperative resumption of these medications, which can be more readily managed for elective surgeries. However, there is a paucity of literature detailing best practice guidelines for the perioperative management of direct oral anticoagulants when a patient presents with a hip fracture. This review article summary of the periprocedural management of DOACs for hip surgery was developed by examining the American College of Chest Physicians evidence-based clinical practice guidelines, Perioperative Guidelines on Antiplatelet and Anticoagulant Agents written by anesthesiologists, various retrospective studies, and drug labels for pharmacokinetic data. These recommendations should be used as a guideline, along with the collaboration of multidisciplinary hospital teams during inpatient admission, to manage these complex patients.

What are patients asking and reading online? An analysis of online patient searches for rotator cuff repair.

BACKGROUND: Patients undergoing rotator cuff surgery often search the internet for information regarding the procedure. One popular source, Google, compiles frequently asked questions and links to websites that may provide answers. This study provides an analysis of the most frequently searched questions associated with rotator cuff surgery. We hypothesize that there will be distinct search patterns associated with online queries about rotator cuff surgery that could provide unique insights into patient concerns. METHODS: A set of search terms were entered into Google Web Search using a clean-install Google Chrome browser. Frequently associated questions and their webpages were extracted to a database via a data mining extension. Questions were categorized by topics relevant for rotator cuff arthroscopy. Websites were categorized by source and scored for quality using the JAMA Benchmark Criteria. Pearson's χ2 tests were used to analyze nominal data. Student t tests were performed to compare JAMA Benchmark Scores. RESULTS: Of the 595 questions generated from the initial search, 372 unique questions associated with 293 websites were extracted and categorized. The most popular question topics were activities/restrictions (20.7%), pain (18.8%), and indications/management (13.2%). The 2 most common websites searched were academic (35.2%) and medical practice (27.4%). Commercial websites were significantly more likely to be associated with questions about cost (57.1% of all cost questions, P = .01), anatomy/function (62.5%, P = .001), and evaluation of surgery (47.6%, P < .001). Academic websites were more likely to be associated with questions about technical details of surgery (58.1%, P < .001). Medical practice and social media websites were more likely associated with activities/restrictions (48.1%, P < .001, and 15.6%, P < .001, respectively). Government websites were more likely associated with timeline of recovery (12.8%, P = .01). On a scale of 0-4, commercial and academic websites had the highest JAMA scores (3.06 and 2.39, respectively). CONCLUSION: Patients seeking information regarding rotator cuff repair primarily use the Google search engine to ask questions regarding postoperative activity and restrictions, followed by pain, indications, and management. Academic websites, which were associated with technical details of surgery, and medical practice websites, which were associated with activities/restrictions, were the 2 most commonly searched resources. These results emphasize the need for orthopedic surgeons to provide detailed and informative instructions to patients undergoing rotator cuff repair, especially in the postoperative setting.

Bromocriptine-QR Therapy Reduces Sympathetic Tone and Ameliorates a Pro-Oxidative/Pro-Inflammatory Phenotype in Peripheral Blood Mononuclear Cells and Plasma of Type 2 Diabetes Subjects.

Bromocriptine-QR is a sympatholytic dopamine D2 agonist for the treatment of type 2 diabetes that has demonstrated rapid (within 1 year) substantial reductions in adverse cardiovascular events in this population by as yet incompletely delineated mechanisms. However, a chronic state of elevated sympathetic nervous system activity and central hypodopaminergic function has been demonstrated to potentiate an immune system pro-oxidative/pro-inflammatory condition and this immune phenotype is known to contribute significantly to the advancement of cardiovascular disease (CVD). Therefore, the possibility exists that bromocriptine-QR therapy may reduce adverse cardiovascular events in type 2 diabetes subjects via attenuation of this underlying chronic pro-oxidative/pro-inflammatory state. The present study was undertaken to assess the impact of bromocriptine-QR on a wide range of immune pro-oxidative/pro-inflammatory biochemical pathways and genes known to be operative in the genesis and progression of CVD. Inflammatory peripheral blood mononuclear cell biology is both a significant contributor to cardiovascular disease and also a marker of the body's systemic pro-inflammatory status. Therefore, this study investigated the effects of 4-month circadian-timed (within 2 h of waking in the morning) bromocriptine-QR therapy (3.2 mg/day) in type 2 diabetes subjects whose glycemia was not optimally controlled on the glucagon-like peptide 1 receptor agonist on (i) gene expression status (via qPCR) of a wide array of mononuclear cell pro-oxidative/pro-inflammatory genes known to participate in the genesis and progression of CVD (OXR1, NRF2, NQO1, SOD1, SOD2, CAT, GSR, GPX1, GPX4, GCH1, HMOX1, BiP, EIF2α, ATF4, PERK, XBP1, ATF6, CHOP, GSK3ß, NFkB, TXNIP, PIN1, BECN1, TLR2, TLR4, TLR10, MAPK8, NLRP3, CCR2, GCR, L-selectin, VCAM1, ICAM1) and (ii) humoral measures of sympathetic tone (norepinephrine and normetanephrine), whole-body oxidative stress (nitrotyrosine, TBARS), and pro-inflammatory factors (IL-1ß, IL-6, IL-18, MCP-1, prolactin, C-reactive protein [CRP]). Relative to pre-treatment status, 4 months of bromocriptine-QR therapy resulted in significant reductions of mRNA levels in PBMC endoplasmic reticulum stress-unfolded protein response effectors [GRP78/BiP (34%), EIF2α (32%), ATF4 (29%), XBP1 (25%), PIN1 (14%), BECN1 (23%)], oxidative stress response proteins [OXR1 (31%), NRF2 (32%), NQO1 (39%), SOD1 (52%), CAT (26%), GPX1 (33%), GPX4 (31%), GCH1 (30%), HMOX1 (40%)], mRNA levels of TLR pro-inflammatory pathway proteins [TLR2 (46%), TLR4 (20%), GSK3ß (19%), NFkB (33%), TXNIP (18%), NLRP3 (32%), CCR2 (24%), GCR (28%)], mRNA levels of pro-inflammatory cellular receptor proteins CCR2 and GCR by 24% and 28%, and adhesion molecule proteins L-selectin (35%) and VCAM1 (24%). Relative to baseline, bromocriptine-QR therapy also significantly reduced plasma levels of norepinephrine and normetanephrine by 33% and 22%, respectively, plasma pro-oxidative markers nitrotyrosine and TBARS by 13% and 10%, respectively, and pro-inflammatory factors IL-18, MCP1, IL-1ß, prolactin, and CRP by 21%,13%, 12%, 42%, and 45%, respectively. These findings suggest a unique role for circadian-timed bromocriptine-QR sympatholytic dopamine agonist therapy in reducing systemic low-grade sterile inflammation to thereby reduce cardiovascular disease risk.

Experimental dopaminergic neuron lesion at the area of the biological clock pacemaker, suprachiasmatic nuclei (SCN) induces metabolic syndrome in rats.

BACKGROUND: The daily peak in dopaminergic neuronal activity at the area of the biological clock (hypothalamic suprachiasmatic nuclei [SCN]) is diminished in obese/insulin resistant vs lean/insulin sensitive animals. The impact of targeted lesioning of dopamine (DA) neurons specifically at the area surrounding (and that communicate with) the SCN (but not within the SCN itself) upon glucose metabolism, adipose and liver lipid gene expression, and cardiovascular biology in normal laboratory animals has not been investigated and was the focus of this study. METHODS: Female Sprague-Dawley rats received either DA neuron neurotoxic lesion by bilateral intra-cannula injection of 6-hydroxydopamine (2-4 µg/side) or vehicle treatment at the area surrounding the SCN at 20 min post protriptyline ip injection (20 mg/kg) to protect against damage to noradrenergic and serotonergic neurons. RESULTS: At 16 weeks post-lesion relative to vehicle treatment, peri-SCN area DA neuron lesioning increased weight gain (34.8%, P < 0.005), parametrial and retroperitoneal fat weight (45% and 90% respectively, P < 0.05), fasting plasma insulin, leptin and norepinephrine levels (180%, 71%, and 40% respectively, P < 0.05), glucose tolerance test area under the curve (AUC) insulin (112.5%, P < 0.05), and insulin resistance (44%-Matsuda Index, P < 0.05) without altering food consumption during the test period. Such lesion also induced the expression of several lipid synthesis genes in adipose and liver and the adipose lipolytic gene, hormone sensitive lipase in adipose (P < 0.05 for all). Liver monocyte chemoattractant protein 1 (a proinflammatory protein associated with metabolic syndrome) gene expression was also significantly elevated in peri-SCN area dopaminergic lesioned rats. Peri-SCN area dopaminergic neuron lesioned rats were also hypertensive (systolic BP rose from 157 ± 5 to 175 ± 5 mmHg, P < 0.01; diastolic BP rose from 109 ± 4 to 120 ± 3 mmHg, P < 0.05 and heart rate increase from 368 ± 12 to 406 ± 12 BPM, P < 0.05) and had elevated plasma norepinephrine levels (40% increased, P < 0.05) relative to controls. CONCLUSIONS: These findings indicate that reduced dopaminergic neuronal activity in neurons at the area of and communicating with the SCN contributes significantly to increased sympathetic tone and the development of metabolic syndrome, without effect on feeding.

Career Longevity and Performance After Shoulder Instability in National Football League Athletes.

PURPOSE: To investigate the career longevity, game utilization, and performance of National Football League (NFL) athletes after glenohumeral instability events treated operatively versus nonoperatively. METHODS: Using public resources, we identified NFL players who sustained a shoulder instability event from September 2000 to February 2019. Players with prior shoulder instability, without NFL experience before injury, or who did not return to play (RTP) after injury were excluded. Demographic information, utilization (games and seasons), and season approximate value (SAV) statistics were recorded 1 year prior to injury and 3 years after RTP. Statistical analysis compared utilization and the SAV after RTP for athletes managed operatively versus nonoperatively. RESULTS: We identified 97 NFL players who sustained their first instability event while playing in the NFL, 91 of whom returned to play (93.8%). Quarterbacks were significantly more likely to undergo immediate surgical management compared with players in other positions (P = .023). The final analysis included 58 players managed operatively and 33 managed nonoperatively by the end of the index season. Players treated operatively played in significantly more seasons after RTP during their remaining careers (4.1 ± 2.7 seasons vs 2.8 ± 2.5 seasons, P = .015). There were no differences in games played or started, offensive or defensive snap count percentage, or performance (SAV) before and after injury when compared between cohorts (P > .05). After surgical stabilization, time to RTP (36.62 ± 10.32 weeks vs 5.43 ± 12.33 weeks, P < .05) and time interval before recurrent instability (105.7 ± 100.1 weeks vs 24.7 ± 40.6 weeks, P < .001) were significantly longer than with nonoperative treatment. Additionally, the operative cohort experienced less recurrent instability (27% vs 50%, P = .035). CONCLUSIONS: Athletes who RTP in the NFL after a shoulder instability injury do so with a similar workload and performance irrespective of surgical or nonsurgical management. Whereas nonoperative treatment is associated with faster RTP, operative management is associated with fewer recurrent instability events, greater time between recurrent instability events, and greater career longevity. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Bromocriptine mesylate improves glucose tolerance and disposal in a high-fat-fed canine model.

Bromocriptine mesylate treatment was examined in dogs fed a high fat diet (HFD) for 8 wk. After 4 wk on HFD, daily bromocriptine (Bromo; n = 6) or vehicle (CTR; n = 5) injections were administered. Oral glucose tolerance tests were performed before beginning HFD (OGTT1), 4 wk after HFD began (Bromo only), and after 7.5 wk on HFD (OGTT3). After 8 wk on HFD, clamp studies were performed, with infusion of somatostatin and intraportal replacement of insulin (4× basal) and glucagon (basal). From 0 to 90 min (P1), glucose was infused via peripheral vein to double the hepatic glucose load; and from 90 to 180 min (P2), glucose was infused via the hepatic portal vein at 4 mg·kg-1·min-1, with the HGL maintained at 2× basal. Bromo decreased the OGTT glucose ΔAUC0-30 and ΔAUC0-120 by 62 and 27%, respectively, P < 0.05 for both) without significantly altering the insulin response. Bromo dogs exhibited enhanced net hepatic glucose uptake (NHGU) compared with CTR (~33 and 21% greater, P1 and P2, respectively, P < 0.05). Nonhepatic glucose uptake (non-HGU) was increased ~38% in Bromo in P2 (P < 0.05). Bromo vs. CTR had higher (P < 0.05) rates of glucose infusion (36 and 30%) and non-HGU (~40 and 27%) than CTR during P1 and P2, respectively. In Bromo vs. CTR, hepatic 18:0/16:0 and 16:1/16:0 ratios tended to be elevated in triglycerides and were higher (P < 0.05) in phospholipids, consistent with a beneficial effect of bromocriptine on liver fat accumulation. Thus, bromocriptine treatment improved glucose disposal in a glucose-intolerant model, enhancing both NHGU and non-HGU.