Tranexamic acid in endoscopic sinus and skull base surgery: A systematic review and meta-analysis.

OBJECTIVE: Endoscopic sinus surgery (ESS) and endoscopic skull base surgery (ESBS) approaches have revolutionized the management of sinonasal and intracranial pathology. Maintaining surgical hemostasis is essential as bleeding can obscure the visibility of the surgical field, thus increasing surgical duration, risk of complications, and procedural failure. Tranexamic acid (TXA) acts to reduce bleeding by inhibiting fibrin degradation. This review aims to assess whether TXA improves surgical field quality and reduces intraoperative blood loss compared with control. METHODS: We searched PubMed, MEDLINE, Embase, Web of Science, and Cochrane Library from inception until September 1, 2022. Two reviewers independently screened citations, extracted data, and assessed methodological quality using the Cochrane risk-of-bias tool for randomized trials. Data were pooled using a random-effect model, with continuous data presented as mean differences and dichotomous data presented as odds ratios. RESULTS: Seventeen ESS randomized controlled trials (n = 1377) and one ESBS randomized controlled trial (n = 50) were reviewed. Significant improvement in surgical field quality was achieved with both systemic TXA (six studies, p < 0.00001) and topical TXA (six studies, p = 0.01) compared with the control. Systemic TXA (eight studies) and topical TXA (three studies) both achieved a significant reduction in intraoperative blood loss compared with the control (p < 0.00001). There were significant differences in operative times (p < 0.001) but no significant difference in perioperative outcomes (p = 0.30). CONCLUSION: This meta-analysis demonstrated that the administration of TXA in ESS can improve surgical field quality and reduce intraoperative blood loss. TXA use did not result in increased perioperative complications including thrombotic events.

Routine tonsillar bed oversew after diathermy tonsillectomy: does it reduce secondary tonsillar haemorrhage?

Tonsillectomy is a common otolaryngological procedure and is associated with a small risk of postoperative pharyngeal haemorrhage. This study compares secondary post tonsillectomy haemorrhage rates between two operative techniques: diathermy tonsillectomy and diathermy tonsillectomy with tonsillar bed oversew. A total of 424 patients underwent tonsillectomies with or without other procedures such as adenoidectomy and grommet insertion by two ears, nose and throat surgeons at three hospitals from May 2012 to July 2013. A diathermy tonsillectomy was performed in 266 patients, while a diathermy tonsillectomy with tonsillar bed oversew was performed in 158 patients. All patients were followed up within 2-4 weeks of surgery. Primary haemorrhage did not occur in either surgical technique groups. Secondary haemorrhage occurred in 20 patients (7.52 %) in the diathermy tonsillectomy group and in 9 patients (5.70 %) in the diathermy with tonsillar bed oversew group. This result was not significantly different (OR = 0.74, 95 % CI 0.33-1.67, p = 0.47). Sex, age, indication for surgery and whether or not a tonsillectomy was performed alone or with other procedures were not significant factors for secondary haemorrhage. In summary, routine tonsillar bed oversew after diathermy tonsillectomy does not reduce the risk of secondary tonsillar haemorrhage.

Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors.

Despite the use of the sirolimus (rapamycin) drug-eluting coronary stent, diabetics are at increased risk of developing in-stent restenosis for unclear reasons. Hyperleptinemia, which often coexists with diabetes and metabolic syndrome, is an independent risk factor for progression of coronary artery disease. It has not been determined whether elevated circulating leptin decreases the efficacy of the sirolimus drug-eluting stent in inhibiting neointimal hyperplasia, the process underlying restenosis after stenting. Here we show that leptin activates the mammalian target of rapamycin (mTOR) signaling pathway in primary murine vascular smooth muscle cells (VSMC) and stimulates VSMC proliferation in a PI3K-dependent fashion. Exogenous leptin, administered at levels comparable to those found in obese humans, promotes neointimal VSMC hyperplasia in a murine femoral artery wire injury model. Leptin significantly increases the dose of the mTOR inhibitor sirolimus that is required for effective inhibition of neointimal formation. Combination therapy with LY294002, a PI3K inhibitor, and sirolimus effectively inhibits leptin-enhanced neointimal hyperplasia. These data show that, in the setting of hyperleptinemia, higher doses of an mTOR inhibitor, or combination therapy with mTOR and PI3K inhibitors, inhibits neointimal hyperplasia after arterial injury. These studies may explain the higher rates of restenosis observed in diabetics treated with a sirolimus-eluting coronary stent and suggest a potential novel therapeutic approach for inhibiting in-stent restenosis in such patients.

Central command regulation of circulatory function mediated by descending pontine cholinergic inputs to sympathoexcitatory rostral ventrolateral medulla neurons.

Central command is a feedforward neural mechanism that evokes parallel modifications of motor and cardiovascular function during arousal and exercise. The neural circuitry involved has not been elucidated. We have identified a cholinergic neural circuit that, when activated, mimics effects on tonic and reflex control of circulation similar to those evoked at the onset of and during exercise. Central muscarinic cholinergic receptor (mAChR) activation increased splanchnic sympathetic nerve activity (SNA) as well as the range and gain of the sympathetic baroreflex via activation of mAChR in the rostral ventrolateral medulla (RVLM) in anesthetized artificially ventilated Sprague-Dawley rats. RVLM mAChR activation also attenuated and inhibited the peripheral chemoreflex and somatosympathetic reflex, respectively. Cholinergic terminals made close appositions with a subpopulation of sympathoexcitatory RVLM neurons containing either preproenkephalin mRNA or tyrosine hydroxylase immunoreactivity. M2 and M3 receptor mRNA was present postsynaptically in only non-tyrosine hydroxylase neurons. Cholinergic inputs to the RVLM arise only from the pedunculopontine tegmental nucleus. Chemical activation of this region produced increases in muscle activity, SNA, and blood pressure and enhanced the SNA baroreflex; the latter effect was attenuated by mAChR blockade. These findings indicate a novel role for cholinergic input from the pedunculopontine tegmental nucleus to the RVLM in central cardiovascular command. This pathway is likely to be important during exercise where a centrally evoked facilitation of baroreflex control of the circulation is required to maintain blood flow to active muscle.

Characterization and expression of mammalian cyclin b3, a prepachytene meiotic cyclin.

We report the identification and expression pattern of a full-length human cDNA and a partial mouse cDNA encoding cyclin B3. Cyclin B3 (CCNB3) is conserved from Caenorhabditis elegans to Homo sapiens and has an undefined meiotic function in female, but not male Drosophila melanogaster. We show that H. sapiens cyclin B3 interacts with cdk2, is localized to the nucleus, and is degraded during anaphase entry after the degradation of cyclin B1. Degradation is dependent on sequences conserved in a destruction box motif. Overexpression of nondegradable cyclin B3 blocks the mitotic cell cycle in late anaphase, and at higher doses it can interfere with progression through G(1) and entry into S phase. H. sapiens cyclin B3 mRNA and protein are detected readily in developing germ cells in the human testis and not in any other tissue. The mouse cDNA has allowed us to further localize cyclin B3 mRNA to leptotene and zygotene spermatocytes. The expression pattern of mammalian cyclin B3 suggests that it may be important for events occurring in early meiotic prophase I.