Arousal from sleep in response to CO is a critical protective phenomenon. Dysregulation of CO-induced arousal contributes to morbidity and mortality from prevalent diseases, such as obstructive sleep apnea and sudden infant death syndrome. Despite the critical nature of this protective reflex, the precise mechanism for CO-induced arousal is unknown. Because CO is a major regulator of breathing, prevailing theories suggest that activation of respiratory chemo- and mechano-sensors is required for CO-induced arousal. However, populations of neurons that are not involved in the regulation of breathing are also chemosensitive. Among these are serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) that comprise a component of the ascending arousal system. We hypothesized that direct stimulation of these neurons with CO could cause arousal from sleep independently of enhancing breathing. Dialysis of CO-rich acidified solution into DRN, but not medullary raphe responsible for modulating breathing, caused arousal from sleep. Arousal was lost in mice with a genetic absence of 5-HT neurons, and with acute pharmacological or optogenetic inactivation of DRN 5-HT neurons. Here we demonstrate that CO can cause arousal from sleep directly, without requiring enhancement of breathing, and that chemosensitive 5-HT neurons in the DRN critically mediate this arousal. Better understanding mechanisms underlying this protective reflex may lead to interventions to reduce disease-associated morbidity and mortality. Although CO-induced arousal is critical to a number of diseases, the specific mechanism is not well understood. We previously demonstrated that serotonin (5-HT) neurons are important for CO-induced arousal, as mice without 5-HT neurons do not arouse to CO Many have interpreted this to mean that medullary 5-HT neurons that regulate breathing are important in this arousal mechanism. Here we found that direct application of CO-rich aCSF to the dorsal raphe nucleus, but not the medullary raphe, causes arousal from sleep, and that this arousal was lost with genetic ablation or acute inhibition of 5-HT neurons. We propose that 5-HT neurons in the dorsal raphe nucleus can be activated directly by CO to cause arousal independently of respiratory activation.

PurposeAcute administration of remifentanil may lead to opioid-induced hyperalgesia (OIH). Studies in mice suggest that OIH is mediated by impaired anionic homeostasis in spinal lamina I neurons due to a down-regulation of the K+-Cl− co-transporter KCC2, which was reverted using acetazolamide (ACTZ), a carbonic anhydrase inhibitor. We propose that ACTZ prevents remifentanil-mediated OIH in humans.Patients and methodsWe conducted a randomized, double-blind, placebo-controlled clinical trial between December 2016 and September 2018. Patients were randomly allocated to receive ACTZ (250 mg of ACTZ 2 h before surgery) or placebo. To detect hyperalgesia, mechanical pain threshold (MPT) were measured before and after surgery using hand-held von Frey filaments in the forearm. Anesthesia was maintained with remifentanil at a target effect site of 4.5 ± 0.5 ng/mL, and sevoflurane at an end-tidal concentration of 0.8 MAC corrected for age.ResultsIn total, 47 patients completed the study. Both groups were comparable in the baseline characteristics and intraoperative variables. Baseline MPT were similar in both groups. However, MPT in the forearm significantly diminished in the time in both groups. Finally, postoperative pain and morphine consumption were similar between groups.ConclusionBoth groups developed remifentanil-mediated OIH at 12–18 h after surgery. However, ACTZ did not prevent the MPT reduction in patients undergoing total thyroidectomy.

<p class="abstract">Polymorphous low-grade adenocarcinoma (PLGA) is an infrequent type of malignant epithelial tumor that occurs almost exclusively in minor salivary glands. It commonly presents in women between the sixth and eighth decade of life, usually as an asymptomatic mass of long evolution and slow growth in the oral cavity but can erode and infiltrate adjacent bone. We present 2 case reports and review the literature on the subject. One case presented with a growing mass that developed over the course of 12 years, incorrectly diagnosed in the first incisional biopsy as a benign tumor. The second case presented as a recurring PLGA 19 years after the first, which appeared at an unusually young age. Both cases were managed with the treatment of choice: surgery with wide excision margins. Although prophylactic neck dissection is not the rule, it was part of the postoperative treatment in both cases, along with life-long follow-ups to find recurrences at early stages. A high level of suspicion and knowledge regarding its presentation are essential for correct diagnosis and management.</p>

<p>Diffuse idiopathic skeletal hyperostosis (DISH) is a degenerative disorder of unknown etiology that most often occurs in male patients over 50. Dysphagia is its main symptom, but they can also have dyspnea, otalgia, cough, sore throat, foreign body sensation in the pharynx, sleep apnea and glottic alterations. We present a case report and review the literature about this entity. We report a case of an oral squamous cell carcinoma that received a commando surgery and tracheostomy tube. Decanulations attempts were unsuccessful initially due to DISH. Conservative management was successful and complete rehabilitation performed, achieving decannulation 18 months after surgery. DISH can be a source of many different symptoms that may appear or be exacerbated after any surgery, and produce a postoperative complication. Conservative management is usually the best treatment, leaving surgical interventions for severe symptomatic patients. The knowledge of this entity and a high level of suspicion are very important for a proper diagnosis and management.</p>