Antibodies from Rabbits Immunized with HIV-1 Clade B SOSIP Trimers Can Neutralize Multiple Clade B Viruses by Destabilizing the Envelope Glycoprotein.

The high viral diversity of HIV-1 is a formidable hurdle for the development of an HIV-1 vaccine. Elicitation of broadly neutralizing antibodies (bNAbs) would offer a solution, but so far immunization strategies have failed to efficiently elicit bNAbs. To overcome these obstacles, it is important to understand the immune responses elicited by current HIV-1 envelope glycoprotein (Env) immunogens. To gain more insight, we characterized monoclonal antibodies (MAbs) isolated from rabbits immunized with Env SOSIP trimers based on the clade B isolate AMC008. Four rabbits that were immunized three times with AMC008 trimer developed robust autologous and sporadic low-titer heterologous neutralizing responses. Seventeen AMC008 trimer-reactive MAbs were isolated using antigen-specific single B-cell sorting. Four of these MAbs neutralized the autologous AMC008 virus and several other clade B viruses. When visualized by electron microscopy, the complex of the neutralizing MAbs with the AMC008 trimer showed binding to the gp41 subunit with unusual approach angles, and we observed that their neutralization ability depended on their capacity to induce Env trimer dissociation. Thus, AMC008 SOSIP trimer immunization induced clade B-neutralizing MAbs with unusual approach angles with neutralizing effects that involve trimer destabilization. Optimizing these responses might provide an avenue to the induction of trimer-dissociating bNAbs. IMPORTANCE Roughly 32 million people have died as a consequence of HIV-1 infection since the start of the epidemic, and 1.7 million people still get infected with HIV-1 annually. Therefore, a vaccine to prevent HIV-1 infection is urgently needed. Current HIV-1 immunogens are not able to elicit the broad immune responses needed to provide protection against the large variation of HIV-1 strains circulating globally. A better understanding of the humoral immune responses elicited by immunization with state-of-the-art HIV-1 immunogens should facilitate the design of improved HIV-1 vaccine candidates. We identified antibodies with the ability to neutralize multiple HIV-1 viruses by destabilization of the envelope glycoprotein. Their weak but consistent cross-neutralization ability indicates the potential of this epitope to elicit broad responses. The trimer-destabilizing effect of the neutralizing MAbs, combined with detailed characterization of the neutralization epitope, can be used to shape the next generation of HIV-1 immunogens to elicit improved humoral responses after vaccination.

Deltoid Ligament Injuries Associated With Ankle Fractures: Arguments For and Against Direct Repair.

Ankle fractures are an extremely common orthopaedic injury treated by surgeons on a routine basis. The deltoid ligament is torn in a large number of these fractures and is commonly seen with associated radiographic changes of medial clear space widening. The clinical relevance of addressing the injured deltoid ligament with acute surgical repair has been debated for decades. The early literature documenting repair or reconstruction of the deltoid ligament dates back to the 1950s. Most commonly, orthopaedic surgeons restore the lateral column directly with fibula fracture fixation. The injury may then be further evaluated intraoperatively by stress testing to ensure syndesmosis integrity and mortise stability with indirect medial column reduction, which allows for secondary healing of the medial deltoid ligamentous complex. This popular treatment paradigm is based primarily on literature from the 1980s and has not been thoroughly evaluated with modern surgical implants, techniques, and research methods. A review and background of the supportive literature for and against deltoid ligament repair in the setting of acute ankle fractures is presented. Undeniably, the deltoid ligament complex has been proven to confer some element of stability to maintaining a congruent ankle mortise. The commonly cited data in favor of not repairing the deltoid ligament warrants careful consideration to allow accuracy in obtaining the best patient outcomes with the most predictable surgical methods available.

Radiographic Outcomes, Union Rates, and Complications Associated With Plantar Implant Positioning for Midfoot Arthrodesis.

BACKGROUND: Midfoot arthrodesis has long been successfully included in the treatment paradigm for a variety of pathologic foot conditions. A concern with midfoot arthrodesis is the rate of nonunion, which historically has been reported between 5% and 10%. Plantar plating has also been noted to be more biomechanically stable when compared to traditional dorsal plating in previous studies. Practical advantages of plantar plating include less dorsal skin irritation and the ability to correct flatfoot deformity from the same medial incision. The purpose of this study is to report the arthrodesis rate, the success of deformity correction, and the complications associated with plantar-based implant placement for arthrodesis of the medial column. METHODS: A retrospective review was undertaken of all consecutive patients between 2012 and 2019 that underwent midfoot arthrodesis with plantar-positioned implants. Radiographic outcomes and complications are reported on 62 patients who underwent midfoot arthrodesis as part of a correction for hallux valgus deformity, flatfoot deformity, degenerative arthritis, Lisfranc injury, or Charcot neuroarthropathy correction. RESULTS: Statistically significant improvement was seen in the lateral talus-first metatarsal angle (Meary angle) and medial arch sag angle for patients treated for flatfoot deformity correction. In patients treated for hallux valgus deformity, there was a reduction in the intermetatarsal angle from 15.4 to 6.8 degrees. The overall nonunion rate was 6.45% in all patients. The rate of nonunion was higher at the NC joint compared to the TMT joint and with compression claw plates. One symptomatic nonunion required revision surgery (1.7%). There were no nonunions when excluding neuroarthropathy patients and smokers. The odds ratio (OR) for nonunion in patients with neuroarthropathy was 6.05 (P < .05), and in active smokers the OR was 2.33 (P < .05). CONCLUSION: Plates placed on the plantar bone surface for midfoot arthrodesis achieved and maintained deformity correction with rare instances of symptomatic hardware for a variety of orthopedic conditions. An overall clinical and radiographic union rate of 94% was achieved. The radiographic union rate improved to 100% when excluding both neuroarthropathy patients and smokers. The incidence of nonunion was higher in smokers, neuroarthropathy patients, naviculocuneiform joint fusions, use of compression claw plates, and when attempting to fuse multiple joints. Incisional healing complications were rarely seen other than in active smokers. LEVEL OF EVIDENCE: Level IV, case series.

Ventilation use in nonmedical settings during COVID-19: Cleaning protocol, maintenance, and recommendations.

Coronavirus disease 2019, otherwise referred to as COVID-19, started in China and quickly became a worldwide pandemic. Beginning in March 2020, nonessential businesses in the United States were closed, and many communities were under shelter-in-place orders. As of May 2020, some business sectors started reopening, even amidst concerns of worker health as the pandemic continued. In addition to physical distancing, cleaning and disinfection routines, and using face coverings, building ventilation can also be an important risk mitigation measure for controlling exposure to SARS-CoV-2 indoors. A number of studies to date, however, have focused on ventilation in medical facilities (e.g. hospitals) as the risk of transmission of SARS-CoV-2 is higher there (because of the close proximity of workers to patients who have the disease and their treatment procedures). Few studies have focused on ventilation use in nonmedical settings (e.g. office buildings and school classrooms), despite the large population of workers and community members in these facilities. In this article, we review the role that building ventilation can play in minimizing the risk of SARS-CoV-2 transmission in nonmedical environments and some recommended protocols to follow for its proper use, including cleaning and maintaining mechanical ventilation systems for businesses, schools, and homes.

Removal of Cadmium (II) using water hyacinth (Eichhornia crassipes) biochar alginate beads in aqueous solutions.

Biochar produced from water hyacinths (Eichhornia crassipes) has been demonstrated to be an effective adsorbent for the removal of certain heavy metals and as a means of control for this highly invasive species. This study involved examined the Cd2+ sorption dynamics of an alginate encapsulated water hyacinth biochar (BAC) generated at different temperatures and modified using ferric/ferrous sulfate (MBAC). The maximum Cd2+ sorption occurred at a pH of 6 and at a solution temperature of 37 °C. Sorption equilibria for the biochar-alginate capsule (BAC) and modified biochar-alginate capsule (MBAC) treatments fit both the Langmuir (R2 = 0.876 to 0.99) and Freundlich (R2 = 0.849 to 0.971) equations. Langmuir isotherms had a better fit than the Freundlich isotherms, with maximum sorption capacities ranging from 24.2 to 45.8 mg Cd2+ g-1. Larger KL values in Freundlich modeling suggest strong bonding of the BAC and MBAC sorbents to Cd2+, with values of KL in the MBAC treatments ranging between 31 and 178% greater than the BAC treatments. Cd2+ sorption followed pseudo first-order kinetics (R2 = 0.926 to 0.991) with greater efficiency of removal using treatments with biochar generated at temperatures >500 °C. Results from this study highlight the potential for biochar-alginate capsules derived from water hyacinth to be effective for the removal of Cd2+ from wastewaters.

Repeat posterior wall acetabular fracture-dislocation: High-energy trauma as a 'second hit phenomenon'.

Acetabular fractures are injuries that require significant force transmission, especially when associated with a femoral head dislocation. The mechanism of injury is typically in the setting of a high-speed motor vehicle collision. In a similar manner, this is an injury that is highly demanding for the orthopaedic trauma surgeon to treat as well. We present a patient who sustained an initial posterior wall acetabular fracture with an associated posterior dislocation. This was treated surgically with open reduction, internal fixation without complication. The patient subsequently sustained a second posterior wall acetabular fracture with dislocation fifteen years later through the plated and healed previous fracture. Both injuries were sustained in high-speed motor vehicle collisions, so it is difficult to presume the patient was predisposed for the repeat injury. At any rate, the repeat injury makes the surgical management significantly more challenging. In complicated acetabular fractures like these, a post or intra-operative CT scan can be of utility to determine quality of reduction as well as assessing for retained bony fragments. Our patient underwent a post-operative CT scan with the finding of intra-articular bony fragments that subsequently required arthroscopic removal. Given the rare nature of this complicated injury occurring twice in a patient, it is difficult to make evidence-based comments on long-term prognosis and functional outcomes. This unique case and the applied treatment will serve as a guide for future similar cases.

A Multimodal Approach to Pain Management for Patients with Chronic Back Pain: Outcome Measures at 1 Year.

PURPOSE OF REVIEW: The purpose of this study is to evaluate the effectiveness of a multimodal approach to treating chronic low back pain. RECENT FINDINGS: Chronic non-cancer-related back pain is often a frustrating and poorly managed problem for patients. It poses a significant public health issue worsened by the widespread use of narcotics. In 2016, the CDC released guidelines with noticeably more strict recommendations on prescription of narcotics for pain. Veterans at an interventional pain clinic presenting with chronic back pain refractory to medical and to surgical care were enrolled in an 8-week interdisciplinary pain management program. Pain scores were significantly reduced 1 year after completion of the program. Patients in this study benefitted from lower and sustained pain scores, a reduction in emergency room, and urgent care clinic visits, as well as generally high satisfaction with the interdisciplinary program.

Effects of naloxegol on whole gut transit in opioid-naïve healthy subjects receiving codeine: A randomized, controlled trial.

BACKGROUND: Nausea, vomiting, and constipation (OIC) are common adverse effects of acute or chronic opioid use. Naloxegol (25 mg) is an approved peripherally active mu-opiate opioid receptor antagonist. AIM: To compare the effects on pan-gut transit of treatment with codeine, naloxegol, or combination in healthy volunteers. METHODS: We conducted a randomized, double-blind, placebo-controlled, single-center, parallel-group study in 72 healthy opioid-naïve adults, randomized to: codeine (30 mg q.i.d.), naloxegol (25 mg daily), codeine and naloxegol, or matching placebo. During 3 days of treatment, we measured gastric emptying (GE) T1/2 , colonic filling at 6 hours (CF6), colonic geometric center at 24 and 48 hours, and ascending colon emptying (ACE) T1/2 . KEY RESULTS: Participants were 59.7% women, median BMI 25.0 kg/m2 , and median age 33.8 years. Codeine significantly retarded GE T1/2, CF6, overall colonic transit, and ACE T1/2 . There was significant difference (P = .026) in GE T1/2 between codeine (144.0 min [IQR 110.5-238.6]) and naloxegol (95.5 min [89.1-135.4]). There was a significant overall group difference in CF6 (P = .023), with significant difference (P = .019) between codeine (11.0% [0.0-45.0]) and naloxegol (51% [18.8-76.2]). However, no significant differences were found between codeine-treated participants concomitantly receiving placebo or naloxegol. CONCLUSIONS AND INFERENCES: Short-term administration of naloxegol (25 mg) in healthy, opioid-naïve volunteers does not reverse the retardation of gastric, small bowel, or colonic transit induced by acute administration of codeine. Further studies with naloxegol at higher dose are warranted to assess the ability to reverse the retardation of transit caused by acute administration of codeine in opioid-naïve subjects.

Performance characteristics of serum C4 and FGF19 measurements to exclude the diagnosis of bile acid diarrhoea in IBS-diarrhoea and functional diarrhoea.

BACKGROUND: The serum biomarkers, elevated 7αC4 (C4) and decreased FGF19, have been proposed as screening tests for bile acid diarrhoea. AIM: To analyse prevalence, specificity and reproducibility of fasting C4 and FGF19 in identifying bile acid diarrhoea in patients with irritable bowel syndrome with predominant diarrhoea or functional diarrhoea (summarised as IBS-D). METHODS: We prospectively studied fasting serum C4 and FGF19 in 101 IBS-D patients; we reviewed data from 37 of the 101 patients with prior fasting serum C4 and FGF19 and from 30 of the 101 patients with prior faecal bile acids per 48 hours. We compared results with normal values (C4 ≥52.5 ng/mL [n=184], FGF-19 ≤61.7 pg/mL [n=50]). We used Spearman correlation and Bland-Altman plots to appraise reproducibility. RESULTS: Among the 101 patients, there was a negative correlation between serum C4 and FGF19 (Rs=-.342, P=.0005). Bile acid diarrhoea was diagnosed in 10 patients based on elevated serum C4 levels (mean 23.5±23.1 [SD] ng/mL) and 21 patients based on decreased FGF19 levels (121.6±84.2 pg/mL). With replicate tests in patients with stable IBS-D, 78% of C4 and 70% of FGF19 measurements remained concordant, with 3% and 11% respectively consistently positive for bile acid diarrhoea in the 101 patients. Compared to 48 hours faecal bile acids, specificity for C4 and FGF19 was 83% and 78%, respectively. Bland-Altman plots demonstrated greater reliability of C4 than FGF19. CONCLUSIONS: Among 101 patents with IBS-D, fasting FGF19 and C4 levels had good specificity and negative predictive value, suggesting utility as screening tests to exclude bile acid diarrhoea.

Pharmacology of Antiemetics: Update and Current Considerations in Anesthesia Practice.

Postoperative nausea and vomiting (PONV) is associated with delayed recovery and dissatisfaction after surgical procedures. A key component to management is identifying risk factors and high-risk populations. Advances in pharmacologic therapeutics have resulted in agents targeting different pathways associated with the mediation of nausea and vomiting. This review focuses on these agents and the clinical aspects of their use in patients postoperatively. Combination therapies are reviewed, and studies demonstrate that when 2 or more antiemetic agents acting on different receptors are used, an overall improved efficacy is demonstrated when compared with a single agent alone in patients.

Lipid (per) oxidation in mitochondria: an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease.

A case of paradoxical presentation of a postural postdural puncture headache after combined spinal-epidural anesthesia.

We report a case of paradoxical presentation of a postural postdural puncture headache secondary to dural puncture with a 25-gauge Whitacre needle for combined spinal-epidural anesthesia. This 27-year-old female patient presented to the emergency department with elevated blood pressure and a global headache 9 days after administration of epidural anesthesia for a spontaneous vaginal delivery after an uncomplicated pregnancy. The patient reported that the headache was more intense when lying down and immediately improved when she sat or stood up from a recumbent position. The patient was discharged from emergency department after an improvement following treatment with labetalol, ondansetron, ketorolac, and fluid resuscitation.

Prescription Opioid Abuse in Chronic Pain: An Updated Review of Opioid Abuse Predictors and Strategies to Curb Opioid Abuse: Part 1.

Chronic pain and prescription opioid abuse are extremely prevalent both in this country and worldwide. Consequences of opioid misuse can be life-threatening with significant morbidity and mortality, exacting a heavy toll on patients, physicians, and society. Individuals with chronic pain and co-occurring substance use disorders and/or mental health disorders, are at a higher risk for misuse of prescribed opioids. Opioid abuse and misuse occurs for a variety of reasons, including self-medication, use for reward, compulsive use because of addiction, and diversion for profit. There is a significant need for treatment approaches that balance treating chronic pain; while minimizing risks for opioid abuse, misuse, and diversion. The use of chronic opioid therapy for chronic non-cancer pain has increased dramatically in the past 2 decades in conjunction with associated increases in the abuse of prescribed opioids and accidental opioid overdoses. Consequently, a validated screening instrument which provides an effective and rational method of selecting patients for opioid therapy, predicting risk, and identifying problems once they arise could be of enormous benefit in clinical practice. Such an instrument could potentially curb the risk of iatrogenic addiction. Although several screening instruments and strategies have been introduced in recent years, there is no single test or instrument which can reliably and accurately predict those patients not suitable for opioid therapy or identify those who need increased vigilance or monitoring during therapy. At present, screening for opioid abuse includes assessment of premorbid and comorbid substance abuse; assessment of aberrant drug-related behaviors; risk factor stratification; and utilization of opioid assessment screening tools. Multiple opioid assessment screening tools and instruments have been developed by various authors. In addition, urine drug testing, monitoring of prescribing practices, prescription monitoring programs, opioid treatment agreements, and utilization of universal precautions are essential. Presently, a combination of strategies is recommended to stratify risk, to identify and understand aberrant drug related behaviors, and to tailor treatments accordingly. This manuscript builds on the 2012 opioid guidelines published in Pain Physician and the 2016 guidelines released by the Centers for Disease Control and Prevention. It reviews the current state of knowledge regarding the growing problem of opioid abuse and misuse; known risk factors; and methods of predicting, assessing, monitoring, and addressing opioid abuse and misuse in patients with chronic non-cancer pain.Key words: Opioids, misuse, abuse, chronic pain, prevalence, risk assessment, risk management, drug monitoring, aberrant drug-related behavior.

Prescription Opioid Abuse in Chronic Pain: An Updated Review of Opioid Abuse Predictors and Strategies to Curb Opioid Abuse (Part 2).

Chronic pain and prescription opioid abuse are extremely prevalent in the United States and worldwide. The consequences of opioid misuse can be life-threatening with significant morbidity and mortality, exacting a heavy toll on patients, physicians, and society. The risk for misuse of prescribed opioids is much higher in patients with chronic pain, especially those with concurrent substance use and /or mental health disorders. Several reasons can account for the occurrence of opioid abuse and misuse, including self-medication, use for reward, compulsive use related to addiction, and diversion for profit. There is a need, therefore, for therapeutic approaches that balance treating chronic pain, while minimizing risks for opioid abuse, misuse, and diversion. Chronic opioid therapy for chronic non-cancer pain has seen a dramatic increase throughout the past 2 decades in conjunction with associated increases in the abuse of prescribed opioids and accidental opioid overdoses. Consequently, a validated screening instrument that provides an effective and rational method for selecting patients for opioid therapy, predicting risk, and identifying problems once they have arisen, could be of enormous benefit in clinical practice. An instrument as such has the potential to attenuate the risk of iatrogenic addiction. Despite the recent introduction of various screening strategies and instruments, no single test or instrument can reliably and accurately predict those patients unsuitable for opioid therapy or pinpoint those requiring heightened degrees of surveillance and monitoring throughout their therapy. Current opioid abuse screening tactics include assessing premorbid and comorbid substance abuse; assessing aberrant drug-related behaviors; stratification of risk factors; and utilizing opioid assessment screening tools. Several authors have contributed numerous screening tools and instruments to aid the assessment of appropriate opioid therapy. Additional essential measures include urine drug testing, prescription practice monitoring programs, opioid treatment agreements, and implementing universal precautions. Presently accepted recommendations consist of a combination of strategies designed to stratify risk, to identify and to understand aberrant drug-related behaviors, and to tailor treatments accordingly. This manuscript, Part 2 of a 2 part update, builds on the 2012 opioid guidelines published in Pain Physician, and the 2016 guidelines released by the Centers for Disease Control and Prevention. It reviews screening, monitoring, and addressing opioid abuse and misuse in patients with chronic non-cancer pain. Opioids, misuse, abuse, chronic pain, prevalence, risk assessment, risk management, drug monitoring, aberrant drug-related behavior.

A single-center, prospective, double-blind, sham-controlled, randomized study of the effect of a vibrating capsule on colonic transit in patients with chronic constipation.

BACKGROUND: In an open-label study of 26 patients with IBS-C and chronic constipation, treatment with a vibrating (VIBRANT) capsule twice a week for 7.5 weeks resulted in 88.5% responders. Effects on colonic transit are unclear. We aimed to compare effects of VIBRANT and sham capsule treatment on colonic transit in patients with functional constipation. METHODS: Patients with functional constipation (Rome III criteria) were randomized to VIBRANT or sham capsule treatment for 8 weeks and underwent scintigraphic colonic transit measurements during week 8. We estimated the overall rate of colonic transit from the slope of progression of colonic geometric center over 48 hours. The capsule was activated 8 hours after ingestion, and the vibration sequence included 240 cycles. KEY RESULTS: There were no significant group differences in overall colonic transit [GC48, 2.76 (IQR 2.42-4.03) for sham group and 3.46 (2.55-4.61) for active treatment group (P=.13)]. Additionally, the progression of the isotope through the colon was numerically faster, though not significantly different (slope, P=.14) in the VIBRANT capsule group compared to the sham group. Three participants in the VIBRANT capsule group had accelerated colonic transit at 32 hours and faster colonic transit slope compared to the 95th percentile of the sham group. CONCLUSIONS AND INFERENCES: Although there were no group differences between VIBRANT and sham capsule treatment on colonic transit, at least one (and possibly three) of 12 patients receiving the VIBRANT capsule had faster colonic transit. The vibration parameters to accelerate colonic transit in patients with functional constipation require further optimization.

Sorption and desorption of selected non-steroidal anti-inflammatory drugs in an agricultural loam-textured soil.

Non-steroidal, anti-inflammatory drugs (NSAIDs) are widely used pharmaceutical products with analgesic and anti-inflammatory effects that are consistently detected in municipal wastewater systems and in municipal biosolids. Land application of biosolids and irrigation with reclaimed wastewater introduces these compounds into agricultural environments, which is an emerging issue of concern for ecosystem health. In this study, the sorption-desorption behaviour of four commonly consumed NSAIDs, including naproxen (NPX), ibuprofen (IBU), ketoprofen (KTF), and diclofenac (DCF), was examined in a loam textured soil exposed to either an individual-compound or a mixture of the four NSAIDs. The proportion of NSAIDs adsorbed to the soil in the mixture-compound system was 72%, 55%, 50% and 45%, for diclofenac, naproxen, ketoprofen, and ibuprofen, respectively, and differed slightly from the individual compound adsorption. Diclofenac displayed strong sorption and low desorption in both the individual-compound and mixture-compound systems. Naproxen and ibuprofen exhibited significant differences between the adsorption isotherms of the individual-compound and mixture-compound systems. Results of this study highlight differences in the sorption behaviour of NSAIDs, when present as mixtures, possibly through multilayer bonding effects or complexation with cationic metals or organo-clays from the soil. Soil organic matter (SOM) may have played a role in determining some of the interactions between the compounds but other factors associated with the mixture-compound system, such as cation bridging or multilayer cooperative adsorption. Desorption data suggests that the mechanisms involved in binding NSAIDs to the soil surface are also influence by the presence of other compounds in a mixture. A reduction in desorption was observed for all four NSAIDs in the mixture-compound system relative to the individual-compound system, but were greatest for naproxen and ibuprofen. The sorption-desorption hysteresis increased for naproxen and ibuprofen in the mixture-compound system. This study suggests that cooperative adsorption plays a role in the interaction of NSAIDs when present as mixtures rather than as individual compounds.

A case of central diabetes insipidus after ketamine infusion during an external to internal carotid artery bypass.

STUDY OBJECTIVE: We report the first teenage case of ketamine-induced transient central diabetes insipidus. CASE SUMMARY: The patient was an 18-year-old woman with moyamoya disease undergoing an external carotid to internal carotid bypass and given a low-dose ketamine infusion. After approximately 2 hours in the supine position, with 0.5 Minimum Alveolar Concentration (MAC) of sevoflurane, a propofol infusion at 50 µg/kg/min, a remifentanil infusion at 0.5 µg/kg/min, and a ketamine infusion at a dose of 10 µg/kg/min, this patient had an excessive urine output. Initially, the Foley catheter contained 50 mL of urine. She was given 1500 mL of crystalloid during the case but produced 2700 mL of urine output. Increasing urine output was noted 1 hour into the procedure around the time that the patient experienced a 2-minute Cushing-like response characterized by bradycardia and hypertension. Several I-Stat samples revealed a worsening hypernatremia. The decision was made to check the urine osmolality and treat the patient with 4 µg of desmopressin (DDAVP). Urine output began to slow down to a normal rate of 2 mg/kg/h, as the patient was transferred from the operating room to the computed tomographic (CT) scanning room for a CT and CT angiogram; both were unremarkable. The neurosurgery team waited until the next day to complete the procedure. The procedure was completed successfully and uneventfully the next day without a ketamine infusion as part of the general anesthetic plan. DISCUSSION: The Naranjo Adverse Drug Reaction score of 4 suggested a possible relationship between the patient's ketamine infusion and subsequent central diabetes insipidus. The 2 previous cases on this topic have suggested that ketamine, as an N-methyl-d-aspartate receptor antagonist, inhibits vasopressin release in the neurohypophysis. CONCLUSION: Urine output, urine osmolarity, and serum osmolarity should be monitored in patients given ketamine anesthetic; desmopressin should be present to prevent dangerous long-term sequela.