Ketone Supplementation Dampens Subjective and Objective Responses to Alcohol: Evidence From a Preclinical Rat Study and a Randomized, Cross-Over Trial in Healthy Volunteers.

BACKGROUND: Previous preclinical and human studies have shown that a high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal. However, the effects of KS on alcohol sensitivity are unknown. METHODS: In this single-blind, cross-over study, 10 healthy participants (3 females) were administered a single, oral dose of a KS (25 g of ketones from D-ß-hydroxybutyric acid and R-1,3-butanediol) or placebo 30 minutes before an oral alcohol dose (0.25 g/kg for women; 0.31 g/kg for men). Assessments of breath alcohol concentration and blood alcohol levels (BAL) and responses on the Drug Effect Questionnaire were repeatedly obtained over 180 minutes after alcohol consumption. In a parallel preclinical study, 8 Wistar rats (4 females) received an oral gavage of KS (0.42 g ketones/kg), water, or the sweetener allulose (0.58 g/kg) followed 15 minutes later by an oral alcohol dose (0.8 g/kg). BAL was monitored for 240 minutes after alcohol exposure. RESULTS: In humans, the intake of KS before alcohol significantly blunted breath alcohol concentration and BAL, reduced ratings of alcohol liking and wanting more, and increased disliking for alcohol. In rats, KS reduced BAL more than either allulose or water. CONCLUSION: KS altered physiological and subjective responses to alcohol in both humans and rats, and the effects were likely not mediated by the sweetener allulose present in the KS drink. Therefore, KS could potentially reduce the intoxicating effects of alcohol.

Ketone supplementation dampens subjective and objective responses to alcohol in rats and humans.

Previous preclinical and human studies have shown that high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal. However, the effects of KS on alcohol sensitivity are unknown. In this single-blind, cross-over study, 10 healthy participants (3 females) were administered a single, oral dose of a KS (25 g of ketones from D-ß-hydroxybutyric acid and R-1,3-butanediol) or placebo 30 min prior to an oral alcohol dose (0.25 g/kg for women; 0.31 g/kg for men). Assessments of breath alcohol concentration (BrAC) and blood alcohol levels (BAL) and responses on the Drug Effect Questionnaire were repeatedly obtained over 180 min after alcohol consumption. In a parallel preclinical study, 8 Wistar rats (4 females) received an oral gavage of KS (0.42 g ketones/kg), water, or the sweetener allulose (0.58 g/kg) followed 15 min later by an oral alcohol dose (0.8 g/kg). BAL were monitored for 240 min after alcohol exposure. In humans, the intake of KS prior to alcohol significantly blunted BrAC and BAL, reduced ratings of alcohol liking and wanting, and increased disliking for alcohol. In rats, KS reduced BAL more than either allulose or water. In conclusion, KS altered physiological and subjective responses to alcohol in both humans and rats and the effects were likely not mediated by the sweetener allulose present in the KS drink. Therefore, KS could potentially reduce the intoxicating and rewarding effects of alcohol and thus be a novel intervention for treating alcohol use disorder.

Pharmacokinetic effects of a single-dose nutritional ketone ester supplement on brain ketone and glucose metabolism in alcohol use disorder - a pilot study.

Introduction: Acute alcohol intake decreases brain glucose metabolism and increases brain uptake of acetate, a metabolite of alcohol. Individuals with alcohol use disorder (AUD) show elevated brain acetate metabolism at the expense of glucose, a shift in energy utilization that persists beyond acute intoxication. We recently reported that nutritional ketosis and administration of ketone bodies as an alternative energy source to glucose reduce alcohol withdrawal severity and alcohol craving in AUD. However, the regional effects of nutritional ketosis on brain ketone (beta-hydroxybutyrate [BHB]) and glucose metabolism have not been studied in AUD. Methods: Five participants with AUD underwent two magnetic resonance imaging (MRI) sessions and 4 participants with AUD underwent two positron emission tomography (PET) sessions with 18 F-fluorodeoxyglucose. All participants completed one session without KE intervention and one session during which they consumed 395 mg/kg (R) -3-hydroxybutyl (R) -3-hydroxybutyrate Ketone Ester (KE) intervention (TdeltaS Global Inc.) before the scan. The order of the sessions was randomized. For the PET cohort, blood glucose and ketone levels were assessed and voxel-wise maps of the cerebral metabolic rate of glucose (CMRglc) were computed at each session. For the MRI cohort, brain anterior cingulate BHB levels were assessed using magnetic resonance spectroscopy. Results: A single dose of KE elevated blood BHB and anterior cingulate BHB levels compared to baseline. Moreover, blood glucose levels were lower with KE than baseline, and whole-brain CMRglc decreased by 17%. The largest KE-induced CMRglc reductions were in the frontal, occipital, cortex, and anterior cingulate cortices. Conclusion: These findings provide preliminary evidence that KE administration elevates ketone and reduces brain glucose metabolism in humans, consistent with a shift from glucose to ketones as a brain energy source. Average reductions in CMRglc of 17% are similar to global average reductions documented with administration of 0.25-0.5 g/kg of alcohol. Documenting the clinical and neurometabolic effects of nutritional ketosis will yield fundamental knowledge as to its potential beneficial effects as a treatment for AUD and its underlying neural mechanisms.

Use, misuse, and overuse of antenatal corticosteroids. A retrospective cohort study.

OBJECTIVES: To evaluate the timing of antenatal corticosteroids (ACS) administration in relation to the delivery timing based on indications and risk factors for preterm delivery. METHODS: We conducted a retrospective cohort study to understand what factors predict the optimal timing of ACS administration (ACS administration within seven days). We reviewed consecutive charts of adult pregnant women receiving ACS from January 1, 2011, to December 31, 2019. We excluded pregnancies under 23 weeks, incomplete and duplicate records, and patients delivered outside our health system. The timing of ACS administration was categorized as optimal or suboptimal. These groups were analyzed regarding demographics, indications for ACS administration, risk factors for preterm delivery, and signs and symptoms of preterm labor. RESULTS: We identified 25,776 deliveries. ACS were administered to 531 pregnancies, of which 478 met the inclusion criteria. Of the 478 pregnancies included in the study, 266 (55.6 %) were delivered in the optimal timeframe. There was a higher proportion of patients receiving ACS for the indication of threatened preterm labor in the suboptimal group as compared to the optimal group (85.4 % vs. 63.5 %, p<0.001). In addition, patients who delivered in the suboptimal timeframe had a higher proportion of short cervix (33 % vs. 6.4 %, p<0.001) and positive fetal fibronectin (19.8 % vs. 1.1 %, p<0.001) compared to those who delivered in the optimal timeframe. CONCLUSIONS: More emphasis should be placed on the judicious use of ACS. Emphasis should be placed on clinical assessment rather than relying solely on imaging and laboratory tests. Re-appraisal of institutional practices and thoughtful ACS administration based on the risk-benefit ratio is warranted.

The Role of Frailty on Surgical Outcomes Following Pelvic Organ Prolapse Surgery in Medicare Beneficiaries: A National Study.

OBJECTIVE: To evaluate the association of frailty with surgical outcomes following pelvic organ prolapse (POP) surgery in Medicare beneficiaries. METHODS: This is a retrospective cohort study of female Medicare beneficiaries ≥65 years of age undergoing POP surgery between 2014 and 2016. Primary outcomes were hospital length-of-stay (LOS) ≥3 days, 30-day post-operative complications (excluding urinary tract infections (UTI)), and 30-day UTI. Frailty was quantified using the validated Claims-Based Frailty Index (CFI) and categorized into not frail (CFI<0.15), pre-frail (0.15≤CFI<0.25), mildly frail (0.25≤CFI<0.35), and moderately to severely frail (0.35≤CFI≤1). RESULTS: Among the 107,890 women included (mean age, 73.3±6 years), 91.3% were White as and 4.3% were classified as mildly or moderately to severely frail. Rates of hospital LOS≥3 days and 30-day UTI increased over 7-fold and rates of 30-day complications increased over 3-fold as CFI increased from not frail to moderately to severely frail (all P values <.001). Compared to women who were not frail, women who were moderately to severely frail demonstrated an increased relative risk of hospital LOS≥3 days (aRR 3.1 [95% CI 2.5-3.8,P <.001]), 30-day complications (aRR 2.8 [95% CI 2.2-3.6, P <.001]), and 30-day UTI (aRR 2.5 [95% CI 2.2-3.0, P <.001]). CONCLUSION: Among Medicare beneficiaries undergoing POP surgery in the United States, frailty is strongly associated with increased risk of prolonged hospital stay and 30-day complications. Frailty should be considered in the preoperative assessment for POP surgeries to improve patient outcomes.

Implementation of a Psychiatry Consultation-Liaison Service "Conseminar".

BACKGROUND: The field of consultation-liaison psychiatry has generated a relatively small number of rigorous clinical trials that guide clinical care. Consequently, there is a need for a consensus-building process to inform best practices for common clinical dilemmas in consultation-liaison psychiatry. OBJECTIVE: We review several consensus-building approaches in academic medicine and describe a novel educational process called a "conseminar," which is intended to minimize the variability in teaching and practice on a service staffed by multiple faculty members. METHODS: The conseminar is an iterative group exercise among faculty who attend on a consultation-liaison service. Faculty members generate a list of candidate topics and then prioritize those topics for a focused and critical literature review, aided by a librarian. In the absence of definitive clinical trial data or established practice guidelines, the faculty articulates a consensus "best-practice" approach and creates a brief document that summarizes specific recommendations for learners on the service. CONCLUSIONS: The conseminar process can minimize variability among consultation-liaison faculty within a single institution with respect to the diagnostic and treatment recommendations conveyed to trainees. Furthermore, conseminar documents can be shared across institutions to promote more consistent teaching and practice within consultation-liaison psychiatry.

Endometrial cancer recurrence in the sacrum and the Psoas: A case report and literature review.

Musculoskeletal metastasis of endometrial carcinoma is rare. Data regarding the management of metastatic disease to these sites is limited. We report a case of a 73-year-old woman who had surgery for endometrial adenocarcinoma (FIGO stage IB, Grade II) followed by vaginal cuff brachytherapy and one year later developed an isolated recurrence in the sacrum and iliopsoas muscle. She was treated with chemotherapy followed by whole pelvis radiation and a complete clinical response was achieved. At her last follow up, 12 months after the completion of the radiation, she had no clinical or radiologic evidence of disease.

Evaluation of the Efficacy of Various Topical Fluorides on Enamel Demineralization Adjacent to Orthodontic Brackets: An In Vitro Study.

AIM: White spot lesions (WSLs) occur frequently after fixed orthodontic treatment. This in vitro study was undertaken to compare the efficacy of 2.26% fluoride varnish, 1.23% APF gel, 0.21% fluoride toothpaste and 0.04% sodium fluoride mouthwashes in preventing enamel demineralization around orthodontic brackets in extracted premolars. MATERIALS AND METHODS: The sample for this study included 100 premolars free of caries and enamel cracks. They were divided into five groups of 20 samples each. Group 1 (FV): light-curable Fluoride varnish (Clinpro™ XT 3M ESPE, Pymble, New South Wales, Australia), group 2 (FG): 1.23% APF gel (Patterson NE. International, USA), group 3 (FTP): 0.21% w/w sodium fluoride toothpaste with tri-calcium phosphate (Clinpro™ Tooth Crème, 3M ESPE, Australia), group 4 (FMW): sodium fluoride 0.044% (w/v) mouthwash (Colgate® Phos-Flur® Ortho Defense Rinse, Colgate-Palmolive, NY) and group 5 (C): control. The samples were subjected to laboratory pH cycling. The demineralization changes in the enamel were assessed before the start of the experiment and after 14 days. RESULTS: There was a significant change in the mean Diagnodent score value (p <0.001) in all groups from day 1-day 14. The mean values were significantly different among groups at day 1 (p = 0.002), day 14 (p = 0.001) and also the change from Day 1 to Day 14 was significantly different among Groups (p = 0.001). The least change in the mean value from baseline to 14 days was seen in group 1 (FV) followed by group 3 (FTP), group 2 (FG), and group 4 (FMW) and then the group 5 (C). CONCLUSION: All the topical fluorides tested were able to reduce the demineralization when compared to the control group under similar testing conditions, but to varying degrees. light-curable fluoride varnish outperformed all the topical fluorides followed by 0.21% w/w dodium fluoride toothpaste with tri-calcium phosphate, 1.23% Acidulated phosphate fluoride gel and sodium fluoride 0.044% (w/v) mouthwash. The control group where no topical fluoride was applied showed the least resistance to demineralization. CLINICAL SIGNIFICANCE: Within the limitations of this study, routine application of light cured fluoride varnish (Clinpro) can be recommended to prevent enamel demineralization to prevent white spot lesions in patients receiving orthodontic treatment.