Proceedings of the Third American Association of Oral and Maxillofacial Surgeons Anesthesia Patient Safety Conference.

The 3rd Anesthesia Patient Safety Conference of the American Association of Oral and Maxillofacial Surgeons was held at the Daniel M Laskin Institute for Oral and Maxillofacial Surgery Education and Innovation at American Association of Oral and Maxillofacial Surgeons headquarters in Rosemont, Illinois on June 6, 2022. The conference provided a platform to scrutinize collective errors, explore optimal practices, comprehend the concepts and principles of human complacency, assessing the system's capacity to handle deviations from the norm, and contemplate ideas and initiatives to enhance our practice model. These safety conferences are designed to foster collaborative, proactive conversations and understand best practices in safe delivery of anesthetic care to our patients.

Survival of microvascular free flaps in mandibular reconstruction: A systematic review and meta-analysis.

BACKGROUND: Free tissue transfer is commonly used in the reconstruction of post-ablative defects of the mandible. Due to lack of statistical power, comparing the survival of various free flaps, even in large studies, is challenging. The purpose of this study was to perform a meta-analysis comparing the survival of the most commonly used free flaps for mandibular reconstruction. METHODS: We searched PubMed, EMBASE, and SCOPUS for relevant studies. A meta-analysis using the Peto one-step odds ratio (OR) with 95% confidence intervals (CI) was used to compare the pooled survival of the most commonly used free flaps for mandibular reconstruction. RESULTS: Of the 25,303 studies reviewed, 17 were selected for data extraction. A total of 1,221 subjects received 1,262 free flaps. Sixty-five free flaps failed. The pooled survival of all free flaps used for mandibular reconstruction was 94.8%. The deep circumflex iliac artery (DCIA) flap was associated with a seven-fold increase in failure when compared to the radial forearm free flap (Peto OR 7.40; 95% CI 1.38, 39.75, P = 0.02). There was no difference in survival when comparing other commonly used free flaps. CONCLUSIONS: The results of this study suggest that free flap reconstruction of the mandible is highly successful. With the exception of the increased survival of the radial forearm when compared to the DCIA, there is no difference in recipient site survival when comparing various free flaps for mandibular reconstruction.

Current Trends and Future Directions for Outpatient Total Joint Arthroplasty: A Review of the Anesthesia Choices and Analgesic Options.

The aging population and the obesity epidemic have led to an increased rate of joint arthroplasty procedures, specifically total knee arthroplasty and total hip arthroplasty. These surgeries are associated with increased hospital length of stay and, consequently, higher costs. Despite the benefits of outpatient surgery, only a small percentage of total joint arthroplasties (TJAs) are done in this manner. We reviewed the most up-to-date trends for outpatient TJA and discussed essential factors for a successful outpatient program, including the proper patient selection process and best available anesthetic and analgesic options, along with their risks and benefits. Risk stratification tools, such as the Outpatient Arthroplasty Risk Assessment, are helpful for predicting outcomes regarding outpatient TJA, and neuraxial anesthesia should be considered to minimize complications and facilitate early discharge. A multimodal analgesia regimen could be effective for pain management in outpatient TJA, and the currently recommended peripheral nerve blocks for total hip arthroplasty and total knee arthroplasty are the fascia iliaca compartment block and adductor canal block, respectively. However, blocks should be carefully considered for outpatient procedures. Enhanced recovery after surgery (ERAS) protocols help to guide perioperative care teams and allow for improved patient recovery, decreased length of stay, and increased patient satisfaction.

OX40, PD-1 and CTLA-4 are selectively expressed on tumor-infiltrating T cells in head and neck cancer.

The tumor microenvironment of squamous cell carcinoma of the head and neck (SCCHN) has been shown to be immune suppressive. Therefore, strategies aimed at overcoming this issue could have a positive therapeutic impact. Hence, we investigated the expression of the known immune-modulatory proteins OX40, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in SCCHN on different T-cell subsets of tumor-infiltrating lymphocytes (TIL) to ascertain whether these proteins could potentially be targeted alone or in combination for future clinical trials. T cells from peripheral blood (PBL) and tumor were analyzed for the expression of OX40, PD-1 and CTLA-4 in 29 patients undergoing surgery. These proteins were all expressed significantly higher in T-cell subsets isolated from tumors compared with PBL of the same patient. OX40 expression was significantly greater in the TIL regulatory T-cell (Treg) population relative to conventional CD4 and CD8 TIL or the Treg isolated from PBL. PD-1 expression was increased in all T-cell subsets relative to PBL. CTLA-4 was also increased in all TIL subsets relative to blood, and similar to OX40, its highest level of expression was observed in the Treg TIL. The highest frequency of PD-1, CTLA-4 and OX40 triple-positive cells were found in the Treg population isolated from the tumor. We analyzed both human papilloma virus-positive and -negative patients and found similar levels and expression patterns of these two patient populations for all three proteins. These data suggest that there may be therapeutic advantages of targeting these pathways independently or in combination for patients with this disease.

Zetidoline metabolism by rat liver microsomes. Formation of metabolites with potential neuroleptic activity.

1-(3'-Chlorophenyl)-3-[2-(3,3-dimethyl-1-azetidinyl)ethyl] imidazolidin-2-one, zetidoline, a new neuroleptic agent, when incubated with rat liver microsomes was rapidly metabolized to six free (mets B, D, I, L, M and N) and two conjugated metabolites (mets E and F). Sites of the metabolic attack (oxidation) were primarily the aromatic moiety, then the imidazolidinone and the azetidine rings. The metabolites were purified and structures assigned by means of EI-MS, 1H-NMR and chemical synthesis (mets B, D, L and M). The main metabolites, zetidoline, some chemical analogues and a few known dopamine antagonists were tested as in vitro inhibitors of 3H-zetidoline and 3H-spiperone binding to rat striatal membranes, and as in vivo inducers of prolactin release in female rats (inhibition of the estrus cycle). Two zetidoline metabolites, namely 4'-hydroxy zetidoline (met. B) and 5-hydroxy zetidoline (met. L), were found to have both in vitro and in vivo activities comparable to those of the parent drug. Identification of these active hydroxylated metabolites appears important both in the search of new leads of neuroleptics and for designing pro-drugs derivatives with improved pharmacokinetic profiles.

Metabolic fate of zetidoline, a new neuroleptic agent, in man.

Healthy volunteers administered orally a single dose (20 mg) of [2-14C]zetidoline, a new dopamine antagonist, exhibited rapid absorption of radioactivity with peak plasma levels of 250-300 ng/ml achieved in 1 h. The compound underwent intensive metabolic first-pass so that plasma radioactivity was represented mostly by two products, metabolite B endowed with neuroleptic activity, and metabolite D inactive, while unchanged zetidoline was not detected. Disappearance of radioactivity from plasma was rapid with a half-life of 1.78 +/- 0.20 h. The simultaneous assay of plasma prolactin showed increased levels of the hormone (+ 464% at the peak time) up to the 6th h after dosing, with plasma concentration profile which mimic those of metabolite B. The radioactive test-dose was eliminated mainly via the kidneys with an average urinary recovery of 84.7 +/- 1.7% in 4 days (73.4 +/- 1.1% within 8 h). The main urinary metabolite (metabolite G) and two minor ones (metabolites B and D) were purified and their structures assigned by IR, MS and NMR spectroscopy, they are: 1-(3-chloro-4-hydroxyphenyl)-3 [2-(3,3-dimethyl-1-azetidinyl)ethyl]imidazolidin-2-one, metabolite B; 1-[2-(3,3-dimethyl-1-azetidinyl)ethyl]-imidazolidin-2-one, metabolite D and the 4'-O-sulphate ester of metabolite B, metabolite G. The metabolic fate of zetidoline in man follows the same phase I reactions demonstrated in rats and dogs, while the phase II reaction is sulphoconjugation instead of the glucuronidation observed in animals.

Structural studies on lipiarmycin. I. Characterization by 1H and 13C NMR spectroscopy and isolation of methyl 2-O-methyl-4-O-homodichloroorsellinate-beta-rhamnoside.

1H and 13C NMR spectral studies of lipiarmycin in CDCl3 and in pyridine-d5 provided evidence for the six partial structures I approximately VI and the two sugar units 1 and 2. Acid methanolysis led to the isolation of methyl 2-O-methyl-4-O-homodichloroorsellinate-beta-rhamnoside, whose structure was determined by spectroscopic methods.

Ramoplanin (A-16686), a new glycolipodepsipeptide antibiotic. III. Structure elucidation.

By combination of chemical, 1H and 13C NMR, and mass spectrometric studies, the structures of the three components of the antibiotic ramoplanin (A-16686), produced by Actinoplanes sp. ATCC 33076, have been elucidated. All the components have structures formed by a common depsipeptide skeleton carrying a dimannosyl group and are differentiated by the presence of various acylamide moieties, derived from C8, C9 and C10 fatty acids.

Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov. sp. V. Aromatic constituents.

Oxidative and hydrolytic degradation reactions were carried out on teicoplanin in order to characterize the aromatic portion of the molecule and relate it to the other members of the class of glycopeptide antibiotics. Seven aromatic rings, obtained as triphenyl ether, diphenyl ether, and diphenyl moieties after oxidation nd hydrolysis of teicoplanin, were identified. They are present in teicoplanin as aromatic amino acids and constitute the peptidic part of the molecule. The diphenyl ether and diphenyl moieties, which were isolated both as esters after oxidation and as alpha-amino acids after acid hydrolysis clearly indicate the nature of the corresponding amino acids in teicoplanin. The triphenyl ether moiety, which was isolated only as ester, allows the hypothesis that the corresponding amino acids are the same as those of the other glycopeptide antibiotics.

Metabolites of 3-hydrazino-6-[bis-(2-hydroxyethyl)amino]pyridazine dihydrochloride in rat urine.

In 24 hr urine of rats orally given 150 mg/kg of 3-hydrazino-6-[bis-(2-hydroxyethyl)amino]pyridazine dihydrochloride (DL 150), no unchanged compound was detected. Three metabolites, less polar than DL 150, were isolated, their structures assigned by UV, MS, IR and 1H NMR spectroscopies, and confirmed by synthesis. They are: 3-[bis-(2-hydroxyethyl)amino]-6-isopropoxypyridazine (1); 3-[bis-(2-hydroxyethyl)amino]pyridazine (2); 3-methyl-6-[bis-(2-hydroxyethyl)amino]-s-triazolo[4,3-b]pyridazine (3). The metabolism of DL 150 in the rat follows some of the metabolic pathways reported for hydralazine.

Robotic surgery: a new approach to tumors of the tongue base, oropharynx, and hypopharynx.

Oropharyngeal cancer was traditionally treated with en bloc resection of the tumor via lip-split mandibulotomy approach, often with adjuvant radiation and chemotherapy. In the 1990s, organ-sparing definitive chemoradiation therapy without surgery became the standard of care for oropharyngeal squamous cell carcinoma. Although organ-sparing treatment provided acceptable locoregional disease control with preservation of anatomic organs adjacent to the tumors and less disfiguration from lack of surgical incisions, it often resulted in significant deficits in speech and swallowing. This article reviews a current organ-and-function preserving approach to oropharyngeal carcinoma using the surgical robot.

Post-therapeutic surveillance schedule for oral cancer: is there agreement?

INTRODUCTION: Patients with oral cavity squamous cell carcinoma represent a diverse group, and the treatment these patients undergo also varies widely. Some patients undergo local excision alone while others require extensive surgery, often with adjuvant chemoradiotherapy. The post-therapeutic surveillance schedule for these patients tends to be a "one size fits all" formula for all head and neck squamous cell carcinoma patients, which has often been dictated by institutional doctrine or a senior surgeon's dogma. The post-therapeutic needs and risks of a T1 oral cancer patient treated with surgery alone differ from those of a patient with advanced laryngeal carcinoma, and the follow-up regimen should be tailored to the specific patient's risk of loco-regional recurrence, distant metastasis, and other related medical issues. RESOURCES AND MATERIALS: A total of 65 papers were identified, 18 of which either focused on follow-up strategy for oral cavity squamous cell carcinoma or their tabular data allowed these cases to be extracted. Internationally recognized cancer entities were also queried. CONCLUSIONS: No international consensus was achieved about the follow-up strategies. The value of post-therapeutic surveillance schedule following oral cancer treatment is generally not in dispute, although patient-initiated symptom-driven visits can be effective in identifying tumor recurrence for oral cancer patients. The range of appointment interval schemes tends to identify a progressive escalation of visit intervals such that there are more visits in the first year than in the second, and fewer yet during the third. Patients may fail to comply with their clinic visit structure. Most references agree that follow-up beyond the third year is unnecessary and may waste medical resources as well as the time of both patient and surgeon. There is no agreement as to the need for or interval of imaging studies.

The reaction of phthalazino(2,3-b)phthalazine-5,12(7H, 14H)-diones with nitrous acid.

3,4-Dihydrophthalazin-1(2H)-one (I) was oxidized to phthalazin-1(2H)-one (III) with nitrous acid or with ferric chloride . Phthalazino [2,3-b] phthalazine-5,12(7H, 14H)-diones (IV) did not react with ferric chloride but they were oxidized with nitrous acid to 2-[1(2H)-oxo-2-phthalazinyl] methylbenzoic acids (V) and (VI). The formation of (V) or (VI) depends upon the substituents of compounds (IV). Strucutres (V) and (VI) were established by pKa measurements in methylcellosolve and by mass and N.M.R. spectra.

Metabolism of deflazacort in the rat, dog and man.

The metabolism of [2'-14C]deflazacort, (11 beta, 16 beta)-21-(acetoxyl)-11-hydroxy-2'-methyl-5'H-pregna-1, 4-dieno[17,16-d]oxazole-3,20-dione, orally given to rats, dogs, and humans, has been studied. From the urine of the three species and from rat bile and liver preparations, five main metabolites I-V have been isolated and their structures investigated by physicochemical analysis: 1,(5 beta,11 beta,16 beta)-11,21-dihydroxy-2'-methyl-5'H-pregn-1-eno[17,16-d]oxazole-3,20-dione; II, (11 beta,16 beta)-11,21-dihydroxy-2'-methyl-5'H-pregna-1,4-dieno[17,16-d]oxazole-3,20-dione; III, (6 beta,11 beta,16 beta)-6,11,21-trihydroxy-2'-methyl-5'H-pregna-1,4-dieno[17,16-d]oxazole-3,20-dione; IV, (3 epsilon,11 beta,16 beta)-3,11,21-trihydroxy-2'-methyl-5'H-pregn-5-eno[17,16-d]oxazol-20-one. Metabolites II and III are quantitatively the most important in the urine of the rat, dog, and man; metabolite V, whose structure is uncertain, has been found in human and rat urine. In the formation of metabolites I-V the fused 2-methyloxazoline ring is unmetabolized, whereas the steroid moiety follows the general metabolic pathways reported for other related corticosteroids.

Influence of metabolism on the activity of a new anti-fertility agent, 2-(3-ethoxyphenyl)-5,6-dihydro-s-triazolo [5,1-a]isoquinoline (DL 204-IT), in the rat and the hamster.

The activity of a new non-hormonal anti-fertility agent, 2-(3-ethoxyphenyl)-5,6-dihydro-s-triazolo[5,1-a]isoquinoline (DL 204-IT), effective in terminating pregnancy after i.m. or s.c. treatment, was tested after single and multiple oral doses given to rats and hamsters. Although the compound was absorbed well from the gastrointestinal tract and the plasma levels of the radioactivity administered were rather high and sustained, the oral activity was by two orders of magnitude lower than the parenteral one. The plasma profile of the metabolites found after both p.o. and i.m. administration indicates that the compound is rapidly metabolized. Seven metabolites (I-VII) were isolated from the urine of pregnant rats and fully characterized by MS, IR and NMR spectroscopy. They are 2-(3-hydroxyphenyl)-5,6-dihydro-s-triazolo[5,1-a]isoquinoline (I); 2-(3,4-dihydroxyphenyl)-5,6-dihydro-s-triazolo[5,1-1]isoquinoline (II); 2-(3-hydroxyphenyl)-5,6-dihydro-6 beta-hydroxy-s-triazolo[5,1-a]isoquinoline (III); metabolite I-sulphate ester (IV); metabolite III-3-sulphate ester (V); metabolite I-beta-D-glucuronide (VI) and metabolite II-3-beta-D-glucuronide (VII). Metabolite I was shown to be from 1/10 (rat) to 1/30 (hamster) as active as the parent compound, while metabolites II and III were completely inactive. The very low oral activity of DL 204-IT seems to be due mainly to its rapid biotransformation.

Disposition and metabolism of a new steroidal anti-inflammatory agent, deflazacort, in cynomolgus monkeys.

The kinetics and metabolic fate of 2'-14C-deflazacort, a new steroidal antiinflammatory agent, were studied in the cynomolgus monkey after both p.o. and i.v. administration (5 mg/kg). There is no unchanged deflazacort in the plasma or urine after either p.o. or i.v. treatment. As judged from the plasma AUC and urinary elimination values, the oral availability of both total 14C and metabolites seems to be lowered because of a route-dependent first-pass. Both radioactivity and the main metabolite (21-desacetyl deflazacort) are eliminated from the plasma with half-lives of 2--3-5 h. The i.v. administered 14C is eliminated mainly in the urine (52--55% of dose), but biliary excretion is also quantitatively important. Six metabolites were isolated from urine and identified by physico-chemical analysis. Among them desacetylated deflazacort and its 6 beta-hydroxy derivative were shown to be the major radioactive products in plasma and urine, respectively. Minor metabolites were: 21-desacetyl, 6 alpha-hydroxy deflazacort; 21-desacetyl, 5 alpha, 1-eno, deflazacort; 21-desacetyl, 20 beta hydroxy deflazacort; and 21-desacetyl, 11-keto deflazacort.

Metabolic pathways of the anti-hypertensive agent, N-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine+ ++ hydrochloride. I. Studies in the rat.

The metabolic fate of a new anti-hypertensive, 1-pyrrolyl pyridazinamine, was studied in male Wistar rats after both p.o. and i.v. administration (1 mg/kg). The compound undergoes rapid metabolism, disappearing from the central compartment with a half-life of about 0.5 h. Plasma concn. of the parent drug and its major metabolite I following i.v. and p.o. administration suggest a route-dependent first-pass metabolism. Ten metabolites were isolated from the urine and identified by u.v., i.r., mass and 1H-n.m.r. spectroscopy. The structure of some was confirmed by 13C-n.m.r. and chemical synthesis. All biotransformations are restricted to the pyrrole ring which undergoes oxidative cleavage followed by a series of chemical rearrangements. A minor pathway leads to the formation of methyl sulphinyl and methyl sulphonyl pyrroles. It is suggested that, as with natural indoles, the pyrrole might be oxidized by a 2,3-dioxygenase. The three major metabolites, I, II and IX, along with two minor ones, VI and VII, were inactive when tested i.v. for antihypertensive activity.