Practical Overview of 123I-Ioflupane Imaging in Parkinsonian Syndromes.

Parkinsonian syndromes are a heterogeneous group of progressive neurodegenerative disorders involving the nigrostriatal dopaminergic pathway and are characterized by a wide spectrum of motor and nonmotor symptoms. These syndromes are quite common and can profoundly impact the lives of patients and their families. In addition to classic Parkinson disease, parkinsonian syndromes include multiple additional disorders known collectively as Parkinson-plus syndromes or atypical parkinsonism. These are characterized by the classic parkinsonian motor symptoms with additional distinguishing clinical features. Dopamine transporter SPECT has been developed as a diagnostic tool to assess the levels of dopamine transporters in the striatum. This imaging assessment, which uses iodine 123 (123I) ioflupane, can be useful to differentiate parkinsonian syndromes caused by nigrostriatal degeneration from other clinical mimics such as essential tremor or psychogenic tremor. Dopamine transporter imaging plays a crucial role in diagnosing parkinsonian syndromes, particularly in patients who do not clearly fulfill the clinical criteria for diagnosis. Diagnostic clarification can allow early treatment in appropriate patients and avoid misdiagnosis. At present, only the qualitative interpretation of dopamine transporter SPECT is approved by the U.S. Food and Drug Administration, but quantitative interpretation is often used to supplement qualitative interpretation. The authors provide an overview of patient preparation, common imaging findings, and potential pitfalls that radiologists and nuclear medicine physicians should know when performing and interpreting dopamine transporter examinations. Alternatives to 123I-ioflupane imaging for the evaluation of nigrostriatal degeneration are also briefly discussed. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Intenzo and Colarossi in this issue.

In vivo evaluation of a novel 18F-labeled PET radioligand for translocator protein 18 kDa (TSPO) in monkey brain.

PURPOSE: [18F]SF51 was previously found to have high binding affinity and selectivity for 18 kDa translocator protein (TSPO) in mouse brain. This study sought to assess the ability of [18F]SF51 to quantify TSPO in rhesus monkey brain. METHODS: Positron emission tomography (PET) imaging was performed in monkey brain (n = 3) at baseline and after pre-blockade with the TSPO ligands PK11195 and PBR28. TSPO binding was calculated as total distribution volume corrected for free parent fraction in plasma (VT/fP) using a two-tissue compartment model. Receptor occupancy and nondisplaceable uptake were determined via Lassen plot. Binding potential (BPND) was calculated as the ratio of specific binding to nondisplaceable uptake. Time stability of VT was used as an indirect probe to detect radiometabolite accumulation in the brain. In vivo and ex vivo experiments were performed in mice to determine the distribution of the radioligand. RESULTS: After [18F]SF51 injection, the concentration of brain radioactivity peaked at 2.0 standardized uptake value (SUV) at ~ 10 min and declined to 30% of the peak at 180 min. VT/fP at baseline was generally high (203 ± 15 mL· cm-3) and decreased by ~ 90% after blockade with PK11195. BPND of the whole brain was 7.6 ± 4.3. VT values reached levels similar to terminal 180-min values by 100 min and remained relatively stable thereafter with excellent identifiability (standard errors < 5%), suggesting that no significant radiometabolites accumulated in the brain. Ex vivo experiments in mouse brain showed that 96% of radioactivity was parent. No significant uptake was observed in the skull, suggesting a lack of defluorination in vivo. CONCLUSION: The results demonstrate that [18F]SF51 is an excellent radioligand that can quantify TSPO with a good ratio of specific to nondisplaceable uptake and has minimal radiometabolite accumulation in brain. Collectively, the results suggest that [18F]SF51 warrants further evaluation in humans.

Candidate 3-benzazepine-1-ol type GluN2B receptor radioligands (11C-NR2B-Me enantiomers) have high binding in cerebellum but not to σ1 receptors.

INTRODUCTION: We recently reported 11C-NR2B-SMe ([S-methyl-11C](R,S)-7-thiomethoxy-3-(4-(4-methyl-phenyl)butyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol) and its enantiomers as candidate radioligands for imaging the GluN2B subunit within rat N-methyl-D-aspartate receptors. However, these radioligands gave unexpectedly high and displaceable binding in rat cerebellum, possibly due to cross-reactivity with sigma-1 (σ1) receptors. This study investigated 11C-labeled enantiomers of a close analogue (7-methoxy-3-(4-(p-tolyl)butyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol; NR2B-Me) of 11C-NR2B-SMe as new candidate GluN2B radioligands. PET was used to evaluate these radioligands in rats and to assess potential cross-reactivity to σ1 receptors. METHODS: NR2B-Me was assayed for binding affinity and selectivity to GluN2B in vitro. 11C-NR2B-Me and its enantiomers were prepared by Pd-mediated treatment of boronic ester precursors with 11C-iodomethane. Brain PET scans were conducted after radioligand intravenous injection into rats. Various ligands for GluN2B receptors or σ1 receptors were administered at set doses in pre-blocking or displacement experiments to assess their impact on imaging data. 18F-FTC146 and enantiomers of 11C-NR2B-SMe were used for comparison. Radiometabolites from brain and plasma were measured ex vivo and in vitro. RESULTS: NR2B-Me enantiomers showed high GluN2B affinity and selectivity in vitro. 11C-NR2B-Me enantiomers gave high early whole rat brain uptake of radioactivity, including high uptake in cerebellum, followed by slower decline. Radioactivity in brain at 30 min ex vivo was virtually all unchanged radioligand. Only less lipophilic radiometabolites appeared in plasma. When 11C-(R)-NR2B-Me was used, three high-affinity GluN2B ligands-NR2B-SMe, Ro25-6981, and CO101,244-showed increasing pre-block of whole brain radioactivity retention with increasing dose. Two σ1 receptor antagonists, FTC146 and BD1407, were ineffective pre-blocking agents. Together, these results strongly resemble those obtained with 11C-NR2B-SMe enantiomers, except that 11C-NR2B-Me enantiomers showed faster reversibility of binding. When 18F-FTC146 was used as a radioligand, FTC146 and BD1407 showed strong pre-blocking effects whereas GluN2B ligands showed only weak blocking effects. CONCLUSION: 11C-NR2B-Me enantiomers showed specific binding to GluN2B receptors in rat brain in vivo. High unexpected specific binding in cerebellum was not due to σ1 receptors. Additional investigation is needed to identify the source of the high specific binding.

30-day morbidity and mortality after transoral robotic surgery for human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma: A retrospective analysis of two prospective adjuvant de-escalation trials (MC1273 & MC1675).

OBJECTIVE: Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials. MATERIALS AND METHODS: Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement. RESULTS: 219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2-26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage. CONCLUSION AND RELEVANCE: TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality.

Observation and Characterization of the Hg-O Diatomic Molecule: A Matrix-Isolation and Quantum-Chemical Investigation.

Mercuric oxide is a well-known and stable solid, but the diatomic molecule Hg-O is very fragile and does not survive detection in the gas phase. However, laser ablation of Hg atoms from a dental amalgam alloy target into argon or neon containing about 0.3 % of 16 O2 or of 18 O2 during their condensation into a cryogenic matrix at 4 K allows the formation of O atoms which react on annealing to make ozone and new IR absorptions in solid argon at 521.2 cm-1 for Hg-16 O or at 496.4 cm-1 for Hg-18 O with the oxygen isotopic frequency ratio 521.2/496.4=1.0499. Solid neon gives a 529.0 cm-1 absorption with a small 7.8 cm-1 blue shift. CCSD(T) calculations found 594 cm-1 for Hg16 O and 562 cm-1 for Hg18 O (frequency ratio=1.0569). Such calculations usually produce harmonic frequencies that are slightly higher than the anharmonic (observed) values, which supports their relationship. These observed frequencies have the isotopic shift predicted for Hg-O and are within the range of recent high-level frequency calculations for the Hg-O molecule. Spectra for the related mercury superoxide and ozonide species are also considered for the first time.

Whole-Body PET Imaging in Humans Shows That 11C-PS13 Is Selective for Cyclooxygenase-1 and Can Measure the In Vivo Potency of Nonsteroidal Antiinflammatory Drugs.

Both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) convert arachidonic acid to prostaglandin H2, which has proinflammatory effects. The recently developed PET radioligand 11C-PS13 has excellent in vivo selectivity for COX-1 over COX-2 in nonhuman primates. This study sought to evaluate the selectivity of 11C-PS13 binding to COX-1 in humans and assess the utility of 11C-PS13 to measure the in vivo potency of nonsteroidal antiinflammatory drugs. Methods: Baseline 11C-PS13 whole-body PET scans were obtained for 26 healthy volunteers, followed by blocked scans with ketoprofen (n = 8), celecoxib (n = 8), or aspirin (n = 8). Ketoprofen is a highly potent and selective COX-1 inhibitor, celecoxib is a preferential COX-2 inhibitor, and aspirin is a selective COX-1 inhibitor with a distinct mechanism that irreversibly inhibits substrate binding. Because blood cells, including platelets and white blood cells, also contain COX-1, 11C-PS13 uptake inhibition from blood cells was measured in vitro and ex vivo (i.e., using blood obtained during PET scanning). Results: High 11C-PS13 uptake was observed in major organs with high COX-1 density, including the spleen, lungs, kidneys, and gastrointestinal tract. Ketoprofen (1-75 mg orally) blocked uptake in these organs far more effectively than did celecoxib (100-400 mg orally). On the basis of the plasma concentration to inhibit 50% of the maximum radioligand binding in the spleen (in vivo IC 50), ketoprofen (<0.24 µM) was more than 10-fold more potent than celecoxib (>2.5 µM) as a COX-1 inhibitor, consistent with the in vitro potencies of these drugs for inhibiting COX-1. Blockade of 11C-PS13 uptake from blood cells acquired during the PET scans mirrored that in organs of the body. Aspirin (972-1,950 mg orally) blocked such a small percentage of uptake that its in vivo IC 50 could not be determined. Conclusion: 11C-PS13 selectively binds to COX-1 in humans and can measure the in vivo potency of nonsteroidal antiinflammatory drugs that competitively inhibit arachidonic acid binding to COX-1. These in vivo studies, which reflect the net effect of drug absorption and metabolism in all organs of the body, demonstrated that ketoprofen had unexpectedly high potency, that celecoxib substantially inhibited COX-1, and that aspirin acetylation of COX-1 did not block binding of the representative nonsteroidal inhibitor 11C-PS13.

Drain-free neck dissection: the use of Artiss fibrin sealant.

OBJECTIVE: To study the safety and efficacy of Artiss fibrin sealant in lateral neck dissection, focusing on drain retention time, length of hospital stay and post-operative complications. METHODS: A retrospective review was conducted of patients who underwent neck dissection in a UK hospital over a 12-month period. RESULTS: Twenty-three patients were identified; 13 patients had Artiss and a drain, 10 patients had Artiss only. All drains were removed by post-operative day 2. No post-operative fluid collections or complications were recorded. Patients who had Artiss only without a drain were discharged on post-operative day 1. CONCLUSION: The use of Artiss reduced the drain retention time and hospital stay, with no post-operative complications. Neck dissection can be safely undertaken with no drain, and can potentially be carried out as a day-case procedure, with the application of Artiss. These findings benefit patients and the National Health Service by improving the patient journey and reducing overall costs.

Factors Affecting Adherence, Intake, and Perceived Palatability of Oral Nutritional Supplements: A Literature Review.

Oral nutritional supplements (ONS) are a clinically effective and relatively inexpensive way to supplement the diet of patients with, or at risk of, undernutrition. Good adherence is a primary determinant of the effectiveness of ONS. However adherence can be problematic for those with the greatest clinical need, such as undernourished older adults. This review aimed to appraise the available literature for the factors (contextual, personal and product related) affecting patient adherence and perceived palatability of ONS, identify areas requiring improvement and uncover gaps in the evidence to guide the focus of future research. Contextual factors identified were healthcare staff and the timing of administration. Personal factors included sensory changes and motivation which alter experience of and desire to consume ONS. The product's sensory characteristics determined palatability and intake, but undesirable attributes, such as off-flavours, can stem from nutritional ingredients. The contribution made by aroma to older adults' experience of ONS was a comparatively under-researched area. Further research should address this evidence gap to optimise the flavour, aroma profile and palatability for undernourished older consumers, thereby optimising intake. A combined multidisciplinary effort involving strategic expansion of research, industry development and clinical practice should simultaneously address the factors identified, to provide the best approach to improve adherence.

Cyclooxygenases as Potential PET Imaging Biomarkers to Explore Neuroinflammation in Dementia.

The most frequently studied target of neuroinflammation using PET is 18-kDa translocator protein, but its limitations have spurred the molecular imaging community to find more promising targets. This article reviews the development of PET radioligands for cyclooxygenase (COX) subtypes 1 and 2, enzymes that catalyze the production of inflammatory prostanoids in the periphery and brain. Although both isozymes produce the same precursor compound, prostaglandin H2, they have distinct functions based on their differential cellular localization in the periphery and brain. For example, COX-1 is located primarily in microglia, a resident inflammatory cell in the brain whose role in producing inflammatory cytokines is well documented. In contrast, COX-2 is located primarily in neurons and can be markedly upregulated by inflammatory and excitatory stimuli, but its functions are poorly understood. This article reviews these 2 isozymes as biomarkers of neuroinflammation, as well as the radioligands that have recently been developed to image them in animals and humans. To place this work into context, the properties of COX-1 and COX-2 are compared with 18-kDa translocator protein, with special consideration of their application in Alzheimer disease as a representative neurodegenerative disorder.

Electrochemotherapy for the palliative management of non-skin-origin head and neck cancer: case series and UK national survey.

OBJECTIVES: Electrochemotherapy uses electric fields to facilitate the influx of chemotherapy into cancer cells, producing a targeted effect. For head and neck cancer, it is mainly used for palliation of non-skin-origin metastases. It is used infrequently in the UK. This paper presents our experience and a UK survey to identify its frequency of use. METHODS: Between 2016 and 2019, a prospective database was created and reviewed. Only patients with non-skin-origin metastatic head and neck cancer, with no other palliative options, were included. Survival length, complications and symptomatic benefit were assessed. The survey was conducted via e-mail. RESULTS: Five patients were included: three with squamous cell carcinoma, one with esthesioneuroblastoma and one with hepatocellular carcinoma. Survival ranged from 1 month to over 20 months. Minor complications were seen. Only 15 out of 69 UK head and neck multidisciplinary teams offer electrochemotherapy. CONCLUSION: Electrochemotherapy is a well-tolerated adjunct to standard palliation of metastatic head and neck cancer, and is offered by a limited number of UK multidisciplinary teams.

Synthesis and Screening in Mice of Fluorine-Containing PET Radioligands for TSPO: Discovery of a Promising 18F-Labeled Ligand.

Translocator protein 18 kDa (TSPO) is a biomarker of neuroinflammation. [11C]ER176 robustly quantifies TSPO in the human brain with positron emission tomography (PET), irrespective of subject genotype. We aimed to develop an ER176 analog with potential for labeling with longer-lived fluorine-18 (t1/2 = 109.8 min). New fluoro and trifluoromethyl analogs of ER176 were prepared through a concise synthetic strategy. These ligands showed high TSPO affinity and low human genotype sensitivity. Each ligand was initially labeled by a generic 11C-methylation procedure, thereby enabling speedy screening in mice. Each radioligand was rapidly taken up and well retained in the mouse brain at baseline after intravenous injection. Preblocking of TSPO showed that high proportions of brain uptake were specifically bound to TSPO at baseline. Overall, the 3-fluoro analog of [11C]ER176 ([11C]3b) displayed the most promising imaging properties. Therefore, a method was developed to label 3b with [18F]fluoride ion. [18F]3b gave similarly promising PET imaging results and deserves evaluation in higher species.

Matrix Infrared Spectroscopic Studies of B-NCCN, B-η2-(NC)-CN, NCBCN, CNBCN, CNBNC, and High-Order Products Produced in Reactions of Boron Atoms with Cyanogen.

The products in reactions of laser-ablated boron atoms with cyanogen in excess argon have been identified via investigation of the matrix spectra and their variation on photolysis, annealing, and isotopic substitutions. DFT calculations have been performed for the plausible products and reaction paths, providing helpful guides. B-NCCN and B-η2-(NC)-CN were observed in the original deposition spectra, but they disappear on photolysis with λ > 220 nm while more stable NCBCN, CNBCN, and CNBNC were produced. Besides these primary products, high-order products [(NC)2B-NCCN, (CN)(NC)B-NCCN, (CN)2B-NCCN, and (NC)2B-B(CN)2] were also observed, which increased in the later stage of annealing. Our calculations show that initially produced B-NCCN is interconvertible to B-η2-(NC)-CN and the more stable boron cyanide and isocyanide, consistent with the observed results. The formation of high-order products demonstrates that boron highly prefers the trivalent state in reactions with cyanogen, similar to aluminum.

The relation between stimulated salivary flow and the temporal consumption experience of a liquid oral nutritional supplement.

Use of oral nutritional supplements (ONS) in undernourished patients has proven clinical benefits, but this can be hampered by low adherence due to poor experience of palatability. Many patients, particularly older patients, experience hyposalivation which can cause taste changes and reduce the enjoyment of foods. The aim of this study was to investigate differences in the temporal consumption experience (comprising sensory perception, in-mouth aroma release and subjective appetite) of a clinically relevant portion of ONS, for groups differing in saliva flow rates (SFR). The SFR (mL/min) of thirty healthy individuals was measured on three occasions. This data was used to categorise individuals into three groups using quartile analysis: low flow (LF) (0.3-0.6 mL/min, n = 5), medium flow (MF) (0.7-1.2 mL/min, n = 16) and high flow (HF) (1.3-1.8 mL/min, n = 9). Over the consumption of eight 15 mL sips of ONS, individuals rated their sensory perception and subjective appetite perception using line scales. Additionally, in-mouth aroma release was measured for each sip, using atmospheric pressure chemical ionisation (APCI). Compared with the MF and HF group, the LF group reported a significantly greater increase of mouth-drying over increased sips (p = 0.02). The LF group also experienced significantly higher aftertaste perception (p < 0.001), and more intense in-mouth aroma release (p = 0.015), compared with the HF group. These findings occurred concurrently with relatively lower hunger sensations in the LF and MF group. Many patients who are prescribed ONS likely experience reduced salivary flow rates. The unique sensory experiences of these individuals should be considered in order to optimise palatability and nutritional intake.

[11C]deschloroclozapine is an improved PET radioligand for quantifying a human muscarinic DREADD expressed in monkey brain.

Previous work found that [11C]deschloroclozapine ([11C]DCZ) is superior to [11C]clozapine ([11C]CLZ) for imaging Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). This study used PET to quantitatively and separately measure the signal from transfected receptors, endogenous receptors/targets, and non-displaceable binding in other brain regions to better understand this superiority. A genetically-modified muscarinic type-4 human receptor (hM4Di) was injected into the right amygdala of a male rhesus macaque. [11C]DCZ and [11C]CLZ PET scans were conducted 2-24 months later. Uptake was quantified relative to the concentration of parent radioligand in arterial plasma at baseline (n = 3 scans/radioligand) and after receptor blockade (n = 3 scans/radioligand). Both radioligands had greater uptake in the transfected region and displaceable uptake in other brain regions. Displaceable uptake was not uniformly distributed, perhaps representing off-target binding to endogenous receptor(s). After correction, [11C]DCZ signal was 19% of that for [11C]CLZ, and background uptake was 10% of that for [11C]CLZ. Despite stronger [11C]CLZ binding, the signal-to-background ratio for [11C]DCZ was almost two-fold greater than for [11C]CLZ. Both radioligands had comparable DREADD selectivity. All reference tissue models underestimated signal-to-background ratio in the transfected region by 40%-50% for both radioligands. Thus, the greater signal-to-background ratio of [11C]DCZ was due to its lower background uptake.

Matrix Infrared Spectroscopic and Theoretical Investigations of M···NCCN, M···CNCN, M···C(N)CN, NCMCN, CNMNC, CNMCN, and [M···NCCN]+ Produced in the Reactions of Group 11 Metal Atoms with Cyanogen.

Reactions of group 11 metals with cyanogen, N≡C-C≡N, in excess argon and neon have been carried out, and the products were identified via examination of the matrix spectra and their variation upon photolysis, annealing, and isotopic substitutions. Density functional theory calculations provided helpful information for the plausible products and reaction paths. While M···NCCN and M···CNCN were observed in all three metal systems, the cyanide and isocyanide products (NCMCN, NCMNC, and CNMNC) were identified only in the Cu reactions, and M···C(N)CN was identified in the Cu and Au spectra. Intrinsic reaction coordinate calculation results along with the observed spectral variation upon photolysis and annealing suggest that Cu···C(N)CN was the pathway to cyanide and isocyanide. The product absorptions with exceptionally high C-N stretching frequencies in the Au system have been tentatively assigned to a cation [Au···NCCN+]. The group 11 metal cyanides and isocyanides that require two chemical bonds to the central metal are energetically favorable only in the lightest metal system.

Synthesis of [18F]PS13 and Evaluation as a PET Radioligand for Cyclooxygenase-1 in Monkey.

Cyclooxygenase-1 (COX-1) and its isozyme COX-2 are key enzymes in the syntheses of prostanoids. Imaging of COX-1 and COX-2 selective radioligands with positron emission tomography (PET) may clarify how these enzymes are involved in inflammatory conditions and assist in the discovery of improved anti-inflammatory drugs. We have previously labeled the selective high-affinity COX-1 ligand, 1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1H-1,2,4-triazole (PS13), with carbon-11 (t1/2 = 20.4 min). This radioligand ([11C]PS13) has been successful for PET imaging of COX-1 in monkey and human brain and in periphery. [11C]PS13 is being used in clinical investigations. Alternative labeling of PS13 with fluorine-18 (t1/2 = 109.8 min) is desirable to provide a longer-lived radioligand in high activity that might be readily distributed among imaging centers. However, labeling of PS13 in its 1,1,1-trifluoroethoxy group is a radiochemical challenge. Here we assess two labeling approaches based on nucleophilic addition of cyclotron-produced [18F]fluoride ion to gem-difluorovinyl precursors, either to label PS13 in one step or to produce [18F]2,2,2-trifluoroethyl p-toluenesulfonate for labeling a hydroxyl precursor. From the latter two-step approach, we obtained [18F]PS13 ready for intravenous injection in a decay-corrected radiochemical yield of 7.9% and with a molar activity of up to 7.9 GBq/µmol. PET imaging of monkey brain with [18F]PS13 shows that this radioligand can specifically image and quantify COX-1 without radiodefluorination but with some radioactivity uptake in skull, ascribed to red bone marrow. The development of a new procedure for labeling PS13 with fluorine-18 at a higher molar activity is, however, desirable to suppress occupancy of COX-1 by carrier at baseline.

Transoral laser resection of hypopharyngeal liposarcoma.

Liposarcomas are rare malignant tumours of the connective tissue. Microscopically they resemble lipomas. They are usually found on the limbs or trunk. Fewer than 40 cases of hypopharyngeal liposarcoma have been reported in the literature. Surgical excision with a cervical or endoscopic approach has been the first-line treatment for these cases. We present a patient with the first documented primary excision via carbon dioxide laser using an entirely transoral approach. This case suggests a new standard of management but also highlights the difficulties with investigation and diagnosis in a rare presentation.

Colchicine is not effective for reducing osteoarthritic hand pain compared to placebo: a randomised, placebo-controlled trial (COLAH).

BACKGROUND: Colchicine may offer relief in osteoarthritis. This has never been investigated for hand osteoarthritis. OBJECTIVES: To investigate the effect of 1 mg daily colchicine vs placebo on hand pain and function over 12 weeks in older adults with hand osteoarthritis. METHODS: Community-dwelling adults with diagnosed osteoarthritis of the hand aged 40-80 years were randomised to receive colchicine (0.5 mg twice daily) or matching placebo. Primary outcome measure was VAS hand pain score (0-100 mm). Secondary outcome measures included tender and swollen joint count, grip strength, C-reactive protein, and Michigan Hand Questionnaire total, function and pain scores. In an exploratory assessment, we compared synovial grade and power Doppler. All outcome measures were obtained at baseline and week 12. Stata v16 was used to perform constrained longitudinal data analysis models. RESULTS: 64 adults (54 females, 10 males) aged 48-79 years of age were enrolled. 59 participants completed the study (N = 28 colchicine, N = 31 placebo) (withdrawal rate 8%). Adverse reactions to the study medication occurred in nine patients. VAS score was not significantly different at baseline (61 ± 17 mm in the colchicine, 64 ± 17 mm in the placebo group). Between-group difference for VAS score at week 12 was 7.6 mm (95% CI -3.5-18.7, p-value 0.18). There were no significant differences between groups for any secondary outcomes at baseline or week 12. CONCLUSIONS: 1 mg colchicine daily for 12 weeks was not effective for reducing pain, tender and swollen joint count or increasing grip strength in symptomatic hand osteoarthritis. Our results do not support the use of colchicine in hand osteoarthritis.

Discovery, Radiolabeling, and Evaluation of Subtype-Selective Inhibitors for Positron Emission Tomography Imaging of Brain Phosphodiesterase-4D.

We aimed to develop radioligands for PET imaging of brain phosphodiesterase subtype 4D (PDE4D), a potential target for developing cognition enhancing or antidepressive drugs. Exploration of several chemical series gave four leads with high PDE4D inhibitory potency and selectivity, optimal lipophilicity, and good brain uptake. These leads featured alkoxypyridinyl cores. They were successfully labeled with carbon-11 (t1/2 = 20.4 min) for evaluation with PET in monkey. Whereas two of these radioligands did not provide PDE4D-specific signal in monkey brain, two others, [11C]T1660 and [11C]T1650, provided sizable specific signal, as judged by pharmacological challenge using rolipram or a selective PDE4D inhibitor (BPN14770) and subsequent biomathematical analysis. Specific binding was highest in prefrontal cortex, temporal cortex, and hippocampus, regions that are important for cognitive function. [11C]T1650 was progressed to evaluation in humans with PET, but the output measure of brain enzyme density (VT) increased with scan duration. This instability over time suggests that radiometabolite(s) were accumulating in the brain. BPN14770 blocked PDE4D uptake in human brain after a single dose, but the percentage occupancy was difficult to estimate because of the unreliability of measuring VT. Overall, these results show that imaging of PDE4D in primate brain is feasible but that further radioligand refinement is needed, most likely to avoid problematic radiometabolites.

Impact of an enhanced recovery program for cesarean delivery on postoperative opioid use.

BACKGROUND: Cesarean delivery is one of the most common surgeries performed worldwide and the adoption of enhanced recovery programs for cesarean delivery is gaining popularity. We tested the hypothesis that implementation of an enhanced recovery program for cesarean delivery would be associated with a decrease in postoperative opioid consumption. METHODS: We compared a retrospective cohort of women delivered by elective cesarean delivery (January 1, 2017 to June 30, 2018) to a prospective cohort exposed to the enhanced recovery protocol (July 1, 2018 to December 31, 2018). The primary outcome was inpatient maternal opioid use, measured as total oral morphine equivalents. Secondary outcomes included postoperative 0-10 pain scores, length of stay, 30-day postoperative complication rates, and hospital re-admissions. RESULTS: Data from 541 patients were analyzed. The enhanced recovery cohort used significantly less oral morphine equivalents compared with the pre-enhanced recovery cohort (60.3 mg vs 104.3 mg, P <0.001). The number of patients who required opioid medication within 24 h of discharge was significantly reduced in the enhanced recovery cohort (41.1% vs 74.6%, P <0.001). There were no significant differences in average pain scores (1.6 vs 1.9, P=0.037). CONCLUSIONS: The implementation of an enhanced recovery program for cesarean delivery was associated with a significant reduction in postoperative opioid consumption throughout hospitalization, with average pain scores remaining <2. Implementation of this program was also associated with an increase in the number of patients who were opioid-free 24 h prior to discharge.