MR elastography-based slip interface imaging (SII) for functional assessment of myofascial interfaces: A feasibility study.

PURPOSE: Abnormal adherence at functional myofascial interfaces is hypothesized as an important phenomenon in myofascial pain syndrome. This study aimed to investigate the feasibility of MR elastography (MRE)-based slip interface imaging (SII) to visualize and assess myofascial mobility in healthy volunteers. METHODS: SII was used to assess local shear strain at functional myofascial interfaces in the flexor digitorum profundus (FDP) and thighs. In the FDP, MRE was performed at 90 Hz vibration to each index, middle, ring, and little finger. Two thigh MRE scans were performed at 40 Hz with knees flexed and extended. The normalized octahedral shear strain (NOSS) maps were calculated to visualize myofascial slip interfaces. The entropy of the probability distribution of the gradient NOSS was computed for the two knee positions at the intermuscular interface between vastus lateralis and vastus intermedius, around rectus femoris, and between vastus intermedius and vastus medialis. RESULTS: NOSS map depicted distinct functional slip interfaces in the FDP for each finger. Compared to knee flexion, clearer slip interfaces and larger gradient NOSS entropy at the vastus lateralis-vastus intermedius interface were observed during knee extension, where the quadriceps are not passively stretched. This suggests the optimal position for using SII to visualize myofascial slip interface in skeletal muscles is when muscles are not subjected to any additional force. CONCLUSION: The study demonstrated that MRE-based SII can visualize and assess myofascial interface mobility in extremities. The results provide a foundation for investigating the hypothesis that myofascial pain syndrome is characterized by changes in the mobility of myofascial interfaces.

Photoinduced Organocatalyzed Atom Transfer Radical Polymerization (O-ATRP): Precision Polymer Synthesis Using Organic Photoredox Catalysis.

The development of photoinduced organocatalyzed atom transfer radical polymerization (O-ATRP) has received considerable attention since its introduction in 2014. Expanding on many of the advantages of traditional ATRP, O-ATRP allows well-defined polymers to be produced under mild reaction conditions using organic photoredox catalysts. As a result, O-ATRP has opened access to a range of sensitive applications where the use of a metal catalyst could be of concern, such as electronics, certain biological applications, and the polymerization of coordinating monomers. However, key limitations of this method remain and necessitate further investigation to continue the development of this field. As such, this review details the achievements made to-date as well as future research directions that will continue to expand the capabilities and application landscape of O-ATRP.

Halide Noninnocence and Direct Photoreduction of Ni(II) Enables Coupling of Aryl Chlorides in Dual Catalytic, Carbon-Heteroatom Bond-Forming Reactions.

Recent mechanistic studies of dual photoredox/Ni-catalyzed, light-driven cross-coupling reactions have found that the photocatalyst (PC) operates through either reductive quenching or energy transfer cycles. To date, reports invoking oxidative quenching cycles are comparatively rare and direct observation of such a quenching event has not been reported. However, when PCs with highly reducing excited states are used (e.g., Ir(ppy)3), photoreduction of Ni(II) to Ni(I) is thermodynamically feasible. Recently, a unified reaction system using Ir(ppy)3 was developed for forming C-O, C-N, and C-S bonds under the same conditions, a prospect that is challenging with PCs that can photooxidize these nucleophiles. Herein, in a detailed mechanistic study of this system, we observe oxidative quenching of the PC (Ir(ppy)3 or a phenoxazine) via nanosecond transient absorption spectroscopy. Speciation studies support that a mixture of Ni-bipyridine complexes forms under the reaction conditions, and the rate constant for photoreduction increases when more than one ligand is bound. Oxidative addition of an aryl iodide was observed indirectly via oxidation of the resulting iodide by Ir(IV)(ppy)3. Intriguingly, the persistence of the Ir(IV)/Ni(I) ion pair formed in the oxidative quenching step was found to be necessary to simulate the observed kinetics. Both bromide and iodide anions were found to reduce the oxidized form of the PC back to its neutral state. These mechanistic insights inspired the addition of a chloride salt additive, which was found to alter Ni speciation, leading to a 36-fold increase in the initial turnover frequency, enabling the coupling of aryl chlorides.

Allogeneic haematopoietic stem cell transplantation for myelofibrosis: prognostic indicators and the role of JAK2V617F measurable-residual disease monitoring by droplet-digital polymerase chain reaction.

Relapse after allogeneic haematopoietic stem cell transplantation (HSCT) is one of the key determinants of outcome in myelofibrosis (MF) and remains an important unmet need. In this retrospective single-centre study, we evaluated 35 consecutive patients with MF receiving allogeneic HSCT. At 30 days post-HSCT, full donor chimerism was achieved in 31 patients (88.6%). The median time to neutrophil engraftment was 16.8 (10-42) days and the median time to platelet engraftment was 26 (12-245) days. Four patients (11.4%) experienced primary graft failure. With a median duration of follow-up of 33 (1-223) months, with the 5-year overall survival (OS) and progression-free survival (PFS) were 51.6% and 46.3%, respectively. Relapse after HSCT (P < 0.001), leucocyte count ≥ 18 × 109/L at HSCT (P = 0.003) and accelerated/blast phase disease at HSCT (P < 0.001) were significantly associated with worse OS. Age at HSCT ≥ 54 years (P = 0.01), mutated ETV6 (P = 0.03), leucocyte count ≥ 18 × 109/L (P = 0.02), accelerated/blast phase MF (P = 0.001), and grade 2-3 bone marrow reticulin fibrosis at 12 months post-HSCT (P = 0.002) were significantly associated with worse PFS. JAK2V617F MRD ≥ 0.047 [sensitivity 85.7%; positive predictive value (PPV) 100%; AUC 0.984; P = 0.001] at 6 months and JAK2V617F MRD ≥ 0.009 (sensitivity 100%; PPV 100%; AUC 1.0; P = 0.001) at 12 months were highly predictive of post-HSCT relapse. Inferior OS and PFS were significantly associated with detectable JAK2V617F MRD at 12 months (P = 0.003 and P = 0.0001, respectively).

Biosynthesis of Lyngbyastatins 1 and 3, Cytotoxic Depsipeptides from an Okeania sp. Marine Cyanobacterium.

Lyngbyastatins (Lbns) 1 (1) and 3 (2) belong to a group of cyclic depsipeptides that inhibit cancer cell proliferation. These compounds have been isolated from different marine cyanobacterial collections, while further development of these compounds relies on their lengthy total synthesis. Biosynthetic studies of these compounds can provide viable strategies to access these compounds and develop new analogs. In this study, we report the identification and characterization of one Lbn biosynthetic gene cluster (BGC) from the marine cyanobacterium Okeania sp. VPG18-21. We initially identified 1 and 2 in the organic extract by mass spectrometry and performed the targeted isolation of these compounds, which feature a (2S,3R)-3-amino-2-methylpentanoic acid (MAP) and a (2S,3R)-3-amino-2-methylhexanoic acid (Amha) moiety, respectively. Parallel metagenomic sequencing of VPG18-21 led to the identification of a putative Lbn BGC that encodes six megaenzymes (LbnA-F), including one polyketide synthase (PKS, LbnE), four nonribosomal peptide synthetases (NRPSs, LbnB-D and -F), and one PKS-NRPS hybrid (LbnA). Bioinformatic analysis of these enzymes suggested that the BGC produces 1 and 2. Furthermore, our biochemical studies of three recombinant adenylation domains uncovered their substrate specificities, supporting the identity of the BGC. Finally, we identified near-complete Lbn-like BGCs in the genomes of two other marine cyanobacteria.

Multimodality evaluation of transfascial muscle and other soft tissue herniations of the extremities.

This review illustrates the multimodality assessment of transfascial muscle and other soft tissue herniations of the extremities. Transfascial herniations of the extremities can develop from congenital or acquired disruptions of the deep fascia, resulting in herniation of the underlying muscle, nerve, or soft tissue tumor into the subcutaneous tissues. While most patients present with a painless subcutaneous nodule that may change in size with muscle activation, some may experience focal or diffuse extremity symptoms such as pain and paresthesias. Although the diagnosis may be clinically suspected, radiologic evaluation is useful for definitive diagnosis and characterization. Ultrasound is the preferred modality for initial workup through a focused and dynamic examination. Magnetic resonance imaging can be utilized for equivocal, complicated, and preoperative cases. Computed tomography is less useful in the evaluation of transfascial herniations in the extremities due to similarities in the attenuation between muscle and fascia, which can decrease the conspicuity of small defects.

Feasibility of photon-counting CT for femoroacetabular impingement syndrome evaluation: lower radiation dose and improved diagnostic confidence.

OBJECTIVE: The feasibility of low-dose photon-counting detector (PCD) CT to measure alpha and acetabular version angles of femoroacetabular impingement (FAI). MATERIAL AND METHODS: FAI patients undergoing an energy-integrating detector (EID) CT underwent an IRB-approved prospective ultra-high-resolution (UHR) PCD-CT between 5/2021 and 12/2021. PCD-CT was dose-matched to the EID-CT or acquired at 50% dose. Simulated 50% dose EID-CT images were generated. Two radiologists evaluated randomized EID-CT and PCD-CT images and measured alpha and acetabular version angles on axial image slices. Image quality (noise, artifacts, and visualization of cortex) and confidence in non-FAI pathology were rated on a 4-point scale (3 = adequate). Preference tests of standard dose PCD-CT, 50% dose PCD-CT, and 50% dose EID-CT relative to standard dose EID-CT were performed using Wilcoxon Rank test. RESULTS: 20 patients underwent standard dose EID-CT (~ CTDIvol, 4.5 mGy); 10 patients, standard dose PCD-CT (4.0 mGy); 10 patients, 50% PCD-CT (2.6 mGy). Standard dose EID-CT images were scored as adequate for diagnostic task in all categories (range 2.8-3.0). Standard dose PCD-CT images scored higher than the reference in all categories (range 3.5-4, p < 0.0033). Half-dose PCD-CT images also scored higher for noise and cortex visualization (p < 0.0033) and equivalent for artifacts and visualization of non-FAI pathology. Finally, simulated 50% EID-CT images scored lower in all categories (range 1.8-2.4, p < 0.0033). CONCLUSIONS: Dose-matched PCD-CT is superior to EID-CT for alpha angle and acetabular version measurement in the work up of FAI. UHR-PCD-CT enables 50% radiation dose reduction compared to EID while remaining adequate for the imaging task.

7T for clinical imaging of benign peripheral nerve tumors: preliminary results.

PURPOSE: MRI has become an essential diagnostic imaging modality for peripheral nerve pathology. Early MR imaging for peripheral nerve depended on inferred nerve involvement by visualizing downstream effects such as denervation muscular atrophy; improvements in MRI technology have made possible direct visualization of the nerves. In this paper, we share our early clinical experience with 7T for benign neurogenic tumors. MATERIALS: Patients with benign neurogenic tumors and 7T MRI examinations available were reviewed. Cases of individual benign peripheral nerve tumors were included to demonstrate 7T MRI imaging characteristics. All exams were performed on a 7T MRI MAGNETOM Terra using a 28-channel receive, single-channel transmit knee coil. RESULTS: Five cases of four pathologies were selected from 38 patients to depict characteristic imaging features in different benign nerve tumors and lesions using 7T MRI. CONCLUSION: The primary advantage of 7T over 3T is an increase in signal-to-noise ratio which allows higher in plane resolution so that the smallest neural structures can be seen and characterized. This improvement in MR imaging provides the opportunity for more accurate diagnosis and surgical planning in selected cases. As this technology continues to evolve for clinical purposes, we anticipate increasing applications and improved patient care using 7T MRI for the diagnosis of peripheral nerve masses.

Incidence of complications related to shoulder arthroplasties identified on computed tomography.

PURPOSE: Determine incidence of shoulder arthroplasty complications identified on computed tomography (CT). MATERIALS AND METHODS: Retrospective institutional database review of patients with shoulder arthroplasties who underwent CT between 01/2006-11/2021 at a tertiary academic referral center with subspecialized orthopedic shoulder surgeons. CT reports were reviewed for arthroplasty type and complication. Data were stratified and summarized. Associations between complications and arthroplasty types were determined with Chi-squared goodness of fit test. RESULTS: Eight hundred twelve CTs in 797 unique patients were included (438 (53.9%) females and 374 (46.1%) males; mean age 67 ± 11 years). There were 403 total shoulder arthroplasties (TSA), 317 reverse total shoulder arthroplasties (rTSA), and 92 hemiarthroplasties (HA). Complications were present in 527/812 (64.9%) and incidences were: loosening/aseptic osteolysis 36.9%, periprosthetic failure 21.6%, periprosthetic fracture 12.3%, periprosthetic dislocation 6.8%, joint/pseudocapsule effusion 5.9%, prosthetic failure 4.8%, infection 3.8%, and periprosthetic collection 2.1%. Complications per arthroplasty were: 305/403 (75.7%) TSAs, 176/317 (55.5%) rTSAs, and 46/92 (50%) HAs (p < 0.001). Periprosthetic fracture (20.8%), prosthetic dislocation (9.8%), and prosthetic failure (7.9%) were highest in rTSAs (p < 0.001, p < 0.013, p < 0.001, respectively). Loosening/aseptic osteolysis most frequent in TSAs (54.1%) (p < 0.001). Periprosthetic failure most frequent in HA (32.6%) (p < 0.001). Significant associations were identified with joint/pseudocapsule effusion and loosening/aseptic osteolysis (p = 0.04) and prosthetic dislocation (p < .001). CONCLUSION: In this single tertiary academic referral center cohort, the incidence of shoulder arthroplasty complication identified on CT was 64.9% and the most commonly occurring complication was loosening/aseptic osteolysis (36.9%). TSA had the highest incidence of complication (75.7%).

Ruxolitinib in the management of steroid-resistant/-dependent acute and chronic graft-versus-host disease: results of routine practice in an academic centre.

Graft-versus-host disease (GVHD) is an important complication after allogeneic haematopoietic stem cell transplantation (HSCT). Corticosteroids are the standard first-line treatment. Steroid-resistant/-dependent (SR/D) acute and chronic GVHD (aGVHD, cGVHD) lead to significant morbidity/mortality. The JAK2 inhibitor ruxolitinib has recently been shown in clinical trials to be effective in SR/D aGVHD and cGVHD. We retrospectively analysed the efficacy and safety of ruxolitinib in a cohort of SR/D aGVHD and cGVHD patients treated in a non-trial setting. In the aGVHD cohort, there were 14 men and 12 women, median age at 38 (19-63) years. At day 28 post-ruxolitinib, the overall response rate (ORR) was 86% (complete response, CR, 36%; partial response, PR, 50%). Continued ruxolitinib beyond day 28 resulted in a final CR of 68%. However, 3/15 (20%) of CR patients developed cGVHD. In the cGVHD cohort, there were 16 men and 15 women, median age at 33 (21-64) years. The ORR, CR and PR rates changed with continued ruxolitinib treatment, being 86%, 17% and 69% at 1 month; 79%, 38% and 41% at 3 months; and 83%, 52% and 31% at 6 months. Five patients had overlap GVHD, four of whom achieved CR. Multivariate analysis showed that superior overall survival and failure-free survival were associated with CR at day 28 for aGVHD, and CR at 1 year for cGVHD. Ruxolitinib treatment was efficacious for SR/D aGVHD and cGVHD, and continued treatment for at least 6 months was needed to maximize benefit.

Evolving Role of Dual-Energy CT in the Clinical Workup of Gout: A Retrospective Study.

BACKGROUND. Dual-energy CT (DECT) allows noninvasive detection of monosodium urate (MSU) crystal deposits and has become incorporated into the routine clinical evaluation for gout at many institutions over the past decade. OBJECTIVE. The purpose of this study was to compare two time periods over the past decade in terms of radiologists' interpretations of DECT examinations performed for the evaluation of gout and subsequent clinical actions. METHODS. This retrospective study included 100 consecutive adult patients who underwent DECT to evaluate for gout in each of two periods (one beginning in March 2013 and one beginning in September 2019). Examinations performed in 2013 were conducted using a second-generation DECT scanner (80 kV [tube A] and 140 kV [tube B] with a 0.4-mm tin filter), and those performed in 2019 were conducted using a third-generation DECT scanner (80 kV [tube A] and 150 kV [tube B] with a 0.6-mm tin filter) that provides improved spectral separation. Original DECT reports were classified as positive, negative, or equivocal for MSU crystals indicative of gout. Joint aspirations occurring after the DECT examinations were recorded on the basis of findings from medical record review. A single radiologist performed a post hoc retrospective blinded image review, classifying examinations as positive, negative, or equivocal. RESULTS. In 2013, 44.0% of DECT examinations were interpreted as positive, 23.0% as negative, and 33.0% as equivocal; in 2019, 37.0% were interpreted as positive, 47.0% as negative, and 16.0% as equivocal (p < .001). The frequency of joint aspiration after DECT was 14.0% in 2013 versus 2.0% in 2019 (p = .002), and that after DECT examinations with negative interpretations was 17.4% in 2013 versus 2.1% in 2019 (p = .02). In post hoc assessment by a single radiologist, the distribution of interpretations in 2013 was positive in 49.0%, negative in 22.0%, and equivocal in 29.0%, and in 2019 it was positive in 39.0%, negative in 50.0%, and equivocal in 11.0% (p < .001). CONCLUSION. When DECT examinations performed for gout in 2013 and 2019 were compared, the frequency of equivocal interpretations was significantly lower in 2019, possibly in relation to interval technologic improvements. Negative examinations were less frequently followed by joint aspirations in 2019, possibly reflecting increasing clinical acceptance of the DECT results. CLINICAL IMPACT. The findings indicate an evolving role for DECT in the evaluation of gout after an institution's routine adoption of the technology for this purpose.

Estimates of COVID-19 vaccine uptake in major occupational groups and detailed occupational categories in the United States, April-May 2021.

BACKGROUND: While other studies have reported estimates of COVID-19 vaccine uptake by broad occupational group, little is known about vaccine uptake by detailed occupational category. METHODS: Data on COVID-19 vaccination were provided by US adults ages ≥18 years old who responded to the Facebook/Delphi Group COVID-19 Trends and Impact Survey (Delphi US CTIS) in April-May 2021, reported working for pay in the past 4 weeks, and answered questions about their COVID-19 vaccine status. Percentages of occupational groups reporting having had at least one COVID-19 vaccination were weighted to resemble the US general population and calculated for 23 major occupational groups and 120 detailed occupational categories in 15 major groups. RESULTS: COVID-19 vaccine uptake for all 828,401 working adult respondents was 73.6%. Uptake varied considerably across the 23 major occupational groups, from 45.7% for Construction and Extraction to 87.9% for Education, Training, and Library. Percentage vaccinated was also very low for Installation, Maintenance, and Repair at 52.1% and Farming, Fishing, and Forestry at 53.9%. Among the 120 detailed occupational categories, the highest percentage vaccinated was 93.9% for Postsecondary Teacher and the three lowest values were 39.1% for Any Extraction Worker in Oil, Gas, Mining, or Quarrying; 40.1% for Vehicle or Mobile Equipment Mechanic, Installer, or Repairer; and 42.0% for Any Construction Trades Worker. CONCLUSION: Low vaccination percentages were seen in many US occupations by the end of May 2021, early in the period of widespread availability of vaccines for adults. These findings could help inform the deployment of occupation-specific vaccinepromotion activities during future viral epidemics and pandemics.

Preoperative ultrasound accurately characterizes surgically confirmed extracranial spinal accessory nerve injuries.

OBJECTIVE: To determine the accuracy of preoperative ultrasound and MRI in surgically confirmed spinal accessory nerve injuries and present the benefits of a multimodality image review. MATERIALS AND METHODS: A retrospective review of 38 consecutive patients referred to a peripheral nerve surgical practice at an academic teaching hospital with surgically confirmed spinal accessory nerve injuries. All cases were reviewed for patient demographics, date and cause of injury, preoperative EMG, and surgical diagnosis and management. Additionally, prospective interpretation of preoperative ultrasound and MRI reports were reviewed for concordance or discordance with the surgical diagnosis. RESULTS: Iatrogenic injury was present in 37 (97%) cases and most commonly a result of an excisional lymph node biopsy (68%). Surgically confirmed spinal accessory nerve injury diagnoses consisted of 25 (66%) stump neuromas and 13 (34%) incomplete nerve injuries. Nine months was the average time from injury to surgery. Twenty-nine patients underwent preoperative ultrasound and/or MRI evaluation: 12 ultrasound only, 10 MRI only, and seven with both ultrasound and MRI. Eighteen (95%) preoperative ultrasound reports compared to four (24%) preoperative MRI reports were concordant with the surgical diagnosis. In the seven cases with both preoperative ultrasound and MRI, six had discordant ultrasound and MRI imaging diagnoses for which the ultrasound was concordant with the surgical diagnoses in all cases. CONCLUSION: Preoperative ultrasound more accurately characterizes spinal accessory nerve injuries compared to MRI and should serve as the modality of choice when a spinal accessory nerve injury is suspected.

Aldoximes are precursors of auxins in Arabidopsis and maize.

Two natural auxins, phenylacetic acid (PAA) and indole-3-acetic acid (IAA), play crucial roles in plant growth and development. One route of IAA biosynthesis uses the glucosinolate intermediate indole-3-acetaldoxime (IAOx) as a precursor, which is thought to occur only in glucosinolate-producing plants in Brassicales. A recent study showed that overproducing phenylacetaldoxime (PAOx) in Arabidopsis increases PAA production. However, it remains unknown whether this increased PAA resulted from hydrolysis of PAOx-derived benzyl glucosinolate or, like IAOx-derived IAA, is directly converted from PAOx. If glucosinolate hydrolysis is not required, aldoxime-derived auxin biosynthesis may occur beyond Brassicales. To better understand aldoxime-derived auxin biosynthesis, we conducted an isotope-labelled aldoxime feeding assay using an Arabidopsis glucosinolate-deficient mutant sur1 and maize, and transcriptomics analysis. Our study demonstrated that the conversion of PAOx to PAA does not require glucosinolates in Arabidopsis. Furthermore, maize produces PAA and IAA from PAOx and IAOx, respectively, indicating that aldoxime-derived auxin biosynthesis also occurs in maize. Considering that aldoxime production occurs widely in the plant kingdom, aldoxime-derived auxin biosynthesis is likely to be more widespread than originally believed. A genome-wide transcriptomics study using PAOx-overproduction plants identified complex metabolic networks among IAA, PAA, phenylpropanoid and tryptophan metabolism.

Biosynthesis and Heterologous Production of Mycosporine-Like Amino Acid Palythines.

Mycosporine-like amino acids (MAAs) are a family of natural products that are produced by a variety of organisms for protection from ultraviolet damage. In this work, we combined different bioinformatic approaches to assess the distribution of the MAA biosynthesis and identified a putative gene cluster from Nostoc linckia NIES-25 that encodes a short-chain dehydrogenase/reductase and a nonheme iron(II)- and 2-oxoglutarate-dependent oxygenase (MysH) as potential new biosynthetic enzymes. Heterologous expression of refactored gene clusters in E. coli produced two known biosynthetic intermediates, 4-deoxygadusol and mycosporine-glycine, and three disubstituted MAA analogues, porphyra-334, shinorine, and mycosporine-glycine-alanine. Importantly, the disubstituted MAAs were converted into palythines by MysH. Furthermore, biochemical characterization revealed the substrate preference of recombinant MysD, a d-Ala-d-Ala ligase-like enzyme for the formation of disubstituted MAAs. Our study advances the biosynthetic understanding of an important family of natural UV photoprotectants and opens new opportunities to the development of next-generation sunscreens.

Percutaneous MR Imaging-Guided Laser Ablation and Cryoablation for the Treatment of Pediatric and Adult Symptomatic Peripheral Soft Tissue Vascular Anomalies.

PURPOSE: To evaluate the safety and effectiveness of percutaneous magnetic resonance (MR) imaging-guided laser ablation and cryoablation for the treatment of symptomatic soft tissue vascular anomalies (VAs) of the trunk and extremities. MATERIALS AND METHODS: An institutional review board-approved retrospective review was undertaken of all pediatric and adult patients who underwent MR imaging-guided and monitored laser ablation and/or cryoablation for the treatment of symptomatic peripheral soft tissue VA. Preablation and postablation MR imaging was independently reviewed. Pain scores on the visual analog scale (0 to 10) and self-reported subjective symptomatic improvement were assessed. Change in VA size and pain scores were compared using a paired t test. RESULTS: Thirty patients (24 females; age, 10-75 years) with 34 VAs were treated for moderate to severe pain (n = 27) or swelling/mass effect (n = 3) with 60 total ablation sessions. The baseline maximum VA diameter was 9.5 cm ± 8.6. At baseline, all VAs (100%) demonstrated variable T2-weighted signal hyperintensity and enhancement. The baseline pain score was 6.4 ± 1.6. Clinical follow-up was available for 23 patients. At a mean follow-up time of 12.2 months ± 10.1, 19 of 20 (95%) patients treated for pain and 2 of 3 (67%) patients treated for swelling/mass effect reported partial or complete symptomatic relief. There was a significant decrease in the postablation pain scores (-5.7 ± 1.0, P < .001) and maximum VA size (-2.3 cm ± 2.7, P = .004), with >50% reduction in VA T2 signal (59%) and enhancement (73%). Nine of 30 (30%) patients experienced minor complications. CONCLUSIONS: MR imaging-guided and monitored percutaneous laser ablation and cryoablation appear to be safe and effective for the treatment of symptomatic peripheral soft tissue VAs.

Interrogation of O-ATRP Activation Conducted by Singlet and Triplet Excited States of Phenoxazine Photocatalysts.

Organocatalyzed ATRP (O-ATRP) is a growing field exploiting organic chromophores as photoredox catalysts (PCs) that engage in dissociative electron-transfer (DET) activation of alkyl-halide initiators following absorption of light. Characterizing DET rate coefficients (kact) and photochemical yields across various reaction conditions and PC photophysical properties will inform catalyst design and efficient use during polymerization. The studies described herein consider a class of phenoxazine PCs, where synthetic handles of core substitution and N-aryl substitution enable tunability of the electronic and spin characters of the catalyst excited state as well as DET reaction driving force (ΔGET0). Using Stern-Volmer quenching experiments through variation of the diethyl 2-bromo-2-methylmalonate (DBMM) initiator concentration, collisional quenching is observed. Eight independent measurements of kact are reported as a function of ΔGET0 for four PCs: four triplet reactants and four singlets with kact values ranging from 1.1 × 108 M-1 s-1, where DET itself controls the rate, to 4.8 × 109 M-1 s-1, where diffusion is rate-limiting. This overall data set, as well as a second one inclusive of five literature values from related systems, is readily modeled with only a single parameter of reorganization energy under the frameworks of the adiabatic Marcus electron-transfer theory and Marcus-Savéant theory of DET. The results provide a predictive map where kact can be estimated if ΔGET0 is known and highlight that DET in these systems appears insensitive to PC reactant electronic and spin properties outside of their impact on the driving force. Next, on the basis of measured kact values in selected PC systems and knowledge of their photophysics, we also consider activation yields specific to the reactant spin states as the DBMM initiator concentration is varied. In N-naphthyl-containing PCs characterized by near-unity intersystem crossing, the T1 is certainly an important driver for efficient DET. However, at DBMM concentrations common to polymer synthesis, the S1 is also active and drives 33% of DET reaction events. Even in systems with low yields of ISC, such as in N-phenyl-containing PCs, reaction yields can be driven to useful values by exploiting the S1 under high DBMM concentration conditions. Finally, we have quantified photochemical reaction quantum yields, which take into account potential product loss processes after electron-transfer quenching events. Both S1 and T1 reactant states produce the PC•+ radical cation with a common yield of 71%, thus offering no evidence for spin selectivity in deleterious back electron transfer. The subunity PC•+ yields suggest that some combination of solvent (DMAc) oxidation and energy-wasting back electron transfer is likely at play and these pathways should be factored in subsequent mechanistic considerations.

Preoperative sonographic ulnar nerve mapping in the postoperative elbow.

OBJECTIVE: To describe the technique of sonographic ulnar nerve mapping in the postoperative elbow for surgical planning. MATERIALS AND METHODS: A retrospective review of a surgical databank identified 24 patients, all aged 18 years and older with a history of orthopedic elbow surgery, who were referred for preoperative sonographic mapping of the ulnar nerve prior to subsequent surgery. All cases were reviewed for patient demographics, clinical presentation, prior surgical interventions, and ultrasound technique. Charts were reviewed for intraoperative and postoperative outcomes, including nerve injury. RESULTS: The cohort included 12 males and 12 females with a mean age of 51 years (range 22-68 years) and a mean BMI of 29 (range 20-48). Preoperative sonographic ulnar nerve mapping occurred following various elbow surgeries including ulnar nerve transposition to assess nerve location prior to subsequent elbow surgery. Of the 24 patients with preoperative sonographic ulnar nerve mapping, subsequent surgery was performed arthroscopically in 14 and open in 10 cases. In 11 of the 24 cases, there was specific mention of a modified approach to joint access which was guided by the ulnar nerve map. There were no perioperative ulnar nerve-related complications, such as nerve transection. CONCLUSION: Preoperative mapping can facilitate planning of surgical access and ulnar nerve dissection. Sonographic mapping of the ulnar nerve reduces the potential uncertainty of nerve palpation in a complex postoperative elbow following ulnar nerve transposition. This technique may mitigate the risk of ulnar nerve injury.

Organocatalyzed Birch Reduction Driven by Visible Light.

The Birch reduction is a powerful synthetic methodology that uses solvated electrons to convert inert arenes to 1,4-cyclohexadienes-valuable intermediates for building molecular complexity. Birch reductions traditionally employ alkali metals dissolved in ammonia to produce a solvated electron for the reduction of unactivated arenes such as benzene (Ered < -3.42 V vs SCE). Photoredox catalysts have been gaining popularity in highly reducing applications, but none have been reported to demonstrate reduction potentials powerful enough to reduce benzene. Here, we introduce benzo[ghi]perylene imides as new organic photoredox catalysts for Birch reductions performed at ambient temperature and driven by visible light from commercially available LEDs. Using low catalyst loadings (<1 mol percent), benzene and other functionalized arenes were selectively transformed to 1,4-cyclohexadienes in moderate to good yields in a completely metal-free reaction. Mechanistic studies support that this unprecedented visible-light-induced reactivity is enabled by the ability of the organic photoredox catalyst to harness the energy from two visible-light photons to affect a single, high-energy chemical transformation.

Sorafenib and omacetaxine mepesuccinate as a safe and effective treatment for acute myeloid leukemia carrying internal tandem duplication of Fms-like tyrosine kinase 3.

BACKGROUND: Omacetaxine mepesuccinate (OME) has antileukemic effects against acute myeloid leukemia (AML) carrying an internal tandem duplication of Fms-like tyrosine kinase 3 (FLT3-ITD). A phase 2 clinical trial was conducted to evaluate a combination treatment of sorafenib and omacetaxine mepesuccinate (SOME). METHODS: Relapsed or refractory (R/R) or newly diagnosed patients were treated with sorafenib (200-400 mg twice daily) and OME (2 mg daily) for 7 (first course) or 5 days (second course onward) every 21 days until disease progression or allogeneic hematopoietic stem cell transplantation (HSCT). The primary endpoint was composite complete remission, which was defined as complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi). Secondary endpoints were leukemia-free survival (LFS) and overall survival (OS). RESULTS: Thirty-nine R/R patients and 5 newly diagnosed patients were recruited. Among the R/R patients, 28 achieved CR or CRi. Two patients showed partial remission, and 9 patients did not respond. Among the 5 newly diagnosed patients, 4 achieved CR, and 1 achieved CRi. The median LFS and OS were 5.6 and 10.9 months, respectively. Prior Fms-like tyrosine kinase 3 (FLT3) inhibitor exposure (P = .007), 2 or more inductions (P = .001), and coexisting IDH2 (P = .008) and RUNX1 mutations (P = .003) were associated with lower CR/CRi rates. HSCT consolidation and deep molecular responses (defined as an FLT3-ITD variant allelic frequency [VAF] ≤ 0.1% or a nucleophosmin 1 [NPM1] mutant VAF ≤ 0.01%) were associated with better OS and LFS. Prior FLT3 inhibitor exposure and 2 or more inductions were associated with inferior LFS. CONCLUSIONS: SOME was safe and effective for R/R and newly diagnosed FLT3-ITD AML.