Arizona Pain Specialists

To identify patient and intervention factors that moderate the effects of running on intervertebral disc health (IVD) in adults with non‑specific chronic low back pain. Pre‑planned secondary analysis of a 12-week parallel-group (1:1) randomised controlled trial of 40 adults with non-specific CLBP (mean [SD] age: 33 [6] years, female: 50%). Participants were allocated to a digitally-delivered progressive run-walk interval exercise training program (3 days/week, 30 min/session) or waitlist control. Magnetic resonance imaging at baseline, six, and 12 weeks quantified primary outcome IVD composition as whole-disc T2 (ms) from T11/T12 to L5/S1. Moderators included baseline degeneration (Pfirrmann grade; aggregated Pfirrmann score), sex, body mass index, and intervention factors (cumulative running volume, mean speed, and dominant surface). Linear mixed models were fitted at the IVD level to estimate group-by-time effects within each moderator-defined subgroup (α = 0.05). The highest aggregated Pfirrmann scores reflecting greater multi-level degeneration (estimated marginal mean net difference [95%CI]: 3.42 [0.22, 6.62] ms, P = 0.036), cumulative running volumes between 28.6 and 46.1 kms (4.80 [2.51, 7.10] ms, P < 0.001), mean running speeds between 10.5 and 11.7km/h (2.46 [0.14, 4.79] ms, P = 0.038), and running on grass (2.93 [0.10, 5.76] ms, P = 0.043) positively moderated between-group IVD T2 changes. In this pre-planned secondary analysis of a randomised control trial of a run-walk program, our data suggest running speed, volume and surface, as well as more multi-level IVD degeneration, may be associated with more favourable 12-week IVD T2 changes. Findings are hypothesis-generating and may inform future trials designed to optimise IVD health.

Tooth extraction is the most common oral surgical procedure performed in human and veterinary dentistry. One possible complication during extraction is root fragment displacement into adjacent anatomical spaces. Root fragment displacement into adjacent anatomical spaces can lead to serious side effects including pain and infection; therefore, displaced fragments should be removed when possible. Root fragment removal techniques from the mandibular canal have not been studied in veterinary or human dentistry. A reported complication of dental implant placement in humans is displacement into the mandibular canal, and techniques have been developed to remove these displaced implants. This report compares 2 techniques to remove displaced root fragments from the mandibular canal in canine cadavers based on previously published methods to remove displaced dental implants from the mandibular canal in humans.

e17032 Background: Mevrometostat (M) is a potent and selective small molecule inhibitor of EZH2. Dose exploration of M in combination with enzalutamide (E) showed a manageable safety profile and promising activity in patients with CRPC in a phase 1 study (NCT03460977). M exhibited dose-dependent pharmacokinetic (PK) exposure increases up to 1250 mg twice daily (BID) in combination with E (160 mg once daily [QD]). We report the corresponding PD effects of EZH2 inhibition and tumor gene expression changes by M + E in patients with CRPC. Methods: Serial whole blood and paired tumor biopsy samples were collected during dose escalation of M from 150 to 1250 mg BID in combination with E (160 mg QD) given on empty stomach in patients with CRPC. Paired tumor biopsy samples were collected before the study and after 21 days of M + E or E. H3K27Me3 PD marker was evaluated in peripheral granulocytes by flow cytometry and in paired tumor biopsy samples by an immunohistochemistry assay. Tumor gene expression was profiled by whole transcriptomic RNA sequencing. Pre- and post-treatment sample gene expression levels and gene signature Gene Set Variation Analysis (GSVA) enrichment scores were analyzed by a simple linear model with transformation, if appropriate. Results: Dose-dependent H3K27Me3 PD marker reduction by M + E was observed in peripheral granulocytes and paired tumor biopsies in patients with CRPC. Strong H3K27Me3 reduction (≥75%) in granulocytes was achieved at ≥375 mg of M + E. Tumor H3K27Me3 levels were effectively reduced from baseline in 6 patients receiving M at 1250 mg + E with a group mean change of –67% determined by H scores (95% CI: –86%, –23%; P =0.020) and –75% determined by H3K27Me3 staining (positive cells with high and medium intensity in tumor area; 95% CI: –93%, –11%; P =0.038). No significant change in tumor H3K27Me3 levels was observed in 4 patients receiving M at 500 mg + E. Consistent with strong EZH2 inhibition observed in tumor samples from patients receiving M at 1250 mg + E, M + E increased the expression of genes reported to be repressed by the PRC2/EZH2 complex (e.g., BMP7 , CPAMD8 , EYA4 , FHL1 , IGFBP3, and NOV ), and decreased expression of EZH2 and other genes involved in the E2F pathway, the G2M checkpoint, Myc responsive genes, and/or cell cycle progression (e.g., AURKA , CDK1 , FOXM1 , RAD54L , TOP2A, and TYMS ). Conclusions: These data indicate that M at 1250 mg BID on an empty stomach in combination with E effectively inhibits EZH2 in tumor tissue and may overcome drug resistance and/or enhance androgen-targeting drug activity by restoring the function of tumor suppressor genes and blocking tumor cell proliferation and cell cycle progression. These data support dose recommendation for phase 3 pivotal studies and enhance understanding of mechanism of action for M + E in CRPC. Clinical trial information: NCT03460977 .

Antimicrobial stewardship is critical for the prevention of antimicrobial resistance. A lack of prescribing guidelines makes overprescribing in veterinary dentistry likely and represents an opportunity for improvement of stewardship practices. This study described prescribing practices of residency-trained and board-certified veterinary dentists for dogs and cats undergoing dental procedures. Antibiotic-use data were collected from the first 10 patients presenting for a dental procedure at each of 22 participating clinics beginning on October 2, 2023. 35% of patients undergoing procedures received 1 or more systemically administered antibiotic, most commonly amoxicillin-clavulanic acid, ampicillin-sulbactam, and clindamycin. Half (43 of 85 [50.6%]) of prescriptions for dogs were for perioperative or postoperative prophylaxis. For dogs, antibiotic duration for prophylactic versus treatment purposes was not significantly different. Common conditions included periodontal disease, tooth fractures, and oral masses. Comorbid conditions were present in 22.3% (49 of 220) of patients. Presence of comorbid conditions was not a risk factor for antibiotic prescribing. Tooth extractions were a risk factor for antibiotic prescribing among patients with periodontal disease, and those with ≥ 11 were more likely to receive antibiotics than those with < 5 extractions. This study characterized antibiotic use among canine and feline dental procedures performed by residency-trained and board-certified veterinary dentists and identified tooth extractions as a risk factor for antibiotic prescribing. The results obtained from this study provide insight into prescribing practices in a referral setting and impetus to develop outcomes-based studies to determine the need for prophylactic antibiotics during specific procedures, especially tooth extractions.

From the theoretical foundations of laser and energy-based applications for the skin to the development of advanced medical devices, the field of dermatologic surgery has undergone transformative changes. To review the scientific and clinical advancement of laser and energy-based therapies within dermatologic surgery. A literature search was conducted to identify important scientific advancements and landmark studies on light, laser, and energy-based devices within the field of dermatologic surgery. Since the introduction of selective photothermolysis principles in the 1980s, numerous laser and energy-based devices have been developed to effectively treat vascular lesions, target pigmentation, remove tattoos, rejuvenate the skin, and remove hair. Beyond aesthetic applications, photodynamic therapy was introduced to treat various neoplastic and inflammatory conditions. Lasers have also been employed to enhance transcutaneous drug delivery, and new lasers continue to emerge for treating common inflammatory conditions, such as acne. These innovations have contributed to a paradigm shift toward safe and effective, but less invasive, procedure-based treatment in addressing medical and aesthetic concerns in dermatology. Dermatologists have consistently led the way in the continuous development and innovative application of laser and energy-based devices to effectively address a variety of skin conditions.