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Background: Heterotopic ossification in the elbow, often caused by trauma or neurogenic factors, can lead to limited range of motion and physical impairment, while severe cases may result in debilitating loss of function. Complete bony ankylosis of the elbow, though rare, presents challenges in treatment due to complex anatomy and high recurrence rates, with limited literature on management and outcomes. This study retrospectively investigates cases of elbow ankylosis secondary to heterotopic ossification, assessing long-term functional outcomes following operative intervention and standardized rehabilitation. Methods: A retrospective case series was performed on patients who underwent surgical excision of heterotopic ossification of the elbow at our institution. Outcomes of interest were intraoperative flexion-extension arc, flexion-extension arc at the final long-term postoperative follow-up, visual analog scale pain scores at long-term follow-up, and Mayo Elbow Performance scores at long-term follow-up. The Wilcoxon signed-rank test was performed to identify a statistically significant difference between arc of motion achieved intraoperatively and the arc of motion maintained at the final long-term postoperative follow-up. Results: Between September 1999 and July 2021, 107 patients underwent operative resection for heterotopic ossification around the elbow, with 13 patients (16 elbows) exhibiting complete ankylosis at time of surgery. Patients were followed up for a minimum of 2 years. Long-term outcomes demonstrated an average visual analog scale pain score of 1.4 +/− 1.7, and an average Mayo Elbow Performance score of 85.9 +/−12.8, with 75% of cases maintaining at least 100 degrees of flexion-extension arc at the final long-term postoperative follow-up. On average, the flexion-extension arc of motion at the final follow-up was preserved at 95% of intraoperative levels. Patients did have an average residual flexion contracture of 18 +/− 9 degrees at the final follow-up. Conclusion: Surgical excision for complete elbow ankylosis secondary to heterotopic ossification presents challenges due to potential complications. Our study shows favorable long-term outcomes in pain scores, range of motion, and Mayo Elbow Performance scores. Despite reported complications in the literature, our series exhibited no adverse events, supporting operative excision as a standard treatment with overall fair to excellent outcomes. Further research, particularly involving multicenter, randomized, prospective studies, is warranted to refine protocols and understand predictors for improved outcomes in this patient population.

Abstract Background Food malabsorption and intolerance is implicated in gastrointestinal symptoms among patients with irritable bowel syndrome (IBS). Key triggers include fructose and fructan. Prior studies examined fructose and fructan malabsorption separately in IBS patients. None have concurrently assessed both within the same patient group. We aimed to investigate the association between fructose and fructan malabsorption in the same patients with IBS using hydrogen breath testing (HBT). Methods We retrospectively identified patients with IBS who underwent fructose and fructan HBTs and abstracted their results from the electronic medical record. Fructose and fructan HBTs were performed by administering a 25 g fructose solution or 10 g fructan solution, followed by breath hydrogen readings every 30 min for 3 h. Patients were positive for fructose or fructan malabsorption if breath hydrogen levels exceeded 20 ppm. Results Of 186 IBS patients, 71 (38.2%) were positive for fructose malabsorption and 91 (48.9%) were positive for fructan malabsorption. Of these patients, 42 (22.6%) were positive for fructose malabsorption and fructan malabsorption. Positive fructose HBT readings were significantly associated with positive fructan HBT readings (p = 0.0283). Patients positive for fructose malabsorption or fructan malabsorption had 1.951 times higher odds of testing positive for the other carbohydrate. Conclusions Our results reveal a clinically significant association between fructose malabsorption and fructan malabsorption in patients with IBS. Fructan malabsorption should be assessed in patients with fructose malabsorption, and vice versa. Further studies are required to identify the mechanisms underlying our findings.

Purpose: To compare the biomechanical performance of a suture with proposed dynamic self-tensioning properties with that of commonly used high-tensile sutures by evaluating suture loop length changes, responses to cyclic loading, and failure testing with intermittent saline soaks. Methods: Six knots each of 4 different sutures were studied: 3 high-tensile sutures (ORTHOCORD, FiberWire, and ETHIBOND), and a dynamically self-tensioning suture (DYNACORD). After we measured loop length, knots were soaked in 37°C saline for 24 hours. Loop lengths were remeasured and tensile testing was performed. Cyclic elongation, first-cycle excursion, and elongation amplitude were recorded. Knots were then resoaked and retested. Finally, knots were pulled to failure, and peak load and stiffness were measured. Values were compared using nonparametric statistical tests. Results: DYNACORD loop length decreased by 27% after the first soak (P = .002), whereas the other sutures demonstrated no length change (P > .05). Although DYNACORD loop length increased during cyclic load testing (P = .009), it was still significantly reduced after the second saline soak compared with its initial length (P = .002), whereas all other suture loops had elongated. ETHIBOND (P = .004) and ORTHOCORD (P = .002) had significantly less cyclic elongation from cycle I to cycle II testing compared with the other sutures. ETHIBOND had the lowest peak load at failure (P = .002). FiberWire had the greatest stiffness (P = .006). Conclusions: Compared with other suture types, the self-tensioning suture showed dynamic properties, demonstrating a decrease in loop length when soaked in a saline bath. This length was maintained after a second soak despite increased loop length during interval cyclic loading. Clinical Relevance: Knot and loop security are of paramount importance to arthroscopic soft-tissue procedures. The ability for a suture to self-tension has implications for how it may interact with tissues in vivo to increase construct stability after arthroscopic soft tissue repair procedures.

Accurate urethra contouring is critical in prostate SBRT. We compared urethra contouring on CT-urethrogram and T2-weighted MRI. The dice similarity coefficient, Jaccard index, Hausdorff distance and mean distance to agreement were evaluated. All four metrics indicate better agreement and less variability in urethra contouring on CT-urethrogram, compared to T2-weighted MRI.

Abstract Radiotherapy is a non-invasive standard treatment for prostate cancer (PC). However, PC develops radio-resistance, highlighting a need for agents to improve radiotherapy response. Canagliflozin, an inhibitor of sodium-glucose co-transporter-2, is approved for use in diabetes and heart failure, but is also shown to inhibit PC growth. However, whether canagliflozin can improve radiotherapy response in PC remains unknown. Here, we show that well-tolerated doses of canagliflozin suppress proliferation and survival of androgen-sensitive and insensitive human PC cells and tumors and sensitize them to radiotherapy. Canagliflozin blocks mitochondrial respiration, promotes AMPK activity, inhibits the MAPK and mTOR-p70S6k/4EBP1 pathways, activates cell cycle checkpoints, and inhibits proliferation in part through HIF-1α suppression. Canagliflozin mediates transcriptional reprogramming of several metabolic and survival pathways known to be regulated by ETS and E2F family transcription factors. Genes downregulated by canagliflozin are associated with poor PC prognosis. This study lays the groundwork for clinical investigation of canagliflozin in PC prevention and treatment in combination with radiotherapy.

Metastatic prostate cancer can be difficult to biopsy and characterise. Here, the authors use cell-free DNA methylation analysis to illustrate changes in hypermethylation in metastatic disease.

Background: Prostate Specific Membrane Antigen (PSMA) – positron emission tomography (PET) guides metastasis-directed radiotherapy (MDRT) in prostate cancer (PrCa). However, its value as a treatment response assessment tool after MDRT remains unclear. Importantly, there is limited understanding of the potential of radiotherapy (RT) to alter PSMA gene (folate hydrolase 1; FOLH1) expression. Methodology: We reviewed a series of 11 men with oligo-metastatic PrCa (25 metastasis sites) treated with MDRT before re-staging with 18F-DCFPyL (PSMA) PET upon secondary recurrence. Acute effects of RT on PSMA protein and mRNA levels were examined with qPCR and immunoblotting in human wild-type androgen-sensitive (LNCap), castrate-resistant (22RV1) and castrate-resistant neuroendocrine (PC3 and DU145) PrCa cell lines. Xenograft tumors were analyzed with immunohistochemistry. Further, we examined PSMA expression in untreated and irradiated radio-resistant (RR) 22RV1 (22RV1-RR) and DU145 (DU145-RR) cells and xenografts selected for survival after high-dose RT. Results: The majority of MDRT-treated lesions showed lack of PSMA-PET/CT avidity, suggesting treatment response even after low biological effective dose (BED) MDRT. We observed similar high degree of heterogeneity of PSMA expression in both human specimens and in xenograft tumors. PSMA was highly expressed in LNCap and 22RV1 cells and tumors but not in the neuroendocrine PC3 and DU145 models. Single fraction RT caused detectable reduction in PSMA protein but not in mRNA levels in LNCap cells and did not significantly alter PSMA protein or mRNA levels in tissue culture or xenografts of the other cell lines. However, radio-resistant 22RV1-RR cells and tumors demonstrated marked decrease of PSMA transcript and protein expression over their parental counterparts. Conclusions: PSMA-PET may be a promising tool to assess RT response in oligo-metastatic PrCa. However, future systematic investigation of this concept should recognize the high degree of heterogeneity of PSMA expression within prostate tumors and the risk for loss of PSMA expression in tumor surviving curative courses of RT.

A 30-year-old woman presented with angina pectoris. Coronary angiography revealed severe stenosis in the left main and right coronary arteries that did not improve with intracoronary nitroglycerin. Coronary computed tomography angiography and positron emission tomography revealed coronary ostia inflammation and aortic root fat stranding. She was diagnosed with vasculitis and valvulitis and received immunotherapy and coronary bypass. (Level of Difficulty: Advanced.)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is considered a non‐immunogenic tumor, and immune checkpoint inhibitor monotherapy lacks efficacy in this disease. Radiotherapy (RT) can stimulate the immune system. Here, we show that treatment of KPC and Pan02 murine PDAC cells with RT and gemcitabine upregulated PD‐L1 expression in a JAK/Stat1‐dependent manner. In vitro, PD‐L1 inhibition did not alter radio‐ and chemosensitivity. In vivo, addition of anti‐PD‐L1 to high (12, 5 × 3, 20 Gy) but not low (6, 5 × 2 Gy) RT doses significantly improved tumor response in KPC and Pan02 allografts. Radiosensitization after PD‐L1 blockade was associated with reduced CD11b+Gr1+ myeloid cell infiltration and enhanced CD45+CD8+ T‐cell infiltration with concomitant upregulation of T‐cell activation markers including CD69, CD44, and FasL, and increased CD8:Treg ratio. Depletion of CD8+ T cells abrogated radiosensitization by anti‐PD‐L1. Blockade of PD‐L1 further augmented the effect of high RT doses (12 Gy) in preventing development of liver metastases. Exploring multiple mathematical models reveals a mechanism able to explain the observed synergy between RT and anti‐PD‐L1 therapy. Our findings provide a rationale for testing the use of immune checkpoint inhibitors with RT in PDAC.