Vascularized Composite Allograft Versus Prosthetic for Reconstruction After Facial and Hand Trauma: Comparing Cost, Complications, and Long-term Outcome.

ABSTRACT: In the past decade, vascularized composite allotransplantation (VCA) has become clinical reality for reconstruction after face and hand trauma. It offers patients the unique opportunity to regain form and function in a way that had only been achieved with traditional reconstruction or with the use of prostheses. On the other hand, prostheses for facial and hand reconstruction have continued to evolve over the years and, in many cases, represent the primary option for patients after hand and face trauma. We compared the cost, associated complications, and long-term outcomes of VCA with prostheses for reconstruction of the face and hand/upper extremity. Ultimately, VCA and prostheses represent 2 different reconstructive options with distinct benefit profiles and associated limitations and should ideally not be perceived as competing choices. Our work adds a valuable component to the general framework guiding the decision to offer VCA or prostheses for reconstruction after face and upper extremity trauma.

Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy.

Patient-derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for pancreatic ductal adenocarcinoma (PDAC) where most patients are diagnosed at an advanced stage with non-resectable tumors and where patient tissue is in the form of needle biopsies. Here the development and characterization of microfluidic devices for testing therapies using a limited amount of tissue or PDOs available from PDAC biopsies is described. It is demonstrated that microfluidic PDOs are phenotypically and genotypically similar to the gold-standard Matrigel organoids with the advantages of 1) spheroid uniformity, 2) minimal cell number requirement, and 3) not relying on Matrigel. The utility of microfluidic PDOs is proven by testing PDO responses to several chemotherapies, including an inhibitor of glycogen synthase kinase (GSKI). In addition, microfluidic organoid cultures are used to test effectiveness of immunotherapy comprised of NK cells in combination with a novel biologic. In summary, our microfluidic device offers considerable benefits for personalizing oncology based on cancer biopsies and may, in the future, be developed into a companion diagnostic for chemotherapy or immunotherapy treatments.

Cutaneous Ureterostomy Following Radical Cystectomy for Bladder Cancer: A Contemporary Series.

OBJECTIVE: To report peri-operative outcomes of a contemporary series of bladder cancer patients undergoing radical cystectomy (RC) with cutaneous ureterostomy (CU) urinary diversion at a tertiary referral center. METHODS: We retrospectively identified patients who underwent RC with CU at Mayo Clinic between 2016 and 2021. Clinicopathologic and perioperative characteristics were analyzed using standard descriptive statistics. RESULTS: A total of 31 patients underwent RC with CU at our institution. Median age was 72years and 21 were male. This was highly comorbid cohort (83% had an American Society of Anesthesiologists [ASA] Physical Status Classification System ≥3; median Charlson Comorbidity index= 8). Median time to flatus, tolerating regular diet, and length of stay were 3 (interquartile range [IQR] 3-3), 3 (IQR 3-4), and 4days (IQR 4-7), respectively. A total of 14 patients experienced a high-grade complication (Clavien-Dindo ≥3) within 30days of surgery, and 8 were readmitted. The most common 30-day complication was sepsis, which affected 13% (4/31) of patients. At 90days postsurgery, the readmission rate was 32% (10/31), most commonly for sepsis. Three patients required reoperation within 90days, including one patient who required CU revision due to stomal ischemia. One patient died within this time frame from causes unrelated to bladder cancer. CONCLUSION: In a comorbid, relatively elderly bladder cancer cohort undergoing RC, the use of CU was associated with expeditious surgery and postoperative recovery. CU represents an option for urinary diversion in high-risk patients undergoing RC. Higher rate of postoperative ureteral obstruction can be pre-emptively addressed with chronic stent placement.

Population-based incidence of intraocular tumours in Olmsted County, Minnesota.

BACKGROUND/AIMS: To determine population-based incidence of intraocular tumours in Olmsted County, Minnesota. METHODS: Record review of the Rochester Epidemiology Project medical record linkage system from 1 January 2006 to 31 December 2015 for patient demographics, tumour type by clinical diagnosis and presence or absence of confirmation by histopathology. The incidence rate of any intraocular tumour and of each tumour type was calculated per million person-years. Poisson regression analysis was used to analyse changes in incidence over time. RESULTS: There were 948 patients diagnosed with intraocular tumours resulting in an age-adjusted and sex-adjusted incidence rate of 727.5 per million (95% CI: 680.8 to 774.2, p<0.05). Most tumours were benign (953, 98%). Of the benign lesions, melanocytic lesions were the majority (942, 97%), with adjusted incidence rates of 646.9 (95% CI: 602.8 to 691.1) for choroidal nevus and 55.8 (95% CI: 43.2 to 64.8) for iris nevus. Malignant lesions were rare (16, 2%) with 13 cases of choroidal melanoma and 1 case each of iris melanoma, retinal leukaemic infiltration and metastasis. The adjusted incidence rate for choroidal melanoma was 7.1 (95% CI: 2.5 to 11.8). CONCLUSION: In a population-based setting, most intraocular tumours are benign and melanocytic. Although malignant lesions are less common, it is important to remain vigilant with appropriate monitoring given the potential for vision loss and life-threatening malignancy.

Transforming growth factor beta signaling functions during mammalian kidney development.

Aberrant transforming growth factor beta (TGFß) signaling during embryogenesis is implicated in severe congenital abnormalities, including kidney malformations. However, the molecular mechanisms that underlie congenital kidney malformations related to TGFß signaling remain poorly understood. Here, we review current understanding of the lineage-specific roles of TGFß signaling during kidney development and how dysregulation of TGFß signaling contributes to the pathogenesis of kidney malformation.