Aggregate culture is a useful method for inducing chondrogenic differentiation of human mesenchymal stem cells (hMSC) in a three-dimensional in vitro culture environment. Conventional aggregate culture, however, typically requires repeated growth factor supplementation during media changes, which is both expensive and time-intensive. In addition, homogenous cell differentiation is limited by the diffusion of chondrogenic growth factor from the culture medium into the aggregate and peripheral cell consumption of the growth factor. We have engineered a technology to incorporate growth factor-loaded polymer microspheres within hMSC aggregates themselves. Here, we report on the system’s capacity to induce chondrogenesis via sustained delivery of transforming growth factor-b1 (TGF-β1). Cartilage formation after 3 weeks in the absence of externally supplied growth factor approached that of aggregates cultured by conventional methods. Chondrogenesis in the central region of the aggregates is enabled at TGF-β1 levels much lower than those required by conventional culture using exogenously supplied TGF-β1, which is likely a result of the system’s ability to overcome limitations of growth factor diffusion from cell culture media surrounding the exterior of the aggregates. Importantly, the inclusion of growth factor-releasing polymer microspheres in hMSC aggregates could enable in vivo chondrogenesis for cartilage tissue engineering applications without extensive in vitro culture.
Objective To determine age- and sex-specific incidence rates of inguinal hernia repairs (IHR) in a well defined USA population and examine trends over time. Summary Background Data IHR represent a substantial burden to the US healthcare system. An up to date appraisal will identify future healthcare needs. Methods A retrospective review of all IHR performed on adult residents of Olmsted County, MN from 1989 to 2008 was performed. Cases were ascertained through the Rochester Epidemiology Project, a record-linkage system with >97% population coverage. Incidence rates were calculated by using incident cases as the numerator and population counts from the census as the denominator. Trends over time were evaluated using Poisson regression. Results During the study period, a total of 4,026 IHR were performed on 3,599 unique adults. Incidence rates per 100,000 person-years were greater for men: 368 vs 44 for women, and increased with age: from 194 to 648 in men, and from 28 to 108 in women between 30 and 70 years of age. Initial, unilateral IHR comprised 74% of all IHR types. The life-long cumulative incidence of an initial, unilateral or bilateral IHR in adulthood was 42.5% in men and 5.8% in women. Over time (from 1989 to 2008), the incidence of initial, unilateral IHR in men decreased from 474 to 373 (relative reduction, RR=21%). Bilateral IHR increased from 42 to 71 (relative increase=70%), contralateral metachronous IHR decreased from 29 to 11 (RR=62%), and recurrent IHR decreased from 66 to 26 (RR=61%), all changes p<0.001. Conclusions IHR are common, their incidence varies greatly by age and sex, and has decreased substantially over time in Olmsted County, Minnesota.
Background and Objectives. While excisional biopsy is recommended to diagnose cutaneous melanoma, various biopsy techniques are used in practice. We undertook this study to identify how frequently final tumor stage and treatment recommendations changed from diagnostic biopsy to final histopathology after wide local excision (WLE). Methods. We compared the histopathology of the dermatopathologist-reviewed diagnostic biopsy and final WLE in 332 cutaneous melanoma patients. Results. Tumor sites were extremity (51%), trunk (33%), and head/neck (16%). Initial biopsy types were excisional (56%), punch (21%), shave (18%), and incisional (5%). Most diagnostic biopsies were margin positive regardless of technique, and 36% of patients had residual melanoma on WLE. T-stage changed in 8% of patients, of whom 59% were diagnosed by punch biopsy, 15% by incisional biopsy, 15% by shave biopsy, and 11% by excisional biopsy (P < 0.0001). Treatment recommendations changed in 6%: 2% after excisional biopsy, 5% after shave biopsy, 18% after punch biopsy, and 18% after incisional biopsy (P < 0.0001). Conclusions. Although most biopsy margins were positive, T-stage and treatment changed for only a minority of melanoma patients. Our data provide valuable information to inform patient discussion regarding the likelihood of a change in prognosis and the need for secondary procedures after WLE. These data support the superiority of dermatopathologist-reviewed excisional biopsy when feasible.
Purpose The relationship between body mass index (BMI) and the risk of inguinal hernia development is unclear. To explore the relationship, we determined whether the incidence of inguinal hernia repairs (IHR) varied across patients in different BMI categories. Study Design A population-based incidence study was undertaken. We reviewed all IHR performed on adult residents of Olmsted County, MN from 2004 to 2008. Cases were ascertained through the Rochester Epidemiology Project, a records-linkage system with more than 97% population coverage. Results During the study period, a total of 1,168 IHR were performed on 879 men and 107 women. The median BMI of the cohort was 26.7 kg/m2 (range 14.9 – 58.1; interquartile range 23.9 – 28.9). Incidence rates varied significantly as a function of BMI (p<0.001). Rates were highest among men who were either normal weight or overweight (419.8 and 421.1 per 100,000 person years for BMI<25 and BMI 25–29.9, respectively), and lowest for obese and morbidly obese men (273.5 and 99.4 per 100,000 person years for BMI 30–34.9 and BMI ≥35, respectively). Findings were similar across all age categories and in patients who had an IHR that was initial or recurrent, direct or indirect, and unilateral or bilateral. Conclusions The incidence of IHR decreased as BMI increased. Obese and morbidly obese patients had a lower incidence of IHR than those who were normal weight or overweight. The causal mechanisms leading to such a relationship are unclear and warrant further study.
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