Study Design. Experimental and descriptive study of a xenotransplantation model in minipigs. Objective. To study survival and function of human mesenchymal stem cells (hMSCs) after transplantation into injured porcine spinal discs, as a model for cell therapy. Summary of Background Data. Biologic treatment options of the intervertebral disc are suggested for patients with chronic low back pain caused by disc degeneration. Methods. Three lumbar discs in each of 9 minipigs were injured by aspiration of the nucleus pulposus (NP), 2 weeks later hMSCs were injected in F12 media suspension (cell/med) or with a hydrogel carrier (Puramatrix) (cell/gel). The animals were sacrificed after 1, 3, or 6 months. Disc appearance was visualized by magnetic resonance imaging. Immunohistochemistry methods were used to detect hMSCs by antihuman nuclear antibody staining, and further performed for Collagen II, Aggrecan, and Collagen I. SOX 9, Aggrecan, Versican, Collagen IA, and Collagen IIA and Collagen IIB human mRNA expression was analyzed by real-time PCR. Results. At magnetic resonance imaging all injured discs demonstrated degenerative signs. Cell/gel discs showed fewer changes compared with cell/med discs and only injured discs at later time points. hMSCs were detected in 9 of 10 of the cell/gel discs and in 8 of 9 of the cell/med discs. Immunostaining for Aggrecan and Collagen type II expression were observed in NP after 3 and 6 months in gel/cell discs and colocalized with the antihuman nuclear antibody. mRNA expression of Collagen IIA, Collagen IIB, Versican, Collagen 1A, Aggrecan, and SOX9 were detected in both cell/med and cell/gel discs at the time points 3 and 6 months by real-time PCR. Conclusion. hMSCs survive in the porcine disc for at least 6 months and express typical chondrocyte markers suggesting differentiation toward disc-like cells. As in autologous animal models the combination with a three-dimensional-hydrogel carrier seems to facilitate differentiation and survival of MSCs in the disc. Xenotransplantation seems to be valuable in evaluating the possibility for human cell therapy treatment for intervertebral discs.

Transplantation of mesenchymal stem cells (MSCs) has been suggested for disk degeneration, which is characterized by dysfunctional cells and low proteoglycan production. The aim of this study was to examine the effects of a 3D co-culture system using human disk cells (DCs) and MSCs on collagen and proteoglycan production. DCs and MSCs were expanded in monolayer and grown in pellet cultures for 7, 14 and 28 days and analyzed for hydroxyproline (HP), reflecting total collagen production, and glycosaminoglycan (GAG) accumulation. DCs and MSCs co-cultured at different ratios (25/75, 50/50 and 75%/25%) were examined for GAG accumulation. Collagen type II expression was analyzed immunohistochemically. In a second series, conditioned media were added to pellet cultures of degenerated DCs or MSCs. DCs from degenerated disks and MSCs demonstrated lower total collagen production than non-degenerated DC pellets. GAG production was comparable in DCs and MSCs, except in the youngest donor, with MSC producing about 10 times higher GAG/DNA. Co-cultures resulted in approximately 1.5 times higher GAG/DNA production than DCs. Increased collagen type II expression was seen in co-cultures compared to DC or MSC culture alone, except in the case with highly active MSCs. No positive effect of conditioned media was seen. In conclusion, co-culture of MSCs with degenerated DCs increased proteoglycan and collagen-type ceII production, indicating that in future clinical therapy MSCs can be transplanted without pre-differentiation in vitro. The lack of effect of conditioned media suggests that the positive effect of co-culture on matrix production is not due to soluble factors.

Background: For a few types of cancer, lower socioeconomic status (SES) is associated with higher incidence, and for even more cancer types it is associated with having a less favorable tumor stage at diagnosis. For endometrial cancer (EC), however, there is no clear evidence of such associations with SES. There is a need for analysis of sociodemographic disparities in EC incidences according to stage at diagnosis, which may provide support for trying to improve early detection of EC. Material and methods: Stage-specific incidences of endometrioid and non-endometrioid endometrial carcinomas [EECs (∼90% of all EC cases) and NECs (∼10%)] were analyzed for the population of the Western Swedish Healthcare Region, taking into account year (1995–2016), age, educational level (low, intermediate and high), and immigrant status (Swedish-born, foreign-born). All EC cases were identified and data were obtained from population-based registries. Results: Stage distribution of diagnosed EECs differed significantly according to the educational level of patients who were aged between 50 and 74 years at diagnosis, but not in the case of younger or older patients. An analysis based on 3113 EEC cases aged 50–74 years at diagnosis revealed marked disparities in the stage-II to stage-IV EEC incidences but not in the stage-I EEC incidence. Compared to women with a high level of education, the incidence rate ratios of stage-I, stage-II and stage-III and -IV EEC in women with a low level of education were 1.00 (95% CI: 0.90–1.12), 1.65 (1.13–2.42), and 1.82 (1.33–2.49), respectively. For NEC, we found no such association. Conclusions: Elevated incidences of stage-II to stage-IV EEC in 50- to 74-year-old women with a low level of education suggest that there should be targeted health service trials aimed at improving awareness of EC. Well-targeted EC awareness programs might lead to considerable health benefits.

Background: The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. We evaluated maternal and perinatal outcomes after a national shift from expectancy and induction at 42⁺⁰ weeks to a more active management of late-term pregnancies in Sweden offering induction from 41⁺⁰ weeks or an individual plan aiming at birth or active labour no later than 42⁺⁰ weeks. Methods and findings: Women with a singleton pregnancy lasting 41⁺⁰ weeks or more with a fetus in cephalic presentation (N = 150,370) were included in a nationwide, register-based cohort study. Elective cesarean sections were excluded. Outcomes during period 1, January 2017 to December 2019 (before the shift) versus outcomes during period 2, January 2020 to October 1, 2023 (after the shift) were analysed. For comparison, outcomes of pregnancies lasting 39⁺⁰ to 40⁺⁶ weeks (N = 358,548) were also studied. Primary outcomes were: First, peri/neonatal death (stillbirth or neonatal death before 28 days); second, composite adverse peri/neonatal outcome (peri/neonatal death, Apgar score <4 at 5 min, hypoxic ischemic encephalopathy grades 1–3, meconium aspiration syndrome, birth trauma, or admission to a neonatal intensive care unit (NICU) ≥4 days); third, composite adverse peri/neonatal outcome excluding admission to NICU; and fourth, emergency cesarean section. Secondary outcomes included the components of the primary composite outcomes. Relative risks (RRs) with 95% confidence intervals (CIs) for binary outcomes period 2 versus period 1 were computed using modified Poisson regression analyses with adjustments for maternal age, parity, body mass index (BMI), smoking, and educational level. Induction rates among pregnancies lasting 41⁺⁰ weeks or more increased from 33.7% in period 1 to 52.4% in period 2. Mean (standard deviation) gestational age at birth decreased from 290.7 (2.9) days to 289.6 (2.3) days. Infants born during period 2 were at lower risk of peri/neonatal death compared to infants born during period 1; 0.9/1,000 versus 1.7/1,000 born infants (adjusted RR 0.52; 95% CI [0.38, 0.69]; p < 0.001), and they had a lower risk of having the composite adverse neonatal outcome, both including (50.5/1,000 versus 53.9/1,000, adjusted RR 0.92; 95% CI [0.88, 0.96]; p < 0.001) or excluding NICU admission (18.5/1,000 versus 22.5/1,000, adjusted RR 0.79; 95% CI [0.74, 0.85]; p < 0.001). The cesarean section rate increased from 10.5% in period 1 to 11.9% in period 2 (adjusted RR 1.07; 95% CI [1.04, 1.10]; p < 0.001). For births at 39 to 40 weeks the adjusted RR for peri/neonatal death was 0.86 (95% CI [0.72, 1.02]). One limitation of the study is that we had no data on to what extent monitoring of fetal health was performed. Conclusions: A more active management of pregnancies lasting 41⁺⁰ weeks or more was associated with a decrease in peri/neonatal deaths, and a decrease in composite adverse peri/neonatal outcomes. Increased rate of emergency cesarean sections was observed. Women with pregnancies advancing towards 41 gestational weeks should be given balanced information on the benefits and risks of induction of labour at 41 weeks compared to expectant management until 42 weeks and be offered induction of labour at 41 weeks or active surveillance of pregnancies from 41 weeks in order to decrease peri/neonatal mortality.

Introduction: The majority of data on COVID‐19 in pregnancy are not from sound population‐based active surveillance systems.Material and methods: We conducted a multi‐national study of population‐based national or regional prospective cohorts using standardized definitions within the International Network of Obstetric Survey systems (INOSS). From a source population of women giving birth between March 1 and August 31, 2020, we included pregnant women admitted to hospital with a positive SARS‐CoV‐2 PCR test ≤7 days prior to or during admission and up to 2 days after birth. The admissions were further categorized as COVID‐19‐related or non‐COVID‐19‐related. The primary outcome of interest was incidence of COVID‐19‐related hospital admission. Secondary outcomes included severe maternal disease (ICU admission and mechanical ventilation) and COVID‐19‐directed medical treatment.Results: In a source population of 816 628 maternities, a total of 2338 pregnant women were admitted with SARS‐CoV‐2; among them 940 (40%) were COVID‐19‐related admissions. The pooled incidence estimate for COVID‐19‐related admission was 0.59 (95% confidence interval 0.27–1.02) per 1000 maternities, with notable heterogeneity across countries (I² = 97.3%, P = 0.00). In the COVID‐19 admission group, between 8% and 17% of the women were admitted to intensive care, and 5%–13% needed mechanical ventilation. Thromboprophylaxis was the most frequent treatment given during COVID‐19‐related admission (range 14%–55%). Among 908 infants born to women in the COVID‐19‐related admission group, 5 (0.6%) stillbirths were reported.Conclusions: During the initial months of the pandemic, we found substantial variations in incidence of COVID‐19‐related admissions in nine European countries. Few pregnant women received COVID‐19‐directed medical treatment. Several barriers to rapid surveillance were identified. Investment in robust surveillance should be prioritized to prepare for future pandemics.

Objective: To evaluate whether the results of a previous study that showed a decrease in blood loss and transfusions with a multidisciplinary approach, including a fixed team when delivering women diagnosed with placenta accreta spectrum at Sahlgrenska University Hospital, remained low throughout time, and to investigate hospital stay and maternal and neonatal complications during a time period with varying team structure compared with previous periods.Methods: A retrospective observational cohort study comparing data from medical records including three cohorts of women diagnosed with placenta accreta spectrum between October 2003 and December 2020. Cohort 1 consisted of women delivered before the multidisciplinary approach was introduced. Cohort 2 and cohort 3 were both managed in a multidisciplinary manner, but while cohort 2 was managed by a fixed team, cohort 3 was managed by several different senior specialists. The data were analyzed using Kruskal‐Wallis test.Results: Blood loss and need for transfusion were significantly lower for cohort 3 and cohort 2 compared with cohort 1. No significant difference was found between cohort 3 and cohort 2.Conclusion: The multidisciplinary management and surgical method employed at Sahlgrenska University Hospital have lowered blood loss and the need for transfusions, even over time.