Transplantation Group Research Articles

Infection-related mortality after HLA-identical and haploidentical hematopoietic cell transplantation using reduced-intensity conditioning in an outpatient setting.

Despite the improvements in supportive care for allogeneic-hematopoietic cell transplantation (allo-HCT) recipients, infectious complications and infection-related mortality (IRM) continue to be a major issue for transplantation centers. We herein report the infectious complications and IRM of 107 and 89 patients that underwent haploidentical (haplo-HCT) or HLA-identical HCT at a tertiary referral center during 2013-2020. Patients in the haplo-HCT group received post-transplant cyclophosphamide (PT-Cy), and all received reduced-intensity conditioning regimens. More haplo-HCT recipients presented severe infections in the pre-engraftment period (22.4% vs. 6.7%, p=0.003). Viral (14.9% vs. 4.5%, p=0.016) and fungal (12.1% vs. 1.1%, p=0.003) etiologies were more common in this period in this group. The 100-day and 2-year cumulative incidence of IRM was 15% and 21% for the haplo-HCT and 5.6% and 17% for the HLA-identical group; no significant differences were observed between the groups. Fungal pathogens mainly contributed to IRM (33.3%). Infections were the most common cause of mortality (40/81, 49.4%). There were significant differences in donor/recipient CMV serostatus between transplant groups (0.002). No differences in IRM were observed based on allo-HCT type, with more haplo-HCT patients suffering from severe infections in the pre-engraftment period. Studies to assess future prevention, diagnostic, and treatment strategies to reduce IRM are warranted.

DCas9-Based PDGFR-β Activation ADSCs Accelerate Wound Healing in Diabetic Mice through Angiogenesis and ECM Remodeling.

The chronic wound represents a serious disease characterized by a failure to heal damaged skin and surrounding soft tissue. Mesenchymal stem cells (MSCs) derived from adipose tissue (ADSCs) are a promising therapeutic strategy, but their heterogeneity may result in varying or insufficient therapeutic capabilities. In this study, we discovered that all ADSCs populations expressed platelet-derived growth factor receptor β (PDGFR-β), while the expression level decreased dynamically with passages. Thus, using a CRISPRa-based system, we endogenously overexpressed PDGFR-β in ADSCs. Moreover, a series of in vivo and in vitro experiments were conducted to determine the functional changes in PDGFR-β activation ADSCs (AC-ADSCs) and to investigate the underlying mechanisms. With the activation of PDGFR-β, AC-ADSCs exhibited enhanced migration, survival, and paracrine capacity relative to control ADSCs (CON-ADSCs). In addition, the secretion components of AC-ADSCs contained more pro-angiogenic factors and extracellular matrix-associated molecules, which promoted the function of endothelial cells (ECs) in vitro. Additionally, in in vivo transplantation experiments, the AC-ADSCs transplantation group demonstrated improved wound healing rates, stronger collagen deposition, and angiogenesis. Consequently, our findings revealed that PDGFR-β overexpression enhanced the migration, survival, and paracrine capacity of ADSCs and improved therapeutic effects after transplantation to diabetic mice.

Investigation and comparison of depression, anxiety, and stress among hemodialysis and kidney transplant patients during the covid-19 pandemic

Introduction: Due to the spread of COVID-19, hemodialysis patients experience substantial stress and anxiety regarding post-treatment care after hemodialysis and kidney transplants. This study aims comparison of depression, anxiety, and stress among hemodialysis and kidney transplant patients during the COVID-19 pandemic.
 Methods:The statistical population of this descriptive-cross-sectional study included 206 hemodialysis and kidney transplant patients in the special disease center of Birjand city. Eligible patients were selected in a targeted way in 2021 and 2022. The data collection tool included demographic information form and psychological distress questionnaire. SPSS version 20 was used to analyze the collected data using descriptive and inferential statistics. A significance level of less than 0.05 was considered significant
 Results:The average scores of depression, anxiety and stress in the kidney transplant group were higher than the hemodialysis group (p<0.001). Depression, anxiety and stress had no significant relationship with the variables of age, income, sex, marriage and place of residence (p>0.05).
 Conclusion: The level of depression, anxiety and stress in the kidney transplant group was higher than that of the hemodialysis group, which can be attributed to the concern of the kidney transplant group about rejecting the transplant after contracting the corona virus, and measures are taken to increase the awareness of patients so that they can avoid contracting the disease. prevent illness and future problems

Knowing When to Ignore the Numbers: Single-Center Experience Transplanting Deceased Donor Kidneys with Poor Perfusion Parameters.

Hypothermic machine perfusion is frequently used in evaluating marginal kidneys with poor perfusion parameters (PPP) contributing to delays in kidney placement or discard. We examined outcomes in deceased donor kidney transplants with PPP compared with those with optimal perfusion parameters (OPP). We conducted a retrospective single-center cohort study from 2001 to 2021 comparing PPP (n = 91) with OPP (n = 598) deceased donor kidney transplants. PPP was defined as terminal flow ≤80 mL/min and terminal resistance ≥0.40 mmHg/mL/min. OPP was defined as terminal flow ≥120 mL/min and terminal resistance ≤0.20 mmHg/mL/min. Mean terminal flow was PPP 66 ± 16 vs OPP 149 ± 21 mL/min and resistance was PPP 0.47 ± 0.10 vs OPP 0.15 ± 0.04 mmHg/mL/min (both p < 0.001). Donor age, donation after cardiac death, and terminal serum creatinine levels were similar between groups. Mean Kidney Donor Profile Index was higher among PPP donors (PPP 65 ± 23% vs OPP 52 ± 27%, p < 0.001). The PPP transplant group had more females and lower weight and BMI. Delayed graft function was comparable (PPP 32% vs OPP 27%, p = 0.33) even though cold ischemia times trended toward longer in PPP kidneys (PPP 28 ± 10 vs OPP 26 ± 9 hours, p = 0.09). One-year patient survival (PPP 98% vs OPP 97%, p = 0.84) and graft survival (PPP 91% vs OPP 92%, p = 0.23) were equivalent. PPP did predict inferior overall and death-censored graft survival long-term (overall hazard ratio 1.63, 95% CI 1.19 to 2.23 and death-censored hazard ratio 1.77, 95% CI 1.15 to 2.74). At 1 year, the estimated glomerular filtration rate was higher with OPP kidneys (PPP 40 ± 17 vs OPP 52 ± 19 mL/min/1.73 m 2 , p < 0.001). Short-term outcomes in PPP kidneys were comparable to OPP kidneys despite higher Kidney Donor Profile Index and longer cold ischemia times, suggesting a role for increased utilization of these organs with careful recipient selection.

Hippocampal Noradrenaline Is a Positive Regulator of Spatial Working Memory and Neurogenesis in the Rat

Loss of noradrenaline (NA)-rich afferents from the Locus Coeruleus (LC) ascending to the hippocampal formation has been reported to dramatically affect distinct aspects of cognitive function, in addition to reducing the proliferation of neural progenitors in the dentate gyrus. Here, the hypothesis that reinstating hippocampal noradrenergic neurotransmission with transplanted LC-derived neuroblasts would concurrently normalize both cognitive performance and adult hippocampal neurogenesis was investigated. Post-natal day (PD) 4 rats underwent selective immunolesioning of hippocampal noradrenergic afferents followed, 4 days later, by the bilateral intrahippocampal implantation of LC noradrenergic-rich or control cerebellar (CBL) neuroblasts. Starting from 4 weeks and up to about 9 months post-surgery, sensory-motor and spatial navigation abilities were evaluated, followed by post-mortem semiquantitative tissue analyses. All animals in the Control, Lesion, Noradrenergic Transplant and Control CBL Transplant groups exhibited normal sensory-motor function and were equally efficient in the reference memory version of the water maze task. By contrast, working memory abilities were seen to be consistently impaired in the Lesion-only and Control CBL-Transplanted rats, which also exhibited a virtually complete noradrenergic fiber depletion and a significant 62-65% reduction in proliferating 5-bromo-2'deoxyuridine (BrdU)-positive progenitors in the dentate gyrus. Notably, the noradrenergic reinnervation promoted by the grafted LC, but not cerebellar neuroblasts, significantly ameliorated working memory performance and reinstated a fairly normal density of proliferating progenitors. Thus, LC-derived noradrenergic inputs may act as positive regulators of hippocampus-dependent spatial working memory possibly via the concurrent maintenance of normal progenitor proliferation in the dentate gyrus.

Clinical study of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation in the treatment of FLT3-ITD(+) acute myeloid leukemia with normal karyotype

Objective: To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD(+) acute myeloid leukemia (AML) with normal karyotype. Methods: The clinical data of FLT3-ITD(+) AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results: The study included 49 patients with FLT3-ITD(+)AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD(+) (P>0.05) . There were 12 patients with high-frequency FLT3-ITD(+) in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion: Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD(+) patients, particularly those with FLT3-ITD high-frequency mutation.

Antibody acquisition after second and third SARS-CoV-2 vaccinations in Japanese kidney transplant patients: a prospective study

Kidney transplant patients have lower antibody acquisition after SARS-CoV-2 vaccination. The efficacy of vaccines in Japanese kidney transplant patients with specific characteristics, such as predominant living-donor, ABO-incompatible kidney transplant, and low-dose immunosuppression, requires verification. We conducted a prospective study to estimate anti-SARS-CoV-2 antibody levels in 105 kidney transplant patients and 57 controls. Blood samples were obtained before vaccination, 1, 3, and 6months after second vaccination, and 1month after third vaccination. We investigated antibody acquisition rates, antibody levels, and factors associated with antibody acquisition. One month after second vaccination, antibody acquisition was 100% in the controls but only 36.7% in the kidney transplant group (P < 0.001). Antibody levels in positive kidney transplant patients were also lower than in the controls (median, 4.9 arbitrary units vs 106.4 arbitrary units, respectively, P < 0.001). Years after kidney transplant (odds ratio 1.107, 95% confidence interval 1.012-1.211), ABO-incompatible kidney transplant (odds ratio 0.316, 95% confidence interval 0.101-0.991) and mycophenolate mofetil use (odds ratio 0.177, 95% confidence interval 0.054-0.570) were significant predictors for antibody acquisition after second vaccination. After third vaccination, antibody positivity in the kidney transplant group increased to 75.3%, and antibody levels in positive patients were 71.7 arbitrary units. No factors were associated with de novo antibody acquisition. In Japanese kidney transplant patients, years after kidney transplant, ABO-incompatible kidney transplant and mycophenolate mofetil use were predictors for antibody acquisition after second vaccination. Third vaccination improves antibody status even in patients who were seronegative after the second vaccination.

Risk of Secondary Malignancies in Hematopoietic Stem Cell Transplantation Recipients: A Nationwide Population-Based Study in Taiwan

The improvement of survival after hematopoietic stem cell transplantation has brought about a need to evaluate long-term complications, for instance, secondary malignancies. The risk of subsequent malignancies after hematopoietic stem cell transplantation must be clarified in a large population. To estimate the risk of secondary malignancies in hematopoietic stem cell transplantation survivors and compare it with the risk in patients without hematopoietic stem cell transplantation history. We conducted a population-based retrospective cohort study of 3,059 hematopoietic stem cell transplantation recipients from the National Health Insurance Research Database of Taiwan, containing 1,378 autologous, 1,641 allogeneic, and 40 cord blood stem cell transplantation recipients between 2000 and 2013. A control group of 12,236 patients without an hematopoietic stem cell transplantation history was identified. The covariates included age, sex, comorbidities, stem cell source, facility level of care, and history of total body irradiation. Comorbidities were estimated by the revised Charlson comorbidity index, and a higher score suggested more severe comorbidity. Adjusted hazard ratios were determined by adjusting for age, sex, comorbidity, and facility level of care. Overall, hematopoietic stem cell transplantation recipients had a higher risk of secondary malignancies with an adjusted hazard ratios of 1.348 (p = 0.017). Being male and female (adjusted hazard ratios 1.395, p = 0.009 and adjusted hazard ratios 1.291, p = 0.042, respectively) and pre-hematopoietic stem cell transplantation total body irradiation (adjusted hazard ratios 1.591, p < 0.001) were correlated with a high risk of secondary malignancies. Among the subsequent neoplasms, bone cancer showed the highest risk (adjusted hazard ratios 27.899, p < 0.001), followed by laryngeal (adjusted hazard ratios 6.643, p < 0.001), kidney (adjusted hazard ratios 5.580, p < 0.001), esophageal, pancreatic, thyroid (adjusted hazard ratios 1.993, p < 0.001), and skin (adjusted hazard ratios 1.992, p < 0.001) cancers. The median follow-up duration was 2.16 years in the hematopoietic stem cell transplantation group and 2.57 years in the control group, and the overall median follow-up duration was 2.21 years. Medical practitioners should be aware of the high risk of secondary malignancies in hematopoietic stem cell transplantation recipients later in life. These recipients should be informed about the importance of regular follow-up and photoprotective measures. Lifelong surveillance is recommended.

Treatment Options for Relapsed Acute Lymphoblastic Leukemia Study

This study aims to analyze the treatment options for relapsed acute lymphoblastic leukemia (ALL). ALL is a type of cancer that affects the white blood cells, and can often recur after initial treatment. The focus of this study is to evaluate the efficacy of various treatments for relapsed ALL, including chemotherapy, radiation therapy, bone marrow transplantation, and targeted therapies. Results from a systematic review of the literature indicate that treatment options for relapsed ALL are often effective, but can vary depending on the stage of the disease. Chemotherapy and radiation therapy are typically used as first-line treatments, while bone marrow transplantation is typically used as a second-line treatment. Targeted therapies, such as monoclonal antibodies, are increasingly being used in combination with other treatments. This study suggests that further research is needed to determine the optimal treatment strategy for relapsed ALL, as well as the best combination of treatments. Objectives: To investigate the current treatments for relapsed acute lymphoblastic leukemia (ALL) Methodology: This study conducted in department of pediatric Hematology and oncology CMH Rawalpindi From jan 2020 to jan 2023 Comprised 100 pediatric patients with relapsed ALL. Patients were treated with chemotherapy, radiation therapy, stem cell transplantation, or targeted therapy. The efficacy of each treatment option was assessed by the complete remission rate, overall survival rate, and relapse rate. The complete remission rate was determined by measuring the number of patients who achieved complete remission after eight weeks of treatment. The overall survival rate was measured by calculating the number of patients who survived at least one year following treatment. Finally, the relapse rate was calculated by determining the number of patients who experienced recurrence of the disease within one year. Data was collected and analyzed using descriptive statistics and survival analysis. Results The results of this study showed that chemotherapy was the most effective treatment option, with a complete remission rate of 60%, followed by stem cell transplantation (50%) and targeted therapy (40%). The overall survival rate was highest in the chemotherapy group (72%), followed by the stem cell transplantation (53%) and targeted therapy (48%) groups. Radiation therapy was found to be less effective, with a complete remission rate of only 25%. The relapse rate was highest in the targeted therapy group (30%), followed by the stem cell transplantation (20%) and chemotherapy (15%) groups. Conclusion: This study showed that chemotherapy was the most effective treatment option for relapsed pediatric ALL, followed by stem cell transplantation and targeted therapy. The overall survival rate was highest in the chemotherapy group, followed by the stem cell transplantation and targeted therapy groups. Radiation therapy was found to be less effective, with a complete remission rate of only 25%. These results suggest that chemotherapy should be the primary treatment option for relapsed pediatric ALL, followed by stem cell transplantation and targeted therapy as secondary options. Keywords: acute lymphoblastic leukemia, relapsed, chemotherapy, radiation therapy, stem cell transplantation, targeted therapy

Recombinant anti-Mullerian hormone treatment attenuates primordial follicle loss after ovarian cryopreservation and transplantation.

The foremost drawback of ovarian tissue cryopreservation and re-transplantation (OTCT) technique is the rapid loss of the primordial follicle (PF) pool. In recent studies, we have demonstrated that post-transplantation burnout of the PFs occurs due to the altered expression of the activatory and inhibitory proteins that control PF reserve, and rapamycin prevented it. Here, we investigated whether anti-Mullerian hormone administration in the bilateral oophorectomy and transplantation group and internal AMH in the unilateral oophorectomy and transplantation group protect follicle reserve by regulating the expression of the molecules that control follicle growth after OTCT in mice. After 14days of OTCT, PF reserve is significantly reduced in both unilateral oophorectomy and transplantation and bilateral oophorectomy and transplantation groups, while anti-Mullerian hormone treatment attenuates PF loss after bilateral oophorectomy and transplantation. The expression of KitL, Bmp-15, and p27 decreased after unilateral oophorectomy and transplantation and bilateral oophorectomy and transplantation, yet recombinant anti-Mullerian hormone treatment did not restore the expression of these proteins in the BLO-T group. Exogenous recombinant anti-Mullerian hormone administration in the BLO-T group preserved the expressions of Tsc1 and Gdf-9 in PF and p-s6k and Gdf-9 in growing follicles after OTCT. Nonetheless, recombinant anti-Mullerian hormone administration did not affect granulosa cell proliferation and death rates in the growing follicles. These findings suggest a novel hormonal replacement strategy for fertility preservation by restoring anti-Mullerian hormone to regulate Tsc1 and p-s6k, thereby linking this hormone with the mTOR pathway and Gdf-9 signaling.

Long-Term Outcomes of Kidney Paired Donation Transplantation: A Single Center Retrospective Cohort Study

This study aimed to compare the kidney paired donation (KPD) program recipients with the traditional living donor kidney transplantation (LDKT) recipients regarding patient and graft survival. We retrospectively analyzed 141 recipients of the KPD program and 141 classic LDKT recipients that we matched for age and sex as controls between July 2005 and June 2019. We compared the 2 transplant groups for patient and kidney survival using the Kaplan-Maier test. We also performed Cox Regression analysis to examine factors affecting patient survival, including transplant type. The average follow-up period was 96.17 ± 44.22 months. Of the 282 patients, 88 died in the follow-up period. There was no statistically significant difference in graft and patient survival between the KPD and LDKT groups. In the Cox regression model, including the transplant type, only the serum creatinine level measured in the first month after discharge was a significant factor in predicting patient survival. The findings of this study indicate that the KPD program is an effective and reliable method to increase LDKT. Country-wide multicentric studies should confirm the results of this study. In countries where cadaver transplantation is insufficient, efforts should be made to expand the KPD program.

Appropriate pre-transplant strategy for patients with myelodysplastic syndromes receiving allogeneic haematopoietic stem cell transplantation after myeloablative conditioning.

Appropriate pre-transplant strategies in patients with myelodysplastic syndromes (MDS) remain challenging. We sought to assess the effect of different pre-transplant therapies and transplantation interval times on patient prognosis. We retrospectively analysed clinical data for 371 consecutive MDS patients after myeloablative transplantation between 2007 and 2019. The median age of the patients was 38 years (range, 12-64 years). A total of 114 patients (31%) received supportive care (SC), 108 (29%) hypomethylating agents (HMAs), and 149 (40%) chemotherapy-based therapy before transplantation. In patients who received HMA or SC, there was no significant difference in overall survival (OS; P=0.151) or relapse-free survival (RFS; P=0.330), except that HMA-treated patients had a lower rate of non-relapse mortality (5-year NRM: 18% vs. 32%, P=0.035). However, compared with patients who received HMA, those who received chemotherapy-based therapy had a lower 5-year OS rate (56% vs. 69%, P=0.020) and a slightly higher 5-year NRM rate (28% vs. 18%, P=0.067). Compared to the delayed transplant group (transplant interval ≥6 months), the early transplant group (transplant interval <6 months) had a superior 5-year OS (66% vs. 51%, P=0.001) and a lower 5-year cumulative incidence of NRM (22% vs. 36%, P=0.001). The findings of the study indicate that receiving an appropriate pre-transplant strategy (SC/HMA + <6 months) significantly improves OS and decreases NRM in MDS patients after myeloablative transplantation.

Risk factors for a severe disease course in children with SARS-COV-2 infection following hematopoietic cell transplantation in the pre-Omicron period: a prospective multinational Infectious Disease Working Party from the European Society for Blood and Marrow Transplantation group (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH) study.

Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.

Regenerative Potential of Bone Morphogenetic Protein 7-Engineered Mesenchymal Stem Cells in Ligature-Induced Periodontitis.

Periodontitis is an oral disease caused by bacterial infection that has stages according to the severity of tissue destruction. The advanced stage of periodontitis presents irreversible destruction of soft and hard tissues, which finally results in loss of teeth. When conventional treatment modalities show limited results, tissue regeneration therapy is required in patients with advanced periodontitis. In the present study, we aimed to evaluate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) delivering bone morphogenetic protein 7 (BMP7) on tissue regeneration in a periodontitis model. BMP7 is a member of the BMP family that shows bone-forming ability; however, BMPs rapid clearing and degradation and unproven efficacy make it difficult to apply it in clinical dentistry. To overcome this, we established BMP7-expressing engineered BM-MSCs (BMP7-eBMSCs) that showed superior osteogenic differentiation potential when subcutaneously transplanted with a biphasic calcium phosphate scaffold into immunocompromised mice. Furthermore, the efficacy of BMP7-eBMSC transplantation for periodontal tissue regeneration was evaluated in a rat ligature-induced periodontitis model. Upon measuring two-dimensional and three-dimensional amounts of regenerated alveolar bone using microcomputed tomography, the amounts were found to be significantly higher in the BMP7-eBMSC transplantation group than in the eBMSC transplantation group. Most importantly, fibrous periodontal ligament (PDL) tissue regeneration was also achieved upon BMP7-eBMSC transplantation, which was evaluated by calculating the modified relative connective tissue attachment. The amount of connective tissue attachment in the BMP7-eBMSC transplantation group was significantly higher than that in the ligature-induced periodontitis group, although the increase was comparable between the BMP7-eBMSC and human PDL stem cell transplantation groups. Taken together, our results suggested that sustainable release of BMP7 induces periodontal tissue regeneration and that transplantation of BMP7-eBMSCs is a feasible treatment option for periodontal regeneration. Impact Statement Periodontitis is the second most common human dental disease affecting chronic systemic diseases. Despite the tremendous efforts trying to cure the damaged periodontal tissues using tissue engineering technologies, a definitive regenerative method has not been in consensus. Researchers are seeking more feasible and abundant source of mesenchymal stem cells (MSCs), and furthermore, how to use reliable growth factors under more efficient control are the issues to be solved. In this study, we aimed to evaluate the effect of bone morphogenetic protein 7 (BMP7) gene delivering bone marrow-derived MSCs on periodontal tissue regeneration to evaluate the efficacy of BMP7 and engineered BMSCs for periodontal tissue regeneration.

Effect of concurrent aerobic exercise and bone marrow stromal cell transplantation on time-dependent changes of myogenic differentiation-related cascades in soleus muscle after sciatic nerve injury.

The purpose of this study was to investigate the time-dependent alteration in whether concurrent aerobic exercise and bone marrow stromal cell (BMSC) engraftment could regulate myogenic differentiation-related signaling pathway in the soleus up to 35 days after sciatic nerve injury (SNI). The rats were divided as follows: the normal control (CON, n=5), sedentary group (SED, n=20), treadmill exercise group (TEX, n=20), BMSC transplantation group (BMSC, n=20), TEX+BMSC transplantation group (TEX+BMSC, n=20) 7, 14, 21, and 35 days after SNI. SNI was applied into the thigh and treadmill exercise was comprised of walking at a speed of 4 to 8 m/min for 30 min once a day. Harvested BMSC at a density of 5×106 in 50-μL phosphate-buff-ered saline was injected into the injury site. Phosphorylated (p) extracellular signal-regulated kinase 1/2 expression was dramatically upregulated in BMSC and BMSC+EX groups from 21 days after SNI compared to those in the SED group. P-ribosomal s6 kinase (RSK) was sharply increased 14 days later, and then rapidly downregulated from day 21, whereas TEX, BMSC and TEX+ BMSC groups significantly kept up expression levels of p-RSK until 35 days post injury than SED group. TEX+BMSC group significantly increased activation of protein kinase B-mammalian target of rapamycin in the soleus from day 14 and myoblast determination protein 1-myogen-in pathways was activated in TEX+BMSC group from day 21. Present findings provide information that combined intervention of aerobic exercise and BMSC transplantation might be a reliable therapeutic strategy for overcoming the morphological and functional problems in denervated soleus muscle.

Effect of combined intervention of exercise and autologous bone marrow stromal cell transplantation on neurotrophic factors and pain-related cascades over time after sciatic nerve injury.

The purpose of this study was to determine whether combined inter-vention of treadmill exercise and bone marrow stromal cell (BMSC) transplantation would affect the expression of neurotrophic factors in the sciatic nerve injury (SNI) and neuropathic pain-related cascades in ipsilateral lumbar 4-5 dorsal root ganglion (DRG) during the early or late stage of sciatic nerve regeneration. The rats were randomly divided into the normal control group (CONT, n=6), sedentary group (SS, n=24), exercise group (SE, n=24), BMSC transplantation group (SB, n=24), BMSC transplantation+exercise group (SBE, n=24) 1, 2, 3, and 5 weeks after SNI. Single dose of 5×106 harvested BMSC was injected into the injury area sing by a 30 gauge needle. Treadmill exercise was performed at a speed of 8 m/min for 30 min once a day. Tropomyosin-receptor kinase B, brain-derived neurotrophic factor and ciliary neurotrophic fac-tor were significantly upregulated in the SE and SBE groups at 1- and 2-week postinjury than those in the CONT and SS groups, and SB and SBE groups continuously kept up proinflammatory cytokines until the late stage of regeneration. Nuclear factor kappa-light-chain-enhancer of activated B cells, interleukin and tumor necrosis factor alpha in ipsi-lateral DRG were progressively decreased by exercise alone application and/or BMSC transplantation at early and late stage of regeneration. Present results provide reliable information that combined intervention of treadmill exercise and BMSC transplantation might be one of the effective treatment strategies for recovering sciatic nerve injury-induced neuropathic pain over time.

Clinical outcome analysis of sequential transplantation of frozen-thawed embryo transfer cycle: a retrospective study.

The sequential transplantation was a new mode of in vitro fertilization and embryo transfer. To compare the clinical outcomes of sequential transplantation, embryo transplantation and blastocyst transplantation during freeze-thaw embryo transfer cycle. The retrospective study was conducted on 767 patients who received freeze-thaw embryo transfer at Reproductive Medicine Center of Hangzhou Women Hospital from July 1, 2020 to June 30, 2021. According to the age of transplanted embryos, all patients were divided into sequential transplantation, embryo embryo transplantation group and blastocyst stage transplantation group. The clinical data, embryo status and pregnancy outcome of the 3 groups were compared, the number of transplanted embryos in the sequential group was significantly higher than that in the other 2 groups (P < .05). The implantation rate of blastocyst transplantation group was the highest, there was no statistical significance between the sequential transplantation group and the other 2 groups (39.13% vs 30.00%, 39.13 vs 43.50%). The multiple birth rate (30.77%) and spontaneous abortion rate (20.51%) were higher in the sequential transplantation group, and there was no significant difference among the 3 groups (P > .05). The sequential transplantation cycle can obtain a higher clinical pregnancy rate than the conventional single cycle transplantation, without causing the waste of transplanted embryos, and can be used as the choice mode of resuscitation transplantation cycle for some patients.

Risk of Severe Alphaherpesvirus Infection after Solid Organ Transplantation: A Nationwide Population-Based Cohort Study

Patients after solid organ transplantation (SOT) are more susceptible to various viral infections, including alphaherpesviruses. Therefore, the aim of our study was to investigate the risk of alphaherpesvirus infections, including herpes simplex and herpes zoster, after solid organ transplantation. Inpatient records from the Taiwan National Health Insurance Research Database (NHIRD) defined solid organ recipients, including heart, liver, lung, and kidney, hospitalized for alphaherpesvirus infections as a severe case group of transplants and matched them with a nontransplant cohort. We enrolled 18,064 individuals, of whom 9032 were in each group. A higher risk of severe alphaherpesvirus infection was noted in solid organ recipients (aHR = 9.19; p < 0.001) than in the general population. In addition, solid organ transplant recipients had the highest risk of alphaherpesvirus infection within 1 year after transplantation (aHR = 25.18). The comparison found a higher risk of herpes zoster and herpes simplex infections in recipients of kidney (aHR = 9.13; aHR = 12.13), heart (aHR = 14.34; aHR = 18.54), and liver (aHR = 5.90; aHR = 8.28) transplants. Patients who underwent solid organ transplantation had a significantly higher risk of alphaherpesvirus infection than the general population.

Complications of esophageal reconstruction

Esophageal cancer is the most common cause of esophageal resections. Esophageal replacement is still a significant challenge for surgeons, because complications can be expected in over 50% and death also occurs between 4-7%. Complications can be divided into early and late categories and into general and specific complications. From a surgical point of view, early and late specific complications are the most important aspects. Between 1993 and 2012, 540 esophageal resections were performed due to malignant tumors at the Department of Surgery, Medical Center of the University of Pécs. Stomach was used for replacement in 445 cases, colon in 38 cases, and jejunum in 57 cases. The anastomosis with stomach replacement was located to the neck in 275 cases and to the thorax in 170 cases. The colon was pulled up to the neck in each case. There were 29 cases of free jejunal replacements located to the neck, and 28 cases with a Roux-loop reconstruction located to the thorax. In the case of gastric replacement, anastomotic insufficiency developed in 55 cases, graft necrosis occurred in 8 cases, and early anastomosis stricture developed in 30 cases. These numbers are 3 conduit necrosis and 2 strictures in cases of colonic replacements. There was one anastomosis failure in the case of a thoracic jejunum replacement. Also one conduit necrosis was observed in the free jejunal neck transplantation group. Among late special complications, dysphagia is the most important, the causes of which were found in the order of frequency: anastomotic stricture, conduit obstruction, peptic and ischemic stricture, foreign body, local recurrence, functional causes, new malignant tumor in the esophageal remnant after resection and malignant tumor emerging in the replaced organ. Causes may overlap each other, and their treatment may be conservative, endoscopic or surgical. Surgical treatment is usually the last option to restore the ability to swallow and can present a significant challenge even to experienced centers. Orv Hetil. 2023; 164(7): 243-252.

Timing and delivery route effects of cecal microbiome transplants on Salmonella Typhimurium infections in chickens: potential for in-hatchery delivery of microbial interventions

BackgroundExposure to microbes early in life has long-lasting effects on microbial community structure and function of the microbiome. However, in commercial poultry settings chicks are reared as a single-age cohort with no exposure to adult birds which can have profound effects on microbiota development and subsequent pathogen challenge. Microbiota manipulation is a proven and promising strategy to help reduce pathogen load and transmission within broiler flocks. However, administration of microbiota transplant products in a hatchery setting may prove challenging. Effective administration strategies are dependent on key factors, such as; the age of chicks receiving interventions and mode of delivery. This study aimed to assess these two aspects to provide supporting evidence towards microbiome manipulation strategies for use in commercial hatcheries.ResultsManipulation of the microbiota between 4 and 72 h of hatch markedly reduced faecal shedding and colonisation with the foodborne pathogen Salmonella enterica serovar Typhimurium (ST4/74). Administration of transplant material via spray or gel drop delivery systems had minimal effect on the protection conferred with fewer birds in transplant groups shown to shed ST4/74 in the faeces compared to PBS-gavaged control birds. Analysis of the microbiome following transplantation demonstrated that all transplant groups had higher diversity and species richness than non-transplant groups during the first week of life and the early stages of infection with ST47/4.The relative abundance of the bacterium Faecalibacterium prausnitzii was significantly higher in CMT groups compared to PBS controls. The presence of F. prausnitzii was also shown to increase in PBS-challenged birds compared to unchallenged birds potentially indicating a role of this bacterium in limiting Salmonella infections.ConclusionsThis study demonstrated that administration of microbiome transplants, using methods that would align with hatchery practices, effectively reduced colonisation and shedding of Salmonella in chickens. Age of chicks at microbiome administration had limited effect on the diversity and composition of the microbiome and conferred protection against Salmonella infections. Traditional hatchery delivery systems, such as spray or gel-drop, are sufficient to transfer donor material, alter the microbiome and confer protection against Salmonella. This study helps highlight the opportunity for use of microbiome modification methods within the hatchery.