Cell therapies and its derivatives as immunomodulators in vascularized composite allotransplantation.

The adverse effects of traditional pharmaceutical immunosuppressive regimens have been a major obstacle to successful allograft survival in vascularized composite tissue allotransplantation (VCA) cases. Consequently, there is a pressing need to explore alternative approaches to reduce reliance on conventional immunotherapy. Cell therapy, encompassing immune-cell-based and stem-cell-based regimens, has emerged as a promising avenue of research. Immune cells can be categorized into two main systems: innate immunity and adaptive immunity. Innate immunity comprises tolerogenic dendritic cells, regulatory macrophages, and invariant natural killer T cells, while adaptive immunity includes T regulatory cells and B regulatory cells. Investigations are currently underway to assess the potential of these immune cell populations in inducing immune tolerance. Furthermore, mixed chimerism therapy, involving the transplantation of hematopoietic stem and progenitor cells and mesenchymal stem cells (MSC), shows promise in promoting allograft tolerance. Additionally, extracellular vesicles (EVs) derived from MSCs offer a novel avenue for extending allograft survival. This review provides a comprehensive summary of cutting-edge research on immune cell therapies, mixed chimerism therapies, and MSCs-derived EVs in the context of VCAs. Findings from preclinical and clinical studies demonstrate the tremendous potential of these alternative therapies in optimizing allograft survival in VCAs.

Turbocharging as a strategy to boost extended perforator flap vascularity in head and neck reconstruction-A report of two cases.

Perforator flap has been applied as the most common flap for soft tissue defect reconstruction. Here, we presented two cases using turbocharging procedure of perforator to perforator as a salvage strategy. The first case was a 54-year-old male with recurrent squamous cell carcinoma (SCC) in the left buccal area and mouth floor. A 6 × 22 cm posteromedial thigh (PMT) flap was designed for reconstruction. The two eccentric perforators of the PMT flap could not conjoin together during dissection nearby the main pedicle of profunda femoral artery (PFA) resulting in inadequate perfusion. Side branched stump before clipped the branch of distal perforator was preserved, then the proximal perforator was divided and end-to-end anastomosis of side branch of distal perforator was done successfully. The second case was a 52-year-old male underwent wide composite excision of right tongue SCC. After excision, anterolateral thigh (ALT) flap around 7 × 15 cm was harvested from left thigh and two perforators were included which one tiny perforator supplied by the descending branch (DB) and the other major perforator originated from oblique branch (OB) of lateral circumflex femoral artery (LCFA). However, the OB main perforator injury showed inadequate perfusion of flap. We trimmed the injury zone of OB perforator, and shift to re-anastomosis of OB perforators to side branch of DB of LCFA directly. The flap demonstrated excellent perfusion immediately after the operation, and it exhibited complete survival 2 weeks postoperatively. These results indicated that the turbocharging procedure, from perforator to perforator, could serve as a strategy for salvaging perfusion-compromised flaps, especially in cases of eccentric perforators or perforator injury resulting in inadequate perfusion.

The synergistic effect of full-spectrum light therapy and transient immunosuppressants prolonged allotransplant survival.

BACKGROUND: The lifelong administration of immunosuppressants remains its largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model. METHODS: Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term anti-lymphocyte serum and cyclosporine-A. Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis. RESULTS: The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared to the control (group 1). However, group 4 with FBLT combined with short-term ALS/CsA significantly prolonged median composite tissue allograft survival time (266 days) compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) (p<0.01). Group 4 also showed a significant increase in Treg cells (p = 0.04) and TGF-ß1 levels (p = 0.02), and a trend toward a decrease in IL-1ß levels (p = 0.03) at 16 weeks after transplantation as compared to control Group 1. CONCLUSIONS: FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and anti-inflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival.

Breast infiltrating ductal carcinoma with metastasis to stomach: A case report.

The most common metastatic sites in breast cancer include the liver, bone, the lungs, and the brain. Metastasis to the gastrointestinal system is rare and can occur years after breast cancer diagnosis. This case report features a woman who was diagnosed with infiltrating ductal carcinoma 10 years ago and was discovered to have stomach metastasis this year. Immunohistochemical staining was employed to distinguish the metastasis from primary gastric cancer. This case is presented to raise awareness of the risk of gastric metastasis from breast cancer after years of breast cancer therapy.

Detrimental correlation between air pollution with skin aging in Taiwan population.

Dissecting the complex relationships between skin aging and air pollution has been an ongoing effort. The increased exposure to air pollution over time imposed a negative effect on skin. This study explores the correlation between skin aging in the Asian population and levels of air pollutants to show different relationship between the two. This study was retrospective and included 389 patients, age between 30 and 74, who planned to receive a session of laser treatment for skin disorders in Kaohsiung Medical University Hospital (KMUH) from 2006 to 2019. Preoperative skin condition quantified by VISIA Complexion Analysis System (Canfield Imaging Systems, Fierfield, NJ, US). Eight air pollutants such as carbon monoxide (CO), non-methane hydrocarbon (NMHC), nitrogen oxides (NO, NO2, and NOx), particulate matters (PM2.5 and PM10), ozone (O3), sulfur dioxide (SO2) and 8 skin condition such as spots, wrinkles, textures, pores, ultraviolet spots (UV spots), brown spots, red area, and porphyrin were analyzed to explore correlation between air pollution and skin aging. Strong correlation was found between NMHC exposure and texture, pores and brown spots formation. A positive correlation between O3 and better VISIA texture and pores scores was found. Brown spots was found to negatively associate with CO, NMHC, NO2, NOx, PM10, PM2.5, and SO2. The skin condition of population over age 45 affected by CO, NMHC, NO2, NOx, PM2.5, PM10, and SO2. Skin condition of the bottom 10% strongly correlates with exposure to PM10 and SO2, whereas skin condition of the top 10% was affected by PM10. Air pollutants such as CO, NO2, NOx, PM2.5, PM10, SO2, and NMHC were found to correlate with negative skin quality strongly. In contrast, O3 exposure is associated with less texture and pores. Future studies are warranted to further appreciate the relationships between air pollutants and skin condition.

Synchronous surgery and immediate reconstruction of double primary cancers of the ovary and breast.

INTRODUCTION: There has been an ongoing debate about the benefits and risks between synchronous surgery and two independent surgery of ovary tumor removal and breast reconstruction. Here we report a synchronous oncological surgery and immediate postmastectomy reconstruction of double primary cancers of the ovary and breast. PATIENT CONCERNS: A 58-year-old woman presented with a right breast lump and ascites. DIAGNOSIS: Computed tomography (CT) indicated synchronous breast and ovarian cancer with multiple metastases. Double primary mammary and ovarian cancer was confirmed after a series of evaluations, such as core needle biopsy of the breast tumor. INTERVENTIONS AND OUTCOMES: Synchronous surgery and immediate reconstruction of double primary cancers of the ovary and breast were performed. Post-operative results showed complete resection of ovarian tumor, no post-operative complication, and excellent life quality. CONCLUSION: Synchronous surgery is warranted as a treatment option for selected cases of double primary cancer. The surgery not only achieved complete removal of one cancer and reduction of the other but also reached excellent breast reconstruction and body shape recovery.

Associations and Interactions between Heavy Metals with White Blood Cell and Eosinophil Count.

The accumulation of heavy metals in the body has been associated with an elevated immune response. The aim of this study was to investigate the associations among heavy metals and white blood cell (WBC) and eosinophil count in the general population in southern Taiwan. We also explored the interactions and synergetic effects of heavy metals on WBC and eosinophil count. We conducted a health survey in the general population living in southern Taiwan between June 2016 and September 2018. Seven heavy metals were measured: blood lead (Pb), and urine cadmium (Cd), copper (Cu), nickel, arsenic (As), chromium and manganese (Mn). A total of 2,447 participants were enrolled. In multivariable analysis, high concentrations of Pb (log per 1 mg/L; coefficient ß, 0.332; p = 0.005) and Cu (log per 1 µg/dL; coefficient ß, 0.476; p < 0.001) were significantly associated with a high WBC count. In addition, high concentrations of Pb (log per 1 mg/L; coefficient ß, 0.732; p < 0.001), As (log per 1 µg/L; coefficient ß, 0.133; p = 0.015), Cu (log per 1 µg/dL; coefficient ß, 0.181; p = 0.018), and Cd (log per 1 µg/L; coefficient ß, 0.139; p = 0.002) were significantly associated with a high eosinophil count. Further, the effect of interactions between Pb and As (coefficient ß, 0.721; p = 0.029) and Mn and Cu (coefficient ß, 0.482; p = 0.018) on WBC count, and As and Cu (unstandardized coefficient ß, 0.558; p = 0.002) on eosinophil count were statistically significant. In conclusion, the heavy metals Pb, As, Cu, and Cd were associated with WBC and eosinophil count. In addition, synergistic effects of heavy metal poisoning on the association with WBC and eosinophil count were also observed.

Modified Le Fort II approach with adequate vascularization preservation in midface allotransplantation: Mock surgery.

INTRODUCTION: It is critical to preserve adequate vascularization in midface allotransplantation, the major complication of which is inadequate blood supply in palate area supplying mainly by internal maxillary artery. Therefore, the aim of this study is to explore a modified Le Fort II approach entailing midface vascularization enhancement. MATERIALS AND METHODS: Ten cadaveric heads were used in mock surgery. A conventional approach was used on seven cadaveric heads to harvest external carotid artery-facial artery-internal maxillary artery axis. On the remaining three cadaveric heads, modified Le Fort II approach was applied where the internal maxillary artery was harvested after cutting off zygomatic arches and rami of the mandible. RESULTS: The conventional approach had difficulty harvesting internal maxillary artery, which left the facial artery the only blood supply to midface. Modified Le Fort II approach with Computerized surgical planning (CSP) assisted, on the other hand, could completely unveil and harvest intact internal maxillary artery after osteotomy of mandibular ramus. CONCLUSION: The modified Le Fort II approach with CSP and ultrasonic bone cutter assisted can maximally preserve internal maxillary system with ease. This approach optimizes midface allotransplantation in clinical practice in future.

Reconstruction of the orbital floor using supercritical CO2 decellularized porcine bone graft.

Orbital floor fractures subsequently lead to consequences such as diplopia and enophthalmos. The graft materials used in orbital floor fractures varied from autografts to alloplastic grafts, which possess certain limitations. In the present study, a novel porcine bone matrix decellularized by supercritical CO2 (scCO2), ABCcolla® Collagen Bone Graft, was used for the reconstruction of the orbital framework. The study was approved by the institutional review board (IRB) of Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH). Ten cases underwent orbital floor reconstruction in KMUH in 2019. The orbital defects were fixed by the implantation of the ABCcolla® Collagen Bone Graft. Nine out of ten cases used 1 piece of customized ABCcolla® Collagen Bone Graft in each defect. The other case used 2 pieces of customized ABCcolla® Collagen Bone Graft in one defect area due to the curved outline of the defect. In the outpatient clinic, all 10 cases showed improvement of enophthalmos on CT (computerized tomography) at week 8 follow-up. No replacement of implants was needed during follow-ups. To conclude, ABCcolla® Collagen Bone Graft proved to be safe and effective in the reconstruction of the orbital floor with high accessibility, high stability, good biocompatibility, low infection rate and low complication rate.

Betel Nut Chewing Was Associated with Obstructive Lung Disease in a Large Taiwanese Population Study.

The prevalence of betel nut chewing in Taiwan is high at approximately 7%, however, few studies have evaluated the relationship between betel nut chewing and lung disease. Therefore, the aim of this study was to investigate associations between betel nut chewing and lung function in 80,877 participants in the Taiwan Biobank (TWB). We further investigated correlations between betel nut chewing characteristics such as years of use, frequency, daily amount, and accumulative dose, with obstructive lung disease. We used data from the TWB. Lung function was assessed using spirometry measurements of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The participants were classified into normal lung function and obstructive lung function (FEV1/FVC < 70%) groups. The participants were asked questions about betel nut chewing, including years of use, frequency, and daily amount. After multivariable analysis, betel nut chewing (odds ratio [OR] = 1.159; p < 0.001) was significantly associated with FEV1/FVC < 70% in all participants (n = 80,877). Further, in the participants who chewed betel nut (n = 5135), a long duration of betel nut chewing (per 1 year; OR = 1.008; p = 0.012), betel nut use every day (vs. 1-3 days/month; OR = 1.793; p = 0.036), 10-20 quids a day (vs. <10 quids; OR = 1.404; p = 0.019), 21-30 quids a day (vs. <10 quids; OR = 1.662; p = 0.010), ≥31 quids a day (vs. <10 quids; OR = 1.717; p = 0.003), and high cumulative dose (per 1 year × frequency × daily score; OR = 1.001; p = 0.002) were significantly associated with FEV1/FVC < 70%. In this large population-based cohort study, chewing betel nut was associated with obstructive lung disease. Furthermore, a long duration of betel nut chewing, more frequent use, higher daily amount, and high cumulative dose were associated with obstructive lung disease. This suggests that preventing betel nut chewing should be considered to reduce obstructive lung disease in Taiwan.

Gender Difference in the Associations among Heavy Metals with Red Blood Cell Hemogram.

This study aimed to investigate gender differences in the association between heavy metals and hemograms including hemoglobin (Hgb), mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC). A health survey of 2447 participants was conducted in southern Taiwan between June 2016 and September 2018. Seven heavy metals were measured: blood lead (Pb), urine nickel (Ni), urine chromium (Cr), urine manganese, urine arsenic (As), urine copper and urine cadmium (Cd). The results show that in females, Pb and Ni were significantly negatively associated with Hgb. In addition, As and Cd were significantly positively, and Pb and Ni were significantly negatively, associated with MCV, in males and females, respectively. The interactions between gender and Ni and gender and Cd in MCV were statistically significant. Further, Pb, in males, and Pb, Ni and Cr, in females, were significantly negatively associated with MCHC. In conclusion, in females, associations of red blood cell (RBC) hemograms with heavy metals such as Pb and Ni were found. In males, heavy metals such as Pb, As and Cd were found to associate with RBC hemograms. Further research is warranted to discuss the mechanism behind these associations.

Sirt1 Activation by Post-ischemic Treatment With Lumbrokinase Protects Against Myocardial Ischemia-Reperfusion Injury.

Lumbrokinase is used as an oral supplement to support and maintain healthy cardiovascular function, and to treat cardiovascular diseases in clinical for more than 10 years. Up until now, the mechanism of the cardioprotective effects of post-ischemic treatment with lumbrokinase has remained unclear. We therefore investigated the signaling pathways involved in the amelioration of myocardial ischemia-reperfusion (I-R) injury in rats treated with lumbrokinase 20 min after myocardial ischemia. Compared to vehicle-treated rats, post-ischemic treatment with lumbrokinase was associated with significant reductions in myocardial I-R-induced arrhythmias and myocardial damage, and an improvement in cardiac function. Moreover, lumbrokinase significantly upregulated levels of silent information regulator 1 (Sirt1). In addition, lumbrokinase significantly increased manganese-dependent superoxide dismutase expression, decreased Cleaved-Caspase-3 expression, and induced deacetylation of FoxO1. On the other hand, lumbrokinase also significantly downregulated levels of succinate dehydrogenase, cytochrome c oxidase, nuclear factor kappa B (NF-κB) and elevated levels of microtubule-associated protein light chain 3. Notably, the cardioprotective effects of lumbrokinase were abolished by administration of the specific Sirt1 inhibitor EX527. These findings demonstrate that post-ischemic treatment with lumbrokinase attenuates myocardial I-R injury through the activation of Sirt1 signaling, and thus enhances autophagic flux and reduces I-R-induced oxidative damage, inflammation and apoptosis.