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Rodent animal models for vital pulp therapy are commonly used in dental research because their tooth anatomy and cellular processes are similar to the anatomy and processes in humans. However, most studies have been conducted using uninfected sound teeth, which makes it difficult to adequately assess the inflammatory shift after vital pulp therapy. In the present study, we aimed to establish a caries-induced pulpitis model based on the conventional rat caries model and then evaluate inflammatory changes during the wound-healing process after pulp capping in a model of reversible pulpitis induced by carious infection. To establish the caries-induced pulpitis model, the pulpal inflammatory status was investigated at different stages of caries progression by immunostaining targeted to specific inflammatory biomarkers. Immunohistochemical staining revealed that both Toll-like receptor 2 and proliferating cell nuclear antigen were expressed in moderate and severe caries-stimulated pulp, indicating that an immune reaction occurred at both stages of caries progression. M2 macrophages were predominant in moderate caries-stimulated pulp, whereas M1 macrophages were predominant in the severe caries-stimulated pulp. Pulp capping in teeth with moderate caries (i.e., teeth with reversible pulpitis) led to complete tertiary dentin formation within 28 d after treatment. Impaired wound healing was observed in teeth with severe caries (i.e., teeth with irreversible pulpitis). During the wound-healing process in reversible pulpitis after pulp capping, M2 macrophages were predominant at all time points; their proliferative capacity was upregulated in the early stage of wound healing compared with healthy pulp. In conclusion, we successfully established a caries-induced pulpitis model for studies of vital pulp therapy. M2 macrophages have an important role in the early stages of the wound-healing process in reversible pulpitis.

To estimate the health-promoting effects of Lacticaseibacillus paracasei (previously Lactobacillus casei) strain Shirota (LcS) that reached the lower gastrointestinal tract alive, we investigated the characteristics of gut microbiome, organic acid profiles, defecatory symptoms and serum viral antibody indexes of healthy Japanese adults between the group in whom live LcS was detected or not from stool. The β-diversity index of the gut microbiome constituted a significant difference between the live-LcS-detected-group (LLD) and the live-LcS-not-detected-group (LLnD). In the LLD, the Bifidobacteriaceae, Lactobacillaceae, and Coriobacteriaceae counts were significantly higher, and the succinate concentration was significantly lower than that in the LLnD. The serum herpes simplex virus (HSV) immunoglobulin (Ig)M antibody index in the LLD tended to be lower than that of the LLnD in HSV IgG-positive subjects. Of the LLD, those in the fermented milk products containing LcS (FML)-high-frequency-group (FML-HF) and those in the FML-low-frequency-group (FML-LF) had different gut microbiome and organic acid profiles. However, the pattern of differences between FML-HF and FML-LF was dissimilar those between LLD and LLnD. In contrast, among subjects with FML-LF, those in the group with LLD in stool (LF-LLD) and those in the LLnD in stool (LF-LLnD) showed a similar pattern of differences in their gut microbiome and organic acid profiles as those in the LLnD and LLD. The LLD and LF-LLD commonly had lower caloric and carbohydrate intakes from the diet than their respective control groups. In this study, we found that the presence of live LcS in stool is associated with a healthy gut environment and inhibition of the reactivation of latently infected viruses in the host. However, these health-promoting effects on the host were not related to the frequency of FML intake. Furthermore, dysbiosis of the gut microbiome and diet including caloric intake was related to the viability of ingested LcS in the gut.

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018–2020) and post-AC (2020–2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96–74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15–0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

Information about respiratory mechanics such as resistance, elastance, and muscular pressure is important to mitigate ventilator-induced lung injury. Particularly during pressure support ventilation, the available options to quantify breathing effort and calculate respiratory system mechanics are often invasive or complex. We herein propose a robust and flexible estimation of respiratory effort better than current methods. We developed a method for non-invasively estimating breathing effort using only flow and pressure signals. Mixed-integer quadratic programming (MIQP) was employed, and the binary variables were the switching moments of the respiratory effort waveform. Mathematical constraints, based on ventilation physiology, were set for some variables to restrict feasible solutions. Simulated and patient data were used to verify our method, and the results were compared to an established estimation methodology. Our algorithm successfully estimated the respiratory effort, resistance, and elastance of the respiratory system, resulting in more robust performance and faster solver times than a previously proposed algorithm that used quadratic programming (QP) techniques. In a numerical simulation benchmark, the worst-case errors for resistance and elastance were 25% and 23% for QP versus0.1% and0.1% for MIQP, whose solver times were 4.7s and 0.5s, respectively. This approach can estimate several breathing effort profiles and identify the respiratory system's mechanical properties in invasively ventilated critically ill patients. This article is protected by copyright. All rights reserved.

Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography–tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

Backgrounds Healed plaques in native coronary artery indicate the repair phenomenon of ruptured fibrous caps and erosions [1, 2, 3]. Healed plaques associated with plaque vulnerability [4]. A similar phenomenon is considered to occur in neointima after stent implantation [5]. However, there are few reports in the literature regarding neointimal vulnerability and procedure outcomes of healed tissue in neointima. Objective The aims of this study are to investigate clinical characteristics, slow flow during percutaneous coronary intervention (PCI), and neointimal vulnerability of healed neointima by optical coherence tomography (OCT). Methods We treated 67 lesions by PCI for in-stent restenosis (ISR) and conducted OCT examinations. Healed neointima was defined as neointima having one or more layers with different optical densities and a clear demarcation from underlying components. ISR with healed neointima was found in 49% (33/67) of the lesions. The angiographic slow flow was defined as a decrease of at least 1 grade in TIMI flow during PCI or final TIMI flow grade 0 and 1 or 2, with no evidence of thrombus, spasm, or dissection. Stents with a strut thickness ≥100 μm were classified as thick [6]. Results Compared to ISR without healed neointima, ISR with healed neointima showed significantly longer stent age (102±72 months vs. 31±39 months, p Conclusions ISR with healed neointima was associated with neointimal vulnerability, stent age, stent type, stent strut thickness, stent expansion, antiplatelet therapy, HDL-C and triglycerides levels, and use of ACE-I or ARB. There were no relations between with healed neointima and slow flow during PCI. Funding Acknowledgement Type of funding sources: None.

By presenting the first case report of true operational tolerance in an intestinal transplant patient, we aim to demonstrate that tolerance is possible in a field that has been hampered by suboptimal outcomes. Although operational tolerance has been achieved in liver and kidney transplantation, and some intestinal transplant patients have been able to decrease immunosuppression, this is the first instance of true operational tolerance after complete cessation of immunosuppression. A patient received a deceased-donor small intestinal and colon allograft with standard immunosuppressive treatment, achieving excellent graft function after overcoming a graft-versus-host-disease episode 5 months posttransplant. Four years later, against medical advice, the patient discontinued all immunosuppression. During follow-up visits 2 and 3 years after cessation of immunosuppression, the patient exhibited normal graft function with full enteral autonomy and without histological or endoscopic signs of rejection. Mechanistic analysis demonstrated immune competence against third party antigen, with in vitro evidence of donor-specific hyporesponsiveness in the absence of donor macrochimerism. This proof of principle case can stimulate future mechanistic studies on diagnostic and therapeutic strategies, for example, cellular therapy trials, that can lead to minimization or elimination of immunosuppression and, it is hoped, help revitalize the field of intestinal transplantation.

Purpose of review It has been well established that antibody to donor HLA pretransplant and the development of anti-human leukocyte antigen (HLA) antibodies posttransplant contribute to inferior graft survival outcomes. This article serves to review the current status of the management of pretransplant sensitized intestinal transplant candidate as well as to review posttransplant care of patients that harbor antidonor HLA antibodies. Recent findings The intestinal transplant candidate oftentimes presents for transplant listing with high levels of anti-HLA antibodies that necessitate a careful preoperative strategy to avoid a donor-recipient pair that would result in a positive crossmatch. In the end, donor intestine offer acceptance is based on a balance between recipient clinical needs and allowable immunologic risk tolerance. The use of virtual crossmatching (VXM) enables the transplant center to effectively gauge the immunologic risk of each potential donor-recipient pair far in advance of allocating resources toward pursuing a donor organ. In those candidates with high levels of preformed donor anti-HLA antibodies, desensitization with a novel technique of donor splenic perfusion has been described as well as a single-center experience with a conventional desensitizing protocol. Posttransplant, with the use of a denovo donor-specific antibody (dnDSA) monitoring and treatment protocol, the well known deleterious effects of dnDSA can potentially be ameliorated, thus improving outcome. Efforts to establish a formal histologic criteria for antibody-mediated rejection (ABMR) in the intestinal graft continues to evolve with recent findings describing the relationship between DSA and histopathologic findings. Summary Techniques such as the use of VXM, novel desensitization methods and protocols, monitoring and eradicating dnDSA, along with establishing new criteria for ABMR have all contributed to improving the outcomes in transplanting the immunologically challenging intestine.

BACKGROUND AND PURPOSE: With the increasing use of the Pipeline Embolization Device for the treatment of aneurysms, predictors of clinical and angiographic outcomes are needed. This study aimed to identify predictors of incomplete occlusion at last angiographic follow-up. MATERIALS AND METHODS: In our retrospective, single-center cohort study, 105 ICA aneurysms in 89 subjects were treated with Pipeline Embolization Devices. Patients were followed per standardized protocol. Clinical and angiographic outcomes were analyzed. We introduced a new morphologic classification based on the included angle of the parent artery against the neck location: outer convexity type (included angle, 200°), and lateral wall type (160° ≤ included angle ≤200°). This classification reflects the metal coverage rate and flow dynamics. RESULTS: Imaging data were acquired in 95.3% of aneurysms persistent at 6 months. Complete occlusion was achieved in 70.5%, and incomplete occlusion, in 29.5% at last follow-up. Multivariable regression analysis revealed that 60 years of age or older (OR, 5.70; P = .001), aneurysms with the branching artery from the dome (OR, 10.56; P = .002), fusiform aneurysms (OR, 10.2; P = .009), and outer convexity–type saccular aneurysms (versus inner convexity type: OR, 30.3; P

The aim of this study is to critically examine the multidisciplinary approach to abdominal wall reconstruction (AWR) in the solid organ transplant (SOT) population at our institution, MedStar Georgetown University Hospital, using a modified component separation technique (CST). A retrospective review of AWR utilizing modified open CST with biologic mesh in SOT patients was performed from January 2010 to June 2018. Patient demographics, comorbidities, operative details, complications, and outcomes were recorded. Descriptive statistics, logistic and linear regression analyses were performed to appraise outcomes. Thirty-five patients were included; mean age was 53 years. Patient demographics and comorbidities were: 82.9% male, 45.7% history of tobacco use, and 28.6% diabetes. Fifty-one percent had undergone prior hernia repair. Transplant types were: kidney (9), liver (16), liver/kidney (1), small bowel (7), multivisceral (2). All were on an immunosuppressive regimen at time of surgery; 22.9% included steroids. Average defect size was 361 cm2. Additional soft tissue procedures were performed in 65.7% (n = 23) of patients. Median time to healing was 29.0 days. Complication rate was 31.4% (n = 11); six patients required reoperation within 90 days. Recurrence rate was 5.7% (n = 2) at mean of follow up of 3.0 years. Additional soft tissue procedures were statistically significant for healing time (p = 0.037). Steroid use was statistically significant for reoperation within 90 days (OR = 12.500; 95% CI 1.694–92.250); however, steroid use was not significant after correction for confounders. Modified open CST with biologic mesh is a safe, efficacious approach to complex AWR in the SOT population with recurrence rates comparable to the general population.

Short bowel syndrome is the most common etiology of intestinal failure, resulting from either resections of different intestinal segments or a congenital condition. Due to the absence or considerable reduction of intestinal loops in the abdominal cavity, patients with short bowel syndrome present with atrophy and muscle retraction of the abdominal wall, which leads to loss of abdominal domain and elasticity. This complication is an aggravating factor of intestinal transplantation since it can prevent the primary closure of the abdominal wall. A vast array of surgical techniques to overcome the challenges of the complexity of the abdominal wall have been described in the literature. The aim of our study was to review the modalities of abdominal wall closure in intestinal/multivisceral transplantation. Our study consisted of a systematic review following the methodological instructions described in the PRISMA guidelines. Duplicate studies and studies that did not meet the criteria for the systematic review were excluded, especially those without relevance and an explicit relationship with the investigated theme. After this step, 63 articles were included in our study. The results obtained with these techniques have been encouraging, but a high incidence of wound complications in some reports has raised concerns. There is no consensus among transplantation centers regarding which technique would be ideal and with higher success rates and lower rates of complications.