The enchanting canvas of CAR technology: Unveiling its wonders in non-neoplastic diseases.

Chimeric antigen receptor (CAR) T cells have made a groundbreaking advancement in personalized immunotherapy and achieved widespread success in hematological malignancies. As CAR technology continues to evolve, numerous studies have unveiled its potential far beyond the realm of oncology. This review focuses on the current applications of CAR-based cellular platforms in non-neoplastic indications, such as autoimmune, infectious, fibrotic, and cellular senescence-associated diseases. Furthermore, we delve into the utilization of CARs in non-T cell populations such as natural killer (NK) cells and macrophages, highlighting their therapeutic potential in non-neoplastic conditions and offering the potential for targeted, personalized therapies to improve patient outcomes and enhanced quality of life.

Accuracy of open-sleeved vs. closed-sleeved static computer-assisted implant systems in immediate maxillary molar implant placement: An in vitro study.

OBJECTIVES: The objective of this study is (1) to compare the accuracy of an open-sleeved static computer-assisted implant system (sCAIS) with a closed-sleeve sCAIS and free-hand approach in immediate implant placement (IIP) of maxillary molar sites and (2) to investigate the influence of socket morphology on these approaches. MATERIALS AND METHODS: Ninety partially edentulous duplicated maxillary models simulating three different molar sockets (type A, B, and C based on Smith and Tarnow's classification) were investigated. Three modalities, including sCAIS with open-sleeves, sCAIS with closed-sleeves, and free-hand approach, were applied separately to 30 models with 120 sockets. A customized Python script automatically measured the deviations between the virtual and actual implant positions for all 360 implants. RESULTS: The 3D deviations of sCAIS were significantly influenced by the socket and sleeve types. Both guided groups exhibited significantly less deviation than the free-hand approach. Type A and C sockets resulted in better implant positions than type B socket sites. In type B sockets, the open-sleeve group achieved significantly less deviation compared to the closed-sleeve group, with respect to apical global (1.34 ± 0.53 vs. 1.84 ± 0.59 mm), coronal horizontal (0.68 ± 0.36 vs. 0.93 ± 0.34 mm), apical horizontal (1.21 ± 0.59 vs. 1.74 ± 0.63 mm), and angular (3.30 ± 1.41 vs. 4.41 ± 1.96°) deviations. CONCLUSIONS: Guided implant surgery significantly reduces deviations during molar IIP compared to free-hand procedures. Furthermore, the use of open-sleeve sCAIS appears to be more effective in minimizing deviations in type B sockets when compared with the closed-sleeve guided system.

Co-delivery of fucoxanthin and Twist siRNA using hydroxyethyl starch-cholesterol self-assembled polymer nanoparticles for triple-negative breast cancer synergistic therapy.

INTRODUCTION: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer with an extremely dismal prognosis and few treatment options. As a desmoplastic tumor, TNBC tumor cells are girdled by stroma composed of cancer-associated fibroblasts (CAFs) and their secreted stromal components. The rapidly proliferating tumor cells, together with the tumor stroma, exert additional solid tissue pressure on tumor vasculature and surrounding tissues, severely obstructing therapeutic agent from deep intratumoral penetration, and resulting in tumor metastasis and treatment resistance. OBJECTIVES: Fucoxanthin (FX), a xanthophyll carotenoid abundant in marine algae, has attracted widespread attention as a promising alternative candidate for tumor prevention and treatment. Twist is a pivotal regulator of epithelial to mesenchymal transition, and its depletion has proven to sensitize antitumor drugs, inhibit metastasis, reduce CAFs activation and the following interstitial deposition, and increase tumor perfusion. The nanodrug delivery system co-encapsulating FX and nucleic acid drug Twist siRNA (siTwist) was expected to form a potent anti-TNBC therapeutic cyclical feedback loop. METHODS AND RESULTS: Herein, our studies constituted a novel self-assembled polymer nanomedicine (siTwist/FX@HES-CH) based on the amino-modified hydroxyethyl starch (HES-NH2) grafted with hydrophobic segment cholesterol (CH). The MTT assay, flow cytometry apoptosis analysis, transwell assay, western blot, and 3D multicellular tumor spheroids growth inhibition assay all showed that siTwist/FX@HES-CH could kill tumor cells and inhibit their metastasis in a synergistic manner. The in vivo anti-TNBC efficacy was demonstrated that siTwist/FX@HES-CH remodeled tumor microenvironment, facilitated interstitial barrier crossing, killed tumor cells synergistically, drastically reduced TNBC orthotopic tumor burden and inhibited lung metastasis. CONCLUSION: Systematic studies revealed that this dual-functional nanomedicine that targets both tumor cells and tumor microenvironment significantly alleviates TNBC orthotopic tumor burden and inhibits lung metastasis, establishing a new paradigm for TNBC therapy.

A skeleton in a huff: insights in etiologies of osteosclerosis.

A 30-yr-old man developed right lower leg pain and a palpable solid mass. Radiographic imaging revealed a periosteal reaction with an exostotic mass arising from the right distal fibula. Generalized skeletal osteosclerosis with periosteal reaction was discovered on a radiographic skeletal survey. A biopsy of the right fibular mass revealed reactive woven bone. The patient was referred to a metabolic bone disease clinic, where laboratory values were consistent with secondary hyperparathyroidism and increased bone turnover. A DXA bone density scan revealed high bone density, with an L1-4 spine Z-score of +9.3, a left femoral neck Z-score of +8.5, and a total hip Z-score of +6.5. A dental exam revealed generalized gingival inflammation, teeth mobility, generalized horizontal alveolar bone loss and widening of the periodontal ligament space, increased bone density around the teeth, and thickening of the radicular lamina dura. An extensive evaluation was performed, with the result of a single test revealing the diagnosis. The differential diagnoses of osteosclerosis affecting the skeleton, teeth, and oral cavity are discussed.

A 30-yr-old man developed, over a short period, pain in his lower right leg accompanied by a hard mass. He also reported weight loss and night sweats for the past 6 months. After evaluation by his primary physician, an X-ray was ordered that reported a bony mass arising from the right fibula bone. A biopsy was performed of the mass, but no evidence of cancer or any other specific abnormality was found. The patient was then referred to a bone disease specialty clinic. Laboratory tests revealed a large increase in how quickly the patient's skeleton was remodeling, affecting the balance of bone formation and removal involved in maintaining a healthy skeleton. A bone density scan reported that the patient had very dense bones. Other unusual changes were also discovered in a dental exam, suggesting bone thickening. After an extensive evaluation, a single blood test revealed the cause of the fibular bone mass and dense bones.

Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies.

BACKGROUND: Chimeric antigen receptor T (CAR-T) therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignancies, but the cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet to be fully understood. This study aims to explore the molecular determinants of cancer cell sensitivity to CAR-T cell-mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical efficacy. METHODS: The human whole-genome CRISPR/Cas9-based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR-T-cell-mediated killing. The in vitro cytotoxicity assays and evaluation of tumor tissue and bone marrow specimens were further conducted to confirm the role of the key genes in cancer cell susceptibility to CAR-T cells. In addition, the specific mechanisms influencing CAR-T cell-mediated cancer clearance were elucidated in mouse and cellular models. RESULTS: The CRISPR/Cas9-based knockout screening showed that the enrichment of autophagy-related genes (ATG3, BECN1, and RB1CC1) provided protection of cancer cells from CD19 CAR-T cell-mediated cytotoxicity. These findings were further validated by in vitro cytotoxicity assays in cells with genetic and pharmacological inhibition of autophagy. Notably, higher expression of the three autophagy-related proteins in tumor samples was correlated with poorer responsiveness and worse survival in patients with relapsed/refractory B-cell lymphoma after CD19 CAR-T therapy. Bulk RNA sequencing analysis of bone marrow samples from B-cell leukemia patients also suggested the clinical relevance of autophagy to the therapeutic response and relapse after CD19 CAR-T cell therapy. Pharmacological inhibition of autophagy and knockout of RB1CC1 could dramatically sensitize tumor cells to CD19 CAR-T cell-mediated killing in mouse models of both B-cell leukemia and lymphoma. Moreover, our study revealed that cancer-intrinsic autophagy mediates evasion of CAR-T cells via the TNF-α-TNFR1 axis-mediated apoptosis and STAT1/IRF1-induced chemokine signaling activation. CONCLUSIONS: These findings confirm that autophagy signaling in B-cell malignancies is essential for the effective cytotoxic function of CAR-T cells and thereby pave the way for the development of autophagy-targeting strategies to improve the clinical efficacy of CAR-T cell immunotherapy.

Harnessing Biomaterials for Safeguarding Chimeric Antigen Receptor T Cell Therapy: An Artful Expedition in Mitigating Adverse Effects.

Chimeric antigen receptor T cell (CAR-T) therapy has emerged as a groundbreaking approach in cancer treatment, showcasing remarkable efficacy. However, the formidable challenge lies in taming the formidable side effects associated with this innovative therapy, among which cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and on-target off-tumor toxicities (OTOT) are typical representatives. Championing the next frontier in cellular immunotherapy, this comprehensive review embarks on an artistic exploration of leveraging biomaterials to meticulously navigate the intricate landscape of CAR-T cell therapy. Unraveling the tapestry of potential toxicities, our discourse unveils a symphony of innovative strategies designed to elevate the safety profile of this revolutionary therapeutic approach. Through the lens of advanced medical science, we illuminate the promise of biomaterial interventions in sculpting a safer and more efficacious path for CAR-T cell therapy, transcending the boundaries of conventional treatment paradigms.

Recommendations for successful virtual patient-assisted esthetic implant rehabilitation: A guide for optimal function and clinical efficiency.

OBJECTIVE: Complete arch implant rehabilitation necessitates meticulous treatment planning and high-level collaboration between surgical and prosthetic dental teams. Emerging virtual technologies hold considerable promise in streamlining this process. The aim of this article is to extend recommendations to clinicians venturing into the virtual patient-assisted esthetic implant rehabilitation workflow. OVERVIEW: This article summarizes recommendations for virtual patient-assisted esthetic implant rehabilitation in the following five aspects: three-dimensional data handling and superimposition, occlusion and virtual articulator integration in creating virtual patients, streamlined face- and prosthetic-driven surgical planning, reuse of presurgical data ("Copy & Paste"), and final impression for passive fitting of final restoration. To illustrate these principles, a case with complete-mouth implant rehabilitation completed within six visits using this virtual patient workflow is presented. CONCLUSION: The virtual patient workflow serves as an invaluable tool to perform treatment planning, enhance efficiency, and ensure predictable outcomes in esthetic complete arch implant rehabilitation. CLINICAL SIGNIFICANCE: Virtual workflows are increasingly prevalent in esthetic implant rehabilitation. Nevertheless, these workflows necessitate a distinct set of knowledge and tools divergent from conventional dentistry practices. This article offers guidelines and recommendations for dental clinicians who are new to this field.

Advances in CAR-Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies.

Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a highly efficacious treatment modality for refractory and relapsed hematopoietic malignancies in recent years. Furthermore, CAR technologies for cancer immunotherapy have expanded from CAR-T to CAR-natural killer cell (CAR-NK), CAR-cytokine-induced killer cell (CAR-CIK), and CAR-macrophage (CAR-MΦ) therapy. Nevertheless, the high cost and complex manufacturing processes of ex vivo generation of autologous CAR products have hampered broader application. There is an urgent need to develop an efficient and economical paradigm shift for exploring new sourcing strategies and engineering approaches toward generating CAR-engineered immune cells to benefit cancer patients. Currently, researchers are actively investigating various strategies to optimize the preparation and sourcing of these potent immunotherapeutic agents. In this work, the latest research progress is summarized. Perspectives on the future of CAR-engineered immune cell manufacturing are provided, and the engineering approaches, and diverse sources used for their development are focused upon.

circ_SPEF2 Regulates the Balance of Treg Cells by Regulating miR-16-5p/BACH2 in Lymphoma and Participates in the Immune Response.

BACKGROUND: This study aims to explore the potential mechanism of action of the newly discovered hsa_circ_0128899 (circSPEF2) in diffuse large B-cell lymphoma (DLBCL). METHODS: circSPEF2, miR-16-5p and BTB and CNC homologue 2 (BACH2) expression patterns in DLBCL patients and cell lines were studied by RT-qPCR. The biological function of circSPEF2 in vitro and in vivo was investigated by function acquisition experiments. The proliferation activity of lymphoma cells was detected by MTT. Bax, Caspase-3, and Bcl-2 were determined by Western Blot. Apoptosis and the ratio of CD4 to Treg of immune cells in the co-culture system were analyzed by flow cytometry. The mechanism of action of circSPEF2 in DLBCL progression was further investigated by RIP and dual luciferase reporter experiments. RESULTS: circSPEF2 was a circRNA with abnormally down-regulated expression in DLBCL. Increasing circSPEF2 expression inhibited the proliferative activity and induced apoptosis of lymphoma cells in vitro and in vivo, as well as increased CD4+T cells and decreased Treg cell proportion of immune cells in the tumor microenvironment. Mechanically, circSPEF2 was bound to miR-16-5p expression, while BACH2 was targeted by miR-16-5p. circSPEF2 overexpression-mediated effects on lymphoma progression were reversible by upregulating miR-16-5p or downregulating BACH2. CONCLUSIONS: circSPEF2 can influence DLBCL progression by managing cellular proliferation and apoptosis and the proportion of immune cells Treg and CD4 through the miR-16-5p/BACH2 axis.

Prosthetic articulator-based implant rehabilitation virtual patient: A technique bridging implant surgery and reconstructive dentistry.

This technique report describes a fully digital workflow to create a prosthetic articulator-based implant rehabilitation (PAIR) virtual patient for complete-arch or complete-mouth implant rehabilitation. This workflow uses a custom gothic arch tracer during the cone beam computed tomography (CBCT) scan and a 3-dimensional virtual facebow when superimposing data. The PAIR virtual patient possesses reliable centric relation and vertical dimension of occlusion and is compatible with virtual articulators. Computer-aided implant planning and a digital prosthetic design can be seamlessly integrated by using this virtual patient.

Accuracy of Intraoperative Measuring Guide and Conventional Surgical Guide in Anterior Implant Surgery: A Retrospective Case-Control Study

PURPOSE: To verify a novel method that improves the accuracy of static computer-aided implant surgery (sCAIS) through intraoperative measurement. MATERIALS AND METHODS: Forty-seven patients were selected for this study, each with a missing tooth or a tooth that required extraction from the anterior area. The patients were divided into the intraoperative measuring guide (MG) and conventional guide (CG) groups. Following the preoperative implant planning, the surgical guides were designed and fabricated. In the MG group, the drill was guided by double-armed zirconia sleeves, and the axial direction of the drill was assessed using the indicator components. The implant was guided using a resin guide tube. In the CG group, the drills were guided using a metal sleeve and handles, and the implants were placed with the guidance of the metal sleeve only. The angular and linear deviations at the entry and apex between the planned and actual implant positions were measured after matching the preoperative and postoperative CBCT data. The independent-samples t test was used to compare the deviation between the MG and CG groups. RESULTS: The 3D deviations for the MG group at the entry and apex were 0.67 ± 0.44 mm and 0.93 ± 0.40 mm, respectively. The angular deviation was 2.27 ± 0.96 degrees. Statistical differences were found in the 3D deviation at the entry point and apical position between the MG and CG groups, yielding relatively smaller deviations in the MG group. CONCLUSION: The use of an intraoperative measuring guide could improve the accuracy of implant placement in sCAIS.

Soft tissue phenotype modification impacts on peri-implant stability: a comparative cohort study.

OBJECTIVES: Soft tissue phenotype modification (STPM) could be performed to maintain peri-implant health. Therefore, the aim of the study was to analyze tissue alteration around implants following soft tissue phenotype modification during implant uncovering surgery. MATERIALS AND METHODS: Patients who had STPM (either pouch roll or modified roll technique) during implant second-stage surgery with at least 12-month follow-up were included. Clinical and radiographic parameters including mucosal tissue thickness (MTT), recession (REC), keratinized mucosa width (KMW), probing pocket depth (PPD), marginal bone loss (MBL), emergence profile, and emergence angle were extracted from 2-week, 2-month, and 12-month visits after second-stage surgery. RESULTS: Twenty-eight patients with 33 implants that fulfilled the inclusion criteria were included. After soft tissue phenotype modification, at 2 weeks, REC was negatively correlated to mean MTT at mid-buccal site (r = - 0.41, p = 0.018) and borderline correlated at mid-lingual site (r = - 0.343, p = 0.051). Stable KMW was maintained from 2 weeks to 12 months with minimal shrinkage rate (3 ~ 14%). MBL change was limited (0.24 ~ 0.47 mm) after STPM. All implants had shallow PPD (≤ 3 mm) with the absence of bleeding on probing. Emergence angle at the mesial side, however, was significantly correlated to surgical techniques, which indicated pouch roll technique would have 6.96 degrees more than modified roll technique (p = 0.024). CONCLUSIONS: Soft tissue phenotype modification, either pouch roll or modified roll technique, during uncovering surgery resulted in favorable clinical outcomes. Thin mucosal tissue thickness and pouch roll technique are the factors related to more recession at 2 weeks. Pouch roll technique could influence the restorative design by having a wide emergence angle at the mesial side. CLINICAL RELEVANCE: Modified and pouch roll techniques during uncovering surgery were viable methods to yield favorable peri-implant health, while the preciseness of pouch roll technique was required to avoid mucosal recession and inadequate restorative design.

Orthologous genes Pm12 and Pm21 from two wild relatives of wheat show evolutionary conservation but divergent powdery mildew resistance.

Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a devastating disease that threatens wheat production worldwide. Pm12, which originated from Aegilops speltoides, a wild relative of wheat, confers strong resistance to powdery mildew and therefore has potential use in wheat breeding. Using susceptible mutants induced by gamma irradiation, we physically mapped and isolated Pm12 and showed it to be orthologous to Pm21 from Dasypyrum villosum, also a wild relative of wheat. The resistance function of Pm12 was validated via ethyl methanesulfonate mutagenesis, virus-induced gene silencing, and stable genetic transformation. Evolutionary analysis indicates that the Pm12/Pm21 loci in wheat species are relatively conserved but dynamic. Here, we demonstrated that the two orthologous genes, Pm12 and Pm21, possess differential resistance against the same set of Bgt isolates. Overexpression of the coiled-coil domains of both PM12 and PM21 induces cell death in Nicotiana benthamiana leaves. However, their full-length forms display different cell death-inducing activities caused by their distinct intramolecular interactions. Cloning of Pm12 will facilitate its application in wheat breeding programs. This study also gives new insight into two orthologous resistance genes, Pm12 and Pm21, which show different race specificities and intramolecular interaction patterns.

The Impact of Implantoplasty in Regenerated and Nonregenerated Treatment Modalities in Peri-implantitis: A Systematic Review and Meta-analysis.

PURPOSE: To investigate the impact of implantoplasty (IP) with or without regenerative procedures on treatment outcomes of peri-implantitis. MATERIALS AND METHODS: Electronic and manual literature searches were conducted for clinical trials published up to October 2020 that evaluated clinical outcomes (at least 6-month follow-up) after peri-implantitis treatment involving IP. The implant survival rate and clinical parameters (eg, probing depth [PD], bleeding on probing [BOP], marginal bone loss [MBL], clinical attachment level [CAL], and mucosal recession [REC]) at baseline and follow-ups were extracted from original articles for qualitative analyses. Risk ratio and weighted mean difference with 95% CI were calculated using a random-effects model. RESULTS: Out of 322 studies, 17 (9 randomized controlled trials, 4 controlled clinical trials, and 4 case series) were included in the present study. The regeneration group presented a 97% (95% CI: 0.95 to 1.00) implant survival rate, and the nonregeneration group showed a 94% (95% CI: 0.90 to 0.98) survival rate. Both groups revealed similar outcomes in PD and BOP reductions and soft tissue REC. However, the regeneration group had more favorable results in MBL. CONCLUSION: Data from this study suggested that applying implantoplasty during a regeneration or nonregeneration surgical approach resulted in a high implant survival rate and peri-implantitis resolution. Although no differences were found in the majority of clinical parameters in both groups, the regenerative approach resulted in more radiographic bone fill than the nonregenerative treatment.

Does guided level (fully or partially) influence implant placement accuracy at post-extraction sockets and healed sites? An in vitro study.

OBJECTIVES: The aim of this study is to evaluate the effect of guide level on the accuracy of static computer-aided implant surgery (sCAIS) at post-extraction sockets and healed sites. MATERIALS AND METHODS: A total of 30 duplicate dental models, with 300 potential implant sites, were used. All the models were equally randomized into three groups: fully guided (FG, n = 100), partially guided (PG, n = 100), and free handed (FH, n = 100) surgeries. After implant placement, the mean global, horizontal, depth, and angular deviations between the virtually planned and actual implant positions were measured automatically by a Python script within software Blender. RESULTS: Both FG and PG surgeries showed significantly higher accuracy than FH surgery at post-extraction sockets and healed sites. In both sCAIS groups, there were nearly 50% more deviations from implants placed at sockets than those from delayed placement. For the immediate implant placement, the accuracy of sCAIS was significantly affected by the level of guidance. The FG group exhibited lower deviations than the PG group, with a significant difference in coronal global and horizontal deviations (p < .05). For the healed sites, two guided groups exhibited similar outcomes (p > .05). CONCLUSIONS: sCAISs provide more accuracy than the free-handed approach in position transferring from planning to a model simulation. Full guidance can significantly increase the accuracy, especially at post-extraction sites. CLINICAL RELEVANCE: Guided protocols showed significantly higher accuracy than free-handed surgery regardless of implantation timing, but both had nearly 50% more deviations in immediate implant placement.

Improvement in Osseointegration of Titanium Dental Implants After Exposure to Ultraviolet-C Light for Varied Durations: An Experimental Study in Beagle Dogs.

PURPOSE: Ultraviolet-mediated photofunctionalization is a valid technology for enhancing the osseointegration of titanium implants. However, there is no consensus on the effective exposure time to ultraviolet light. The objective of this study was to evaluate the effect of different exposure times of ultraviolet-C (UVC) light on aged titanium implants and explore the optimal treatment duration of UVC photofunctionalization for osseointegration in an animal model. METHODS: Eight male beagle dogs (n = 48) were divided into a control group (n = 12) and 3 experimental groups (n = 12/12/12) which received 4-week-old implants without UVC treatment (C) or treated with UVC for 1/6 hour, 1/2 hour, and 1 hour (UVC-1/6 hour, UVC-1/2 hour, UVC-1 hour) immediately before placement. All the implants were placed 12 weeks after mandibular premolars extraction. Four dogs were euthanized after 4 and 12 weeks of healing, respectively. The marginal bone level and implant stability quotient were measured at implant placement and after sacrifice. Subsequently, micro-CT and histomorphometric analyses were performed following block harvesting. RESULTS: No significant difference in marginal bone loss between the UVC-untreated and UVC-treated groups was found at 4 or 12 weeks. At 4 weeks, significantly higher BV/TV and bone-implant contact were observed in the UVC groups than in the C group, irrespective of the UVC-photofunctionalization duration (BV/TV: UVC-1/6 hour 0.48 ± 0.11, UVC-1/2 hour 0.50 ± 0.06, and UVC-1 hour 0.47 ± 0.08, C 0.34 ± 0.04; bone-implant contact : UVC-1/6 hour 84.30 ± 5.02%, UVC-1/2 hour 85.82 ± 5.05%, and UVC-1 hour 84.98 ± 3.86%, C 71.69 ± 3.52%. P < .05), whereas, no significant difference was observed among the UVC groups. At 12 weeks, there were no significant differences between the C group and UVC groups. After 4 and 12 weeks of healing, no significant difference in implant stability quotient values was observed between the C group and UVC groups. CONCLUSIONS: UVC photofunctionalization improved the early osseointegration of aged titanium implants. However, the effect was not dependent on the UVC-light duration within the range from 1/6 hour to 1 hour.

Open-sleeve templates for computer-assisted implant surgery at healed or extraction sockets: An in vitro comparison to closed-sleeve guided system and free-hand approach.

OBJECTIVE: A buccal opening guide provides better view and better irrigation. The aim of this study was to investigate the accuracy of this open-sleeve system. MATERIAL AND METHODS: Thirty duplicated maxillary models, each with six extraction sockets and four healed sites, were used. Based on the same digital plan, three modalities, sCAIS with open-sleeves, closed-sleeves, and free-hand approach, were used to place implants. The global, horizontal, depth, and angular deviations between the virtual and actual implant positions were measured. RESULTS: Both sCAIS groups exhibited better accuracy than the free-hand group in two clinical scenarios. At healed sites, the closed-sleeve group showed a significantly fewer error than the open-sleeve group in global apical (0.68 ± 0.33 vs. 0.96 ± 0.49 mm), horizontal coronal (0.28 ± 0.15 vs. 0.44 ± 0.25 mm), horizontal apical (0.64 ± 0.32 vs. 0.94 ± 0.48 mm), and angular deviations (1.83 ± 0.95 vs. 2.86 ± 1.46°). For extraction sockets, the open-sleeve group exhibited fewer deviations than the closed-sleeve group in terms of global (coronal: 0.77 ± 0.29 vs. 0.91 ± 0.22 mm; apical: 1.08 ± 0.49 vs. 1.37 ± 0.52 mm) and horizontal (coronal: 0.60 ± 0.24 vs. 0.86 ± 0.20 mm; apical: 0.95 ± 0.50 vs. 1.32 ± 0.51 mm) deviations. However, the closed-sleeve group was more accurate in the depth control (0.26 ± 0.20 vs. 0.40 ± 0.31 mm). CONCLUSION: In this in vitro investigation, open-sleeve sCAIS proved better accuracy than free-hand surgery for both delayed and immediate implant placement. Compared with a closed-sleeve sCAIS system, open sleeve have the potential of providing better outcomes in extraction sockets but not in healed sites.

Risk factors for urinary infection after retrograde upper urinary lithotripsy: Implication for nursing.

ABSTRACT: There are needs to evaluate the risk factors for urinary infection after retrograde upper urinary lithotripsy, to provide insights into the management and nursing care of patients with retrograde upper urinary lithotripsy.Patients who received retrograde upper urinary lithotripsy with a Foley 20 urinary tube insertion from June 1, 2019 to December 31, 2020 in our hospital were selected. Patients were grouped urinary infection and no infection group according to the culture results of urine, and the clinical data of the 2 groups of patients were collected and compared. Single factor and logistic regression analysis were used to analyze the risk factors of urinary tract infection after retrograde upper urinary lithotripsy.Four hundred ten patients with retrograde upper urinary lithotripsy were included, of whom 62 patients had the urinary tract infection, the incidence of urinary tract infection was 15.12%. There were significant differences in the gender, age, diabetes, stone diameter, duration of urinary tube insertion and duration of surgery between infection and no-infection group (all P < .05). The Escherichia coli (62.90%) was the most commonly seen bacterial in patients with urinary tract infection. Female (odds ratio [OR]: 1.602, 95% confidence interval 95% [CI]: 1.132∼2.472), age >50 years (OR: 2.247, 95% CI: 1.346∼3.244), diabetes (OR: 2.228, 95% CI: 1.033∼3.451), stone diameter ≥2 cm (OR: 2.152, 95% CI: 1.395∼3.099), duration of urinary tube insertion ≥3 days (OR: 1.942, 95% CI:1.158∼2.632), duration of surgery ≥90 minutes (OR: 2.128, 95% CI: 1.104∼3.846) were the independent risk factors for the postoperative urinary tract infection in patients with retrograde upper urinary lithotripsy (all P < .05).The incidence of urinary tract infection in patients undergoing retrograde upper urinary lithotripsy was high, counteractive measures targeted on those risk factors are needed to prevent and reduce the postoperative urinary infection in clinical settings.

Pharmacokinetics and Safety of the Selective Progesterone Receptor Modulator Vilaprisan in Chinese Healthy Postmenopausal Women.

Vilaprisan is a novel selective progesterone receptor modulator for the long-term treatment of uterine fibroids and endometriosis. This study investigated the pharmacokinetics, safety, and tolerability of vilaprisan in healthy Chinese postmenopausal women. Twelve participants received multiple doses of vilaprisan once daily over 14 days as a 2-mg tablet. Plasma vilaprisan concentrations were determined using liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters of vilaprisan were assessed with noncompartmental analysis, including maximum observed concentration (Cmax ), systemic exposure (area under the plasma concentration-time curve), time to reach Cmax and terminal half-life. Safety assessments include the documentation of adverse events, measurement of clinical/anthropometric parameters and vital signs, electrocardiogram, and physical and gynecologic examination. The participants had a mean age of 53.3 (± 4.2) years and a body mass index of 23.8 ± 2.8 kg/m2 . Median time to reach Cmax was 1.5 hours after both single and multiple vilaprisan administration. Mean Cmax values obtained after multiple dosing (23.3 µg/L [standard deviation (SD) = 6.73]) were 1.92-fold (SD = 0.554) higher compared to single dosing (12.5 µg/L [SD = 3.04]). Mean area under the plasma concentration-time curve in the dosing interval increased with an accumulation factor of 2.98 (SD = 0.767) between single (91.3 µg · h/L [SD = 20.4]) and multiple dosing (276 µg · h/L [SD = 109]). The mean terminal half-life of vilaprisan was 44.5 hours (SD = 10.3) after multiple dosing. Mild to moderate adverse events were observed similar to previous studies. Overall, daily oral administration of the therapeutic dose of 2 mg of vilaprisan over 14 days was safe and well tolerated by all participants.

Does a fully digital workflow improve the accuracy of computer-assisted implant surgery in partially edentulous patients? A systematic review of clinical trials.

BACKGROUND: Accurate implant placement is essential in reducing post-treatment complications and in ensuring a successful treatment outcome. PURPOSE: To compare the accuracy of fully-guided static computer-assisted implant surgery (s-CAIS) using partially- and fully-digital workflows. MATERIALS AND METHODS: Electronic and manual literature searches were performed to collect evidence concerning the accuracy of fully-guided s-CAIS procedures utilizing tooth-supported guides. Quantitative analysis was conducted to evaluate the accuracy of partially- and fully-digital workflows, and survival rates and complications were qualitatively analyzed. RESULTS: Thirteen studies, including 6 randomized controlled trials and 7 prospective clinical studies, were selected for quantitative and qualitative synthesis. A total of 669 implants in 325 patients using s-CAIS were available for review. Meta-analysis of the accuracy revealed a total mean angular deviation of 2.68° (95% CI: 2.32°-3.03°); mean global coronal deviation of 1.03 mm (95% CI: 0.88-1.18 mm); mean global apical deviation of 1.33 mm (95% CI: 1.17-1.50 mm); and mean depth deviation of 0.59 mm (95% CI: 0.46-0.70 mm). Minimal differences were found between the two different workflows. Few complications were reported, and survival rates were between 97.8% to 100% (range of follow-up: 12 to 24 months) in the available studies. CONCLUSION: Similar accuracy is obtained when implants are placed in partially edentulous patients using fully-guided s-CAIS, independently of the workflow utilized.