Digital light 4D printing of bioresorbable shape memory elastomers for personalized biomedical implantation.

Four-dimensional (4D) printing unlocks new potentials for personalized biomedical implantation, but still with hurdles of lacking suitable materials. Herein, we demonstrate a bioresorbable shape memory elastomer (SME) with high elasticity at both below and above its phase transition temperature (Ttrans). This SME can be digital light 3D printed by co-polymerizing glycerol dodecanoate acrylate prepolymer (pre-PGDA) with acrylic acid monomer to form crosslinked Poly(glycerol dodecanoate acrylate) (PGDA)-Polyacrylic acid (PAA), or PGDA-PAA network. The printed complex, free-standing 3D structures with high-resolution features exhibit shape programming properties at a physiological temperature. By tuning the pre-PGDA weight ratios between 55 wt% and 70 wt%, Ttrans varies between 39.2 and 47.2 ℃ while Young's moduli (E) range 40-170 MPa below Ttrans with fractural strain (εf) of 170 %-200 %. Above Ttrans, E drops to 1-1.82 MPa which is close to those of soft tissue. Strikingly, εf of 130-180 % is still maintained. In vitro biocompatibility test on the material shows > 90 % cell proliferation and great cell attachment. In vivo vascular grafting trials underline the geometrical and mechanical adaptability of these 4D printed constructs in regenerating the aorta tissue. Biodegradation of the implants shows the possibility of their full replacement by natural tissue over time. To highlight its potential for personalized medicine, a patient-specific left atrial appendage (LAA) occluder was printed and implanted endovascularly into an in vitro heart model. STATEMENT OF SIGNIFICANCE: 4D printed shape-memory elastomer (SME) implants particularly designed and manufactured for a patient are greatly sought-after in minimally invasive surgery (MIS). Traditional shape-memory polymers used in these implants often suffer from issues like unsuitable transition temperatures, poor biocompatibility, limited 3D design complexity, and low toughness, making them unsuitable for MIS. Our new SME, with an adjustable transition temperature and enhanced toughness, is both biocompatible and naturally degradable, particularly in cardiovascular contexts. This allows implants, like biomedical scaffolds, to be programmed at room temperature and then adapt to the body's physiological conditions post-implantation. Our studies, including in vivo vascular grafts and in vitro device implantation, highlight the SME's effectiveness in aortic tissue regeneration and its promising applications in MIS.

Intrahepatic cholangiocarcinoma: a dose threshold evaluation in those undergoing transarterial radioembolization.

Background: Intrahepatic cholangiocarcinoma (ICC) is a rare primary hepatic malignancy. One of the treatment strategies which has shown some promise is transarterial radioembolization (TARE). However, data on dose thresholds, arguably the most important aspect of the procedure itself, is still limited. The study aims to evaluate the relationship between dose to tumor and radiologic response in intrahepatic cholangiocarcinoma patients undergoing transarterial radioembolization. Methods: Twenty-patients who underwent treatment for 26 tumors were retrospectively reviewed. Radiologic response at 3-month was evaluated and post yttrium-90 bremsstrahlung single photon emission computerized tomography computed tomography was evaluated to determine tumor dose. Other factors such as particle load and activity per particle were evaluated. Results: The mean tumor dose for those with progressive disease or stable disease, partial response, and complete response (CR) by European Association for the Study of Liver (EASL) criteria for the glass cohort was 294±0, 465.4±292.4 and 951.8±666.5 Gy respectively (P=0.039). A receiver operating characteristic (ROC) curve analysis of tumor dose demonstrated an area under the curve (AUC) of 0.738 (P=0.038) with Youden-index analysis demonstrated a cutoff point of >541.7 Gy (sensitivity: 55.56%; specificity: 92.86%) for the glass cohort. Significantly longer survival was noted in those who achieved a CR [HR: 4.79 (95% CI: 1.41-16.25)] and those treated with glass as compared to resin [HR: 5.02 (95% CI: 1.23-20.55), P=0.025]. Of the 17 treatments in 13 patients which were done concomitantly with chemotherapy 7/17 (41.2%) required a delay in chemotherapy, however all patients reinitiated chemotherapy after a delay. Conclusions: There appears to be a relationship between tumor dose and radiologic response, with this study suggesting a target of ≥541.7 Gy being warranted in patients receiving treatment with glass microspheres.

Cancer Immunology: Impact of Radioembolization of Hepatocellular Carcinoma on Immune Response Modulation.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and the fourth most common cause of cancer mortality. The tumor microenvironment is increasingly recognized as having a central role in HCC carcinogenesis; factors such as tumor and immune cell interactions, cytokines, and extracellular matrix have key roles. Transarterial radioembolization (TARE) is a locoregional therapy for HCC that not only has a direct tumoricidal effect but also induces an immune response against tumor cells with subsequent immunogenic cell death. This TARE-induced tumor immunogenicity occurs through enhancement of tumor-associated antigen expression and recruitment and diversification of tumor-infiltrating lymphocytes. In addition, immunologic biomarkers, including neutrophil-to-lymphocyte ratio, lymphocyte count, and cytokine levels, may be useful for predicting outcomes after TARE. Early data are promising regarding the potential synergistic benefit of treatment algorithms that combine TARE and immunotherapies, and interest is growing in the clinical application of such combinations. The purpose of this article is to provide an overview of cancer immunology, summarize the available data on the biologic effects of TARE on local and systemic immune responses, and explore the potential role of the combination of TARE and immunotherapy for HCC.

Diffusion-weighted imaging (DWI) in diagnosis, staging, and treatment response assessment of multiple myeloma: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the role of diffusion-weighted imaging (DWI) in the initial diagnosis, staging, and assessment of treatment response in patients with multiple myeloma (MM). MATERIALS AND METHODS: A systematic literature review was conducted in PubMed, the Cochrane Library, EMBASE, Scopus, and Web of Science databases. The primary endpoints were defined as the diagnostic performance of DWI for disease detection, staging of MM, and assessing response to treatment in these patients. RESULTS: Of 5881 initially reviewed publications, 33 were included in the final qualitative and quantitative meta-analysis. The diagnostic performance of DWI in the detection of patients with MM revealed pooled sensitivity and specificity of 86% (95% CI: 84-89) and 63% (95% CI: 56-70), respectively, with a diagnostic odds ratio (OR) of 14.98 (95% CI: 4.24-52.91). The pooled risk difference of 0.19 (95% CI: - 0.04-0.42) was reported in favor of upstaging with DWI compared to conventional MRI (P value = 0.1). Treatment response evaluation and ADCmean value changes across different studies showed sensitivity and specificity of approximately 78% (95% CI: 72-83) and 73% (95% CI: 61-83), respectively, with a diagnostic OR of 7.21 in distinguishing responders from non-responders. CONCLUSIONS: DWI is not only a promising tool for the diagnosis of MM, but it is also useful in the initial staging and re-staging of the disease and treatment response assessment. This can aid clinicians with earlier initiation or change in treatment strategy, which could have prognostic significance for patients.

Advanced Imaging in Multiple Myeloma: New Frontiers for MRI.

Plasma cell dyscrasias are estimated to newly affect almost 40,000 people in 2022. They fall on a spectrum of diseases ranging from relatively benign to malignant, the malignant end of the spectrum being multiple myeloma (MM). The International Myeloma Working Group (IMWG) has traditionally outlined the diagnostic criteria and therapeutic management of MM. In the last two decades, novel imaging techniques have been employed for MM to provide more information that can guide not only diagnosis and staging, but also treatment efficacy. These imaging techniques, due to their low invasiveness and high reliability, have gained significant clinical attention and have already changed the clinical practice. The development of functional MRI sequences such as diffusion weighted imaging (DWI) or intravoxel incoherent motion (IVIM) has made the functional assessment of lesions feasible. Moreover, the growing availability of positron emission tomography (PET)-magnetic resonance imaging (MRI) scanners is leading to the potential combination of sensitive anatomical and functional information in a single step. This paper provides an organized framework for evaluating the benefits and challenges of novel and more functional imaging techniques used for the management of patients with plasma cell dyscrasias, notably MM.

Lung shunt fraction quantification methods in radioembolization: What you need to know.

In some patients undergoing radioembolization, lung toxicity is a limiting factor when calculating their dose. At the same time, it is known that the lung shunt fraction (LSF) is overestimated by the mapping exam. Furthermore, there are multiple methods to measure LSF. Planar measurement is both the most commonly utilized and easiest to perform, however new dosimetry software provides the ability to use more advanced 3D techniques. This paper reviews the different LSF calculation methods and elucidates the available data comparing the techniques, clinical relevance, and dose calculation.

Effectiveness of Transarterial Embolization in Treatment of Symptomatic Hepatic Hemangiomas: Systematic Review and Meta-analysis.

PURPOSE: To evaluate the current evidence for the effectiveness of transarterial embolization (TAE) in treatment of symptomatic hepatic hemangiomas. MATERIALS AND METHODS: A systematic literature review was conducted in PubMed, CINAHL and Scopus databases to identify studies of hepatic hemangiomas treated with transarterial embolization. Main outcome was defined as the mean difference between pre- and post-TAE hemangioma diameters. Treatment agents were categorized as Lipiodol based [bleomycin (L + BE), pingyangmycin (L + PYG) or ethanol (L + ethanol)] and non-Lipiodol based (polyvinyl-alcohol-only). Conventional random-effect meta-analysis technique was applied to analyze data. RESULTS: Of 3080 initially inspected publications, 21 studies were included in the meta-analysis comprising of 1450 patients with total of 1871 hemangiomas (36.2% male, mean age: 46.3 ± 3.6 years). One hundred and twenty-six, 1666, 41 and 38 lesions were treated with L + BE, L + PYG, L + ethanol and PVA, respectively. Median follow-up time after embolization was 12 months. Lipiodol-based treatments showed significant effect in reducing hemangioma size after TAE compared to PVA (P < 0.001). Pooled diameter reduction (cm) (95% confidence interval) was - 4.37( - 5.32, - 3.42), - 4.70( - 5.70, - 3.71), - 0.93( - 2.02, 0.16) for overall TAE treatment, Lipiodol-based and non-Lipiodol-based treatments, respectively. Main complications included post-embolization syndrome and transient liver enzyme elevation (pooled incidence for Lipiodol-based and non-Lipiodol-based techniques: 36% and 33%; and 37% and 0, respectively). No fatal complications were reported. Symptomatic improvement was reported in 63.3%-100% of the cases with majority of studies (15/21) reporting improvement in all cases (pooled response rate: 98%). CONCLUSIONS: Transarterial embolization with bleomycin, pingyangmycin or ethanol in combination with Lipiodol is safe and associated with reduced size of hemangiomas resulting in symptoms alleviation.

Fibrin sealants in lumbar annuloplasty after endoscopic discectomy as a method to prevent recurrent lumbar disc herniation.

Fibrin sealant as a promising agent for providing scaffold and efficient hemostasis is widely accepted in several specialties. However, the outcome of Fibrin sealants in lumbar annuloplasty after endoscopic discectomy has not been evaluated in patients with disc herniation. The goal of this study was to evaluate the efficacy, response, and probability of future recurrence rates in herniated nucleus pulposus (HNP) with the use of fibrin sealant in conjunction with endoscopic disc surgery. A total of 35 patients (28 men, 7women) were evaluated, including 18 patients who underwent endoscopic discectomy alone and 17 patients that received fibrin sealant at the site of annulus tear and endoscopic discectomy. All patients were followed through both clinical and imaging methods for an average of 10.5 months. Primary outcome measure was defined as lumbar decompression approved by imaging and symptom alleviation after endoscopic spinal discectomy with Visual Analogue Scale (VAS) score ≤ 4 (cut-off point). Median size of annular tearing was significantly lower in the endoscopic discectomy group (median, 3) (minimum, 2; maximum, 5); however, the corresponding factor in the endoscopic discectomy plus fibrin sealant group was significantly larger (median, 6) (minimum, 5; maximum, 10), with P <0.001. Only one patient in the endoscopic discectomy group had an HNP recurrence during follow-up compared to two patients in the endoscopic discectomy plus fibrin sealant group. Due to the temporary effects of fibrin sealant in preventing disc herniation and the observed recurrence rate in both the case and control groups, the results of this study suggest a role of fibrin sealants combined with endoscopic discectomy to prevent early HNP recurrence rate.

Long-term Clinical Outcomes of Ahmed and Baerveldt Drainage Device Surgery for Pediatric Glaucoma Following Cataract Surgery.

PRECIS: In this retrospective case series, both Baerveldt and Ahmed glaucoma drainage devices resulted in good long-term outcomes in eyes with pediatric glaucoma following cataract surgery (GFCS). BACKGROUND: The aim of this study was to describe the long-term safety and efficacy of primary glaucoma drainage device surgery in patients with pediatric GFCS. METHODS: We retrospectively identified 28 eyes of 28 patients with GFCS that underwent tube shunt surgery with the Ahmed Glaucoma Valve or Baerveldt Glaucoma Implant. The primary outcome measure was a surgical failure, defined as intraocular pressure (IOP) >21 mm Hg or not reduced by 20% below baseline on 2 consecutive follow-up visits after 3 months, IOP <5 mm Hg on 2 consecutive follow-up visits after 3 months, and reoperation for glaucoma. RESULTS: The mean duration between cataract removal and the diagnosis of glaucoma was 3.6±1.5 years. Kaplan-Meier survival curves indicated a mean time to failure of 41.9±2.1 months after drainage device surgery. The cumulative probability of failure at 1, 2, 3, and 4 years was 3.6%, 19%, 28%, and 28%. IOP was significantly decreased from 29.3±4.1 mm Hg preoperatively to 17.6±1.6 mm Hg at the final follow-up visit (P<0.001). The number of glaucoma medications at baseline was 3.1±0.6, which decreased to 2.1±0.7 at the final visit (P=0.001). CONCLUSIONS: Glaucoma drainage device surgery results in good long-term outcomes in patients with GFCS.

Five-year clinical outcomes of combined phacoemulsification and trabectome surgery at a single glaucoma center.

PURPOSE: To analyze the 5-year results of trabectome ab interno trabeculectomy of a single glaucoma center. METHOD: In this retrospective interventional single-center case series, data of 93 patients undergoing ab interno trabeculotomy between September 2010, and December 2012 were included. Kaplan-Meier analysis was performed using success criteria defined as postoperative intraocular pressure (IOP) ≤ 21 mmHg, and > 20% reduction from preoperative IOP, and no need for further glaucoma surgery. Risk factors for failure were identified using Cox proportional hazards ratio (HR). RESULTS: The retention rate for 5-year follow-up was 66%. The cumulative probability of success at 1, 2, 3, 4, and 5 years was 82.6%, 76.7%, 73.9%, 72.3%, and 67.5%. Risk factors for failure were lower baseline IOP (HR = 0.27, P = 0.001), younger age (HR = 0.25, P = 0.02), and higher central corneal thickness (HR = 0.18, P = 0.01). Exfoliative glaucoma was associated with a higher success rate (HR = 0.39, P = 0.02). IOP was decreased significantly from 20.0 ± 5.6 mmHg at baseline to 15.6 ± 4.6 mmHg at 5-year follow-up (P = 0.001). The baseline number of glaucoma medications was 1.8 ± 1.2, which decreased to 1.0 ± 1.2 medications at 5 years. CONCLUSION: Trabectome surgery was associated with a good long-term efficacy and safety profile in this single-center case series with a high retention rate.

Acute Transient Sixth Nerve Palsy in Chediak-Higashi Syndrome.

Neurologic disorders in Chediak-Higashi syndrome are usually late presentations and also may manifest long after bone marrow stem cell transplantation. To the authors' knowledge, transient neurological deficit has not been reported yet. They describe a 6-year-old boy with Chediak-Higashi syndrome in the accelerated phase who presented with transient sixth nerve palsy. [J Pediatr Ophthalmol Strabismus. 2018;55:e22-e25].

Mini-vitrectomy; a Simple Solution to a Serious Condition.

PURPOSE: To evaluate the safety and efficacy of clear corneal approach irido-zonulo-hyaloido-vitrectomy, which we named "mini-vitrectomy," in the management of pseudophakic aqueous misdirection. METHODS: In this retrospective, non-comparative interventional case series, 24 eyes with diagnosis of pseudophakic aqueous misdirection were enrolled. Medical therapy with cycloplegics and laser therapy, including posterior capsulotomy and hyaloidotomy, was not effective in the management of the condition. The eyes underwent mini-vitrectomy, a simple technique in which iridotomy, zonulectomy, hyaloidectomy, and limited anterior vitrectomy were performed via a clear cornea incision. The main outcome measure was reformation of the anterior chamber, which was evaluated at day 1 and months 1, 3, 6, and 12. RESULTS: The mean age of patients was 75.3 ± 11.3 years (range, 47 to 90), and 13 (54.2%) patients were women. Anterior chamber was deep in 22 patients (91.7%) at the last follow-up visit. The mean intraocular pressure (IOP) was 30.31 ± 1.9 mm Hg at presentation on 2.67 ± 1.09 glaucoma medications. IOP decreased significantly to 14.5 ± 4.6 mm Hg at 12-month follow-up. (P = 0.001). The number of glaucoma medications at final visit was 2.2 ± 0.9 (P = 0.21). CONCLUSION: Mini-vitrectomy is a simple, safe, and effective procedure in the management of pseudophakic aqueous misdirection, and it can be adopted by all ophthalmologists who are involved in glaucoma management and are not comfortable with the pars plana vitrectomy approach.

Low iris and anterior chamber volume is associated with deepening after laser peripheral iridotomy in primary angle closure suspects.

PURPOSE: To evaluate the association between baseline ocular variables and the widening of the anterior chamber angle by laser peripheral iridotomy (LPI) in primary angle closure suspects (PACS) using a new Fourier-domain swept-source anterior segment optical coherence tomography (FD-ASOCT). METHOD: Sixty-six PACS eyes of 41 individuals were enrolled in this prospective interventional case series. An FD-ASOCT (Casia SS-1000 OCT; Tomey, Nagoya, Japan) was used to measure biometric baseline variables and at 1 month after the LPI. Paired t test was used to compare the difference between pre-and post-LPI measurements. Multivariate regression analysis was used to test for an association between baseline iris thickness and volume, anterior chamber depth and volume, and lens vault with a widening of the angle after an LPI. Changes in trabecular iris space area and angle opening distance after the LPI were main outcome measures. RESULTS: The mean age of participants was 58.6 ± 8.7 years, 68.2% of whom were female. The angle opening distance, recess area, and trabecular iris surface area at 500 µm increased by 48 to 73% (all P < 0.001). Lens vault and iris volume did not change. A low anterior chamber volume and low iris volume were associated with angle greater deepening by LPI. CONCLUSION: Eyes with a shallow anterior chamber and thinner irises are more likely to experience angle opening from an LPI.

Transarterial Bleomycin-Lipiodol Embolization (B/LE) for Symptomatic Giant Hepatic Hemangioma.

BACKGROUND: Large hepatic hemangiomas can cause symptoms such as pain and bleeding. No consensus currently exists on the optimal management of large and symptomatic hemangiomas. The purpose of this study was to evaluate the role of transarterial bleomycin-lipiodol embolization (B/LE) in the treatment of symptomatic large hepatic hemangioma. MATERIALS AND METHODS: We retrospectively reviewed 23 patients (29 hemangiomas) treated between July 2011 and August 2017. Transarterial B/LE was performed using 7-15 cc of Lipiodol mixed with 30-45 IU of bleomycin by standard three-way stopcocks. All patients were followed clinically and by imaging for an average of 7.5 months. Patterns of bleomycin-lipiodol distribution in the periphery of hemangiomas were categorized into four different grades. Technical success was defined as proper delivery of bleomycin-lipiodol into the hemangioma confirmed by post-embolization computed tomography. Clinical success was defined as more than 50% reduction of hemangioma volume and symptom improvement during follow-ups. RESULTS: Technical success and clinical success were 100 and 73.9% (17 patients), respectively. Six patients (26.08%) experienced transient post-embolization syndrome. Significant size reduction was seen in patients with grade 4 hemangioma border coverage (P = 0.042). CONCLUSION: Transarterial B/LE is a safe and efficient alternative for controlling symptoms related to large hemangiomas.

Impact of same-session trabectome surgery on Ahmed glaucoma valve outcomes.

PURPOSE: To evaluate the efficacy and survival rates of same session ab interno trabeculectomy with the trabectome and Ahmed glaucoma valve implant (AT) in comparison to the Ahmed glaucoma valve alone (A). METHOD: A total of 107 eyes undergoing primary glaucoma surgery were enrolled in this retrospective comparative case series, including 48 eyes which underwent AT and 59 eyes which received A alone. Participants were identified using the procedural terminology codes, and their medical records were reviewed. The primary outcome measure was success defined as IOP > 5 mmHg, ≤ 21 mmHg and ≥ 20% reduction of IOP from baseline at two consecutive visits after 3 months, and no need for glaucoma reoperation. Secondary outcome measures were IOP, the number of glaucoma medications, incidence of a hypertensive phase, and best corrected visual acuity (BCVA). RESULTS: The cumulative probability of success at 1 year was 70% in AT, and 65% in A (p = 0.85). IOP decreased significantly from 26.6 ± 10.1 mmHg at baseline to 14.7 ± 3.3 mmHg at the final follow-up in AT (p = 0.001). The corresponding numbers for A were 27.8 ± 10.2 and 16.7 ± 4.9, respectively (p = 0.001). The final IOP was significantly lower in AT (p = 0.022). The number of medications at baseline was comparable in both groups (2.6 ± 1.2 in AT and 2.5 ± 1.3 in A, p = 0.851). Corresponding number at 1 year visit was 1.2 ± 2 in AT and 2.8 ± 1.8 in A (p = 0.001). The incidence of a hypertensive phase was 18.7% in AT and 35.5% in A (p = 0.05). HP resolved in only 30% of eyes. The criteria for HP resolution were fulfilled in 9 eyes (30%). There was no difference in the rate of resolution of the hypertensive phase between AT and A (33.3 and 28.5%, respectively, p = 0.67). CONCLUSION: Ahmed glaucoma valve implant with same session trabectome surgery significantly decreased the rate of the hypertensive phase and postoperative IOP as well as the number of glaucoma medications.

The relationship between abduction deficit and reoperation among patients with infantile esotropia.

AIM: To determine the relationship between abduction deficit and reoperation among patients with infantile esotropia (IET). METHODS: The records of 216 patients (432 eyes) with IET who underwent surgery, from 2010 to 2015 were studied. Patients with IET whose deviation appeared before 6mo of age and had stable preoperative deviation in two examinations with at least 2wk apart and a minimum 3mo postoperative follow up were included. Cases with early onset accommodative esotropia, congenital cataract, retinopathy of prematurity (ROP), manifest nystagmus, fundus lesions, neurologic and ophthalmic anomalies, 6th nerve palsy and Duane's syndrome were excluded. Preoperative abduction deficit was considered from -1 to -3 grading scale. Three months after surgery, children were classified into no-need reoperation [deviation≤15 prism diopters (PD)], and need-reoperation groups (deviation>15 PD). RESULTS: In this retrospective study, 117 female and 99 male patients with the mean surgical age of 4.7±6.4y were included. Reoperation rate was 33.3% and 16.0% in IET patients with and without abduction deficit, respectively in patients who had a history of late surgery. Abduction deficit increased the odds of reoperation by 82% [OR=1.82, 95% confidence interval (CI) =1.05 to 3.19, P=0.003] in patients who had a history of late surgery (>2 years old, P=0.021). Abduction deficit was improved significantly after operation (P<0.001). CONCLUSION: Based on our results, abduction deficit can be considered as a risk factor of reoperation in IET patients who are operated at the age of more than 2y.