Preoperative localization of potentially invisible colonic lesions on the laparoscopic operation field: using autologous blood tattooing.

PURPOSE: Preoperative colonoscopic (POC) localization is recommended for patients scheduled for elective laparoscopic colectomy for early colon cancer. Among the various localization method, POC tattooing localization has been widely used. Several dyes have been used for tattooing, but dye has disadvantages, including foreign body reactions. For this reason, we have used autologous blood tattooing for POC localization. This study aimed to evaluate the safety and efficacy of the autologous blood tattooing method. METHODS: This study included patients who required POC localization of the colonic neoplasm among the patients who were scheduled for elective colon resection. The indication for localization was early colon cancer (clinically T1 or T2) or colonic neoplasms that could not be resected endoscopically. POC autologous blood tattooing was performed after saline injection, and 2 hemoclips were applied. RESULTS: A total of 45 patients who underwent autologous blood tattooing and laparoscopic colectomy were included in this study. All POC localization sites were visible in the laparoscopic view. POC localization sites showed almost perfect agreement with intraoperative surgical findings. There were no complications like bowel perforation, peritonitis, hemoperitoneum, and mesenteric hematoma. CONCLUSION: Autologous blood is a safe and effective agent for localizing materials that can replace previous dyes. However, a large prospective case-control study is required for the routine application of this procedure in early colon cancer or colonic neoplasms.

Extended total colonic aganglionosis and total intestinal aganglionosis: Challenging enemies.

AIM: Extended total colonic aganglionosis (ETCA) represents uncommon forms of Hirschsprung disease (HD), with aganglionosis extending into the proximal small bowel. ETCA management is challenging and associated with poor outcomes and high mortality. This study compares management and outcomes of ETCA to more common HD forms. METHODS: A retrospective cohort of HD patients (2012-2023) from two institutions. Three HD forms were compared: short-segment HD (SSHD, n = 19), long-segment HD or total colonic aganglionosis (LS/TCA, n = 9) and ETCA (n = 7). RESULTS: Normally innervated segments in ETCA patients ranged 0-70 cm. Median times to first surgery were; ETCA = 3 days versus TCA = 21 days (p = 0.017) and SSHD = 95 days (p < 0.001), respectively. Median number of surgeries were; ETCA = 4, versus TCA = 2 (p = 0.17) and SSHD = 1 (p = 0.002), respectively. All the patients underwent a definitive pull-through procedure, except four ETCA patients with a permanent jejunostomy and residual aganglionic segment of 57-130 cm. ETCA patients had 92% lower odds of enterocolitis (14%) compared to TCA patients (67%, p = 0.054), and comparable odds to SSHD patients (16%, p = 0.92). ETCA mortality was 14%. CONCLUSION: Extended total colonic aganglionosis patients require earlier and multiple interventions. Leaving an aganglionic segment may be advantageous, without increasing risk for enterocolitis. Tailored surgical treatment and rehabilitation programmes may prevent mortality and need for transplantation.

Comorbidities and survival of multiple myeloma patients diagnosed in Finland between 2000 and 2021.

Advances in treatment have improved the survival of multiple myeloma (MM) patients, but the disease remains incurable. Here, in this nationwide retrospective real-world evidence (RWE) study, we report the patient characteristics, incidence, overall survival outcomes, comorbidities, and healthcare resource utilization (HCRU) of all adult MM patients diagnosed between 2000 and 2021 in Finland. A total of 7070 MM patients and their 21,210 age-, sex- and region-matched controls were included in the analysis. The average MM incidence doubled from 4.11 to 8.33 per 100,000 people during the follow-up. The average age-standardized incidence also showed a significant increase over time (2.51 in 2000 to 3.53 in 2021). An increase in incidence was particularly seen in older population, indicative of improved diagnosis praxis. The median overall survival (mOS) of the MM patients and their matched controls was 3.6 and 15.6 years, respectively. The mOS of all MM patients increased significantly from 2.8 years (2000-2004) to 4.4 years (2017-2021) during the follow-up period. Distinctively, in patients who received autologous stem cell transplantation (ASCT), the mOS was 9.2 years, while in patients who did not receive ASCT, the mOS was only 2.7 years. MM patients showed more comorbidities at index and increased HCRU than their matched controls. The longer median survival and decreased risk of death indicate improved treatment outcomes in MM patients in Finland.

Comparing autologous blood, corticosteroid, and a combined injection of both for treating lateral epicondylitis: a randomized clinical trial.

BACKGROUND: Because lateral epicondylitis is a common musculoskeletal disorder that affects the forearm's extensor tendons, an effective therapeutic approach should reverse the degeneration and promote regeneration. This study aimed to compare the efficacies of autologous blood (AB) injection, corticosteroid (CS) injection, and a combined injection of both in treating lateral epicondylitis (LE), hypothesizing that the combined approach might offer immediate symptom resolution and a lower recurrence. MATERIALS AND METHODS: A total of 120 patients diagnosed with lateral epicondylitis were systematically distributed among three distinct therapeutic injection groups. Those in the AB group were administered 1 ml of autologous venous blood mixed with 2 ml of 2% prilocaine HCl. Participants in the CS category were given 1 ml of 40 mg methylprednisolone acetate mixed with 2 ml of 2% prilocaine HCl. Meanwhile, patients in the combined group received a mixture containing 1 ml each of autologous venous blood and 40 mg methylprednisolone acetate along with 1 ml of 2% prilocaine HCl. Prior to receiving their respective injections, a comprehensive assessment of all participants was carried out. Follow-up assessments were subsequently conducted on days 15, 30, and 90 utilizing metrics of the patient-rated tennis elbow evaluation (PRTEE) and measurements of hand grip strength (HGS). RESULTS: One patient dropped out from the combined group, and 119 patients completed the trial. No complications were recorded during the course of follow-up. By day 15, all groups had demonstrated significant PRTEE improvement, with CS showing the most pronounced reduction (p = 0.001). However, the benefits of CS had deteriorated by day 30 and had deteriorated further by day 90. The AB and AB + CS groups demonstrated sustained improvement, with AB + CS revealing the most effective treatment, achieving a clinically significant improvement in 97.4% of the patients. The improved HGS parallelled the functional enhancements, as it was more substantial in the AB and AB + CS groups (p = 0.001), corroborating the sustained benefits of these treatments. CONCLUSIONS: The study concluded that while AB and CS individually offer distinct benefits, a combined AB + CS approach optimizes therapeutic outcomes, providing swift and sustained functional improvement with a lower recurrence rate. These findings have substantial clinical implications, suggesting a balanced, multimodal treatment strategy for enhanced patient recovery in LE. LEVEL OF EVIDENCE: Randomized clinical trial, level 1 evidence. TRIAL REGISTRATION: NCT06236178.

Autotransplantation with Adjunctive Application of Enamel Matrix Derivatives Using a Digital Workflow: A Prospective Case Series.

OBJECTIVES: Digital protocols and bioactive materials may reduce complications and improve tooth autotransplantation (ATT) success and survival rates. This prospective study assesses the performance of a fully digital autotransplantation protocol of close-apex molars with the adjunctive application of Enamel Matrix Derivatives (EMD). METHODS: Twelve adult patients with 13 hopeless molar teeth were replaced with autotransplantation of closed apex third molars. Outcomes, including success and survival rates, clinical, endodontic, radiographic, patient-reported outcome measures (PROMs), and digital image assessments, were conducted over a two-year follow-up period. RESULTS: Survival and success rates were 100% and 91.2%, respectively, with no progressive inflammatory or replacement root resorption (ankylosis) except for one tooth presenting radiographic furcation involvement. A significant probing depth reduction of 2.4 ± 2.58 mm and CAL gains of 2.8 ± 3.03 mm were observed in transplanted teeth compared to the hopeless receptor teeth. Radiographic bone levels remained stable throughout the study period (-0.37 ± 0.66 mm), and digital image assessments showed minimal alveolar ridge width changes (-0.32 to -0.7 mm) and gingival margin changes (-0.95 to -1.27 mm) from baseline to last visit. PROMs indicated very high patient satisfaction. CONCLUSION: The use of a digital ATT protocol with adjunctive use of EMD in closed-apex third molars demonstrated promising short-term high success and survival rates. Additionally, this type of therapy adequately preserves the dimensions of the alveolar ridge in the receptor site.

[Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in the mobilization of autologous peripheral blood stem cells in patients with multiple myeloma].

Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: ①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d (P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.

Clinical and Genomic Profile of Primary Cranial Neurolymphomatosis.

Primary cranial neurolymphomatosis (PCNL) is a rare subtype of primary CNS lymphoma (PCNSL) in which infiltrative lymphomatous involvement is confined to cranial nerves. Here, we report a case of PCNL with successful genomic profiling. A 57-year-old male had a lengthy prediagnostic phase spanning approximately 30 months, characterized by multiple episodes of cranial neuropathies managed by steroids. At the time of diagnosis, the patient had right-sided cranial neuropathies involving cranial nerves (CN) V, VI, and VII. Pathological findings of the right cavernous lesion biopsy were consistent with large B-cell lymphoma-infiltrating nerve fibers. The clinical course was aggressive and refractory, characterized by relentless progression with the development of cervical spinal neurolymphomatosis, cerebrospinal fluid involvement, and ependymal and intraparenchymal cerebral involvement, despite multiple lines of therapy, including chemoimmunotherapy, Bruton's tyrosine kinase inhibitor, radiation, autologous stem cell transplant, chimeric antigen receptor T-cell therapy (CAR-T), and whole-brain radiation. The patient survived for 22 months from the time of the initial diagnosis and 52 months after the first episode of cranial neuropathy. Next-generation sequencing identified mutations (MYD88, CD79b, and PIM1) that are frequently observed in PCNSL. The unusual findings included a total of 22 mutations involving PIM1, indicating a highly active aberrant somatic hypermutation and two missense CXCR4 mutations. CXCR4 mutations have never been described in PCNSL and may have implications for disease biology and therapeutic interventions. We provide a literature review to further elucidate PCNL.

The Efficacy of Local Autologous Platelet-Rich Plasma Prepared by Single and Double Spin Methods in the Treatment of Chronic Ulcer.

BACKGROUND: Chronic nonhealing ulcers present significant challenges in diabetic, dermatological, and surgical patients. Platelet-rich plasma (PRP), enriched with bioactive factors, offers promise for wound healing enhancement. This study evaluates PRP's efficacy, prepared via single and double spin methods in nonhealing chronic ulcers. METHODS:  Twenty-two patients aged 18-65 years participated and 100 mL of blood was drawn into citrate phosphate dextrose adenine (CPDA) bags with all aseptic precautions. PRP was prepared by single and double spin methods. Patient serum and 10% calcium gluconate were added to fibrin gel. PRP was injected around the ulcer and then dressed. Dressings were changed on the fifth, 15th, and 20th days with PRP. Evaluation occurred on day 30 using surface area and volume assessments by both methods. RESULTS: The single spin PRP group and double spin PRP group had 11 patients each with hemoglobin range of 10.79±1.88 to 12.63±2.22 g/dL. Initial lesions (16.27 cm²) significantly reduced to 14.76 cm² after double spin PRP sessions (p=0.005) and Initial lesions (9.87 cm²) significantly reduced to 7.65 cm² after single spin PRP sessions (p=0.005). Platelet count differences between whole blood and PRP were significant (p<0.05). CONCLUSIONS: The single spin PRP method exhibited considerable improvements in healing parameters, showcasing its potential for chronic ulcer management.

Efficacy of using autologous cells with graft substitutes for spinal fusion surgery: A systematic review and meta-analysis of clinical outcomes and imaging features.

Over the past several decades, there has been a notable increase in the total number of spinal fusion procedures worldwide. Advanced spinal fusion techniques, surgical approaches, and new alternatives in grafting materials and implants, as well as autologous cellular therapies, have been widely employed for treating spinal diseases. While the potential of cellular therapies to yield better clinical results is appealing, supportive data are needed to confirm this claim. This meta-analysis aims to compare the radiographic and clinical outcomes between graft substitutes with autologous cell therapies and graft substitutes alone. PubMed, Scopus, Web of Science, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials were searched for studies comparing graft substitutes with autologous cell therapies and graft substitutes alone up to February 2024. The risk of bias of the included studies was evaluated using the Downs and Black checklist. The following outcomes were extracted for comparison: fusion success, complications/adverse events, Visual Analog Scale (VAS) score, and Oswestry Disability Index (ODI) score. Thirteen studies involving 836 patients were included, with 7 studies considered for the meta-analysis. Results indicated that the use of graft substitutes with autologous cell therapies demonstrated higher fusion success rates at 3, 6, and 12 months, lower VAS score at 6 months, and lower ODI score at 3, 6, and 12 months. The complication rate was similar between graft substitutes with autologous cell therapies and graft substitutes alone. Although the current literature remains limited, this meta-analysis suggests that the incorporation of cellular therapies such as bone marrow and platelet derivatives with graft substitutes is associated with a higher fusion rate and significant improvements in functional status and pain following spinal fusion. Future well-designed randomized clinical trials are needed to definitively assess the clinical effectiveness of cellular therapies in spinal fusion.

Growth Factor Concentrate (GFC) for the Management of Osteoarthritis of the Knee: A Systematic Review.

Introduction: The knee is the most commonly affected joint in osteoarthritis (OA), affecting millions of people worldwide. Knee OA significantly impacts the activities of daily living (ADL) along with affecting overall quality of life of patients (QoL), thereby leading to substantial socio-economic burden. Conservative therapies are prioritized, resorting to surgery only when needed. However, these traditional approaches have limitations. Regenerative medicine, involving the use of orthobiologics, including autologous peripheral blood-derived orthobiologics such as growth factor concentrate (GFC), has evolved and shown potential for managing knee OA. The primary goal of this review is to summarize the results of in vitro, preclinical and clinical studies involving GFC for the management of knee OA. Methods: Multiple databases (PubMed, Scopus, Google Scholar, Web of Science and Embase) were searched applying terms for the intervention 'GFC' and treatment 'knee OA' for the studies published in the English language to March 10, 2024. Results: Only three clinical studies met our pre-defined criteria and were included in this review. Conclusion: Intra-articular administration of GFC is safe and potentially efficacious to manage OA of the knee. More, adequately powered, multi-center, prospective, RCTs are warranted to demonstrate the long-term effectiveness of GFC in patients suffering from mild-to-moderate knee OA and to justify its routine clinical use. Further studies evaluating the efficacy of GFC compared to other orthobiologics are also required to allow physicians/surgeons to choose the optimal orthobiologic for the treatment of OA of the knee.

Establishment of an acute arterial mesenteric ischaemia model in canines with an endovascular approach.

Purpose: This study aimed to evaluate the feasibility of establishing an arterial acute mesenteric ischemia (AMI) model in canines using transcatheter autologous thrombus administration. Materials and methods: Ten canines were divided into the experimental group (Group A, n = 5) and the sham group (Group B, n = 5). The canines in Group A received thrombus administration to the superior mesenteric artery (SMA) through a guiding catheter, while the canines in Group B received normal saline administration. Blood samples were collected and tested at baseline and 2 h after modelling. Canines in Group A underwent manual thromboaspiration after blood and intestine samples were collected. Ischaemic grades of intestinal mucosa were evaluated under light microscopes. Results: The AMI models were successfully conducted in all canines without procedure-related vessel injury or death. At the 2-h follow-up, the high-sensitivity C-reactive protein and D-dimer in Group A were significantly higher than in Group B (5.72 ± 1.8 mg/L vs. 2.82 ± 1.5 mg/L, p = 0.024; 2.25 ± 0.8 µg/mL vs. 0.27 ± 0.10 µg/mL, p = 0.005; respectively). The mean histopathologic intestinal ischaemic grade in Group A was significantly higher than in Group B (2.4 ± 0.5 vs. 0.8 ± 0.4, p < 0.001). After a median of 2 times of thromboaspiration, 80% (4/5) of the canines achieved complete SMA revascularisation. Conclusion: This experimental study demonstrated that establishing an arterial model in canines using endovascular approaches was feasible. The present model may play an important role in the investigation of endovascular techniques in the treatment of arterial AMI.

Patellar reconstruction in primary total knee arthroplasty using bone chips from routine cuts: A case report and review of literature.

BACKGROUND: Total patellectomy is currently reserved for exceptional cases, such as recalcitrant patellofemoral instability and comminuted fractures, due to its demonstrated negative impact on knee biomechanics. Therefore, managing patellectomy is crucial to mitigate its inherent deleterious effects. Various techniques have been described, including autologous or allogeneic bone grafts for reconstruction and soft tissue realignment to enhance the extensor mechanism. CASE SUMMARY: A 73-year-old male underwent a patellectomy due to a comminuted fracture, subsequently developing osteoarthritis and experiencing a decline in functional status. Concurrent with total knee replacement, we conducted a patellar reconstruction, incorporating routine bone cuts and utilizing bone chips to fashion a new patella. This intervention resulted in the restoration of full extension and improvement of knee function. CONCLUSION: Patellar reconstruction demonstrates benefits on knee mechanics and stabilization, contributing to enhanced outcomes and satisfaction following knee replacement. We present an affordable technique for managing patellectomized patients undergoing total knee replacement.

Novel biomarkers to identify complicated course of febrile neutropenia in hematological patients receiving intensive chemotherapy.

Febrile neutropenia (FN) is a common consequence of intensive chemotherapy in hematological patients. More than 90% of the patients with acute myeloid leukemia (AML) develop FN, and 5%-10% of them die from subsequent sepsis. FN is very common also in autologous stem cell transplant recipients, but the risk of death is lower than in AML patients. In this review, we discuss biomarkers that have been evaluated for diagnostic and prognostic purposes in hematological patients with FN. In general, novel biomarkers have provided little benefit over traditional inflammatory biomarkers, such as C-reactive protein and procalcitonin. The utility of most biomarkers in hematological patients with FN has been evaluated in only a few small studies. Although some of them appear promising, much more data is needed before they can be implemented in the clinical evaluation of FN patients. Currently, close patient follow-up is key to detect complicated course of FN and the need for further interventions such as intensive care unit admission. Scoring systems such as q-SOFA (Quick Sequential Organ Failure Assessment) or NEWS (National Early Warning Sign) combined with traditional and/or novel biomarkers may provide added value in the clinical evaluation of FN patients.

Patient-reported outcomes in HSCT for autoimmune diseases: Considerations on behalf of the EBMT ADWP, PAC, and Nurses Group.

Background: Over the last 3 decades, hematopoietic stem cell transplantation (HSCT) has been successfully used to treat severe and refractory autoimmune diseases (AIDs). A multidisciplinary appraisal of potential benefits and risks by disease and transplant specialists is essential to determine individual suitability for HSCT. Objective: Our aim was to observe that patient-reported outcomes (PROs) and health-related quality of life instruments can capture the unique patient perspective on disease burden and impact of treatment. Methods: Herein, we describe the basis and complexity of end points measuring patient-reported perceptions of efficacy and tolerability used in clinical practice and trials for patients with AIDs undergoing autologous HSCT. Results: PRO measures and patient-reported experience measures are key tools to evaluate the impact and extent of disease burden for patients affected by AIDs. For formal scientific assessment, it is essential that validated general instruments are used, whereas adaptations have resulted in disease-specific instruments that may help guide tailored interventions. An additional approach relates to qualitative evaluations, from carefully structured qualitative research to informal narratives, as patient stories. The patients' subjectively reported responses to HSCT may be influenced by their preprocedure expectations and investment in the HSCT journey. Conclusions: The complexity of AIDs advocates for individualized and multidisciplinary approach to positively affect the patient journey. PROs and health-related quality of life need to be collected using validated instruments in clinical practice and trials to enable robustness of data and to ensure the impact of the intervention is comprehensively assessed, addressing the main questions and needs of the involved stakeholders.

Skull base plasmacytoma in young patients aged below 40 years: Radiological perspectives and clinical outcomes.

BACKGROUND: Plasmacytoma of the skull base is a rare manifestation of plasma cell neoplasm with only a few cases documented in literature involving young adults. Plasmacytoma can be an isolated solitary lesion or a secondary manifestation of multiple myeloma (MM). In this study, we report the clinical and radiological characteristics, management, and outcomes of patients under the age of 40 who presented with skull base plasmacytoma and associated neurological manifestations. Additionally, we share our experience in treating a rare case of skull base plasmacytoma diagnosed during pregnancy, in which the patient exhibited a favorable response to myeloma treatment initiated after delivery. CASE SERIES: Four patients were identified, comprising one pregnant female and three male patients, with a median age of 36 years (range 33-37 years). The main presenting symptoms were headache, dizziness, and cranial nerve palsy. All patients received underwent systemic myeloma therapy and radiotherapy with three patients also underwent autologous stem cell transplantation (ASCT). Notably, all patients achieved complete remission. CONCLUSION: Skull base plasmacytoma represents a rare manifestation of plasma cell neoplasms, underscoring the importance of considering it in the differential diagnosis of skull base lesions to ensure early intervention and avoid potential serious complications. Throughout our series, the cornerstone of therapy involved radiotherapy, systemic myeloma therapy, and ASCT, all of which elicited a favorable response in every case.

Impact of a cell salvage device on blood transfusions to dogs undergoing surgery at a referral veterinary hospital.

OBJECTIVE: To determine the number of homologous blood transfusions received by canine surgical patients after introducing a cell salvage device (CSD), trends in surgeries requiring blood transfusion, and the incidence of transfusion reactions. STUDY DESIGN: Retrospective study. SETTING: Single referral hospital. ANIMALS: All dogs having surgery at a single center (November 2015 to February 2021). INTERVENTIONS: Medical records of dogs having surgical treatment, including those that received either an autologous or homologous blood transfusion, were reviewed. The surgical patients were the baseline population, and the 2 transfusion groups were compared within this population to analyze the trends. MAIN RESULTS: A total of 37 and 86 dogs received autologous and homologous blood transfusions, respectively. There was an upward trend in the number of total monthly blood transfusions. No significant increase in the monthly number of homologous transfusions was observed before or after acquisition of the CSD. There was also an upward trend in total monthly surgeries, including those with higher risks of hemorrhage. Dogs receiving homologous blood transfusions had a higher incidence of clinical signs consistent with transfusion reactions (6.98%). CONCLUSIONS: An upward trend in autologous blood transfusions was seen with the introduction of a CSD. Hospitals with large surgical caseloads at high risk of hemorrhage may see a decreased need for outsourced blood products with the use of the CSD. The device can lead to a more responsible use of an increasingly scarce resource and decrease the risk of a blood transfusion reaction in dogs.

3D engineered scaffold for large-scale Vigil immunotherapy production.

Previously, we reported successful cellular expansion of a murine colorectal carcinoma cell line (CT-26) using a three-dimensional (3D) engineered extracellular matrix (EECM) fibrillar scaffold structure. CCL-247 were grown over a limited time period of 8 days on 3D EECM or tissue culture polystyrene (TCPS). Cells were then assayed for growth, electroporation efficiency and Vigil manufacturing release criteria. Using EECM scaffolds, we report an expansion of CCL-247 (HCT116), a colorectal carcinoma cell line, from a starting concentration of 2.45 × 105 cells to 1.9 × 106 cells per scaffold. Following expansion, 3D EECM-derived cells were assessed based on clinical release criteria of the Vigil manufacturing process utilized for Phase IIb trial operation with the FDA. 3D EECM-derived cells passed all Vigil manufacturing release criteria including cytokine expression. Here, we demonstrate successful Vigil product manufacture achieving the specifications necessary for the clinical trial product release of Vigil treatment. Our results confirm that 3D EECM can be utilized for the expansion of human cancer cell CCL-247, justifying further clinical development involving human tissue sample manufacturing including core needle biopsy and minimal ascites samples.

Clinical Practice Recommendations for Hematopoietic Cell Transplantation and Cellular Therapies in Follicular Lymphoma: A Collaborative Effort on behalf of The American Society of Transplantation and Cellular Therapy and the European Society of Blood and Marrow Transplantation.

Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma (NHL), accounting for nearly one-third of all NHL. The therapeutic landscape for patients with FL has significantly expanded over the past decade, but the disease continues to be considered incurable. Hematopoietic cell transplantation (HCT) is potentially curative in some cases. Recently, the emergence of chimeric antigen receptor T-cell therapy (CAR-T) for patients with relapsed/refractory (R/R) FL has yielded impressive response rates and long-term remissions, but definitive statement on the curative potential of CAR-T is currently not possible due to limited patient numbers and relatively short follow up. A consensus on the contemporary role, optimal timing, and sequencing of HCT (autologous or allogeneic) and cellular therapies in FL is needed. As a result, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines endorsed this effort to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 15 consensus statements/recommendations. Of note, the use of bispecific antibodies in R/R FL was not in the scope of this project. Key statements/recommendations are as follows: 1) Autologous HCT is recommended as an option for consolidation therapy in patients with progression of untransformed disease within 24 months of front line chemoimmunotherapy and upon achieving a complete (CR) or partial response (PR) to salvage second line therapies; 2) CAR-T is considered as a treatment option for patients who did not achieve CR or PR after second or subsequent lines of therapies; 3) Allogeneic HCT is considered as consolidative treatment in relapsed FL patients with chemosensitive disease who have received 3 or more lines of systemic therapy and are the following clinical scenarios: post CAR-T failure; lack of access to CAR-T or have therapy related myeloid neoplasm. These clinical practice recommendations will help guide clinicians managing patients with FL.

Proven efficacy in trial of autologous dendritic cell therapy in dogs with stage II hemangiosarcoma of the spleen.

Hemangiosarcoma is an aggressive tumour that most frequently occurs in larger, middle-aged dogs of certain breeds. The most commonly affected organ is the spleen. The aim of this prospective therapy trial was to evaluate the clinical effect of autologous, monocyte-derived dendritic cell (DC) therapy in canine hemangiosarcoma stage II after splenectomy. Dogs (n=452) diagnosed with splenic hemangiosarcoma that underwent splenectomy were enrolled. Of these, 42 dogs with stage II entered the DC therapy trial. The median survival time for the total group of 42 dogs was 203 days. The median survival for the group that received the full DC therapy (≥3 vaccines) was 256 days, with a 29% one-year survival rate and a hazard ratio of 0.30, adjusted to age and bodyweight (P =0.010). We further observed a significant increase in DC yield after each application and demonstrated that DC yield at the beginning of treatment is significantly related to veterinary patient survival. While further evidence is needed, we conclude that autologous, monocyte-derived DC therapy is a viable alternative to standard treatment of canine splenic hemangiosarcoma.

Drop in survivorship 13 years after AMIC procedures in aligned knees: A long-term follow-up.

PURPOSE: Autologous matrix-induced chondrogenesis (AMIC) showed promising short-term results comparable to microfracture. This study aims to assess the 19-year outcomes of AMIC, addressing the lack of long-term data. METHODS: Retrospective cohort of 34 knees treated with AMIC underwent a 19-year follow-up. The primary outcome was AMIC survival, considering total knee arthroplasty as a failure event. Survival analysis for factors that were associated with longer survival of the AMIC was also performed. Clinical and radiological outcome scores were analysed for the AMIC group. RESULTS: Twenty-three knees were available for follow-up analysis. Of these, 14 (61%) underwent revision surgery for total knee arthroplasty (TKA). The mean time was 13.3 ± 2.5 years (range: 9-17 years). Secondary outcomes showed that increased age at surgery (hazard ratio [HR]: 1.05; p = 0.021) and larger defect size (HR: 1.95; p = 0.018) were risk factors for failure. Concomitant proximal tibial osteotomy (HR: 0.22; p = 0.019) was associated with longer survival. The remaining nine knees (39%) were analysed as a single group. The mean clinical score at follow-up of 18.6 ± 0.9 SD years was 79.5 ± 19.7 SD for the Lysholm score, 1.8 ± 1.5 SD for the visual analog scale score, 74.2 ± 22.4 SD for the KOOS score and a median of 3 (range: 3-4) for the Tegner activity scale. CONCLUSIONS: The mean survival time of 13.3 years indicates the durability of AMIC in properly aligned knees. Nonetheless, despite a 61% conversion to TKA, the knees that persisted until the 19-year follow-up remained stable, underscoring the procedure's longevity and consistent clinical outcomes. LEVEL OF EVIDENCE: Level IV.