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.

[Retrospective clinical study on cryopreservation-free integrated autologous hematopoietic stem cell transplantation model for newly diagnosed multiple myeloma].

Objective: To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple myeloma. Methods: A total of 96 patients with newly diagnosed multiple myeloma (NDMM) between July 31, 2020, and December 31, 2022, were retrospectively analyzed, of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode. After hematopoietic stem cells were mobilized and collected, melphalan was started immediately for pre-transplant conditioning, and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning. The control group consisted of 55 patients who received traditional transplantation mode. After hematopoietic stem cells were collected, stem cell cryopreservation was performed in liquid nitrogen, and then the transplant plans were started at the right time. All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor. Results: ① A total of 34 patients (82.9% ) with VGPR plus CR in the observation group were significantly higher than 33 patients (60.0% ) in the control group (P=0.016). ②Compared with the control group, the incidence of grade 1 oral mucosal inflammation was higher in the observation group (P<0.001) ; however, the incidence of grades 2 and 3 oral mucosal inflammation was lower (P=0.004, P=0.048), and neither group experienced grade 4 or above oral mucosal inflammation. The incidence of grade 1 diarrhea was higher in the observation group (P=0.002), whereas the incidence of grade 3 diarrhea was lower (P=0.007). No statistically significant difference was observed in the incidence of grade 4 diarrhea (P=0.506), and neither group experienced grade 5 diarrhea. ③ The incidence of bacterial infection in the observation group was lower than that in the control group (34.1% vs 65.5%, P=0.002), whereas no statistically significant difference was observed in the incidence of fungal infection (29.3% vs 31.4%, P=0.863) and viral infection (4.88% vs 3.64%, P=0.831). ④No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups [10 (8-20) days vs 11 (8-17) days, P=0.501; 13 (10-21) days vs 15 (10-20) days, P=0.245]. ⑤ All patients did not receive lenalidomide treatment 100 days post-transplantation. At 30 days post-transplantation, the CTL, NK, and Th cell counts in the observation group were lower than those in the control group (P<0.001, P=0.002, P=0.049), and the NKT cell counts were higher than those in the control group (P=0.024). At 100 days post-transplantation, the CTL, NKT, and Th cell counts in the observation group were higher than those in the control group (P=0.025, P=0.011, P=0.007), and no statistically significant difference in NK cell counts was observed between the two groups (P=0.396). ⑥ The median follow-up was 18 (4-33) months. The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5% and 78.2%, respectively (P=0.337). The recurrence-free survival rates were 85.3% and 77.6%, respectively (P=0.386), and the cumulative recurrence rates were 9.8% and 16.9%, respectively (P=0.373) . Conclusion: In NDMM, the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models, with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.

Ovarian function in female survivors of high-risk neuroblastoma.

INTRODUCTION: Data on ovarian function in neuroblastoma survivors are limited. We sought to determine the prevalence of ovarian dysfunction in a cohort of high-risk neuroblastoma survivors and compare outcomes among survivors treated with and without autologous stem cell rescue (ASCR) preceded by myeloablative chemotherapy. METHODS: Retrospective review of female survivors of high-risk neuroblastoma ≥5 years from diagnosis, diagnosed between 1982 and 2014, and followed in a tertiary cancer center. Participants were divided into two groups: individuals treated with conventional chemotherapy ± radiation ("non-ASCR") (n = 32) or with chemotherapy ± radiation followed by myeloablative chemotherapy with ASCR ("ASCR") (n = 51). Ovarian dysfunction was defined as follicle-stimulating hormone ≥15 mU/mL, while premature ovarian insufficiency (POI) was defined as persistent ovarian dysfunction requiring hormone replacement therapy. Poisson models were used to determine prevalence ratios of ovarian dysfunction and POI. RESULTS: Among 83 females (median attained age: 19 years [range, 10-36]; median follow-up: 15 years [range, 7-36]), 49 (59%) had ovarian dysfunction, and 34 (41%) developed POI. Survivors treated with ASCR were 3.2-fold more likely to develop ovarian dysfunction (95% CI: 1.8-6.0; p < 0.001) and 4.5-fold more likely to develop POI (95% CI: 1.7-11.7; p = 0.002) when compared with those treated with conventional chemotherapy, after adjusting for attained age. Two participants in the non-ASCR group and six in the ASCR group achieved at least one spontaneous pregnancy. DISCUSSION: Ovarian dysfunction is prevalent in female high-risk neuroblastoma survivors, especially after ASCR. Longitudinal follow-up of larger cohorts is needed to inform counseling about the risk of impaired ovarian function after neuroblastoma therapy.

Efficacy of autologous platelet-rich plasma gel in patients with hard-to-heal diabetic foot ulcers: a multicentre study in Japan.

OBJECTIVE: To evaluate the healing outcome of a platelet-rich plasma (PRP) gel prepared using TKKT01 (a wound care device to prepare the PRP gel) in patients with hard-to-heal diabetic foot ulcers (DFUs) and who showed an inadequate response to ≥4 weeks of standard of care (SoC). METHOD: This open-label, single-arm, multicentre study was conducted in 15 centres in Japan. Eligible patients received PRP gel treatment twice a week for eight weeks, followed by a final evaluation after the completion of week 8 (day 57). The primary endpoint was the percentage of patients who achieved ≥50% reduction in wound radius at the final evaluation (achievement criterion, ≥60% of patients). Secondary endpoints included: wound area and volume reduction rates; time to possible wound closure by secondary intention; time to possible wound closure using a relatively simple procedure (e.g., skin graft and suture); and safety at the final evaluation. RESULTS: A total of 54 patients were included in the full analysis set, with 47 patients included in the per protocol set; the primary endpoint was met in 38/47 (80.9%) (95% confidence interval: 66.7-90.9%) patients who achieved ≥50% wound radius reduction at the final evaluation. High rates of wound area (72.8%) and volume (92.7%) reduction were observed at the final evaluation. The median time to possible wound closure by secondary intention and by use of a relatively simple procedure was 57 and 43 days, respectively. Complete wound closure at the final evaluation was achieved in 27 (57.4%) patients. No safety concerns were raised. CONCLUSION: In this study, the efficacy and safety of PRP gel treatment with TKKT01 in patients with hard-to-heal DFUs in Japan were confirmed by our findings. DECLARATION OF INTEREST: This study was funded by Rohto Pharmaceutical Co., Ltd., Japan. NO has been paid a consulting fee by Rohto Pharmaceutical Co., Ltd. KH is the Chief Medical Officer of Rohto Pharmaceutical. Co., Ltd. The other authors have no conflict of interest to declare.

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.

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.

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.

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.

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.

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.

Skin cancer risk after hematopoietic stem cell transplantation: a systematic review and meta-analysis.

Hematopoietic stem cell transplantation (HSCT) has improved outcomes for severe hematologic, malignant, and immune disorders, yet poses an increased risk of subsequent malignancies. This study aimed to examine the risk of skin cancer following HSCT and identify potential risk factors. The search was conducted in MEDLINE, EMBASE, and CINAHL databases until December 2023. Cohort studies reporting standardized incidence ratios (SIRs) for post-HSCT skin cancer or investigating risk factors were included. SIRs, or hazard ratios (HRs) with 95% confidence interval (CI), were calculated using random-effects inverse-variance models. Outcome endpoints were SIRs of skin cancer post-HSCT and risk factors, including gender, chronic graft-versus-host disease (cGVHD), voriconazole exposure, and total body irradiation (TBI). Twenty-six studies involving 164,944 HSCT recipients (allogeneic HSCT, n = 68,637; autologous HSCT, n = 95,435; mean age: 38.5 ± 13.8 years; 71,354 females [43.3%]) were analyzed. Overall, SIR for skin cancer post-HSCT was 7.21 (95% CI 3.98-13.08), with SIRs of 2.25 (95% CI: 1.37-3.68) for autologous HSCT, and 10.18 (95% CI 5.07-20.43) for allogeneic HSCT. Risk factors for skin cancer risk included cGVHD (HR = 2.86 [95% CI: 2.01-4.07]), specifically for basal cell and squamous cell carcinoma (SCC) (HR = 1.80 [95% CI: 1.31-2.46] and HR = 3.68 [95% CI: 2.39-5.68], respectively), male gender (HR = 1.56 [95% CI: 1.15-2.13]), especially for SCC (HR = 1.70 [95% CI: 1.03-2.80]), and voriconazole exposure (HR = 2.01 [95% CI: 1.12-3.61]). TBI showed no statistically significant association with subsequent skin cancer (HR = 1.12 [95% CI: 0.73-1.71]). These findings highlight the importance of rigorous skin cancer surveillance and preventive strategies in HSCT recipients, particularly in male individuals undergoing allogeneic transplants and those with identifiable risk factors, to enable early detection and intervention.

Autologous stem cell transplant in fit patients with late relapsed diffuse large B-cell lymphoma that responded to salvage chemotherapy.

The standard of care (SOC) for fit patients with relapsed diffuse large B-cell lymphoma (DLBCL) ≥12 months after completing frontline therapy is salvage chemotherapy (ST) followed by autologous stem cell transplant (ASCT). However, this strategy may not be optimal for patients with certain clinical characteristics. We retrospectively studied 151 patients with DLBCL that relapsed ≥12 months after R-CHOP or R-CHOP-like frontline therapy who underwent ST and ASCT at Mayo Clinic between July 2000 and December 2017 or the University of Iowa between April 2003 and April 2020. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using the Kaplan-Meier method. The median time from frontline therapy completion to 1st relapse was 26.9 months. The median line of ST was 1 (range 1-3), and 17 (11%) patients required >1 line of ST. Best response before ASCT was partial response (PR) in 60 (40%) and complete response (CR) in 91 (60%) patients. The median age at ASCT was 64 years (range 19-78), and 36 (24%) patients were of ≥70 years. The median follow-up after ASCT was 87.3 months. The median PFS and OS were 54.5 and 88.9 months, respectively. There was no significant difference in PFS and OS based on the age at ASCT (including patients aged ≥70-78 years), sex, transplant era, time to relapse, LDH, extranodal site involvement, and central nervous system/nerve involvement at relapse. However, patients with advanced-stage relapse had inferior PFS than those with early-stage relapse (median 45.3 vs 124.7 months, P=0.045). Patients who required > 1 line of ST, compared to those requiring 1 line, had significantly inferior PFS (median 6.1 vs 61.4 months, P <0.0001) and OS (17.8 vs 111.7 months, P=0.0004). There was no statistically significant difference in survival in patients who achieved PR vs CR, though numerically inferior in the former, with median PFS of 38.9 vs 59.3 months (P=0.23) and median OS of 78.3 vs 111.7 months (P=0.62). Patients achieving CR after 1 line of ST had excellent post-ASCT outcomes, with median PFS of 63.7 months. In conclusion, survival after ASCT was unfavorable in patients with late relapsed DLBCL (≥12 months) who required more than 1 line of ST to achieve PR or CR, and such patients should be treated with alternative therapies. Conversely, survival was favorable in patients who required only 1 line of ST, supporting the current clinical practice of ASCT consolidation in these patients. Moreover, outcomes were favorable in patients aged ≥70-78 years at ASCT, similar to younger patients, highlighting the safety and feasibility of this approach in such patients.

Skin graft surgery and its impact on platelet counts in Iranian burn patients: a non-randomized clinical trial.

BACKGROUND: Platelets are critical in maintaining homeostasis and immune response in burn patients. The concentration of platelets decreases in burn patients, and any intervention that increases serum platelet concentration can prevent serious consequences and patient death. The present study aimed to assess the impact of skin graft surgery on burn patients' platelet counts. METHODS: In this non-randomized clinical trial, 200 burn patients were investigated. The patients were recruited from the surgical ward of Imam Khomeini Teaching Hospital during the first six months of 2021. After completing the checklist, patients underwent skin graft surgery. Blood was taken from the patients during surgery in the operating room and on the third and fifth day after the surgery to check platelets. Data analysis was conducted using SPSS software (ver. 22.0). RESULTS: Most patients (63.5%) were male, and 73 (36.5%) were female. One hundred eighty-one patients (90.5%) had deep burns, and 19 (9.5%) had superficial burns. The mean burns percentage in the patients was 19.3 ± 15.4%, the lowest was 2%, and the highest was 90%. The most common burns were caused by flame (42%) and boiling water (30.5%). The patients' outcomes revealed that 6% gained complete recovery, 86.5% partial recovery, 2.5% showed transplant rejection, and 5% died. Mean platelet levels in deceased patients had an upward trend. The mean platelet counts of patients were elevated during surgery (289,855 ± 165,378), decreased three days after surgery (282,778 ± 317,310), and elevated again five days after surgery (330,375 ± 208,571). However, no significant difference was found between the mean platelet counts during surgery, the third and fifth days after surgery in patients undergoing skin grafts (P = 0.057). CONCLUSIONS: This study suggests that skin graft positively increases the patient's platelets. Further studies are needed to confirm the findings and elucidate the mechanism. Iranian Registry of Clinical Trial approval code (IRCT# IRCT20131112015390N8 & 06/01/2024).

Precise reconstruction of the aortic valve using glutaraldehyde-treated autologous pericardium in new formula: a case report.

BACKGROUND: The current study presents a novel and precise surgical technique for complete reconstruction of the aortic valve using glutaraldehyde-treated autologous pericardium in a patient with aortic valve disease and endocarditis. The technique aims to provide a more effective and reproducible method for aortic valve repair, with the goal of improving outcomes and quality of life for patients with aortic valve disease. CASE PRESENTATION: A 35-year-old Iranian male with aortic valve disease and endocarditis underwent aortic valve reconstruction surgery. Preoperative echocardiography showed a degenerative aortic valve with severe regurgitation, reduced left ventricular ejection fraction, and specific aortic root dimensions. The surgical technique involved precise measurements and calculations to design the size and shape of the new aortic valve cusps using autologous pericardium, with the goal of optimizing coaptation and function. The surgeon calculated the intercommissural distance based on the aortic annulus diameter to determine cusp size and shape. He tailored the pericardial cusps to have a height equal to 80% of the coaptation margin length. Detailed suturing techniques were used to ensure proper alignment and coaptation of the new cusps. Intraoperative evaluation of the valve function using suction and transesophageal echocardiography showed good coaptation and minimal residual regurgitation. At the 3-year follow-up, the patient had a well-functioning aortic valve with only trivial leak and was in satisfactory clinical condition. CONCLUSIONS: Glutaraldehyde-treated autologous pericardium is a validated leaflet alternative, and the causes of its failure are late annular dilatation and other technique breakdowns. Current evidence reveals that aortic valve reconstruction with glutaraldehyde-treated autologous pericardium is associated with many advantages with the potential to improve patient outcomes and quality of life. Further clinical studies are warranted to evaluate the long-term durability and efficacy of this approach.

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.

Comparison of the therapeutic effects of lens capsular flap transplantation and autologous retinal transplantation in the management of refractory macular holes.

PURPOSE: To report the comparison of the therapeutic effects of lens capsular flap transplantation (LCT) and autologous retinal transplantation (ART) in refractory macular hole (MH) treatment. METHODS: Thirty-one patients (31 eyes) with refractory MH were retrospectively reviewed. The patients were divided into two groups based on the surgical procedures: the LCT group (13 eyes) and the ART group (18 eyes). Patients were monitored for a minimum of 6 months. Best corrected visual acuity (BCVA), hole closure rate, postoperative central foveolar thickness (CFT), and some complications (e.g. graft loss or dislocation, postoperative retinal detachment, or postoperatively elevated intraocular pressure) were the primary outcome measures. RESULTS: The mean preoperative MH diameter was 1104 ± 287 µm in the LCT group and 1066 ± 297 µm in the ART group (t = 0.353, P = 0.727). The MH was closed in 12 patients (92.3%) of the LCT group and 17 patients (94.4%) of the ART group (χ2 = 0.057, P = 0.811); the MHs of 10 patients (76.9%) in the LCT group and 11 patients (61.1%) in the ART group were completely closed (χ2 = 0.864, P = 0.353). The BCVA improved from 2.3 ± 1.0 logMAR preoperatively to 1.3 ± 0.9 logMAR postoperatively in the LCT group and 2.3 ± 0.9 logMAR preoperatively to 1.0 ± 0.6 logMAR postoperatively in the ART group (postoperative BCVA vs preoperative BCVA in the LCT group: t = 4.374, P = 0.001; postoperative BCVA vs preoperative BCVA in the ART group: t = 5.899, P = 0.000018). The visual improvement was 1.3 ± 0.9 logMAR in the ART group and 1.0 ± 0.8 logMAR in the LCT group (t = - 1.033, P = 0.310). The postoperative CFT was 139.7 ± 48.3 µm in the LCT and 199.2 ± 25.1 µm in the ART group (t = - 4.062, P = 0.001). Graft dislocation emerged in 2 patients (15.4%) in the LCT group and 1 patient (5.6%) in the ART group. CONCLUSIONS: Applications of LCT and ART may both enhance anatomical and visual outcomes in refractory MH cases. The ART group exhibited a more optimal postoperative CFT than the LCT group one.

Cartilage regeneration and long term survival in medial OA knee patients treated with HTO and OATS.

Background: Osteoarthritis (OA) of the knee, in most instances primarily, affects medial compartment of knee. Combining Osteochondral Autologous Transfer System (OATS) with Medial Open-Wedge High Tibial Osteotomy (MOWHTO) may represent an integrated approach to sustaining long-term knee functionality in OA patients. Materials and methods: From 2009 to 2016, combined OATS and MOWHTO was performed in 66 knees of 63 patients with medial compartment knee OA. Cartilage regeneration was assessed by 2nd look arthroscopy and Knee function was assessed by knee society scoring (KSS) pre-operatively and post-operatively. The survival rate of MOWHTO plus OATS was assessed. Failure is characterized by the need to convert into total knee replacement. Results: The KSS knee score (from 48.3 to 90.4) and function score (from 42.6 to 88.7) showed a statistically significant improvement (p-value of <0.0001) at a mean follow-up period of 9.49 years. Second look arthroscopy done at the time of implant removal showed 100 % cartilage regeneration with even hyaline cartilage regeneration in 49 out of 57 knees assessed and partial regeneration in 8 knees. The Kaplan Meier survivorship analysis was 96.7 % at the mean 9.49 years after surgery. Only 2 patients needed TKA conversion in follow-up. Conclusion: Combining OATs and valgus MOWHTO provides good option to successfully manage patients of OA and varus malalignment. This resulted in significant improvement in knee function, lowering pain intensity, good cartilage regeneration, and a high survivorship rate for 10 years postoperatively.