Antibody-drug conjugates (ADCs) combine cytotoxic payloads with monoclonal antibodies through chemical linkers. Finding linkers that both enhance circulatory stability and enable effective tumor payload release remains a challenge. The conventional valine-citrulline (Val-Cit) linker is associated with several inherent drawbacks, including hydrophobicity-induced aggregation, a limited drug-antibody ratio (DAR), and premature payload release.
View Article and Find Full Text PDFBackground: Lymphedema can develop during the progression of neoplastic diseases and is a devastating complication in patients with cancer receiving palliative care. This study aimed to investigate the course of treatment for lymphedema in patients receiving palliative care to assess posttreatment outcomes.
Methods: This single-center, retrospective cohort study reviewed the maintained database of patients with lymphedema who presented to our department from January 2015 through December 2022.
Background: Hyperbaric oxygen therapy (HBOT) has shown potential in salvaging compromised flaps, although its application has primarily been focused on local flaps rather than free flaps.
Case: In this case report, we present the successful use of HBOT in a 76-year-old man who underwent free flap reconstruction for calcaneal osteomyelitis. Despite undergoing 2 reoperations on the second and third days post reconstruction, no thrombosis was observed at the anastomotic site.
A traceless site-selective conjugation method, "AJICAP-M", was developed for native antibodies at sites using Fc-affinity peptides, focusing on Lys248 or Lys288. It produces antibody-drug conjugates (ADCs) with consistent drug-to-antibody ratios, enhanced stability, and simplified manufacturing. Comparative in vivo assessment demonstrated AJICAP-M's superior stability over traditional ADCs.
View Article and Find Full Text PDFMorphological dysplasia in haematopoietic cells, defined by a 10% threshold in each lineage, is one of the diagnostic criteria for myelodysplastic neoplasms. Dysplasia limited to the erythroid lineage has also been reported in some cases of aplastic anaemia (AA); however, its significance remains unclear. We herein examined the impact of erythroid dysplasia on immunosuppressive therapy responses and survival in AA patients.
View Article and Find Full Text PDFThis single-centre retrospective cohort study aimed to clarify the superiority of treatment by comparing the outcomes of lymphaticovenular anastomosis with compression therapy and conservative treatment centred on compression therapy in the early stage of breast cancer-related lymphoedema. Data were collected from all patients treated for breast cancer-related lymphoedema between January 2015 and December 2022. The patients were classified into conservative treatment and surgical treatment groups.
View Article and Find Full Text PDFTag-free protein modification has received considerable attention in the field of chemical biology owing to the versatility and simplicity of the reaction sequence. In 2021, a novel tag-free enzymatic modification of antibodies utilizing lipoate ligase A (LplA) was reported to reveal its potential in the production of site-specific antibody conjugates. Primary peptide mapping analysis revealed the biased site specificity of antibodies modified by LplA; however, quantitative analysis remains challenging because of the complicated heterogeneity derived from biased selective modification.
View Article and Find Full Text PDFJ Vasc Surg Venous Lymphat Disord
November 2023
Objective: Several options for the treatment of lower extremity lymphedema (LEL) can be broadly classified into conservative treatment, such as compression garments and decongestive lymphatic therapy, and surgical treatment, such as lymphaticovenular anastomosis (LVA). The purpose of our study was to clarify the superiority of these treatments by comparing the outcomes of LVA with those of conservative treatment for early-stage LEL.
Methods: We performed a single-center, retrospective cohort study.
Introduction: MTX-LPD is a complication that occurs during MTX treatment. Skin lesions in MTX-LPD are often subcutaneous nodules with occasional necrosis and ulceration. Although MTX-LPD regression is frequently observed upon discontinuation of oral MTX treatment, delayed diagnosis of MTX-LPD with associated ulceration may lead to ulcer enlargement and the need for surgical procedures such as skin grafts.
View Article and Find Full Text PDFJ Plast Reconstr Aesthet Surg
August 2023
This case series aimed to investigate the result of venous end-to-side (ETS) anastomosis in the extremities to contribute to a meta-analysis to evaluate the postoperative complications of venous ETS anastomosis in the extremities. This was a single-center case series and meta-analysis of patients who underwent venous ETS anastomosis for free-flap reconstruction of the extremities. We reviewed the records of 41 free flaps in 40 patients and performed a comprehensive search of PubMed, Scopus, and Web of Science for studies published from inception to December 2022.
View Article and Find Full Text PDFBackground: Most lower extremity defects and minor bone defect wounds requiring a free flap are treatable with soft-tissue flaps, whereas large bone defect wounds are treated with bone-based flaps. This study aimed to compare bone-based and soft-tissue-free flaps in terms of operative procedures and postoperative complications, including long-term outcomes of lower extremity reconstruction.
Methods: This two-center retrospective cohort study collected data from all lower-extremity reconstructions with free flaps performed between March 2014 and February 2022; the level of evidence is considered to be therapeutic level III.
The site-directed chemical conjugation of antibodies remains an area of great interest and active efforts within the antibody-drug conjugate (ADC) community. We previously reported a unique site modification using a class of immunoglobulin-G (IgG) Fc-affinity reagents to establish a versatile, streamlined, and site-selective conjugation of native antibodies to enhance the therapeutic index of the resultant ADCs. This methodology, termed "AJICAP", successfully modified Lys248 of native antibodies to produce site-specific ADC with a wider therapeutic index than the Food and Drug Administration-approved ADC, Kadcyla.
View Article and Find Full Text PDFJ Plast Reconstr Aesthet Surg
April 2023
Background: Combined revascularization and free flap reconstruction is one treatment method for chronic limb-threatening ischemia (CLTI) with complex wounds. The purpose of this systematic review and meta-analysis was to investigate the characteristics of this combined procedure and to assess postoperative outcomes.
Methods: A systematic search was performed across PubMed, Scopus, and the Web of Science for studies between January 2000 and February 2022.
Eur J Orthop Surg Traumatol
August 2023
Purpose: This study aims to identify serum biomarkers that contribute to vascular thrombosis and complete flap failure in delayed reconstruction with free flaps, as well as to develop a scoring system of risk assessment including these biomarkers.
Methods: A retrospective review of the database was conducted for lower extremity open fractures reconstructed between 7 and 90 days from injury, from March 2014 to February 2022. We investigated changes in platelet count (PLT), D-dimer, creatine phosphokinase (CPK), and C-reactive protein (CRP) and then, developed a risk assessment system including these biomarkers as risk factors.
Background: Free flaps for soft tissue coverage of the lower extremity can be broadly divided into muscle/musculocutaneous and fasciocutaneous flaps. The purpose of this systematic review and meta-analysis was to assess their different post-operative outcomes.
Methods: A systematic search was performed in PubMed, Scopus, and the Web of Science from their inception to February 2022.
Background: Free flap surgeries are useful procedures for lower-extremity reconstruction. Recipient vein selection for anastomosis is important to avoid venous congestion and thrombosis. Although deep or superficial venous system can be used as a recipient vein site, there is a lack of consensus on which system would be superior to avoid postoperative complications.
View Article and Find Full Text PDFIntroduction: Post-fracture fixation surgical site infection (SSI) is a devastating complication, and the standard-of-care therapeutic regimen is ineffective in managing it. Negative pressure wound therapy with instillation and dwell time (NPWTi-d) can be used to salvage orthopedic fixation hardware in the setting of infection; moreover, NPWTi-d can be used effectively in the management of superficial post-fracture fixation SSI.
Case Report: Two cases were treated with NPWTi-d.
Deep sternal wound infection is a serious postoperative complication of cardiac surgery and often requires flap reconstruction. Herein, we report a case of deep sternal wound infection with an extensive thoracic defect that was successfully treated using a modified technique. This technique, defined as "supercharging," anastomoses the deep inferior epigastric artery and vein of pedicled rectus abdominis musculocutaneous flap to the transverse cervical artery and external jugular vein, respectively.
View Article and Find Full Text PDFOlfactory mucus contributes to the specific functions of the olfactory mucosa, but the composition and source of mucus proteins have not been fully elucidated. In this study, we used comprehensive proteome analysis and identified lipocalin 15 (LCN15), a human-specific lipocalin family protein, as an abundant component of the olfactory mucus. Western blot analysis and enzyme-linked immunosorbent assay (ELISA) using a newly generated anti-LCN15 antibody showed that LCN15 was concentrated in olfactory mucus samples, but not in respiratory mucus samples.
View Article and Find Full Text PDFBackground: Distally based dorsal metacarpal flaps for the reconstruction of finger soft-tissue defects are classified into 3 categories: dorsal metacarpal artery perforator flap, reverse dorsal metacarpal artery (RDMA) flap, and extended reverse dorsal metacarpal artery (ERDMA) flap. The present systematic review aimed to evaluate differences in the outcomes of commonly encountered defects and postoperative complications among these three flaps.
Methods: PubMed, Scopus, and Web of Science were systematically searched from when the flats were first reported to May 2021.
A 65-year-old man with nonsevere aplastic anemia received rabbit anti-thymocyte globulin and cyclosporine and partially responded. Six months after the initiation of treatment, he was diagnosed with stage IV angioimmunoblastic T-cell lymphoma and received chemotherapy. PET/CT scan analysis indicated a complete response.
View Article and Find Full Text PDFThe local full-thickness skin graft (FTSG) method based on the V-Y closure is reported to be the most convenient and reliable technique for free radial forearm flap (FRFF) donor site closure. The spindle-shaped FTSG was the most common local closure method in free osteofasciocutaneous fibula flaps but not FRFF reconstructions, despite being conveniently applicable to FRFF donor sites. The authors devised a spindle-shaped FTSG harvested from the ipsilateral radial forearm as a new concept in repairing the FRFF donor site.
View Article and Find Full Text PDFBackground Venous thrombosis has been shown to be the most frequent cause of free flap failure in traumatic lower extremity injuries. However, the roles of various anastomotic venous factors, including venous anastomosis (end-to-end (ETE) or end-to-side (ETS)), venous outflow (one vein or two veins), and recipient venous selection (deep or superficial vein), remain unclear. This retrospective study aims to investigate factors contributing to microvascular complications in patients with lower extremity Gustilo type IIIB/IIIC injuries reconstructed by free flap with a focus on the three abovementioned venous factors.
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