Success Rates of Finger Revascularization and Replantation.

Background: Revascularization surgery has been reported to have a higher success rate than replantation due to sufficient venous return. However, in complex cases, success depends on a wide range of indications. This study aimed to investigate success rates in cohorts that included severe cases. Methods: This single-center, noninterventional, retrospective cohort study included 292 patients (349 digits) who underwent revascularization or replantation at our institution between January 2000 and December 2022. Sex, age, smoking history, comorbidities, affected digit, amputation level, complete or incomplete amputation, type of fracture and mechanism, artery diameter, needle, vein anastomosis in the revascularization subgroup, vein grafting, warm ischemic time, and outcomes were investigated and compared between the revascularization and replantation subgroups of the distal and proximal amputation groups. Results: In the distal amputation group, the arterial diameter in the revascularization subgroup was larger than that in the replantation subgroup (P < 0.05). In the proximal amputation group, the revascularization subgroup had a lower frequency of multiple amputations than the replantation subgroup (P < 0.05). Vein grafts were more frequently used in both revascularization subgroups than in the replantation subgroups (P < 0.05). However, the other injury severity indices were similar, and the success rates were not significantly different between the subgroups. Conclusions: The revascularization success rate was similar to that of replantation. Vein anastomosis or vein grafting to the veins should be advocated for revascularization in severe cases where skin bridges may not have sufficient venous return.

Results of an Adjustable Traction Method Using Surgical Gloves and K-Wires for the Treatment of Proximal Interphalangeal Joint Fracture Dislocation.

Purpose: This study aimed to evaluate an adjustable traction method using surgical gloves and Kirschner wires (K-wires) for proximal interphalangeal (PIP) fracture dislocations and examine the association between a reduction pin and range of motion (ROM), and between subluxation immediately after removal and ROM. Methods: Patients who underwent this surgical method for PIP joint dislocation fractures between 2003 and 2017 were included. We retrospectively investigated the postoperative results. We defined patients having surgery within 4 weeks after an injury as fresh cases and after 4 weeks as chronic cases. K-wires were inserted at the center of the proximal phalangeal head and the distal part of the middle phalanx to create a frame, and the finger of the surgical glove was used as a traction-force generator. We analyzed the association of ROM with each finger, age, presence of a reduction pin, and subluxation immediately after frame removal. Results: Overall, 37 fingers were included (27 acute and 10 chronic). The mean age of the participants was 40.0 years (range: 13-72 years). The mean follow-up period was 10.5 months (3-47 months). The final active ROM was -4.6°/94.6° (extension/flexion) for acute cases and -27.0°/73.5° for chronic ones. Active ROM was significantly better in patients with a reduction pin than in those without it. Subluxation immediately after frame removal was not associated with postoperative active ROM. Additionally, all PIP joints with subluxation that occurred immediately after frame removal achieved good joint congruity. Conclusions: The results of the adjustable traction method using surgical gloves and K-wires were satisfactory. Postoperative ROM did not decrease because of the additional reduction pin. Subluxation occurring immediately after frame removal did not affect the ROM, ultimately resulting in good joint congruity. Type of study/level of evidence: Therapeutic IV.

Aesthetic Reconstruction of Fingers and Thumbs With the Vascularized Half-Big Toenail Flap With Minimum Donor Site Morbidity.

Purpose: The vascularized half-big toenail flap is a short-pedicle free vascularized flap approximately 30 mm in size that contains a fibular half-nail with a 5-mm skin edge and the partial distal phalanx bone. The fingertip skin of the amputated finger is reflected to cover the skin deficiency. The sensation and function are maintained at the donor site, and primary wound closure of the donor site is possible. This study aimed to evaluate the clinical outcomes of thumb and finger reconstruction operations performed using this flap. Methods: We assessed 16 patients (19 digits) with digit amputation who underwent this procedure. We evaluated the following parameters: reconstructed digits, amputation level, survival rate, period until bone union, elongated length, morphologic indices, feeding artery, vein distribution, static 2-point discrimination, and patient occupation. We used the Michigan Hand Outcomes Questionnaire for the evaluation of the function and appearance of the arm. Results: We reconstructed 3 thumbs and 16 fingers. No patients with zone I or V or palm amputation underwent surgery. Flap survival was obtained in all cases, including one atrophic case. Elongated length was 14.1 mm (range, 0-30 mm). The width and longitudinal/axial convexity of the transferred nail increased and the length decreased, whereas the width of the donor site nail increased at final follow-up. Reasonable sensation of the flap was obtained. The feeding artery was the plantar digital artery in 15 toes, the branch in 1, and the arterial anonymous vessel in 3. We could harvest the vein in the first web in 16 toes. All patients went back to their former jobs. Conclusions: The aesthetic and functional outcomes of the reconstructed thumbs and fingers significantly improved. Donor site functional morbidity was minimum. Nevertheless, patients' expectations regarding the reconstructed digit seemed to be that of an intact digit. Type of study/level of evidence: Therapeutic IV.

The Observation of the Vein Distribution of a Partial Toe-Transfer Flaps with a Short Vascular Pedicle.

BACKGROUND: When performing partial toe-transfer flaps with a short vascular pedicle, as the flap becomes smaller, the likelihood of securing veins in the flap decreases. The purpose of this study was to clarify how frequently the partial toe-transfer flap with a short pedicle (free vascularized half-big toenail flap) contains veins and elucidate how frequently we can secure the veins with an artery via the first web space approach alone, using the Genial Viewer (a near-infrared light transmission imaging device). METHODS: We observed the dorsal vein images of the bilateral big toes of 250 volunteers (male, n = 125; female, n = 125) using the device. We counted the total number of dorsal veins in the big toe, the veins that crossed the margin of the region equivalent to the half-big toenail flap, and the veins that branched off from the fibular side of the flap area. An unpaired Student's t-test was used for the statistical analyses. RESULTS: All of the dorsal big toes contained veins. The mean number of the veins was 2.3 (range, 1-4). Branched-off veins were observed in the area equivalent to the half-big toenail flap in 496 (99.2%) of the big toes, and the mean number of veins was 1.9 (range, 0-4). In four cases, the region contained no veins (unilaterally). Branched-off veins were observed in the first web space in 440 (88.0%) of the big toes, and the mean number of veins was 0.9 (range, 0-2). CONCLUSIONS: The present study indicated high consistency of the veins in partial toe-transfer flaps with a short vascular pedicle and the high possibility of harvesting a flap with only exposing the first web space. In addition, in most cases, the flap will include one or, at most, two veins in the first web space.

Antigen-dependent internalization is related to rapid elimination from plasma of humanized anti-HM1.24 monoclonal antibody.

Anti-HM1.24 monoclonal antibody (AHM) is a humanized anti-HM1.24 monoclonal antibody that binds to the HM1.24 antigen, a protein that is highly expressed in multiple myeloma cells. The pharmacokinetics of AHM was determined in experiments in which AHM was administered intravenously to cynomolgus monkeys. The area under the plasma concentration-time curve increased by more than the dose ratio between 2 and 20 mg/kg, and nonlinear pharmacokinetics was observed. The elimination half-life of AHM from the plasma was 7.56 h at 2 mg/kg and 28.6 h at 20 mg/kg, which was shorter than that observed for other therapeutic humanized monoclonal antibodies, such as trastuzumab and bevacizumab. Although antibodies to AHM were detected in all monkeys on or after 10 days of administration, there was a temporal disassociation between the rapid elimination of AHM and the appearance of anti-AHM antibodies. HM1.24 antigen-dependent internalization and intracellular metabolism of AHM were investigated in peripheral blood mononuclear, KPMM2, and U937 cells. In all cases, AHM was rapidly internalized from the cell surface; this internalization was significantly prevented by phenylarsine oxide in KPMM2 cells, an inhibitor of receptor-mediated endocytosis, and the internalized AHM was subsequently degraded within the cells. Furthermore, immunofluorescence microscopy revealed that the internalized AHM is delivered to and degraded in late endosomes/lysosomes. Taken together, our results suggest that the rapid elimination of AHM from plasma in monkey is due to HM1.24 antigen-dependent internalization followed by delivery to the lysosomes.

HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin.

HM1.24/Bst2/CD317 is a protein highly expressed in multiple myeloma cells and has unique topology with two membrane anchor domains, an NH2-terminal transmembrane domain and a glycosylphosphatidylinositol attached to the COOH terminus. We show here that human HM1.24 is localized not only on the cell surface but also in the trans-Golgi network and/or recycling endosomes, where it resides in detergent-resistant microdomains, lipid rafts. In contrast to other glycosylphosphatidylinositol-anchored proteins, HM1.24 was internalized from lipid rafts on the cell surface by clathrin-mediated endocytosis. Interestingly, a non-canonical tyrosine-based motif, which contains two tyrosine residues, Tyr-6 and Tyr-8, present in the NH2-terminal cytoplasmic tail, was essential for endocytosis through interaction with an Deltaa-adaptin, but not mu2-subunit, of the AP-2 complex. Indeed, an appendage domain of alpha-adaptin was identified as a protein interacting with the cytoplasmic tail of HM1.24. Furthermore, overexpression of the appendage domain of alpha-adaptin in cells depleted of alpha-adaptin could rescue the clathrin-mediated endocytosis of HM1.24 but not of the transferrin receptor. Taken together, our findings suggest that clathrin-dependent endocytosis of human HM1.24 from the cell surface lipid rafts is mediated by direct interaction with alpha-adaptin.

The NH(2)-terminal transmembrane and lumenal domains of LGP85 are needed for the formation of enlarged endosomes/lysosomes.

LGP85 is a lysosomal membrane protein possessing a type III topology and is also known as a member of the CD36 superfamily of proteins, such as CD36 and the scavenger-receptor BI (SR-BI). We have recently demonstrated that overexpression of LGP85 in various mammalian cell lines causes the enlargement of endosomal/lysosomal compartments (ELCs). Using chimeras and deletion mutants, we show here that the lumenal region of LGP85 is necessary, but not sufficient, for the development of ELCs. Effective formation of enlarged ELC was largely dependent on the presence of a preceding NH(2)-terminal transmembrane segment. Analyses of deletion mutants within the lumenal domain further revealed a requirement of the NH(2)-terminal transmembrane proximal lumenal region, with high sequence similarity with SR-BI for the enlargement of ELC. These results suggest that an interaction of the NH(2)-terminal transmembrane proximal lumenal domain of LGP85 with the inner leaflet of endosomal/lysosomal membranes through the connection with the transmembrane domain is an essential determinant for the regulation of endosomal/lysosomal membrane traffic. Interestingly, although the NH(2)-terminal transmembrane domain itself was not sufficient for the enlargement of ELCs, it appeared to be required for direct targeting of LGP85 from the trans-Golgi network to late endosomes/lysosomes. Taken together, these results indicate the involvement of distinct domain of LGP85 in the targeting to, and biogenesis and maintenance of, ELC.

3-Methyladenine specifically inhibits retrograde transport of cation-independent mannose 6-phosphate/insulin-like growth factor II receptor from the early endosome to the TGN.

3-Methyladenine (3-MA), a well-known inhibitor of autophagic sequestration, can also prevent class III phosphatidylinositide (PI) 3-kinase activity, which is required for many processes in endosomal membrane trafficking. Although much is known about the effects of other PI 3-kinase inhibitors, such as wortmannin and LY294002, on endosomal membrane trafficking, little is known about those of 3-MA. Here we show that the treatment of cells with 3-MA results in a specific redistribution of the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor (MPR300) from the trans-Golgi network (TGN) to early/recycling endosomal compartments containing internalized transferrin. Importantly, in contrast to wortmannin and LY294002, 3-MA did not cause the enlargement of late endosomal/lysosomal compartments. The results suggest that the effect of 3-MA is restricted to the retrieval of MPR300 from early/recycling endosomes.

Analysis of post-lysosomal compartments.

Lysosomes are acidic intracellular compartments and are regarded as degradative and the end point, of the endocytic pathway. Here we provide evidence for the generation of acid hydrolase poor and non-acidic post-lysosomal compartments in NRK cells that have accumulated non-digestible macromolecules, Texas red-dextran (TR-Dex), within lysosomes. When TR-Dex was fed to the cells for 6h, most of the internalized TR-Dex colocalized with a lysosomal enzyme, cathepsin D. With an increase in the chase period, however, the internalized TR-Dex gradually accumulated in cathepsin D-negative vesicles. These vesicles were positive for a lysosomal membrane protein, LGP85, and their formation was inhibited by treatment of the cells with U18666A, which impairs membrane transport out of late endosomal/lysosomal compartments, thereby suggesting that the vesicles are derived from lysosomes. Interestingly, these compartments are non-acidic as judged for the DAMP staining. The results, therefore, suggest that the excess accumulation of non-digestible macromolecules within lysosomes induces the formation of acid hydrolase poor and non-acidic post-lysosomal compartments. The fact that treatment of the cells with lysosomotropic amines or a microtubule-depolymerization agent resulted in extensive colocalization of TR-Dex with cathepsin D further indicates that the formation of the post-lysosomal compartments depends on the lysosomal acidification and microtubule organization. Furthermore, these results suggest bi-directional membrane transport between lysosomes and the post-lysosomal compartments, which implies that the latter are not resting compartments.