Safety and Early Return to Sports for Early ACL Reconstruction in Young Athletes: A Retrospective Study.

Background and Objectives: Although previous reports have shown that early anterior cruciate ligament (ACL) reconstruction is associated with an increased risk of stiffness, recommendations for delayed surgery are based on outdated literature. The advent of arthroscopic surgery and accelerated rehabilitation protocols warrants a reexamination of the optimal surgical timing. The purpose of this study was to investigate complications during early ACL reconstruction after injury in young athletes. Materials and Methods: A total of 87 patients (27 males and 60 females) were included in this study. Patients who underwent anatomic ACL reconstruction using hamstring autografts were evaluated. Patients under 25 years of age with a Tegner activity score greater than 6 were included and classified into three groups according to the time from injury to surgical treatment: one week from injury to surgery (early group), three to six weeks from injury to surgery (normal group), and three to six months from injury to surgery (delayed group). We evaluated the rates of various complications such as graft rupture, contralateral injury, the need for manipulation for loss of ROM, infection, and fracture around the knee up to 2 years postoperatively. In addition, we investigated postoperative muscle strength, Lysholm score, Tegner activity score, and period of the return to sport from injury. Results: Patients in the delayed group were younger than those in the other groups (p = 0.009). Patients in the early group had a lower range of motion than those in the other groups preoperationly. However, the 1-month postoperative range of motion was comparable between groups. Patients in the early group had greater postoperative Tegner activity scores than those in the other groups. The period of return to sport from injury in the delayed group was longer than in the other groups. There were no statistically significant differences in the postoperative complication rate, muscle strength, or Lysholm score. Conclusions: ACL reconstruction performed 1 week from injury to surgery in young athletic patients indicated the rate of complications were not significantly different among the groups. Early ACL reconstruction with no postoperative complications may be related to early return to sports and a high level of sports.

Low-affinity LFA1-dependent outside-in signaling mediates avidity modulation via the Rabin8-Rab8 axis.

Lymphocyte interactions mediated by leukocyte integrin lymphocyte function-associated antigen 1 (LFA1) and intercellular adhesion molecules (ICAMs) are important for lymphocyte trafficking and antigen recognition. Integrins are regulated by the modulation of ligand-binding affinity and avidity (valency). Although the mechanism underlying high-affinity LFA1 binding has been investigated extensively, the molecular mechanisms by which low-affinity multivalent binding initiates adhesion remain unclear. We previously showed that ICAM1 and monoclonal antibodies that recognize specific LFA1 conformations induce the accumulation of LFA1 at the contact surface. In this study, we found that the small GTPase Rab8 is critical for intracellular transport and accumulation of LFA1 at cell contact areas mediated by low-affinity LFA1-dependent outside-in signaling. Super-resolution microscopy revealed that Rab8 co-localized with LFA1 in small vesicles near the contact membrane. Inactivation of Rab8 decreased ICAM1-dependent adhesion and substantially reduced LFA1 density on the contact membrane. The GTP-bound active form of Rab8 increased cell adhesiveness and promoted LFA1 accumulation at the contact area through co-trafficking with LFA1. Rab8 activation was induced by low-affinity conformation-dependent outside-in signaling via the guanine exchange factor Rabin8, which induced Rab8 activation at the cell contact area independent of Rap1. Single-molecule imaging of ICAM1 on a supported planner lipid bilayer demonstrated that Rab8 increased the frequency of LFA1-ICAM1 interactions without affecting their binding lifetime, indicating that Rab8 is mainly involved in the modulation of LFA1 avidity rather than LFA1 affinity. The present findings underscore the importance of low-affinity conformation-dependent outside-in signaling via the Rabin8-Rab8 axis leading to the initiation of LFA1 transport to the contact area.

Enhancing Transforaminal Full Endoscopic Discectomy: Efficacy of the Hand Down Outside-In (HDOI) Technique.

Endoscopic lumbar discectomy (ELD) is a key advancement in minimally invasive spinal surgery, particularly for lumbar disc herniation. Interlaminar endoscopic lumbar discectomy (IELD) and transforaminal endoscopic lumbar discectomy (TELD) are the two major methods used for FED. TELD, while less familiar to spine surgeons inexperienced in endoscopic surgery, presents challenges in visualizing the dura mater, a crucial aspect for reducing surgical complications. The hand down outside-in (HDOI) technique introduced by Dezawa enhances this visualization by positioning the cannula tip dorsally on the intervertebral disc and maneuvering it between the dura mater and disc to the spinal canal's midpoint. The cannula is then flipped to directly visualize the dura mater, enabling safe removal of the prolapsed disc material. A comparative study involving 20 patients treated from April 2020 to April 2022 examined the efficacy of the HDOI technique against conventional TELD. Each group, comprising ten patients, underwent ELD for lumbar disc herniation. While both groups showed similar improvements in clinical outcomes, as assessed using the Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS) for pain, the HDOI group exhibited a 100% success rate for dura mater visualization, and this rate is significantly higher than the 60% observed in the conventional TELD group. Additionally, the time required for dura mater visualization was notably shorter for the HDOI technique. These results indicate that the HDOI technique not only enhances the safety and efficacy of TELD but may also encourage its wider use in clinical settings.

SARS-CoV-2 spike protein potentiates platelet aggregation via upregulating integrin αIIbß3 outside-in signaling pathway.

Platelet hyperreactivity is one of the crucial causes of coagulative disorders in patients with COVID-19. Few studies have indicated that integrin αIIbß3 may be a potential target for spike protein binding to platelets. This study aims to investigate whether spike protein interacts with platelet integrin αIIbß3 and upregulates outside-in signaling to potentiate platelet aggregation. In this study, we found that spike protein significantly potentiated platelet aggregation induced by different agonists and platelet spreading in vitro. Mechanism studies revealed that spike protein upregulated the outside-in signaling, such as increased thrombin-induced phosphorylation of ß3, c-Src. Moreover, using tirofiban to inhibit spike protein binding to αIIbß3 or using PP2 to block outside-in signaling, we found that the potentiating effect of spike protein on platelet aggregation was abolished. These results demonstrate that SARS-CoV-2 spike protein directly enhances platelet aggregation via integrin αIIbß3 outside-in signaling, and suggest a potential target for platelet hyperreactivity in patients with COVID-19. HIGHLIGHTS: • Spike protein potentiates platelet aggregation and upregulates αIIbß3 outside-in signaling. • Spike protein interacts with integrin αIIbß3 to potentiate platelet aggregation. • Blocking outside-in signaling abolishes the effect of spike protein on platelets.

1,25-Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS-CoV-2 spike protein via inhibiting integrin αIIbß3 outside-in signaling.

Platelet hyperreactivity contributes to the pathogenesis of COVID-19, which is associated with a hypercoagulability state and thrombosis disorder. It has been demonstrated that Vitamin D deficiency is associated with the severity of COVID-19 infection. Vitamin D supplement is widely used as a dietary supplement due to its safety and health benefits. In this study, we investigated the direct effects and underlying mechanisms of 1,25(OH)2D3 on platelet hyperreactivity induced by SRAS-CoV-2 spike protein via Western blot and platelet functional studies in vitro. Firstly, we found that 1,25(OH)2D3 attenuated platelet aggregation and Src-mediated signaling. We further observed that 1,25(OH)2D3 attenuated spike protein-potentiated platelet aggregation in vitro. Mechanistically, 1,25(OH)2D3 attenuated spike protein upregulated-integrin αIIbß3 outside-in signaling such as platelet spreading and the phosphorylation of ß3, c-Src and Syk. Moreover, using PP2, the Src family kinase inhibitor to abolish spike protein-stimulated platelet aggregation and integrin αIIbß3 outside-in signaling, the combination of PP2 and 1,25(OH)2D3 did not show additive inhibitory effects on spike protein-potentiated platelet aggregation and the phosphorylation of ß3, c-Src and Syk. Thus, our data suggest that 1,25(OH)2D3 attenuates platelet aggregation potentiated by spike protein via downregulating integrin αIIbß3 outside-in signaling.

Ligand binding initiates single-molecule integrin conformational activation.

Integrins link the extracellular environment to the actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside and inside the cell is essential. Single-molecule fluorescence dynamics show that ligand binding to the bent-closed integrin conformation, which predominates on cell surfaces, is followed within milliseconds by two concerted changes, leg extension and headpiece opening, to give the high-affinity integrin conformation. The extended-closed integrin conformation is not an intermediate but can be directly accessed from the extended-open conformation and provides a pathway for ligand dissociation. In contrast to ligand, talin, which links the integrin ß-subunit cytoplasmic domain to the actin cytoskeleton, modestly stabilizes but does not induce extension or opening. Integrin activation is thus initiated by outside-in signaling and followed by inside-out signaling. Our results further imply that talin binding is insufficient for inside-out integrin activation and that tensile force transmission through the ligand-integrin-talin-actin cytoskeleton complex is required.

4'-O-MethylbavachalconeB Targeted 14-3-3ζ Blocking the Integrin ß3 Early Outside-In Signal to Inhibit Platelet Aggregation and Thrombosis.

14-3-3ζ protein, the key target in the regulation and control of integrin ß3 outside-in signaling, is an attractive new strategy to inhibit thrombosis without affecting hemostasis. In this study, 4'-O-methylbavachalconeB (4-O-MB) in Psoraleae Fructus was identified as a 14-3-3ζ ligand with antithrombosis activity by target fishing combined with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) analysis. The competitive inhibition analysis showed that 4-O-MB targeted 14-3-3ζ and blocked the 14-3-3ζ/integrin ß3 interaction with inhibition constant (Ki) values of 9.98 ± 0.22 µM. Molecular docking and amino acid mutation experiments confirmed that 4-O-MB specifically bound to 14-3-3ζ through LSY9 and SER28 to regulate the 14-3-3ζ/integrin ß3 interaction. Besides, 4-O-MB affected the integrin ß3 early outside-in signal by inhibiting AKT and c-Src phosphorylation. Meanwhile, 4-O-MB could inhibit ADP-, collagen-, or thrombin-induced platelet aggregation function but had no effect on platelet adhesion to collagen-coated surfaces in vivo. Administration of 4-O-MB could significantly inhibit thrombosis formation without disturbing hemostasis in mice. These findings provide new prospects for the antithrombotic effects of Psoraleae Fructus and the potential application of 4-O-MB as lead compounds in the therapy of thrombosis by targeting 14-3-3ζ.

Antihistamine and Wound Healing Potential of Gold Nanoparticles Synthesized Using Bulbine frutescens (L.) Willd.

Background: Atopic dermatitis (eczema) is an inflammatory skin condition with synthetic treatments that induce adverse effects and are ineffective. One of the proposed causes for the development of the condition is the outside-in hypothesis, which states that eczema is caused by a disruption in the skin barrier. These disruptions include developing dry cracked skin, which promotes the production of histamine. Bulbine frutescens (BF) is traditionally used to treat wounds and eczema; however, limited research has been conducted to scientifically validate this. Furthermore, gold nanoparticles (AuNPs) have been used to repair damaged skin; however, no research has been conducted on AuNPs synthesized using BF. Purpose: The study aimed to determine whether BF alleviated skin damage through wound healing, reducing the production of histamine and investigate whether AuNPs synthesized using BF would enhance biological activity. Methods: Four extracts and four synthesized AuNPs were prepared using BF and their antiproliferative and wound healing properties against human keratinocyte cells (HaCaT) were evaluated. Thereafter, the selected samples antiproliferative activity and antihistamine activity against phorbol 12-myristate 13-acetate (PMA) stimulated granulocytes were evaluated. Results: Of the eight samples, the freeze-dried leaf juice (BFE; p < 0.01) extract and its AuNPs (BFEAuNPs; p < 0.05) displayed significant wound closure at 100 µg/mL and were further evaluated. The selected samples displayed a fifty percent inhibitory concentration (IC50) of >200 µg/mL against PMA stimulated granulocytes. Compared to the untreated (media with PMA) control (0.30 ± 0.02 ng/mL), BFEAuNPs significantly inhibited histamine production at a concentration of 100 (p < 0.01) and 50 µg/mL (p < 0.001). Conclusion: BFE and BFEAuNPs stimulated wound closure, while BFEAuNPs significantly inhibited histamine production. Further investigation into BFEAuNPs in vivo wound healing activity and whether it can target histamine-associated receptors on mast cells as a potential mechanism of action should be considered.

Study on the Mechanism of the Adrenaline-Evoked Procoagulant Response in Human Platelets.

Adrenaline has recently been found to trigger phosphatidylserine (PS) exposure on blood platelets, resulting in amplification of the coagulation process, but the mechanism is only fragmentarily established. Using a panel of platelet receptors' antagonists and modulators of signaling pathways, we evaluated the importance of these in adrenaline-evoked PS exposure by flow cytometry. Calcium and sodium ion influx into platelet cytosol, after adrenaline treatment, was examined by fluorimetric measurements. We found a strong reduction in PS exposure after blocking of sodium and calcium ion influx via Na+/H+ exchanger (NHE) and Na+/Ca2+ exchanger (NCX), respectively. ADP receptor antagonists produced a moderate inhibitory effect. Substantial limitation of PS exposure was observed in the presence of GPIIb/IIIa antagonist, phosphoinositide-3 kinase (PI3-K) inhibitors, or prostaglandin E1, a cyclic adenosine monophosphate (cAMP)-elevating agent. We demonstrated that adrenaline may develop a procoagulant response in human platelets with the substantial role of ion exchangers (NHE and NCX), secreted ADP, GPIIb/IIIa-dependent outside-in signaling, and PI3-K. Inhibition of the above mechanisms and increasing cytosolic cAMP seem to be the most efficient procedures to control adrenaline-evoked PS exposure in human platelets.

Mechano-chemo-biological model of atherosclerosis formation based on the outside-in theory.

Atherosclerosis is a disease in blood vessels that often results in plaque formation and lumen narrowing. It is an inflammatory response of the tissue caused by disruptions in the vessel wall nourishment. Blood vessels are nourished by nutrients originating from the blood of the lumen. In medium-sized and larger vessels, nutrients are additionally provided from outside through a network of capillaries called vasa vasorum. It has recently been hypothesized (Haverich in Circulation 135:205-207, 2017) that the root of atherosclerotic diseases is the malfunction of the vasa vasorum. This, so-called outside-in theory, is supported by a recently developed numerical model (Soleimani et al. in Arch Comput Methods Eng 28:4263-4282, 2021) accounting for the inflammation initiation in the adventitial layer of the blood vessel. Building on the previous findings, this work proposes an extended material model for atherosclerosis formation that is based on the outside-in theory. Beside the description of growth kinematics and nutrient diffusion, the roles of monocytes, macrophages, foam cells, smooth muscle cells and collagen are accounted for in a nonlinear continuum mechanics framework. Cells are activated due to a lack of vessel wall nourishment and proliferate, migrate, differentiate and synthesize collagen, leading to the formation of a plaque. Numerical studies show that the onset of atherosclerosis can qualitatively be reproduced and back the new theory.

A new arthroscopic repair technique for triangular fibrocartilage complex using an intracapsular suture: an outside-in transfer all-inside repair.

BACKGROUND: Arthroscopic repair is a promising, minimally invasive surgical technique for patients with Palmer type 1B peripheral triangular fibrocartilage complex (TFCC) tears. Although several arthroscopic techniques are effective for repairing Palmer type 1B TFCC tears, some shortcomings remain. So, we report an arthroscopic repair technique for the treatment of Palmer type 1B Atzei class 1 TFCC tears using an intracapsular suture: an outside-in transfer all-inside repair. METHODS: A retrospective analysis of 38 Palmer type 1B TFCC injury patients admitted to our hospital were randomly divided into 2 groups. The group A was sutured from the outside to the inside, with a total of 21 cases; the group B was sutured with the new arthroscopic repair technique, with a total of 17 cases. Observe and compare the VAS scores and modified Mayo wrist function scores of all patients before 3, and 6 months after the operation and evaluate the incidence of thread knots in patients with different treatment methods. The methodology was performed an arthroscopic intracapsular suture using an outside-in transfer, all-inside repair technique, which is a modified method of the outside-in and all-inside technique using the needle of a 10-mL sterile syringe, for Palmer type 1B TFCC tears. A No. 2 polydioxanone suture was threaded through the needle and entered the wrist joint. Next, the needle was withdrawn carefully along the suture to the proximal tear ulnar surface of the TFCC and penetrated the TFCC, exiting the articular cavity surface of the ulnar side of the torn TFCC. Finally, arthroscopic knotting was performed. RESULTS: This new treatment was as effective as the previously arthroscopic techniques and had the advantages of no additional incision and decreased risk of operation-related complications. The incidence of thread knots in the group A (28.57%) was significantly higher than that in the group B (0%), and the difference was statistically significant (P = 0.024). There was no significant difference in VAS score and modified Mayo wrist function scores between the two groups (P > 0.05). CONCLUSIONS: The outside-in transfer, the all-inside repair technique is suitable for Palmer type 1B Atzei class 1 TFCC tears. We recommend this technique as a useful alternative to the conventional methods of repairing Palmer type 1B TFCC tears.

Strategic perspectives, creativity, and financial performance in Vietnamese SMEs.

This study examines the relationships between the inside-out and outside-in perspectives of strategists, organizational creativity, and financial performance in Vietnamese small and medium enterprises (SMEs). Based on the resource-based view and dynamic capabilities view, we collected cross-sectional data from 382 managers at all levels of Vietnamese SMEs. The study employed partial least squares structural equation modeling. The findings confirm that the inside-out perspective positively affects organizational creativity but has a negative impact on financial performance. Conversely, the outside-in perspective positively affects both organizational creativity and financial performance. Additionally, the study reveals that organizational creativity positively affects financial performance and acts as a mediator between both perspectives and financial performance. Thus, the study suggests that SMEs can benefit from adopting an outside-in perspective to enhance both their organizational creativity and financial performance. Overall, the study contributes to the literature on the cognitive school of strategic management in SMEs.

Liposome-Templated Green Synthesis of Mesoporous Metal Nanostructures with Universal Composition for Biomedical Application.

Porous noble metal nanoparticles have received particular attention recently for their unique optical, thermal, and catalytic functions in biomedicine. However, limited progress has been made to synthesize such porous metallic nanostructures with large mesopores (≥25 nm). Here, a green yet facile synthesis strategy using biocompatible liposomes as templates to mediate the formation of mesoporous metallic nanostructures in a controllable fashion is reported. Various monodispersed nanostructures with well-defined mesoporous shape and large mesopores (≈ 40 nm) are successfully synthesized from mono- (Au, Pd, and Pt), bi- (AuPd, AuPt, AuRh, PtRh, and PdPt), and tri-noble metals (AuPdRh, AuPtRh, and AuPdPt). Along with a successful demonstration of its effectiveness in synthesis of various mesoporous nanostructures, the possible mechanism of liposome-guided formation of such nanostructures via time sectioning of the synthesis process (monitoring time-resolved growth of mesoporous structures) and computational quantum molecular modeling (analyzing chemical interaction energy between metallic cations and liposomes at the enthalpy level) is also revealed. These mesoporous metallic nanostructures exhibit a strong photothermal effect in the near-infrared region, effective catalytic activities in hydrogen peroxide decomposition reaction, and high drug loading capacity. Thus, the liposome-templated method provides an inspiring and robust avenue to synthesize mesoporous noble metal-based nanostructures for versatile biomedical applications.

A myristoylated alanine-rich C-kinase substrate (MARCKS) inhibitor peptide attenuates neutrophil outside-in ß2-integrin activation and signaling.

MARCKS is an actin and PIP2-binding protein that plays an essential role in neutrophil migration and adhesion; however, the molecular details regarding MARCKS function in these processes remains unclear. Neutrophil adhesion and migration also require the cell surface receptors ß2-integrins. We hypothesized that MARCKS inhibition would alter neutrophil ß2-integrin activation and signaling. We utilized a MARCKS-targeting peptide to inhibit MARCKS in inside-out and outside-in ß2-integrin activation in neutrophils. MANS-mediated MARCKS inhibition had no significant effect on inside-out ß2-integrin activation. MANS treatment significantly attenuated ICAM-1/Mn2+-stimulated static adhesion, cell spreading and ß2-integrin clustering, suggesting a role for MARCKS function in outside-in ß2-integrin activation. Additional work is needed to better understand the molecular mechanisms of MARCKS role in outside-in ß2-integrin activation and signaling.

Outside-in repair technique is effective in traumatic tears of the meniscus in active adults: a systematic review.

PURPOSE: Meniscal injuries are common. Outside-in meniscal repair is one of the techniques advocated for the management of traumatic meniscal tears. This systematic review investigated the outcomes of the outside-in repair technique for the management of traumatic tears of the menisci. The outcomes of interest were to investigate whether PROMs improved and to evaluate the rate of complications. METHODS: Following the 2020 PRISMA statement, in May 2023, PubMed, Web of Science, Google Scholar, and Embase were accessed with no time constraints. All the clinical investigations which reported data on meniscal repair using the outside-in technique were considered for inclusion. Only studies which reported data on acute traumatic meniscal tears in adults were considered. Only studies which reported a minimum of 24 months of follow-up were eligible. RESULTS: Data from 458 patients were extracted. 34% (155 of 458) were women. 65% (297 of 458) of tears involved the medial meniscus. The mean operative time was 52.9 ± 13.6 min. Patients returned to their normal activities at 4.8 ± 0.8 months. At a mean of 67-month follow-up, all PROMs of interest improved: Tegner scale (P = 0.003), Lysholm score (P < 0.0001), International Knee Documentation Committee (P < 0.0001). 5.9% (27 of 458) of repairs were considered failures. Four of 186 (2.2%) patients experienced a re-injury, and 5 of 458 (1.1%) patients required re-operation. CONCLUSION: Meniscal repair using the outside-in technique can be effectively performed to improve the quality of life and the activity level of patients with acute meniscal tears. LEVEL OF EVIDENCE: Level IV.

Graft impingement increases anterior cruciate ligament graft signal more than acute graft bending angle: magnetic resonance imaging-based study in outside-in anterior cruciate ligament reconstruction.

PURPOSE: In this study, the relationship between patient-specific geometric factors and tunnel placement in graft impingement was identified by using magnetic resonance imaging (MRI) signal intensity of anterior cruciate ligament (ACL) grafts. METHODS: Ninety-two patients, who were treated between 2014 and 2020, were included retrospectively. These patients underwent primary remnant-preserving outside-in ACL reconstruction (ACLR) and were followed up with postoperative MRI at least one year after surgery. Plain radiographs and computed tomography (CT) were used to analyze tibial and femoral tunnel positions. Postoperative MRI was performed, at 32.8 ± 17.5 months after surgery, to evaluate the graft signal intensity, the ACL/posterior cruciate ligament (PCL) ratio (APR), ACL/muscle ratio (AMR), tunnel positions, and graft impingement. Clinical and stability outcomes were analyzed using the International Knee Documentation Committee (IKDC) subjective and objective scores, Lysholm scores, and side-to-side differences (SS-D). RESULTS: The mean APR and AMR of the proximal third of the grafts were significantly lower than those of the middle third of the grafts (p = 0.017 and p = 0.045, respectively). Multivariate regression analysis showed that there was a negative association between the mean APR and AMR of entire intra-articular ACL graft and the distance from the anterior end of the intercondylar roof to the center of the tibial tunnel in the sagittal plane (p < 0.001 and p < 0.001, respectively) and the notch width index (p < 0.001 and p = 0.002, respectively). No significant correlations were found between tunneling and geometric factors, and clinical scores or SS-D. CONCLUSIONS: Graft impingement on the anterior tibial tunnel relative to the end of the intercondylar roof and narrow notch was a more significant contributing factor on increased signal intensities of the ACL graft, compared with the acute femoral bending angle in remnant-preserving outside-in ACLR. Therefore, surgeons should focus on intercondylar notch anatomy during tibial tunnel placement to avoid roof impingement. LEVEL OF EVIDENCE: Level III.

All-Inside Versus Outside-in Repair of Triangular Fibrocartilage Complex Peripheral Tears.

PURPOSE: Triangular fibrocartilage complex (TFCC) peripheral tears with persistent wrist pain can be treated with arthroscopic surgical repair owing to vascularization of the peripheral region. The safety and efficacy of all-inside repair has been shown in prior case series. The purpose of this study was to compare two methods of arthroscopic peripheral TFCC repair: all-inside vertical mattress and outside-in horizontal mattress. METHODS: A 5-year retrospective review was performed on patients treated from 2016 to 2021 with wrist arthroscopy and TFCC repair for Palmer 1B tears. Patients with ulnar extrinsic ligament repair, distal radioulnar joint instability, concomitant ulnar shortening osteotomy, and extensor carpi ulnaris instability were excluded. Patient therapy and office visit records were reviewed. Outcomes including Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH); range of motion; grip strength; immobilization time; complications; and need for revision procedures were compared. RESULTS: Fifty-two patients were included in the study, 32 in the outside-in group and 20 in the all-inside group. The average follow-up length was 24.8 weeks, with similar range of motion and strength in both groups. The average postoperative QuickDASH score was 13 in the outside-in group and 9 in the all-inside group at 43.5 months, compared with the preoperative QuickDASH scores of 47 and 50, respectively. Mean immobilization time was longer for outside-in than for all-inside (5.25 vs 2.0 weeks, respectively). CONCLUSIONS: All-inside arthroscopic peripheral TFCC repair showed range of motion, grip strength, complications, revisions, and postoperative improvement in QuickDASH scores similar to those with the outside-in technique. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV; retrospective comparative study.

Garcinol acts as a novel integrin αIIbß3 inhibitor in human platelets.

AIMS: Platelet activation plays a central role in arterial thrombosis. Platelets are activated by adhesive proteins (i.e., collagen) or soluble agonists (i.e., thrombin), the respective receptor-specific signaling cause inside-out signaling, leading to the binding of fibrinogen to integrin αIIbß3. This binding triggers outside-in signaling, resulting in platelet aggregation. Garcinol, a polyisoprenylated benzophenone, is extracted from the fruit rind of Garcinia indica. Although garcinol exhibits considerable bioactivities, few studies have investigated the effect of garcinol on platelet activation. MAIN METHODS: Aggregometry, immunoblotting, flow cytometer, confocal microscopic analysis, fibrin clot retraction, animal studies such as fluorescein-induced platelet plug formation in mesenteric microvessels, acute pulmonary thromboembolism, and tail bleeding time were performed in this study. KEY FINDINGS: This study indicates that garcinol inhibited platelet aggregation stimulated by collagen, thrombin, arachidonic acid, and U46619. Garcinol reduced integrin αIIbß3 inside-out signaling, including ATP release; cytosolic Ca2+ mobilization; P-selectin expression; and Syk, PLCγ2/PKC, PI3K/Akt/GSK3ß, MAPKs, and NF-κB activation stimulated by collagen. Garcinol directly inhibited integrin αIIbß3 activation by interfering with FITC-PAC-1 and FITC-triflavin by collagen. Additionally, garcinol affected integrin αIIbß3-mediated outside-in signaling, such as decreasing platelet adhesion and the single-platelet spreading area; suppressing integrin ß3, Src, FAK, and Syk phosphorylation on immobilized fibrinogen; and inhibiting thrombin-stimulated fibrin clot retraction. Garcinol substantially reduced mortality caused by pulmonary thromboembolism and prolonged the occlusion time of thrombotic platelet plug formation without extending bleeding time in mice. SIGNIFICANCE: This study identified that garcinol, a novel antithrombotic agent, acts as a naturally occurring integrin αIIbß3 inhibitor.

Failure Rates of Repaired Bucket-Handle Tears of the Medial Meniscus Concomitant With Anterior Cruciate Ligament Reconstruction: A Cohort Study of 253 Patients From the SANTI Study Group With a Mean Follow-up of 94 Months.

BACKGROUND: Failure rates of repaired bucket-handle medial meniscal tears (BHMMTs) concomitant with anterior cruciate ligament reconstruction (ACLR) are as high as 20%. The outcomes of posteromedial portal suture hook repair have not been compared with all-inside repair techniques for this subtype of meniscal lesion. PURPOSE/HYPOTHESIS: The aim of this study was to evaluate the outcomes and failure rates of patients who underwent BHMMT repair concomitant with ACLR using an all-inside technique, suture hook + all-inside technique, or suture hook + outside-in technique. It was hypothesized that no significant differences in failure rates would be found between the groups. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective analysis was performed on patients diagnosed with a BHMMT who underwent meniscal repair during primary ACLR and had a minimum follow-up of 2 years. Patients were grouped based on the meniscal repair technique used: all-inside repair, suture hook + all-inside repair, or suture hook + outside-in repair. At the end of the study period, secondary medial meniscectomy rates were determined. RESULTS: The study population comprised 253 patients who underwent repair of a BHMMT with concomitant ACLR with a mean follow-up of 94.0 ± 47.6 months. A total of 114 patients (45.1%) underwent all-inside repair, 61 patients (24.1%) underwent suture hook + all-inside repair, and 78 patients (30.8%) underwent suture hook + outside-in repair. Overall, there were 36 failures. The failure rates were 20.2%, 14.8%, and 5.1%, respectively (P = .0135). All-inside repairs were >4 times more likely to fail than suture hook + outside-in repairs (hazard ratio [HR], 4.103; 95% CI, 1.369-12.296; P = .0117). Failure was also 3 times higher (HR, 2.943; 95% CI, 1.224-7.075; P = .0159) for patients <30 years of age compared with those aged ≥30 years. An additional anterolateral ligament reconstruction (ALLR) was also found to reduce the failure rate of repaired BHMMTs concomitant with ACLR. CONCLUSION: Combined suture hook + outside-in repair of BHMMTs resulted in significantly fewer failures than all other techniques. Furthermore, age <30 years and no additional ALLR were associated with higher failure rates.

Foveal Triangular Fibrocartilage Complex Tear Repair with Nonabsorbent Suture Tape.

PURPOSE: Arthroscopic repair is performed for fovea injuries of the triangular fibrocartilage complex (TFCC) when instability of the distal radioulnar joint results in pain, decreased grip strength, and mechanical symptoms. During TFCC repair, reconstruction of its attachment to the fovea is important. Nonabsorbent suture tapes have gained attention for ligament repair in the trapeziometacarpal joint, scapholunate ligament, and thumb metacarpophalangeal ligament. However, there are no reports of TFCC repair using suture tapes. We evaluated the early postoperative results of this approach. METHODS: Participants underwent arthroscopic suture tape repair of foveal TFCC tears and were observed for more than 1 year. All repairs were performed using suture tapes and an outside-in technique with a bone tunnel from the ulnar shaft to the fovea. The postoperative complications, postoperative wrist range of motion, grip strength, and the Modified Mayo Score were evaluated. RESULTS: Arthroscopic repair with a suture tape was performed for 20 hands using the outside-in technique. The ranges of motion for the operated and nonoperated hands were comparable 1 year after surgery (pronation, 84° ± 4°; supination, 83° ± 4°). The mean grip strength improved from 65% ± 13% before surgery to 89% ± 9% after a year. The mean Modified Mayo Score improved from 58 ± 11 before surgery to 91 ± 8 after a year. Postoperative complications included abnormal sensation of the dorsal ulnar side in 2 hands. CONCLUSIONS: After using a suture tape to attach the TFCC to the fovea, satisfactory function was achieved in the early postoperative period with grip strength restoration. For the repair of foveal TFCC tears, attachment to the ulnar fovea is important, and repair by a suture tape may be useful. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.