Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring.

Due to the rise in overnutrition, the incidence of obesity-induced hepatocellular carcinoma (HCC) will continue to escalate; however, our understanding of the obesity to HCC developmental axis is limited. We constructed a single-cell atlas to interrogate the dynamic transcriptomic changes during hepatocarcinogenesis in mice. Here we identify fatty acid binding protein 5 (FABP5) as a driver of obesity-induced HCC. Analysis of transformed cells reveals that FABP5 inhibition and silencing predispose cancer cells to lipid peroxidation and ferroptosis-induced cell death. Pharmacological inhibition and genetic ablation of FABP5 ameliorates the HCC burden in male mice, corresponding to enhanced ferroptosis in the tumour. Moreover, FABP5 inhibition induces a pro-inflammatory tumour microenvironment characterized by tumour-associated macrophages with increased expression of the co-stimulatory molecules CD80 and CD86 and increased CD8+ T cell activation. Our work unravels the dual functional role of FABP5 in diet-induced HCC, inducing the transformation of hepatocytes and an immunosuppressive phenotype of tumour-associated macrophages and illustrates FABP5 inhibition as a potential therapeutic approach.

Can a structured home-based rehabilitation program reduce dorsal central wrist pain?

OBJECTIVES: Dorsal central wrist pain, often a consequence of peri-scapholunate ligament injury, can result in a decline in functional performance. There is a scarcity of clinical data evaluating the effectiveness of conservative management on peri-scapholunate ligament injury. Conservative management includes education, immobilization with orthotic devices, scapholunate-stabilizing muscle strengthening, and proprioception training. The identification of the ligamento-muscular reflex and scapholunate-stabilizing muscles formed the rationale for a rehabilitation training program. We have devised an innovative standardized 16-week treatment program for patients with dorsal central wrist pain associated with acute peri-SL ligament injury. We hypothesized that the program can effectively reduce dorsal wrist pain and improve functional performance. MATERIALS AND METHODS: Recruited subjects underwent the 16-week home-based program, which included immobilization and rehabilitation exercises, to improve their wrist stability. Follow-up was arranged every 4 weeks for progress monitoring. The Short-Form 12 item questionnaire version 2, power grip, pinch grip, wrist range of motion, total performance score and total pain score when performing activities of daily living were used to evaluate the effectiveness of the program. An exercise adherence questionnaire was used to evaluate adherence to the home rehabilitation program. RESULTS: Twenty-three subjects (26 wrists) completed the program. Pain on visual analog scale improved by 5.1 cm and total pain score improved from 14.4/20 to 19.5/20. Total performance score reached 39/40, which indicated near-normal wrist function. Power grip and pinch grip increased by 22.3% and 17.8%, respectively. The physical component scale of the Short-Form 12 item questionnaire showed significant improvement, while the mental component scale did not. Overall adherence was fair. DISCUSSION: Conservative management, including immobilization and rehabilitation training, can provide significant clinical improvement in patients with dorsal central wrist pain associated with acute peri-scapholunate ligament injury. CONCLUSION: Standardized wrist rehabilitation can be taken as a reference treatment modality. It is an evidence-based non-invasive treatment option for clinicians and therapists.

A structured non-operative treatment program for traumatic triangular fibrocartilage complex tear: A quasi-experimental study.

OBJECTIVES: Triangular fibrocartilage complex (TFCC) injury is a common cause of ulnar-sided wrist pain. However, treatment protocols vary across clinical settings and a standardized treatment protocol is needed to improve quality of care. We devised a rehabilitation regime which comprised both orthoses and exercises. We hypothesized that the program can effectively reduce pain and improve functional performance. MATERIALS AND METHODS: Thirty-two subjects participated in the 5-phase rehabilitation program. Progress was monitored every 3 weeks. Outcome measures comprised numeric pain rating scale (NPRS), activities of daily living (ADL) pain score, wrist range of motion (ROM), ADL performance score, patient-rated wrist evaluation (PRWE), power grip and distal radioulnar joint (DRUJ) instability grade. RESULTS: NPRS decreased from 5.3/10 to 0.5/10 while the ADL pain score improved from 10/20 to 19.1/20. ROM in flexion/extension and supination/pronation improved by 35%. Functional performance on ADL performance score and PRWE improved from 21/40 to 38/40 and 49.5/100 to 14.6/100, respectively. Power grip increased by 59.5%, and DRUJ stability improved. DISCUSSION: The combination of orthoses and progressive strengthening and proprioception training was effective in re-establishing DRUJ stability, and improving wrist strength and functional performance. CONCLUSIONS: This study provided insight for the development of a rehabilitation protocol for patients with TFCC injury.

Exploiting the Receptor-Binding Domains of R-Spondin 1 to Target Leucine-Rich Repeat-Containin G-Coupled Protein Receptor 5-Expressing Stem Cells in Ovarian Cancer.

Leucine-rich repeat-containing G-protein-coupled receptor (LGR5) and LGR6 mark epithelial stem cells in normal tissues and tumors. They are expressed by stem cells in the ovarian surface and fallopian tube epithelia from which ovarian cancer arises. High-grade serous ovarian cancer is unique in expressing unusually high levels of LGR5 and LGR6 mRNA. R-spondins are the natural ligands for LGR5 and LGR6 to which they bind with nanomolar affinity. To target stem cells in ovarian cancer, we used the sortase reaction to site-specifically conjugate the potent cytotoxin monomethyl auristatin E (MMAE) via a protease sensitive linker to the two furin-like domains of RSPO1 (Fu1-Fu2) that mediate its binding to LGR5 and LGR6 and their co-receptors Zinc And Ring Finger 3 and Ring Finger Protein 43 via a protease-cleavable linker. An immunoglobulin Fc domain added to the N-terminal end served to dimerize the receptor-binding domains so that each molecule carries two MMAE. The resulting molecule, FcF2-MMAE, demonstrated: 1) selective LGR5-dependent low nanomolar cytotoxicity against ovarian cancer cells in vitro; 2) selectivity that was dependent on binding to both the LGR receptors and ubiquitin ligase co-receptors; 3) favorable stability and plasma pharmacokinetic properties when administered intravenously with an elimination half-life of 29.7 hours; 4) selective inhibition of LGR5-rich as opposed to isogenic LGR5-poor tumors in vivo; and, 5) therapeutic efficacy in three aggressive wild-type human ovarian cancer xenograft models. These results demonstrate the successful use of the Fu1-Fu2 domain of RSPO1 as a drug carrier and the ability of FcF2-MMAE to target cells in tumors that express stem cell markers. SIGNIFICANCE STATEMENT: FcF2-MMAE is a novel cancer therapeutic that exploits the high-affinity binding domains of RSPO1 to target monomethyl auristatin E to tumor stem cells that express LGR5. FcF2-MMAE has low nanomolar LGR5-dependent cytotoxicity in vitro, favorable pharmacokinetics, and differential efficacy in an isogenic LGR5-poor versus LGR5-rich ovarian cancer xenograft model when given on a weekly schedule.

Measuring discomfort-An objective method for quantifying peak pressure discomfort and improved fit in adults with transtibial amputation.

BACKGROUND: Prosthetic socket coupling with the residual limb should be comfortable without causing skin breakdown or excessive pressure. However, users report socket discomfort, and there is a scarcity of objective measurements available to assess this feeling of discomfort. Quantifying the specific pressure may enable clinicians and users to determine and improve comfort levels objectively. OBJECTIVES: (1) To evaluate if a peak pressure reduction assists in resolving wounds, redness, and pain inside prosthetic sockets in people with transtibial amputation. (2) To determine if peak pressures measured inside the prosthetic socket due to external forces could be used to quantify the level of improvement in socket discomfort. DESIGN: In this cohort study, we used a pressure sensor to quantify and facilitate adjustments to the prosthetic socket, correlating this information to the user's socket comfort. SETTING: Outpatient clinic in a tertiary hospital in Singapore. PARTICIPANTS: People (N = 16) with unilateral transtibial lower limb amputation using a prosthesis. INTERVENTIONS: NA. MAIN OUTCOME MEASURES: Peak pressure and socket comfort score (SCS). RESULTS: The peak pressure value showed a statistically significant reduction across all participants following adjustments at a 50% delta change in pressure (p = .001). This was achieved with a mean number of 2.6 ± 1.4 adjustments per participant. Following the adjustments, the paired t-test results showed a mean increase between the first SCS and final SCS was 2.6 (p = .001). CONCLUSION: The wound, redness, and pain resolved in 15 of 16 participants regardless of diabetic status following socket adjustments. Although the peak pressures values did not correlate to the SCS score, the reduction in peak pressure saw significant improvement to the SCS. The use of a portable sensor is a fast and efficient means to quantify adjustments inside the prosthetic socket and could potentially be considered as part of future care delivery.

Seafood Paramyosins as Sources of Anti-Angiotensin-Converting-Enzyme and Anti-Dipeptidyl-Peptidase Peptides after Gastrointestinal Digestion: A Cheminformatic Investigation.

Paramyosins, muscle proteins occurring exclusively in invertebrates, are abundant in seafoods. The potential of seafood paramyosins (SP) as sources of anti-angiotensin-converting-enzyme (ACE) and anti-dipeptidyl-peptidase (DPP-IV) peptides is underexplored. This in silico study investigated the release of anti-ACE and anti-DPP-IV peptides from SP after gastrointestinal (GI) digestion. We focused on SP of the common octopus, Humboldt squid, Japanese abalone, Japanese scallop, Mediterranean mussel, Pacific oyster, sea cucumber, and Whiteleg shrimp. SP protein sequences were digested on BIOPEP-UWM, followed by identification of known anti-ACE and anti-DPP-IV peptides liberated. Upon screening for high-GI-absorption, non-allergenicity, and non-toxicity, shortlisted peptides were analyzed via molecular docking and dynamic to elucidate mechanisms of interactions with ACE and DPP-IV. Potential novel anti-ACE and anti-DPP-IV peptides were predicted by SwissTargetPrediction. Physicochemical and pharmacokinetics of peptides were predicted with SwissADME. GI digestion liberated 2853 fragments from SP. This comprised 26 known anti-ACE and 53 anti-DPP-IV peptides exhibiting high-GI-absorption, non-allergenicity, and non-toxicity. SwissTargetPrediction predicted three putative anti-ACE (GIL, DL, AK) and one putative anti-DPP-IV (IAL) peptides. Molecular docking found most of the anti-ACE peptides may be non-competitive inhibitors, whereas all anti-DPP-IV peptides likely competitive inhibitors. Twenty-five nanoseconds molecular dynamics simulation suggests the stability of these screened peptides, including the three predicted anti-ACE and one predicted anti-DPP-IV peptides. Seven dipeptides resembling approved oral-bioavailable peptide drugs in physicochemical and pharmacokinetic properties were revealed: AY, CF, EF, TF, TY, VF, and VY. In conclusion, our study presented in silico evidence for SP being a promising source of bioavailable and safe anti-ACE and anti-DPP-IV peptides following GI digestions.

Converting Double-Stranded DNA-Encoded Libraries (DELs) to Single-Stranded Libraries for More Versatile Selections.

DNA-encoded library (DEL) is an efficient high-throughput screening technology platform in drug discovery and is also gaining momentum in academic research. Today, the majority of DELs are assembled and encoded with double-stranded DNA tags (dsDELs) and has been selected against numerous biological targets; however, dsDELs are not amendable to some of the recently developed selection methods, such as the cross-linking-based selection against immobilized targets and live-cell-based selections, which require DELs encoded with single-stranded DNAs (ssDELs). Herein, we present a simple method to convert dsDELs to ssDELs using exonuclease digestion without library redesign and resynthesis. We show that dsDELs could be efficiently converted to ssDELs and used for affinity-based selections either with purified proteins or on live cells.

Computational Screening for the Anticancer Potential of Seed-Derived Antioxidant Peptides: A Cheminformatic Approach.

Some seed-derived antioxidant peptides are known to regulate cellular modulators of ROS production, including those proposed to be promising targets of anticancer therapy. Nevertheless, research in this direction is relatively slow owing to the inevitable time-consuming nature of wet-lab experimentations. To help expedite such explorations, we performed structure-based virtual screening on seed-derived antioxidant peptides in the literature for anticancer potential. The ability of the peptides to interact with myeloperoxidase, xanthine oxidase, Keap1, and p47phox was examined. We generated a virtual library of 677 peptides based on a database and literature search. Screening for anticancer potential, non-toxicity, non-allergenicity, non-hemolyticity narrowed down the collection to five candidates. Molecular docking found LYSPH as the most promising in targeting myeloperoxidase, xanthine oxidase, and Keap1, whereas PSYLNTPLL was the best candidate to bind stably to key residues in p47phox. Stability of the four peptide-target complexes was supported by molecular dynamics simulation. LYSPH and PSYLNTPLL were predicted to have cell- and blood-brain barrier penetrating potential, although intolerant to gastrointestinal digestion. Computational alanine scanning found tyrosine residues in both peptides as crucial to stable binding to the targets. Overall, LYSPH and PSYLNTPLL are two potential anticancer peptides that deserve deeper exploration in future.

Therapeutic Targeting of Tumor Cells Rich in LGR Stem Cell Receptors.

LGR5 and LGR6 mark epithelial stem cells in many niches including the ovarian surface and fallopian tube epithelia from which ovarian cancer arises. Human ovarian cancers express these receptors at high levels and express one of their ligands, RSPO1, at levels uniquely higher than all other tumor types except mesothelioma. Reasoning that these receptors are also important to tumor stem cells, arming the LGR binding domain of RSPO1 with a cytotoxin may permit depletion of the tumor stem cells. The Fu1-Fu2 receptor binding domain of RSPO1 (R1FF), containing a sortase recognition sequence at the C-terminal end, was produced in bacteria and a single molecule of MMAE was attached to each R1FF through a val-cit-PAB linker using the sortase reaction, thus producing a homogeneous population of armed molecules. R1FF-MMAE demonstrated (1) selective LGR-dependent binding, uptake, and cytotoxicity; (2) low nM cytotoxicity to multiple types of human tumor cell lines in vitro; (3) favorable plasma pharmacokinetic properties when administered iv with an elimination half-life of 27.8 h; (4) favorable absorption from the peritoneal cavity; and (5) therapeutic activity in aggressive xenograft models of ovarian cancer in the absence of any weight loss or other adverse events. These results demonstrate that the Fu1-Fu2 domain of RSPO1 can be exploited to deliver a potent cytotoxin to tumor cells that express the LGR4-6 family of stem cell receptors.

Arthroscopic treatment for nonunion of the scaphoid.

Scaphoid nonunion has traditionally been treated by open surgery where the pseudarthrosis has been cleaned while either a structural wedged bone graft, or chips of cancellous bone has been used to fill the defect. K-wires or a screw has been used to stabilize the bone. Using the arthroscopic technique for treatment of nonunion of the scaphoid gives us small exposure to the joint, however with an excellent view of the bones, the articular surfaces and the intraarticular ligaments. The results from arthroscopic treatment for scaphoid nonunion with bone grafting using chips of cancellous bone are as good as from the open technique. The arthroscopic treatment, though, helps us to diagnose and treat concomitant lesions. There is less damage of blood supply, nerves and capsule, which might lead to a faster recovery and rehabilitation. The technique will be described and discussed.

MRI criteria for diagnosis and predicting severity of carpal tunnel syndrome.

OBJECTIVE: To study MRI criteria for diagnosing and predicting severity of carpal tunnel syndrome (CTS). METHODS: Sixty-nine wrists in 41 symptomatic CTS patients and 32 wrists in 28 asymptomatic subjects were evaluated by MRI. Circumferential surface area (CSA), flattening ratio, relative median nerve signal intensity, and retinacular bowing were measured. CTS severity was classified as mild, moderate, or severe. Parameters for patients with and without CTS and for the three severity groups were compared. ROC curves were plotted to assess accuracy for CTS diagnosis and severity prediction. RESULTS: Significant differences were found between CTS and control wrists for median nerve CSA, flattening ratio at inlet, relative median nerve signal intensity, and retinacular bowing. ROC curve analysis revealed a sensitivity, specificity, and accuracy of median nerve CSA > 15 mm2 proximal to the tunnel (CSAp) of 85.5, 100, and 90.1%. Using either CSAp or CSAd > 15 mm2 as a diagnostic criterion, MRI could achieve a sensitivity of 100% and specificity of 94% for diagnosis of CTS while overall accuracy was 98%. Significant differences were found among the three severity groups. Sensitivity, specificity, and accuracy of prediction of severe CTS using for CSAp > 19 mm2 were 75.0, 65.9, and 69.6%, respectively. CONCLUSIONS: MRI is highly accurate at diagnosing CTS and moderately accurate at determining CTS severity. We recommend using CSA > 15 mm2 either proximal to or distal to the tunnel as a diagnostic criterion for CTS and CSA > 19 mm2 proximal to the tunnel as a marker for severe CTS.

Top-Ten Tips for Imaging the Triangular Fibrocartilaginous Complex.

The triangular fibrocartilage complex (TFCC) is a crucial structure for both maintaining the stability of the distal radioulnar joint (DRUJ) and acting as a cushion for axial loading of the ulnocarpal joint. Injury to the TFCC can lead to early degeneration of the DRUJ and ulnocarpal joint, with resultant chronic wrist pain and weakness. The TFCC is a moderately complex structure with several attachments to the adjacent bony and cartilaginous structures. Familiarity with the anatomy of the TFCC is a prerequisite for identification of TFCC tears. Several pitfalls can occur while assessing the TFCC on magnetic resonance imaging (MRI) if one is not familiar with the MRI appearances. This article illustrates key tips for diagnosing TFCC tears on MRI.

Cross-sectional area of the median nerve at the wrist: Comparison of sonographic, MRI, and cadaveric measurements.

BACKGROUND: This study compares median nerve cross-sectional area (CSA) measurements at the wrist obtained with ultrasound (US) and magnetic resonance imaging (MRI) using cadaveric measurements as the gold standard. METHODS: Median nerve CSA was measured using US and MRI in 9 cadaveric wrists obtained from 5 subjects at 5 locations: distal forearm, proximal to tunnel inlet, at tunnel inlet, at tunnel outlet, and distal to tunnel outlet and then on identical cadaveric transverse sections obtained with a bandsaw. All US, MRI, and cadaveric measurements were repeated to determine reliability. Median nerves of 10 patients with clinical carpal tunnel syndrome (CTS) were measured with US and MRI using an identical method US. RESULTS: Median nerve CSA MRI measurements correlated better (Pearson correlation: 0.80-0.95, P < .05) with cadaveric measurements than with US measurements (Pearson correlation: 0.61-0.79, P < .05). Median nerve CSA US measurements (8.6-12.5 mm2 , P < .05) were smaller at all levels than MRI (11.3-14.7 mm2 ) or cadaveric (11.0-14.9 mm2 ) measurements while MRI and cadaver measurements were similar at all levels. Median nerve CSA MRI measurements in CTS patients were larger than US measurements at all levels. CONCLUSION: Median nerve CSA measurements by MRI are larger than US measurements and correlated better with cadaveric measurements. Median nerve CSA criteria used for diagnosing CTS on US are not likely to be applicable to MRI.

Fibromyalgia: is it a neuropathic pain?

Fibromyalgia is a chronic pain syndrome of unclear pathophysiology. It is believed to be a dysfunction of the CNS, but no definite structural lesion has been identified so far. Despite a number of changes in the diagnostic criteria, diagnosis remains a clinical one. Since the 2011 revision of the IASP definition of neuropathic pain, fibromyalgia has been excluded from the diagnosis of neuropathic pain. More recent studies however found newer evidences of pathophysiology including small fiber neuropathy in patients with fibromyalgia. This may challenge the existing consensus and have implications on future diagnosis and management of this condition.

Comparison of treatment effects on lateral epicondylitis between acupuncture and extracorporeal shockwave therapy.

BACKGROUND: Lateral epicondylitis is one of the most common overuse injuries, and has been reported to reduce function and affect daily activities. There is no standard therapy for lateral epicondylitis. In Hong Kong, acupuncture and extracorporeal shockwave therapy (ESWT) have been popular in treating lateral epicondylitis in recent years. OBJECTIVE: This study is to compare the treatment effects of acupuncture and ESWT on lateral epicondylitis. METHODS: In this study, we evaluated 34 patients (34 elbows) with lateral epicondylitis. Seventeen patients were treated by 3-week ESWT, one session per week. Another 17 were treated by 3-week acupuncture therapy, two sessions per week. The outcome measures included pain score by visual analogue scale, maximum grip strength by Jamar dynamometer, and level of functional impairment by disability of arms, shoulders, and hands questionnaire. Participants were assessed at three time points: baseline; after treatment; and 2-week follow-up. RESULTS: The two treatments showed no significant difference at any assessment time-point. Both treatment groups had significant improvement in pain score in longitudinal comparisons. No significant difference was found in maximum grip strength and functional impairment in either treatment group, but a trend of improvement could be observed. In addition, improvement in pain relief stopped when treatment ended for either groups. CONCLUSIONS: The treatment effects of acupuncture and ESWT on lateral epicondylitis were similar. The pain relief persisted for at least two weeks after treatment.

Palmer Midcarpal Instability: An Algorithm of Diagnosis and Surgical Management.

Background Palmar midcarpal instability (PMCI) is an uncommon form of nondissociative carpal instability. However, it is an important cause of chronic ulnar wrist pain. Diagnosis can be difficult and high index of suspicion is mandatory. Pathomechanics and optimal treatment of PMCI remain uncertain. We propose an algorithm of clinical diagnosis and evaluate the outcome of our management. Materials and Methods Between 2000 and 2011, 16 patients, including 7 males and 9 females, of a mean age of 33.9 diagnosed with PMCI were reviewed for their clinical, radiologic, and arthroscopic features. All patients presented with ulnar wrist pain in their dominant hands except in one. Initial management included a disease-specific anticarpal supination splint. Refractory cases were evaluated by arthroscopy and treated by arthroscopic thermal shrinkage using radiofrequency appliance as an interim or definite surgical intervention. Shrinkage was targeted at the ulnocarpal ligament at the radiocarpal joint and triquetrohamate ligament at the midcarpal joint. Nonresponsive or recurrent cases were managed by a novel technique of dorsal radiocarpal ligament reconstruction procedure using a pisiform-based split flexor carpi ulnaris (FCU) tendon graft. Results In all cases, the midcarpal clunk test was positive with pain. Other common clinical features included lax ulnar column, carpal supination, volar sagging of the wrist, increased pisostyloid distance, wrist pain aggravated by passive hand supination and not by passive forearm supination, and increased wrist pain upon resisted pronation, which could be partially alleviated by manually supporting the pisostyloid interval. Common arthroscopic findings were excessive joint space at triquetrohamate interval and reactive synovitis over the ulnar compartments. Nine patients (56.3%) responded well to splinting alone at an average follow-up of 3.3 years. Arthroscopic thermal shrinkage was performed in five patients with recurrence in two patients. Five patients received split FCU tendon graft for ligament reconstruction. All patients showed improvement in the wrist performance score (preop 21.0, postop 36.6 out of 40) and pain score (preop 10.0, postop 2.2 out of 20) at the final follow-up of average 86 months (range: 19-155 months). Grip strength improved from 66.9 to 82.0% of the contralateral side. Wrist motion slightly decreased from a flexion/extension arc of 132 to 125 degrees. Three patients were totally pain free, one had mild pain, and one had moderate fluctuating pain. All patients returned to their original works. X-ray showed no arthrosis. Conclusion PMCI is an uncommon but significant cause of chronic ulnar wrist pain. We have developed a clinical algorithm for diagnosis of the condition. The natural history seems to favor a benign course. Conservative treatment with an anticarpal supination splint is recommended as the initial management. Surgical options for resistant cases include arthroscopic thermal shrinkage or soft tissue reconstruction. The reconstruction of the dorsal radiocarpal ligament using a pisiform-based split FCU tendon graft provides reliable restoration of the carpal stability with good long-term outcome and few complications. This should be considered a viable alternative to limited carpal fusion.

Arthroscopic Transplantation of Osteochondral Autograft for Treatment of Cartilage Defects in the Wrist.

Focal chondral lesions are a common cause of chronic wrist pain, with no ideal treatment. The authors developed arthroscopic transplantation of osteochondral autograft from lateral femoral condyle to distal radius with satisfactory outcome in 4 consecutive patients between December 2006 and December 2010. In all cases, graft incorporation was completed by 3 months to 4 months postoperation. All patients showed improvement in wrist function with no pain at follow-up at an average of 70.5 months (range 24-116 months). Second-look arthroscopy in 3 patients confirmed the preservation of normal articular cartilage. Patient satisfaction was high with no complications.

Arthroscopic Management of Thumb Carpometacarpal Joint Arthritis.

The thumb carpometacarpal joint (CMCJ1) is born to have good freedom of motion. However, the excellent mobility at this joint also predisposes attenuation of capsuloligamentous structures, joint incongruity, instability, and osteoarthritis. The prevalence of radiographic CMCJ1 arthritis is high. There is no single ideal surgery for all stages of CMCJ1 arthritis, and for all kinds of patients. The arthroscopic approach seems to provide a better alternative with rewarding preliminary results. It includes arthroscopic synovectomy/debridement/thermal shrinkage, arthroscopic partial trapeziectomy and suture button suspensionplasty, and arthroscopic CMCJ1 excision/suture button suspensionplasty/K-wire fixation.