UNASSIGNED: Proximal row carpectomy is a well-accepted surgical procedure for the management of traumatic and degenerative wrist pathologies. It is routinely performed through a dorsal approach; a volar surgical access was presented in order to enable concomitant carpal tunnel release and avoid flexion limitation or disabilities caused by adhesions of the dorsal capsule and extensor tendons. We propose a modification to the volar approach, with detailed description of skin incision (reproducing the standard palmar access to the scaphoid), capsular section (beginning with a longitudinal cut radial to flexor carpi radialis tendon and prolonged transversally along the radio-lunate joint) and sequence of carpal bone removal (starting with the scaphoid rather than the lunate).
UNASSIGNED: The patients who underwent surgical treatment with modified volar proximal row carpectomy between 1992 and 2015 were enrolled in a retrospective analysis.
UNASSIGNED: We report postoperative improvement in both the Mayo Wrist score and total active range of motion in 38 patients, in line with the outcomes of dorsal proximal row carpectomy.
UNASSIGNED: The modified volar approach is highly recommended when better visualization and access to proximal carpal bones are needed (particularly useful for inveterate perilunate dislocations), moreover if concomitant carpal tunnel syndrome or extensor tendon pathologies are present.

OBJECTIVE: Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) is a well-known penetration enhancer widely used in commercial applications. This study aims to broaden its properties through a novel strategy of converting it into its phenolate salts. The objective is to investigate the synthesis of SNAC phenolate salts, specifically SNAC-choline (SNAC-CH), SNAC-sodium (SNAC-Na), and SNAC-phosphatidylcholine (SNAC-PC), and to explore their potential application in improving the oral absorption of semaglutide.
METHODS: The synthesis of SNAC phenolate salts was confirmed through 1H-NMR, FTIR, and an elemental analysis of C, H, N, and O. In vivo testing was conducted to assess the oral delivery of semaglutide using these synthesized SNAC phenolate salts. Pharmacokinetic (PK) values were measured to evaluate the impact on drug absorption.
RESULTS: The synthesis of SNAC phenolate salts (SNAC-CH, SNAC-Na, and SNAC-PC) was successfully achieved under appropriate conditions, and their structures were confirmed using analytical techniques such as IR, NMR, and CHN elemental analysis. The paradigm of their use was evaluated through an oral pharmacokinetic (PK) in vivo study using SNAC phenolate salts, which did not impair the original SNAC PK values. This suggests that this strategy holds promise as a potential new effective enhancer for oral absorption.
CONCLUSIONS: The utilization of SNAC phenolate salts presents a novel and promising strategy for extending the verity of penetration enhancers\' molecules and properties. Synthesizing phenolate salts represents a new chemical strategy that may open new avenues in molecular development. This approach holds future potential to enhance the oral delivery of peptide drugs like semaglutide without compromising therapeutic efficacy. Overall, it offers significant advancements in the field by providing a potential alternative to injectable peptides through oral delivery systems.

3D-printed dosage forms comprised of Carbopol and Eudragit were fabricated through semi-solid extrusion, combining Enoxaparin (Enox) and the permeation enhancer SNAC in a single-step process without subsequent post-processing. Inks were characterized using rheology and Fourier-transform infrared (FTIR) spectroscopy. The stability of Enox in the fabricated dosage forms was assessed by means of Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) analysis. In vitro release studies revealed the release of Enox in a sustained manner, whereas ex vivo experiments demonstrated the mucoadhesive properties of the 3D-printed dosage forms and their ability to enhance Enox permeability across intestinal mucosa. Cellular assays (CCK-8 assay) revealed a dose- and time-dependent response following incubation with the 3D-printed dosage forms. The encapsulation of SNAC in the 3D-printed dosage forms demonstrated their capacity to increase the transcellularly transport of macromolecule across Caco-2 monolayer in a reversible manner, as confirmed by Transepithelial Resistance (TEER) measurements.

This study investigated the antibacterial effects of S-nitroso-N-acetylcysteine (SNAC) and sodium nitrite (NaNO2) against Escherichia coli and their application in beef sausages. Both SNAC and NaNO2 demonstrated pH-responsive antibacterial activity, with SNAC showing greater efficacy than NaNO2 (p < 0.05) at the same pH (3, 5, and 7). The reactive oxygen species (ROS) and reactive nitrogen species (RNS) induced in E. coli by SNAC were significantly higher than those induced by NaNO2 (p < 0.05), and both ROS and RNS values increased as the pH decreased. In addition, a lower pH led to more pores on the E. coli cell surface and increased membrane permeability, resulting in a more pronounced inhibitory effect. When applied to a beef sausage, SNAC-treated sausages had significantly lower total colony counts and carbonyl content compared to NaNO2-treated ones (p < 0.05). Consequently, SNAC shows great potential as a replacement for NaNO2 in meat products.

Background: Perilunate fracture-dislocations are frequently associated with a high risk of developing post-traumatic arthritis. Current studies indicate that during mid-term follow-ups, radiological signs of arthritis do not appear to correspond with functional score. The aim of this study was to assess the occurrence of posttraumatic arthritis and the wrist function after perilunate dislocations (PLD) and fracture dislocations at a mid-term follow-up of 7 years. Methods: We report the clinical and radiological outcomes of 17 wrists treated for PLD or fracture-dislocation by open reduction and internal fixation through a dorsal approach with dorsal ligament repair. Functional outcomes were evaluated using the short version of the Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), the Patient-Rated Wrist Evaluation questionnaire (PRWE) and the Mayo Wrist Score (MWS). Results of radiographs were assessed using the Herzberg Radiological Scoring Chart. Results: The MWS showed five excellent, five good, five fair and two poor results with an average score of 81%. Radiological analysis using the Herzberg classification revealed midcarpal and/or radiocarpal arthritis in 65% of cases, lunate collapse in 59% and an increase in the mean ulnar translocation ratio in 53% of the cases. Complications included one case of lunate osteonecrosis and one case of stage 3 scapholunate advanced collapse that required revision surgery. Conclusions: Although the clinical and functional outcomes are favourable at mid-term follow-up, radiological evaluation shows a progression towards osteoarthritis (OA). Further research is warranted to refine treatment strategies and investigate factors influencing the development of OA. Level of Evidence: Level IV (Therapeutic).

Oral peptide delivery is trending again. Among the possible reasons are the recent approvals of two oral peptide formulations, which represent a huge stride in the field. For the first time, gastrointestinal (GI) permeation enhancers (PEs) are leveraged to overcome the main limitation of oral peptide delivery-low permeability through the intestinal epithelium. Despite some success, the application of current PEs, such as salcaprozate sodium (SNAC), sodium caprylate (C8), and sodium caprate (C10), is generally resulting in relatively low oral bioavailabilities (BAs)-even for carefully selected therapeutics. With several hundred peptide-based drugs presently in the pipeline, there is a huge unmet need for more effective PEs. Aiming to provide useful insights for the development of novel PEs, this review summarizes the biological hurdles to oral peptide delivery with special emphasis on the epithelial barrier. It describes the concepts and action modes of PEs and mentions possible new targets. It further states the benchmark that is set by current PEs, while critically assessing and evaluating emerging PEs regarding translatability, safety, and efficacy. Additionally, examples of novel PEs under preclinical and clinical evaluation and future directions are discussed.

Background  Single- or bicolumn limited intercarpal fusion, also called one- or two-column fusion, has been introduced as an alternative to four-corner fusion. The rationale behind this is obtaining less need for bone grafting and consequently improving the chances of the union. Method  From August 2014 to October 2020, 45 consecutive patients (15 women), with a mean age of 58.4 years (range: 35-79), have been treated for scapholunate advanced collapse or scaphoid nonunion advanced collapse wrist. In 33 cases, the surgery was performed as two-column fusion, and in 12 cases as one-column fusion. The union was determined by a computed tomography (CT) scan or X-ray follow-up studies. The pain assessments (visual analog score: 0-100), range of motion (ROM), grip strength, and Quick Disabilities of the Arm, Shoulder, and Hand score were prospectively included. Results  Of 45 patients, 43 were available for the follow-up, at a mean of 35 months (range: 12-68). All patients but two achieved union at a mean of 9.5 weeks (range: 5-25 weeks). Pain diminished from 60.3 (mean) preoperatively to 16.7 (mean) postoperatively ( p  = 0.0001). Grip strength slightly increased from 28.2 KgF (mean) to 29 KgF (mean) (not significantly, p  = 0.86). Quick Disability of the Arm, Shoulder, and Hand score improved from 39.5 (median) before the surgery to 11 (median) after the surgery ( p  = 0.0004). The postoperative ROM of 62/37 degrees (mean) were recorded for total dorsovolar/radioulnar flexions, respectively. Three patients were converted to total wrist fusion and one to total wrist arthroplasty. One had a rearthrodesis to two-column fusion, which united. Conclusion  One- and two-column fusion showed significant improvement in pain and function, with minimal impairment of the grip strength on the short- to mid-term follow-up. A union rate of 95% and an acceptable complication rate were achieved, without fusing all carpals. Level of Evidence  Prospective, cohort study, level III.

To meet unmet medical needs, middle-to-large molecules, including peptides and oligonucleotides, have emerged as new therapeutic modalities. Owing to their middle-to-large molecular sizes, middle-to-large molecules are not suitable for oral absorption, but there are high expectations around orally bioavailable macromolecular drugs, since oral administration is the most convenient dosing route. Therefore, extensive efforts have been made to create bioavailable middle-to-large molecules or develop absorption enhancement technology, from which some successes have recently been reported. For example, Rybelsus® tablets and Mycapssa® capsules, both of which contain absorption enhancers, were approved as oral medications for type 2 diabetes and acromegaly, respectively. The oral administration of Rybelsus and Mycapssa exposes their pharmacologically active peptides with molecular weights greater than 1000, namely, semaglutide and octreotide, respectively, into systemic circulation. Although these two medications represent major achievements in the development of orally absorbable peptide formulations, the oral bioavailability of peptides after taking Rybelsus and Mycapssa is still only around 1%. In this article, we review the approaches and recent advances of orally bioavailable middle-to-large molecules and discuss challenges for improving their oral absorption.

BACKGROUND: Individuals with wrist osteoarthritis (OA) can suffer from pain, muscular weakness, and impaired motion of the wrist, which can reduce the quality of life. While there is strong evidence that all patients with OA should receive first-line treatment with education and exercises, this approach has not yet been proposed for individuals with wrist OA. Therefore, this trial aimed to evaluate the effectiveness of a first line neuromuscular joint-protective exercise therapy program compared to a training program with range of motion (ROM) exercises in patients with wrist OA.
METHODS: In this randomized controlled trial (RCT), 48 patients with symptomatic and radiographically confirmed wrist OA were randomly allocated to a 12-week self-management program with either a neuromuscular joint-protective exercise therapy program (intervention group) or a training program with ROM exercises only (control group). Our primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE) with secondary outcome measures of grip strength, range of wrist motion, the Numerical Pain Rating, Scale (NPRS), the Disabilities of the Arm, Shoulder, and Hand (DASH) and the Generalized Self-Efficacy Scale (GSES). The outcome measures were evaluated by a blinded assessor at baseline and 12 weeks. Between-groups differences were analyzed using the Mann-Whitney U test and within-group differences were analyzed with the Wilcoxon signed-rank test.
RESULTS: A total of 41 participants were analyzed at 12 weeks. There were no significant differences in PRWE between the groups at 12 weeks (p = 0.27). However, DASH improved significantly in the intervention group compared to the control group (p = 0.02) and NPRS on load within the intervention group (p = 0.006). The difference in DASH should be interpreted with caution since it could be due to a non-significant increase (worsening) from baseline in the control group in combination with a non-significant decrease (improvement) in the intervention group.
CONCLUSIONS: This RCT showed that the novel neuromuscular joint-protective exercise therapy program was not superior in reducing pain and improving function compared to a training program with ROM exercises at 12 weeks. Future research is warranted to evaluate the effectiveness of forthcoming exercise therapy treatment programs for patients with wrist OA.
BACKGROUND: ClinicalTrials.gov, NCT05367817. Retrospectively registered on 10/05/2022. https://clinicaltrials.gov .

The permeation enhancers (PEs) sodium caprate (C10) and sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) have been utilized for the intestinal and gastric delivery of macromolecules, respectively. However, the potential of C10 for the gastric delivery of a peptide and the ability of SNAC to deliver other peptides to the stomach beyond semaglutide have not been investigated. In this study, we have developed and evaluated C10 and SNAC-containing erodible tablets for the gastricdelivery of a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GIP/GLP1) dual agonist peptide (LY) in cynomolgus monkeys. We also evaluated the impact of release rates on the in vivo performance of C10 and SNAC. Furthermore, we compared the oral exposure of the LY peptide and semaglutide with different proteolytic stabilities using a SNAC erodible tablet. Additionally, we investigated the mechanism of action of SNAC for improving gastric absorption of the LY peptide via tissue distribution in monkey. C10 and SNAC tablets released the peptide and PE by erosion from the tablet surface with 100 % release within 60 min at pH 6.8. Following a single oral administration to monkeys, C10 and SNAC erodible tablets at 300 mg exhibited similar LY mean absolute oral bioavailability of 5.7 % and 4.2 %, respectively. The C10 immediate release capsule (500 mg) with faster dissolution profile (10 min) showed a decrease in the LY oral bioavailability; however, a faster dissolution profile (15 min) with erodible SNAC tablet resulted in a relatively higher LY oral bioavailability compared to the slow-release erodible tablets (60 min). Using SNAC as the PE, the combination of slow-release tablet design and LY peptide with higher pepsin stability resulted in about 4-fold higher mean oral bioavailability in the monkeys than semaglutide (4.2 % vs 1.2 %, respectively). In the monkey gastric tissue, SNAC was found to reduce tight junction protein levels and increase the peptide uptake into the gastric epithelium suggesting its permeation enhancing mechanism via both paracellular and transcellular pathways. Taking these data altogether, the enhanced proteolytic stability of the LY peptide combined with the optimal erodible tablets enabled the gastric delivery of the LY peptide with a higher oral bioavailability than semaglutide.