A prospective study of 100 patients with rotator cuff tendinopathy showed no correlation between subacromial bursitis and the efficacy of ultrasound-guided corticosteroid injection.

OBJECTIVES: The objective of this study was to determine whether the presence of subacromial bursitis in patients with rotator cuff tendinopathy (RCT) was associated with a better outcome after ultrasound (US)-guided subacromial corticosteroid injection. METHODS: A single-center prospective study was performed including patients referred for subacromial injection to manage RCT. At baseline, all patients received an US-guided intra-bursal injection of betamethasone (1 ml). The primary endpoint was reduced pain 3 months (M3) after the procedure: a good responder was defined by a decrease in Visual Analogue Scale pain of more than 30%. Secondary endpoints included functional recovery assessed by the Oxford Shoulder Score (OSS) and clinical success at 6 weeks (W6). We also explored the association between good clinical response and other factors, such as US or X-ray features. RESULTS: One hundred patients were included and 49 presented with subacromial bursitis. At M3, 60% of patients (54/100) were considered good responders. The rate of good responders did not differ between the bursitis and non-bursitis groups (p = 0.6). During follow-up, OSS improved over time whether bursitis was present or not. We did not find any US or X-ray features significantly associated with a favorable clinical outcome. CONCLUSION: The presence of subacromial bursitis did not influence clinical outcomes at 3 months post-subacromial injection in patients suffering from RCT. CLINICAL RELEVANCE STATEMENT: The presence of subacromial bursitis did not influence clinical outcomes at 3 months post-subacromial corticosteroid injection in patients with rotator cuff tendinopathy. For patient management, looking for ultrasonographic signs of bursitis does not appear relevant for the indication of the injection. KEY POINTS: • Ultrasound-guided subacromial corticosteroid injections led to a significant improvement in 60% of patients suffering from rotator cuff tendinopathy. • The presence of subacromial bursitis was not associated with better improvement at 3 months post-injection. • Except for the Minnesota score referring to job satisfaction, we did not find any baseline clinical, X-ray, or ultrasound characteristics associated with a successful outcome.

Posttraumatic Osteoarthritis Damage in Mice: From Histological and Micro-Computed Tomodensitometric Changes to Gait Disturbance.

OBJECTIVES: Osteoarthritis is a painful joint disease responsible for walking impairment. Its quantitative assessment by gait analysis in mice may be a relevant and noninvasive strategy to assess the disease severity. In this study, we aimed to determine the severity of osteoarthritis at the tissular and gait levels in unilateral and bilateral posttraumatic murine osteoarthritis. METHODS: Twenty-four C57BL/6 male mice were randomly assigned to 3 groups (n = 8/group): controls, unilateral surgery, and bilateral surgery. Posttraumatic osteoarthritis was induced unilaterally or bilaterally by destabilization of the medial meniscus. Gait analysis was performed weekly with the CatWalkTM XT system until the 16th week after surgery. After animal sacrifices, histological and micro-computed tomographic assessment was performed. RESULTS: Operated knees showed a significant increase in the histological score compared with controls (P < 0.001). Calcified anterior medial meniscal bone volume was higher on the ipsilateral side after unilateral destabilization of the medial meniscus (P < 0.001) and on both sides after bilateral intervention (P < 0.01). One week after surgery, the mice mean speed decreased significantly in both operated groups (P < 0.001 and P < 0.05). In the unilateral group, a significant increase in the contralateral hind print area appeared from week 4 to week 16. CONCLUSIONS: While bilateral destabilization of the medial meniscus induced no detectable gait modification except 1 week after surgery, unilateral model was responsible for a gait disturbance on the contralateral side. Further studies are needed to better define the place of the CatWalkTM in the evaluation of mouse models of osteoarthritis.

Intra-Articular Injections Prior to Total Knee Arthroplasty Do Not Increase the Risk of Periprosthetic Joint Infection: A Prospective Cohort Study.

Periprosthetic joint infections (PJI) occur in 0.5 to 2.8% of total knee arthroplasties (TKA) and expose them to an increase of morbidity and mortality. TKA are mainly performed after failure of non-surgical management of knee osteoarthritis, which frequently includes intra-articular injections of corticosteroids or hyaluronic acid. Concerning the potential impact of intra-articular injections on TKA infection, literature provides a low level of evidence because of the retrospective design of the studies and their contradictory results. In this prospective cohort study, we included patients after a total knee arthroplasty, at the time of their admission in a rehabilitation center, and we excluded patients with any prior knee surgery. 304 patients were included. Mean follow-up was 24.9 months, and incidence proportion of PJI was 2.6%. After multivariate logistic regression, male was the only significant risk factor of PJI (OR = 19.6; p = 0.006). The incidence of PJI did not differ between patients who received prior intra-articular injections and others, especially regarding injections in the last 6 months before surgery. The use of intra-articular injection remains a valid therapeutic option in the management of knee osteoarthritis, and a TKA could still be discussed.

Complementary Site-Selective Halogenation of Nitrogen-Containing (Hetero)Aromatics with Superacids.

Site-selective functionalization of arenes that is complementary to classical aromatic substitution reactions remains a long-standing quest in organic synthesis. Exploiting the generation of halenium ion through oxidative process and the protonation of the nitrogen containing function in HF/SbF5 , the chlorination and iodination of classically inert Csp2 -H bonds of aromatic amines occurs. Furthermore, the superacid-promoted (poly)protonation of the molecules acts as a protection, favoring the late-stage selective halogenation of natural alkaloids and active pharmaceutical ingredients.

Jumper's knee mechanical consequences in professional basketball players: the "Camel's Back curve".

PURPOSE: Jumper's knee is characterized by an anterior knee pain during tendon palpation and can be classified in overuse pathologies, secondary to repetitive jumps. The prevalence is high in professional basketball players. It is responsible for an alteration of the motor control inducing a strength deficit of the quadriceps. We aimed to describe an isokinetic curve anomaly, a double-humped curve called "Camel's Back curve", consequence of a jumper's knee history. METHODS: 170 Professional basketball players were enrolled (24.8 ± 4.6 years; 91.8 ± 12.0 kg, 194 ± 9.0 cm). All players performed isokinetic tests of the knee extensors on a concentric mode at the angular speed of 60°/s and 180°/s. RESULTS: 43 players had a jumper's knee history and 35 (81%) had a "Camel's Back curve" at 60°/s. The sensitivity and the specificity of this curve were 81.3% and 100%, respectively. The minimum torque of strength was decreased from 12 to 18% compared to the 2 maximal peaks. Yet, the strength measured every 5° of ROM was significantly different between the players with "Camel's Back curve" and those with normal curve. CONCLUSIONS: "Camel's Back curve" had never been described in that context. It may be secondary to a protective inhibitory mechanism which could alter jumping. The presence of a "Camel's Back curve" would enable clinicians to adapt physical preparation, knee rehabilitation, and trainings to improve players performances.

Fluoroenesulphonamides: N-sulphonylurea isosteres showing nanomolar selective cancer-related transmembrane human carbonic anhydrase inhibition.

After hydrofluorination of ynesulphonamides in superacid or in the presence of hydrofluoric acid/base reagents, a series of α-fluoroenamides has been synthesised and tested for the inhibition of carbonic anhydrase (CA, EC 4.2.1.1) isoforms. This study reveals a new, highly selective family of cancer-related transmembrane human (h) CA IX/XII inhibitors. These original fluorinated ureido isosters do not inhibit the widespread cytosolic isoforms hCA I and II and selectively inhibit the transmembrane cancer-related hCA IX and XII, offering interesting new leads for future studies.

Cationic polycyclization of ynamides: building up molecular complexity.

Polycyclization reactions are among the most efficient synthetic tools for the synthesis of complex, polycyclic molecules in a single operation from simple starting materials. We report in this manuscript a full account on the discovery and development of a novel cationic polycyclization from readily available ynamides. Simple activation of these building blocks under acidic conditions enables the generation of highly reactive activated keteniminium ions, which triggers an unprecedented cationic polycyclization yielding highly substituted polycyclic nitrogen heterocycles possessing up to seven fused cycles and three contiguous stereocenters.

Chemo- and stereoselective synthesis of fluorinated enamides from ynamides in HF/pyridine: second-generation approach to potent ureas bioisosteres.

(E)- and (Z)-α-fluoroenamides could be easily prepared with high levels of chemo- and regioselectivities by hydrofluorination of readily available ynamides with HF/pyridine. The scope and limitations of this new process for the hydrofluorination of ynamides, as well as the stability of the resulting α-fluoroenamides, have been extensively studied. Theoretical calculations at the MP2 and B3LYP levels of theory showed that the resulting fluoroenamides exhibit geometrical and electronic properties that partially mirror those of ureas, therefore demonstrating that the hydrofluorination of ynamides provides a general, straightforward, and user-friendly approach to bioisosteres of ureas, potent building blocks for biological studies and medicinal chemistry.

Clicked cinnamic/caffeic esters and amides as radical scavengers and 5-lipoxygenase inhibitors.

5-Lipoxygenase (5-LO) is the key enzyme responsible for the conversion of arachidonic acid to leukotrienes, a class of lipid mediators implicated in inflammatory disorders. In this paper, we describe the design, synthesis, and preliminary activity studies of novel clicked caffeic esters and amides as radical scavengers and 5-LO inhibitors. From known 5-LO inhibitor 3 as a lead, cinnamic esters 8a-h and amides 9a-h as well as caffeic esters 15a-h and amides 16a-h were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloaddition with the appropriate azide precursors and terminal alkynes. All caffeic analogs are proved to be good radical scavengers (IC50: 10-20 µM). Esters 15g and 15f possessed excellent 5-LO inhibition activity in HEK293 cells and were equipotent with the known 5-LO inhibitor CAPE and more potent than Zileuton. Several synthesized esters possess activities rivaling Zileuton in stimulated human polymorphonuclear leukocytes.

Keteniminium ion-initiated cascade cationic polycyclization.

A novel and efficient keteniminium-initiated cationic polycyclization is reported. This reaction, which only requires triflic acid or bistriflimide as promoters, affords a straightforward entry to polycyclic nitrogen heterocycles possessing up to three contiguous stereocenters and seven fused cycles. These complex, polycyclic molecules can be obtained in a single operation from readily available ynamides which were shown to be remarkable building blocks for multiple, consecutive cationic transformations.

Superacid synthesized tertiary benzenesulfonamides and benzofuzed sultams act as selective hCA IX inhibitors: toward understanding a new mode of inhibition by tertiary sulfonamides.

A series of tertiary (fluorinated) benzenesulfonamides was synthesized in superacid HF-SbF5. To circumvent the problem of the in situ iminium ion formation, proved by low temperature NMR experiments, a tandem superacid catalysed cross-coupling reaction was employed to synthesize the benzofuzed sultams analogues. These tertiary benzenesulfonamides were tested as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). These compounds did not inhibit the widespread off target hCA II isoform and showed strong selectivity toward tumor-associated carbonic anhydrase isoform IX. A dramatic effect of the electronic and structural shape of the inhibitors on selectivity was demonstrated, confirming the non-zinc-bonding mode of inhibition of this class of sulfonamides. This work allowed identifying a highly selective hCA IX inhibitor lead in this series.

New superacid synthesized (fluorinated) tertiary benzenesulfonamides acting as selective hCA IX inhibitors: toward a new mode of carbonic anhydrase inhibition by sulfonamides.

Tertiary substituted (fluorinated) benzenesulfonamides were synthesized in superacid HF/SbF5 and tested as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). Strong selectivity toward tumor-associated hCA IX, without inhibiting the offtarget hCA II, was observed, pointing out to a new mechanism of action compared to classical sulfonamides.