Phase II trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/ CDKN2A.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors demonstrated activity in terms of progression-free survival (PFS) in advanced dedifferentiated liposarcoma (DD-LPS), a sarcoma with CDK4 amplification. CDK4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK inhibitors. Preclinical investigators of this study found that CDK4 overexpression, while not of CDKN2A, was the most consistent predictive factor for palbociclib efficacy in sarcomas. Advanced adult-type soft-tissue sarcoma, excluding DD-LPS, or bone sarcoma patients, progressing after at least one systemic line, whose tumors overexpressed CDK4, but not CDKN2A at baseline biopsy, were accrued in this single-arm phase II trial (EudraCT number: 2016-004039-19). With the main endpoint of a 6-month PFS rate, 40% was considered promising in this population. Palbociclib was administered orally at 125 mg/day for 21 days in 28-day cycles. A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening, archival material (141), and screening, baseline biopsy (95). There were 28 (29%) with favorable mRNA profiles from 95 screened patients at baseline. From 23 enrolled patients, 21 evaluable, the 6-month PFS rate was 29% (95% CI 9-48), and there were 6 patients out of 21 with a PFS longer than 6 months. The median PFS and overall survival were 4.2 (95% CI 3.6-4.8) and 12 (95% CI 8.7-15.4) months, respectively. Translational research showed a significant correlation between CDK4 mRNA and protein expression. Palbociclib was active in a variety of sarcoma subtypes, selected by CDK4/CDKN2A, and deserves further investigation in the sarcoma context.

Miositis del subescapular. Una evolución infrecuente en la tendinopatía calcificada. Estudio de un caso / Subscapularis myositis: An uncommon complication in calcific tendinopathy. A case study

RESUMEN La tendinopatía calcificada del hombro se caracteriza por el depósito de cristales de hidroxiapatita en uno o varios tendones del hombro. Dentro de los procesos que ocurren en esta entidad está la fase de reabsorción, en la que los depósitos podrían migrar hacia estructuras adyacentes. Una muy rara complicación es la migración hacia la unión miotendinosa del tendón correspondiente, la cual provoca una importante reacción inflamatoria muscular que puede objetivarse en pruebas complementarias específicas. Presentamos un caso clínico de una tendinopatía calcificante del subescapular, con pos terior migración hacia la unión miotendinosa causando una miositis del mismo.

ABSTRACT Calcific tendinopathy of the shoulder is characterised by the deposit of hydroxy apatite crys tals in one or more tendons of the shoulder. Within the processes that occur within this disorder, there is the resorption phase, in which the deposits could migrate towards adjacent structures. A very rare complication is the migration towards the myotendinous junction of the corresponding tendon, which causes a significant muscular inflammatory reaction that can be seen in specific complementary tests. A clinical case is presented of a subscapular calcific tendinopathy, with subsequent migra tion to the myotendinous junction, causing myositis of the same.

Infraspinatus atrophy due to Bennett lesion causing suprascapular nerve palsy.

We report the case of a 19-year-old professional volleyball player who presented with right shoulder pain exacerbated during sports activity. On physical examination, infraspinatus atrophy was evident. As the clinical setting suggested suprascapular nerve entrapment syndrome, shoulder MR and later CT were performed. The results showed radiological signs of subacute-chronic infraspinatus muscle denervation and a Bennett lesion of the shoulder, presumably due to chronic repetitive trauma during the classical overhead swing in volleyball. The patient agreed to surgical treatment, and arthroscopic decompression was achieved. After months of rehabilitation, the pain gradually subsided, the infraspinatus muscle recovered its trophism, and the patient progressively returned to her regular sports activity.

Subscapularis structural integrity and function after arthroscopic Latarjet procedure at a minimum 2-year follow-up.

BACKGROUND: Subscapularis function after arthroscopic Bankart repair has been widely studied. However, data regarding subscapularis performance after arthroscopic Latarjet procedures are lacking. This study aimed to evaluate subscapularis clinical and radiologic performance after arthroscopic Latarjet procedures. METHODS: We included 40 patients who underwent arthroscopic Latarjet procedure with a minimum 2-year follow-up. Clinical evaluation included Western Ontario Shoulder Instability Index and Rowe scores, specific subscapularis isokinetic study, and lift-off tests. Contralateral measurements were used for comparison. Computed tomographic evaluation included graft consolidation, muscle dimensions, and degree of fatty atrophy, calculated as the mean muscle attenuation (MMA). RESULTS: There was a decrease of 8.3% of maximum internal rotation peak torque in the operated arm (P = .02). However, there was no significant difference in the agonist-antagonist ratio: 76.9% in the operated arm and 76% in the contralateral (P = .82). Lift-off strength test demonstrated a decrease in the first year but not at final follow-up (P = .38). There was a significant decrease in lift-off distance of 23% compared to the contralateral side (P < .001). Subscapularis MMA was diminished when compared to the infraspinatus/teres minor (P < .001) at the expense of its upper part (P = .03). Hyperlaxity and number of dislocation episodes were correlated to a lower MMA (P = .046 and P = .005). CONCLUSION: Arthroscopic Latarjet procedures provide satisfactory clinical results. There seems to be a diminished subscapularis MMA depending on its superior half. Hyperlaxity and number of previous dislocations were correlated to a lower MMA. Although there was a decrease in the maximum internal rotation peak torque, we did not find any difference in the agonist-antagonist ratio or in the final lift-off strength between sides.

Isolated AA Amyloidosis of the Radial Nerve.

BACKGROUND: Amyloidosis affecting peripheral nerve is usually seen in primary amyloidosis. METHODS: We are reporting on the case of a 74-year-old man with a 16-month history of progressive left radial nerve paralysis. Perioperative imaging detected an enlarged radial nerve in the middle-distal part of the arm. The patient had an antecedent of amyloid deposits in the lung. RESULTS: A radial nerve amyloidosis was suspected and confirmed with a biopsy assisted by ultrasonography, resulting in a secondary amyloidosis form. CONCLUSIONS: Isolated radial nerve palsy due to nerve damage by amyloidosis has been reported before, but not in AA or secondary amyloidosis.

Remote cerebellar hemorrhage after lumbar spinal surgery.

Remote cerebellar hemorrhage (RCH) is a rare complication after supratentorial or spinal surgery. RCH is poorly known and hence probably underdiagnosed. Diminished consciousness and headache are the most common clinical features. Computed tomography and magnetic resonance reveal a characteristic pattern of linear bleeding between the cerebellar folia. The pathophysiological mechanism is disputed but is probably venous bleeding secondary to significant intraoperative or postoperative loss of cerebrospinal fluid. Multiple risk factors have been described, but postsurgical negative pressure drainage of cerebrospinal fluid is the only clearly predisposing factor. We present a case of RCH after spinal surgery with a literature review.