Involvement of the JAK-STAT pathway in the molecular landscape of tyrosine kinase fusion-negative hypereosinophilic syndromes: A nationwide CEREO study.

We investigated using a custom NGS panel of 149 genes the mutational landscape of 64 consecutive adult patients with tyrosine kinase fusion-negative hypereosinophilia (HE)/hypereosinophilic syndrome (HES) harboring features suggestive of myeloid neoplasm. At least one mutation was reported in 50/64 (78%) patients (compared to 8/44 (18%) patients with idiopathic HE/HES/HEUS used as controls; p < .001). Thirty-five patients (54%) had at least one mutation involving the JAK-STAT pathway, including STAT5B (n = 18, among which the hotspot N642H, n = 13), JAK1 (indels in exon 13, n = 5; V658F/L, n = 2), and JAK2 (V617F, n = 6; indels in exon 13, n = 2). Other previously undescribed somatic mutations were also found in JAK2, JAK1, STAT5B, and STAT5A, including three patients who shared the same STAT5A V707fs mutation and features consistent with primary polycythemia. Nearly all JAK-STAT mutations were preceded by (or associated with) myelodysplasia-related gene mutations, especially in RNA-splicing genes or chromatin modifiers. In multivariate analysis, neurologic involvement (hazard ratio [HR] 4.95 [1.87-13.13]; p = .001), anemia (HR 5.50 [2.24-13.49]; p < .001), and the presence of a high-risk mutation (as per the molecular international prognosis scoring system: HR 6.87 [2.39-19.72]; p < .001) were independently associated with impaired overall survival. While corticosteroids were ineffective in all treated JAK-STAT-mutated patients, ruxolitinib showed positive hematological responses including in STAT5A-mutated patients. These findings emphasize the usefulness of NGS for the workup of tyrosine kinase fusion-negative HE/HES patients and support the use of JAK inhibitors in this setting. Updated classifications could consider patients with JAK-STAT mutations and eosinophilia as a new "gene mutated-entity" that could be differentiated from CEL, NOS, and idiopathic HES.

Chronic pain after posterolateral and axillary approaches to lung surgery: a monocentric observational study.

PURPOSE: Post-thoracotomy pain syndrome (PTPS) and chronic postsurgical neuropathic pain (CPNP) were evaluated 4 months after thoracic surgery whether the approach was a posterolateral (PL) incision or the less invasive axillary (AX) one. METHODS: Patients, 79 in each group, undergoing a thoracotomy between July 2014 and November 2015 were analyzed 4 months after surgery in this prospective monocentric cohort study. RESULTS: More PL patients suffered PTPS (60.8% vs. 40.5%; p = 0.017) but CPNP was equally present (45.8% and 46.9% in the PL and AX groups). Patients with PTPS have more limited daily activities (p < 0.001) but a similar psychological disability (i.e., catastrophism). Patients with CPNP have an even greater limitation of daily activities (p = 0.007) and more catastrophism (p = 0.0002). Intensity of pain during mobilization of the homolateral shoulder at postoperative day 6 (OR = 1.40, CI 95% [1.13-1.75], p = 0.002); age (OR = 0.97 [0.94-1.00], p = 0.022), and presence of pain before surgery (OR = 2.22 [1.00-4.92], p = 0.049) are related to the occurrence of PTPS; while, height of hypoesthesia area on the breast line measured 6 days after surgery is the only factor related to that of CPNP (OR = 1.14 [1.01-1.30], p = 0.036). CONCLUSION: Minimally invasive surgery was associated with less frequent PTPS, but with equal risk of CPNP. Pain before surgery and its postoperative intensity are associated with PTPS. This must lead to a more aggressive care of pain patients before surgery and of a better management of postoperative pain. CPNP can be forecasted according to the early postoperative height of hypoesthesia area on the breast line.

Intraprostatic hormone dosage: Validation of a novel prostate biopsy technique.

BACKGROUND: Advances in chromatography and mass spectrometry have allowed us to develop a novel technique for measuring intraprostatic hormone concentrations directly on prostate needle biopsies, rather than using traditional punch excision. This has significant clinical implications as intraprostatic dihydrotestosterone and testosterone levels could help monitor prostate growth, neoplasia and castration resistance. METHODS: Patients undergoing radical cystoprostatectomy for bladder cancer were prospectively included. Each prostate specimen received one 90mg punch excision and six needle biopsies. Intraprostatic hormones were dosed through gas chromatography-mass spectrometry. RESULTS: We included twenty patients, of which eleven were incidentally diagnosed with prostate cancer; four had ISUP 1 (20%) and seven had ISUP 2 (35%). The prostate biopsy technique was unable to obtain measures for testosterone, Delta-4-androsterone and androstenedione. Tissue concentrations of DHEA, DHT, E1 and E2 can be obtained with no significant difference from the reference established on a punch from a single biopsy core sample. CONCLUSIONS: Our study demonstrates that intraprostatic concentrations of DHEA, DHT, E1 and E2 can be measured without significant difference from the reference established on a single punch excision. This finding opens the way to research on the interactions between endocrinology and prostate oncogenesis and particularly on the mechanisms of resistance to hormone therapies in vivo.

Comprehensive assessment of postoperative mobility during the first days after mini-invasive lung surgery: A prospective observational study.

STUDY OBJECTIVE: Postoperative physical therapy and early mobilization are major elements for enhanced recovery after surgery. In contrast with supervised physical therapy sessions that can be monitored, self-mobilization is not easily quantifiable and has so far been estimated mainly through patient auto-reports. This study aimed to perform a comprehensive and objective evaluation of postoperative mobility. DESIGN: Prospective observational study. SETTING: Postoperative setting. PATIENTS: Patients undergoing mini-invasive lung surgery. INTERVENTIONS: Measurement of postoperative mobility during the first five postoperative days using an accelerometer (ActiGraph GT3X). MEASUREMENTS: The primary outcome was the number of daily steps. Secondary outcomes included physical activity duration and intensity, sedentary time, number of breaks in sedentary time, sedentary patterns, daily evaluation by physiotherapists, postoperative complications, and acceptability of wearing the accelerometer. MAIN RESULTS: Sixty patients were included in the study, of whom 56 provided at least one day of valid accelerometry data. There was no significant change during the first four PODs concerning the number of daily steps nor the mean cadence. One-minute cadence peak, total activity counts, and duration of light-intensity physical activity increased over time (p = 0.032, p = 0.001 and p = 0.001, respectively). Sedentary patterns changed favorably over time, with a decrease in prolonged sedentary bouts (≥ 60 consecutive min) (p < 0.001), and an increase in shorter bouts (< 10 min) (p = 0.001). Similar results were observed when analysis was adjusted for the day of the week when the surgery took place. The median acceptability of wearing the accelerometer was excellent (median 10 [9-10] on a 10-point Likert scale). Three patients had major complications. CONCLUSIONS: Our findings suggest that daily steps may not be the only relevant indicator of early mobility following thoracic surgery and that accelerometry is suitable to follow patients' early postoperative activity.