Background Most pituitary neuroendocrine tumors (PitNETs) show benign behavior, but a substantial number are invasive, recur, or resist medical treatment. Based on a retrospective case-control study, we recently proposed a classification of PitNETs of prognostic relevance. This prospective study aims to test the value of this classification in an independent patient cohort. Methods All patients who underwent PitNET surgery from 2007 to 2012 in one single center were included. Using a grading system based on invasion on magnetic resonance imaging, immunocytochemical profile, Ki-67, mitotic index, and p53 positivity, tumors were classified. Progression-free survival of the graded tumors was calculated by the Kaplan-Meier method and compared using the log-rank test. A multivariate analysis, using a Cox regression model, was also performed. Results In total, 365 patients had grade 1a PitNETs (51.2%), followed by grade 2a (32.3%), 2b (8.8%), and 1b tumors (7.7%). Of 213 patients with a follow-up, 42% had recurrent (n = 52) or progressive disease (n = 37) at 3.5 years. Grade was a significant predictor of progression-free survival (P < 0.001). Multivariate analysis indicated grade (P < 0.001), age (P = 0.035), and tumor type (P = 0.028) as independent predictors of recurrence and/progression. This risk was 3.72-fold higher for a grade 2b tumor compared with grade 1a tumor. Conclusions Our data suggest that classification of PitNETs into five grades is of prognostic value to predict postoperative tumor behavior and identifies patients who have a high risk of early recurrence or progression. It therefore will allow clinicians to adapt their therapeutic strategies and stratify patients in future clinical trials.

Purpose: Manufacturers of total knee arthroplasty (TKA) have introduced narrower femurs to improve bone‐implant fit. However, few studies have reported the clinical consequences of mediolateral oversizing. Our hypothesis was that component oversizing negatively influences the results after TKA.Methods: One hundred and twelve prospectively followed patients with 114 consecutive TKA (64 females and 50 males) were retrospectively assessed. The mean age of the patients was 72 years (range, 56 to 85 years). The dimensions of the femur and tibia were measured on a preoperative CT‐scan and were compared with those of the implanted TKA. The influence of size variation on the clinical outcomes 1 year after surgery was assessed.Results: Mediolateral overhang was observed in at least one area in 66 % of the femurs (84 % in females and 54 % in males) and 61 % of the tibia (81 % in females and 40 % in males). Twenty‐two patients presented no overhang in any area and 16 had overhang in all studied zones. The increase in the Pain and KOOS scores were 43 ± 21 and 36 ± 18 in the patients without overhang and 31 ± 19 and 25 ± 13 in patients with overhang (p = 0.033; p = 0.032). Knee flexion was 127° ± 7 and 121° ± 11, respectively. Regression and latent class analysis showed a significant negative correlation between overall oversizing and overall outcome.Conclusions: This study confirms that oversizing may lead to worse clinical results in TKA. The clinical consequences are that surgeons should pay attention not to oversize implants during implantation nd that oversizing should be ruled out in case of so called unexplained pain.Level of evidence: IV.

Context and Objective: Predicting pituitary tumor behavior remains a challenge. This multiparameter investigation aimed to identify markers for recurrence and progression in prolactin tumors. Design: From a cohort of patients treated for prolactin tumors by surgery, we retrospectively studied clinical data, tumor characteristics, clinical outcome, and the expression of nine genes by quantitative RT-PCR. Results: This study included 94 patients (62 females and 32 men), with long postoperative follow-up periods (mean, 138 ± 46 months); 54.3% of patients had a macro or giant adenoma. Tumors were classified into three pathological groups based on their radiological and histological characteristics (noninvasive, 61; invasive, 22; and aggressive-invasive, 11). Immediately after surgery, 60 patients (63.8%) went into remission (prolactin level normalization). Persistently elevated prolactin levels (36.2%) were associated with increasing age, male sex, high preoperative prolactin levels, large tumor size on univariate analysis, and invasion and pathological classification on univariate and multivariate (P = 8 × 10⁻¹⁰ and 3 × 10⁻⁸) analysis. During follow-up, 19 patients (20%) had tumors that recurred or progressed under dopamine agonist treatment. Invasion and pathological classification were associated with recurrence or progression on univariate analysis. Seven genes (ADAMTS6, CRMP1, PTTG, ASK, CCNB1, AURKB, and CENPE) were associated with tumor recurrence or progression and five of these (ADAMTS6, CRMP1, ASK, CCNB1, and CENPE) were associated with the pathological classification. Conclusion: This study identifies both the clinical and histological factors that relate to prolactin tumor recurrence or progression. Molecular markers give additional information for prognosis of such tumors. Altogether, our results could influence the management of patients with pituitary tumors.

Objective: During septic shock, vasopressors are a cornerstone of therapy. In septic shock, very high doses of vasopressors sometimes have to be used due to vascular desensitization, the mechanisms of which are poorly understood. This study assesses whether α-2 agonists increase pressor responsiveness following lipopolysaccharide administration. Design: Parallel groups of animals (n = 7 per group) subjected to pharmacologic interventions. Setting: Physiology laboratory. Subjects: Rats. Interventions: In anesthetized rats, the pressor responses to increasing doses of norepinephrine (norepinephrine-systolic pressure curve) were assessed during a baseline period, after injection of saline or lipopolysaccharide, and after subsequent injection of saline, dexmedetomidine (100 μg/kg IV), or clonidine (200 μg/kg IV). Measurements and Main Results: Differences in the slopes of the norepinephrine-pressure curves were assessed across drug treatments and intervals. The pressor dose of norepinephrine necessary to increase systolic pressure by 33 and 100 mm Hg (pressor dose 33 and pressor dose 100) was determined. Pressor responsiveness to norepinephrine decreased slightly over time in the saline-saline group (saline 1 or 2 vs baseline: mean decrease of the slope, 2 mm Hg/μg/kg norepinephrine; p < 0.05), whereas there was a large decrease after lipopolysaccharide (lipopolysaccharide vs baseline: mean decrease of the slope, 7.2; p < 0.001). Clonidine alone had no effect, but when administered following lipopolysaccharide, it caused a striking increase in pressor responsiveness (mean slope after lipopolysaccharide, 10.7 [95% CI, 9.9–11.6]; after clonidine, 17.5 [95% CI, 16.7–18.4]). Similarly, dexmedetomidine administered after lipopolysaccharide caused a large increase in pressor responsiveness above lipopolysaccharide values. Accordingly the pressor dose 33 and pressor dose 100 values were lowered following lipopolysaccharide and restored by α-2 agonists. Conclusions: The pressor response to norepinephrine was reduced following lipopolysaccharide and increased to baseline levels following α-2 agonists.