18F-fluoro-ethyl-tyrosine PET co-registered with MRI in patients with persisting acromegaly.

OBJECTIVE: To report our experience with 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRICR) in the care trajectory for persistent acromegaly. DESIGN: Prospective case series. PATIENTS: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options. MEASUREMENTS: FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery. RESULTS: FET-PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRICR was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRICR identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRICR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients. CONCLUSIONS: In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRICR is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team.

Patient-reported outcomes in refractory hormone-producing pituitary adenomas: an unmet need.

PURPOSE: To describe quality and outcomes of patient-reported outcome (PRO) measures (PROMs) used in patients with refractory hormone-producing pituitary adenomas, and to provide an overview of PROs in these challenging pituitary adenomas. METHODS: Three databases were searched for studies reporting on refractory pituitary adenomas. For the purpose of this review, refractory adenomas were defined as tumors resistant to primary therapy. General risk of bias was assessed using a component approach and the quality of PROM reporting was assessed using the International Society for Quality of Life Research (ISOQOL) criteria. RESULTS: 20 studies reported on PROMs in refractory pituitary adenomas, using 14 different PROMs, of which 4 were disease specific (median general risk of bias score: 33.5% (range 6-50%) and ISOQOL score: 46% (range 29-62%)). SF-36/RAND-36 and AcroQoL were most frequently used. Health-related quality of life in refractory patients (measured by AcroQoL, SF-36/Rand-36, Tuebingen CD-25, and EQ-5D-5L) varied greatly across studies, and was not always impaired compared to patients in remission. CONCLUSION: There is a scarcity of data on PROs in the subset of pituitary adenomas that is more difficult to treat, e.g., refractory and these patients are difficult to isolate from the total cohort. The patients' perspective on quality of life, therefore, remains largely unknown in refractory patients. Thus, PROs in refractory pituitary adenomas require adequate analysis using properly reported disease specific PROMs in large cohorts to enable appropriate interpretation for use in clinical practice.

Care trajectories of surgically treated patients with a prolactinoma: why did they opt for surgery?

PURPOSE: To describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery. METHODS: Retrospective observational cohort study of consecutive patients with prolactinoma undergoing surgery from 2017 to 2019 at the referral center (RC), prior to surgery being considered a viable treatment option (i.e. PRolaCT study). Demographics and clinical data (type and duration of pretreatment and surgical indications, goals, and outcomes) were collected from patient records. Care trajectories were divided into three phases: (1) diagnosis and initial treatment, (2) endocrine treatment at the RC, and (3) surgical treatment. RESULTS: 40 patients were included (31 females (77.5%), median age 26.5 (14-63) years. Indications for surgery were dopamine agonist (DA) intolerance (n = 31, 77.5%), resistance (n = 6, 15.0%), and patient/physician preference (n = 3, 7.5%). Patients were pretreated with DA (n = 39 (97.5%)), and surgery (n = 3 (7.5%)). Median disease duration at surgery was 4 (0-27) years. Primary surgical goal was total resection in 38 patients (95.0%), of which biochemical remission was achieved 6 months postoperatively in 23 patients (62.2%), and clinical remission in 6 patients (16.2%), missing data n = 1. CONCLUSION: Care trajectories were highly individualized based on patient and tumor characteristics, as well as the multidisciplinary team's assessment (need for alternative treatment, surgical chances and risks). Most patients were pretreated pharmacologically and had broad variation in timing of referral, undergoing surgery as last-resort treatment predominantly due to DA intolerance. High quality imaging and multidisciplinary consultations with experienced neurosurgeons and endocrinologists enabling treatment tailored to patients' needs were prerequisites for adequate counseling in treatment of patients with prolactinoma.

Recovery of Third, Fourth, and Sixth Cranial Nerve Palsies in Pituitary Adenoma and Meningioma Patients.

BACKGROUND: This retrospective, observational cohort study aimed to determine recovery rate and recovery time of ocular motor nerve palsies (OMP) of third (CN III), fourth (CN IV), or sixth cranial nerves (CN VI)-and associated prognostic factors-in meningioma and pituitary adenoma (PA) patients. METHODS: A total of 25 meningioma (28 eyes) and 33 PA patients (36 eyes), treated at the Leiden University Medical Center in the Netherlands from January 1, 1978 to January 31, 2021, were included. OMPs were evaluated according to a newly created recovery scale using on-clinical and orthoptic examinations, which were performed every 3-4 months until palsy recovery, or at 18 months follow-up. RESULTS: Recovery rates of CN III (meningioma 23.5% vs PA 92.3%), CN IV (meningioma 20% vs PA 100%), and CN VI (meningioma 60% vs PA 100%) palsies were observed at 18 months follow-up, with differences between the 2 tumor types being observed in the treated patients only. Median recovery time of all OMPs combined was significantly longer in meningioma patients (37.9 ± 14.3 months vs 3.3 ± 0.1 months; P < 0.001). No significant protective or risk factors for recovery rate or time were identified. CONCLUSIONS: OMP recovery rates in treated patients were more favorable in patients with PA compared with patients with meningiomas, independent of OMP cause. With these new insights in OMP recovery, more accurate prognoses and appropriate follow-up strategies can be determined for meningioma and PA patients with OMPs.

Clinical and radiographic assessment of peripheral joints in controlled acromegaly.

PURPOSE: Acromegalic arthropathy is a well-known phenomenon, occurring in most patients regardless of disease status. To date, solely hips, knees, hands, and spinal joints have been radiographically assessed. Therefore, this study aimed to assess the prevalence of joint symptoms and radiographic osteoarthritis (OA) of new, and established peripheral joint sites in well-controlled acromegaly. METHODS: Fifty-one acromegaly patients (56% female, mean age 64 ± 12 years) in long-term remission for 18.3 years (median, IQR 7.2-25.4) were included. Nineteen patients currently received pharmacological treatment. Self-reported joint complaints were assessed using standardized interviews. Self-reported disability of the upper and lower limbs, and health-related quality of life (HR-QoL) were evaluated using validated questionnaires. Radiographic OA [defined as Kellgren & Lawrence (KL) ≥ 2] was scored using (modified) KL methods. RESULTS: Radiographic signs of OA were present in 46 patients (90.2%) with ≥ 2 joints affected in virtually all of these patients (N = 44; 95.7%). Radiographic MTP1 OA was as prevalent as radiographic knee OA (N = 26, 51.0%), and radiographic glenohumeral OA was similarly prevalent as hip OA [N = 21 (41.2%) vs. N = 24 (47.1%)]. Risk factors for radiographic glenohumeral OA were higher pre-treatment IGF-1 levels [OR 1.06 (1.01-1.12), P = 0.021], and current pharmacological treatment [OR 5.01 (1.03-24.54), P = 0.047], whereas no risk factors for MTP1 joint OA could be identified. CONCLUSION: Similar to previously-assessed peripheral joints, clinical and radiographic arthropathy of the shoulder and feet were prevalent in controlled acromegaly. Further studies on adequate management strategies of acromegalic arthropathy are needed.

Low prevalence of neuropathic-like pain symptoms in long-term controlled acromegaly.

PURPOSE: Pain is a common symptom of acromegaly, impairing health-related quality of life (HR-QoL) significantly despite long-term disease remission. Neuropathic-like pain (NP-like) symptoms are invalidating, with great impact on HR-QoL. Studies characterizing or investigating the etiology of pain in acromegaly are scarce. Therefore, we aimed to assess NP-like symptoms in a cohort of controlled acromegaly patients. METHODS: Forty-four long-term controlled acromegaly patients (aged 62.6 ± 12.6 years; 56.8% female) were included in this cross-sectional study. NP-like symptoms were assessed using the validated painDETECT questionnaire. Patients were divided in three probability-based NP-like symptoms categories based on the total score (range 0-35): unlikely (≤ 12), indeterminate (13-18) and likely (≥ 19). HR-QoL (physical component score (PCS), and mental component score (MCS)), and self-reported pain were assessed using Short Form-36 (SF-36). Potential risk factors were determined using linear regression analyses. RESULTS: Self-reported pain was reported by 35 patients (79.5%). Likely NP-like symptoms were present in 4/44 patients (9.1%), and indeterminate NP-like symptoms in 6/44 patients (13.6%). All patients with likely NP-like symptoms were female. Higher painDETECT scores were negatively associated with HR-QoL (PCS: r = - 0.46, P = 0.003; MCS: r = - 0.37, P = 0.018), and SF-36 pain scores (r = - 0.63, P < 0.0001). Female sex was a risk factor for NP-like symptoms. CONCLUSIONS: Pain was prevalent in controlled acromegaly patients, whereas NP-like symptoms were relatively infrequent, and only observed in females. NP-like symptoms were associated with lower HR-QoL in acromegaly. Since specific analgesic therapy is available, awareness for characterization, increased understanding, and clinical trials regarding neuropathic pain identification and treatment in acromegaly patients are warranted.

Chiasmal herniation following treatment of pituitary macroadenoma.

PURPOSE: To evaluate whether the occurrence of chiasmal herniation coincides with visual field (VF) deterioration and to compare the course of VF defects in patients with and without radiological chiasmal herniation following treatment of pituitary adenoma. METHODS: This retrospective cohort study included 48 pituitary macroadenoma patients with chiasm compression, divided into three groups: Group 1 (N = 12), downward displaced optic chiasm and deteriorated VFs; Group 2 (N = 16), downward displaced optic chiasm; Group 3 (N = 20), control-group matched for tumour size and follow-up VFs, in mean deviation (dB). VFs were compared over time and a severity index, Chiasm Herniation Scale (CHS), for herniation based on radiological parameters was designed. RESULTS: After treatment, all groups showed improvement of VFs (Gr1: 2.97 dB p = 0.097, Gr2: 4.52 dB p = 0.001 and Gr3: 5.16 dB p = 0.000), followed by long-term gradual deterioration. The course of VFs between patients with and without herniation was not significantly different (p = 0.143), neither was there a difference in the course before and after herniation (p = 0.297). The median time till onset of herniation was 40 months (IQR 6 month-10 years) and did not significantly differ (p = 0.172) between the groups. There was no relation between VFs and the degree of herniation (p = 0.729). CONCLUSION: Herniation does not appear to have clinical relevance with respect to VF outcome. The newly designed CHS is the first scoring system to quantify the severity of herniation and, in the absence of alternatives, may be useful to describe MRI findings to serve future added value in larger sized outcome studies.

Quality of care evaluation in non-functioning pituitary adenoma with chiasm compression: visual outcomes and timing of intervention clinical recommendations based on a systematic literature review and cohort study.

PURPOSE: Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing of surgery related to the preoperative severity of dysfunction is unknown. METHODS: Systematic review for evidence to provide clinical guidance for timing of surgical decompression of the optic chiasm, and a cohort study of 30 NFMA patients, in whom mean deviation (MD), and severity of visual dysfunction was assessed. RESULTS: Systematic review 44 studies were included with a total of 4789 patients. Postoperatively, visual field defects improved in 87.0% of patients, stabilized in 12.8% and worsened in 1.0%. Specific protocols regarding timing of surgery were not reported. Only seven studies (16.7%) reported on either the duration of visual symptoms, or diagnostic, or treatment delay. Cohort study 30 NFMA patients (50% female, 60 eyes, mean age 58.5 ± 14.8 years), had a median MD of - 5.3 decibel (IQR - 3.1 to - 10.1). MD was strongly correlated with clinical severity (r = - 0.94, P < 0.0001), and were used for severity of defects cut-off values: (1) normal > - 2 dB, (2) mild - 2 dB to - 4 dB, (3) moderate - 4 to - 8 dB, (4) severe - 8 to - 17 dB, (5) very severe < - 17 dB. CONCLUSION: Surgical decompression is highly effective in improving visual function. Uniform, quantitative grading of visual dysfunction was lacking. MD is a promising quantitative outcome measure. We provide recommendations for the evaluation of timing of surgery, considering severity of visual impairment, which will need further validation based on expert clinical practice.

Correction to: Quality of care evaluation in non-functioning pituitary adenoma with chiasm compression: visual outcomes and timing of intervention clinical recommendations based on a systematic literature review and cohort study.

The original version of the article unfortunately contained an error in Figure 2. The term 'Refer within 3 days' should read 'Refer as soon as possible'. Corrected version of Figure 2 is given below.

Femoral Vein Catheter is an Important Risk Factor for Catheter-related Thrombosis in (Near-)term Neonates.

Central venous catheters (CVCs) in neonates are associated with an increased risk of thrombosis. Most reports focus on umbilical venous catheters (UVCs) and peripherally inserted central catheters (PICCs), whereas data available on femoral venous catheters (FVCs) are limited. We performed a retrospective cohort study in all neonates (gestational age ≥34 wk) with CVCs. The primary outcome was the occurrence of thrombosis in CVCs. The secondary outcomes were possible risk factors for thrombosis, the thrombotic incidence in FVCs, UVCs, and PICCs, and clinical aspects of thrombosis in these groups. A total of 552 neonates received a total of 656 catheters, including 407 (62%) UVCs, 185 (28%) PICCs, and 64 (10%) FVCs. Thrombosis was detected in 14 cases, yielding an overall incidence of 2.1% or 3.6 events per 1000 catheter days. FVC was significantly associated with the occurrence of thrombosis when compared with UVC (P=0.02; odds ratio, 3.8; 95% confidence interval, 1.2-12.0) and PICC (P=0.01; odds ratio, 8.2; 95% confidence interval, 1.6-41.7). The incidence of thrombosis was higher in FVCs than in UVCs and PICCS, that is, 7.8% (5/64), 1.7% (7/407), and 1.1% (2/185), respectively (P<0.01). The number of thrombotic events per 1000 catheter days was 12.3 in FVCs, 3.2 in UVCs, and 1.5 in PICCs (P<0.05). We concluded that thrombosis occurs more frequently in FVCs than in other CVCs.

Comorbidities in mild autonomous cortisol secretion and the effect of treatment: systematic review and meta-analysis.

OBJECTIVE: To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; > 1.8 µg/dL (>50 nmol/L) cortisol level cut-off following the 1 mg dexamethasone suppression test). DESIGN: Systematic review and meta-analysis. METHODS: Seven databases were searched up to July 14, 2022. Eligible studies were (randomized) trials, cohort studies, and cross-sectional studies assessing comorbidities potentially attributable to cortisol excess or mortality in patients with adrenal incidentaloma with or without MACS or the effects of conservative or surgical management of MACS. Random-effects meta-analysis was performed to estimate pooled proportions (with 95% CIs). RESULTS: In 30 cross-sectional and 16 cohort studies (n = 17 156 patients in total), patients with MACS had a higher prevalence of diabetes (relative risk [RR] 1.44 [1.23-1.69]), hypertension (RR = 1.24 [1.16-1.32]), and dyslipidemia (RR = 1.23 [1.13-1.34]). All-cause mortality (adjusted for confounders) in patients with MACS, assessed in 4 studies (n = 5921), was increased (hazard ratio [HR] = 1.54 [1.27-1.81]). Nine observational studies (n = 856) and 2 randomized trials (n = 107) suggest an improvement in glucometabolic control (RR = 7.99 [2.95-21.90]), hypertension (RR = 8.75 [3.99-19.18]), and dyslipidemia (RR = 3.24 [1.19-8.82]) following adrenalectomy. CONCLUSIONS: The present systematic review and meta-analysis highlight the relevance of MACS, since both cardiometabolic morbidities and mortality appeared to have increased in patients with MACS compared to patients with non-functioning incidentalomas. However, due to heterogeneous definitions, various outcomes, selective reporting, and missing data, the reported pooled estimates need to be interpreted with caution. The small number of patients in randomized trials prevents any strong conclusion on the causality between MACS and these comorbidities.

Cold-Induced Thermogenesis Shows a Diurnal Variation That Unfolds Differently in Males and Females.

CONTEXT: Cold exposure mobilizes lipids to feed thermogenic processes in organs, including brown adipose tissue (BAT). In rodents, BAT metabolic activity exhibits a diurnal rhythm, which is highest at the start of the wakeful period. OBJECTIVE: We investigated whether cold-induced thermogenesis displays diurnal variation in humans and differs between the sexes. METHODS: This randomized crossover study included 24 young and lean male (n = 12) and female (n = 12) participants who underwent 2.5-hour personalized cooling using water-perfused mattresses in the morning (7:45 am) and evening (7:45 pm), with 1 day in between. We measured energy expenditure (EE) and supraclavicular skin temperature in response to cold exposure. RESULTS: In males, cold-induced EE was higher in the morning than in the evening (+54% ±â€…10% vs +30% ±â€…7%; P = 0.05) but did not differ between morning and evening in females (+37% ±â€…9% vs +30% ±â€…10%; P = 0.42). Only in males, supraclavicular skin temperature upon cold increased more in morning than evening (+0.2 ±â€…0.1 °C vs -0.2 ±â€…0.2 °C; P = 0.05). In males, circulating free fatty acid (FFA) levels were increased after morning cold exposure, but not evening (+90% ±â€…18% vs +9% ±â€…8%; P < 0.001). In females, circulating FFA (+94% ±â€…21% vs +20% ±â€…5%; P = 0.006), but also triglycerides (+42% ±â€…5% vs +29% ±â€…4%, P = 0.01) and cholesterol levels (+17% ±â€…2% vs 11% ±â€…2%; P = 0.05) were more increased after cold exposure in morning than in evening. CONCLUSION: Cold-induced thermogenesis is higher in morning than evening in males; however, lipid metabolism is more modulated in the morning than the evening in females.

Low sclerostin levels after long-term remission of acromegaly.

PURPOSE: Bone health is compromised in acromegaly resulting in vertebral fractures (VFs), regardless of biochemical remission. Sclerostin is a negative inhibitor of bone formation and is associated with increased fracture risk in the general population. Therefore, we compared sclerostin concentrations between well-controlled acromegaly patients and healthy controls, and assessed its relationship with bone mineral density (BMD), and VFs in acromegaly. METHODS: Seventy-nine patients (mean age 58.9 ± 11.4 years, 49% women) with controlled acromegaly, and 91 healthy controls (mean age 51.1 ± 16.9 years, 59% women) were included. Plasma sclerostin levels (pg/mL) in patients were measured with an ELISA assay, whereas in controls, serum levels were converted to plasma levels by multiplication with 3.6. In patients, VFs were radiographically assessed, and BMD was assessed using dual X-ray absorptiometry. RESULTS: Median sclerostin concentration in controlled acromegaly patients was significantly lower than in healthy controls (104.5 pg/mL (range 45.7-234.7 pg/mL) vs 140.0 pg/mL (range 44.8-401.6 pg/mL), p < 0.001). Plasma sclerostin levels were not related to age, current growth hormone (GH) or insulin-like factor-1 (IGF-1) levels, gonadal state, treatment modality, remission duration, or BMD, VF presence, severity or progression. CONCLUSION: Patients with long-term controlled acromegaly have lower plasma sclerostin levels than healthy controls, as a reflection of decreased osteocyte activity. Further longitudinal studies are needed to establish the course of sclerostin during different phases of disease and its exact effects in acromegalic osteopathy.

Conditioning cortisol in healthy young women - A randomized controlled trial.

BACKGROUND: Learned placebo effects induced by pharmacological conditioning affect immune and endocrine outcomes and may offer new possibilities for clinical applications. Whether or not cortisol is subject to this type of associative learning processes, and whether conditioning may affect responses to stress, is currently unclear. METHOD: A randomized placebo-controlled trial was conducted in 48 healthy young women. During acquisition, participants received a pill containing either 100 mg hydrocortisone (unconditioned stimulus) or placebo, paired with a gustatory conditioned stimulus on three consecutive days. During evocation, all participants received placebo paired with the conditioned stimulus, again on three consecutive days. During the third evocation trial, participants underwent a psychosocial stress task. The main outcome parameter salivary cortisol and secondary outcome parameters salivary alpha-amylase, self-reported positive affect and tension, heart rate, and skin conductance level were measured at several time points. RESULTS: Significant baseline group differences on cortisol were found at several time points, which complicate the interpretation of group differences. During the first evocation session, the conditioned group showed a moderately smaller cumulative decrease in salivary cortisol from baseline than the placebo control group. No significant differences were found between the groups on cortisol during the second and third evocation or in response to stress, nor on other outcome measures. CONCLUSION: Although the results provide potential further indications for effects of conditioning on cortisol, baseline differences make it impossible to draw clear conclusions. No indications for possible effects of conditioning on the cortisol stress response or autonomous or affective responses to stress were found.

Progression of acromegalic arthropathy in long-term controlled acromegaly patients: 9 years of longitudinal follow-up.

CONTEXT: Joint complaints in patients with acromegaly are common, although the long-term disease course is largely unknown. OBJECTIVE: This study aims to evaluate the long-term course of acromegalic arthropathy. DESIGN AND SETTING: A prospective longitudinal cohort study was conducted in controlled acromegaly patients followed at a tertial referral center, with 3 study visits: at baseline and after a median of 2.6 and 9.1 years. PATIENTS: We included 31 patients with biochemically controlled acromegaly for 2 or more years (49% female; median age, 60 years) at baseline. MAIN OUTCOME MEASURES: Radiographic arthropathy of the knee, hip, hand, and cervical and lumbar spine were evaluated using Kellgren and Lawrence (KL) scores, developed for assessment of primary osteoarthritis (OA). Radiographic progression was defined as a KL increase above the smallest detectable change. Joint symptoms were assessed using self-reported questionnaires. Progression was defined using existing clinically important cutoff values. Risk factors for progression were investigated using a multivariable model. RESULTS: All patients had definite radiographic OA at 1 or more joints at baseline. Radiographic progression was observed in 29%, 48%, 84%, and 94% of patients in the knees, hips, hands, and axial joints, respectively. Deterioration in hand-related pain and function was observed in 10 (32.3%) and 11 patients (35.5%), respectively. Solely baseline KL scores of the hip were associated with hip OA progression (OR 1.88; 95% CI, 1.09-3.16). CONCLUSIONS: Acromegalic arthropathy showed significant radiographic progression over 9.1 years of follow-up in patients in remission, whereas clinical progression was observed less frequently. Future studies should focus on adequate prevention and treatment strategies of acromegalic arthropathy.

The PRolaCT studies - a study protocol for a combined randomised clinical trial and observational cohort study design in prolactinoma.

BACKGROUND: First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size. METHODS: We present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naïve patients; PRolaCT-2: patients with limited duration of DA treatment (4-6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months. DISCUSSION: Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine. TRIAL REGISTRATION: US National Library of Medicine registry (ClinicalTrials.gov) NCT04107480 . Registered on 27 September 2019, registered retrospectively (by 2 months).

Bloodstream Infection Incidence of Different Central Venous Catheters in Neonates: A Descriptive Cohort Study.

Central venous catheters (CVCs) in neonates are associated with a risk of central line-associated bloodstream infections (CLABSI). Most reports on the incidence of CLABSI in neonates focus on umbilical venous catheters (UVCs) and peripherally inserted central catheters (PICCs). We evaluated the incidence and risk factors for CLABSI in a cohort of neonates with femoral venous catheters (FVCs), UVCs, and PICCs, with a gestational age ≥34 weeks born between January 1, 2006 and June 30, 2013. We included 2,986 neonates with a total of 656 catheters. The CLABSI incidence rate varied from 12.3 per 1,000 catheter-days in FVCs to 10.6 per 1,000 catheter-days in UVCs and 5.3 per 1,000 catheter-days in PICCs. In a Kaplan-Meier survival analysis, we did not find a difference in CLABSI risk between the catheter types (p = 0.29). The following factors were independently associated with an increased risk of CLABSI: parenteral nutrition [hazard ratio (HR) 2.60, 95% confidence interval (CI) 1.25-5.41], male gender (HR 2.63, 95% CI 1.17-5.90), and higher birth weight (HR 1.04, 95% CI 1.002-1.09), whereas antibiotic treatment at birth (HR 0.25, 95% CI 0.12-0.52) was associated with a decreased risk. CONCLUSION: In our cohort, we did not find a difference between the CLABSI incidence in FVCs, PICCs, and UVCs. Occurrence of CLABSI is associated with parenteral nutrition, male gender, and higher birth weight. Antibiotic treatment at birth was associated with a decreased risk of CLABSI.

Necrotizing enterocolitis in small-for-gestational-age neonates: a matched case-control study.

BACKGROUND: Small for gestational age (SGA) neonates are at increased risk of mortality and morbidity, including necrotizing enterocolitis (NEC), but detailed information on the incidence and risk factors of NEC in SGA neonates is lacking. OBJECTIVE: This study aims to estimate the incidence of NEC in a large cohort of SGA neonates, compared to appropriate for gestational age (AGA) neonates. METHODS: We included all SGA neonates without congenital malformations admitted to our neonatal nursery between 2004 and 2013. Neonates in the SGA group were matched for gestational age with a control group of AGA neonates admitted during the same study period. We recorded the occurrence of NEC and studied the association with SGA and other potential risk factors. RESULTS: A total of 475 SGA neonates were matched for gestational age at birth to 475 control AGA neonates. The incidence of NEC in the SGA group was 3.2% (15/475) versus 1.3% (6/475) in the AGA group (OR 2.55, 95% CI 0.98-6.63, p = 0.047). The incidence of NEC in the subgroups with mild, moderate and severe SGA was 2.3% (5/215), 4.7% (5/1.07) and 3.2% (5/153), respectively (p = 0.531). CONCLUSIONS: The risk of development of NEC is more than twofold increased in SGA neonates compared to AGA neonates. We found no association between the severity of SGA and NEC.