Abstract
Context
Approximately 10% to 20% of prolactinomas are resistant to dopamine agonist therapy. The ErbB signaling pathway may drive aggressive prolactinoma behavior.
Objective
We evaluated ...lapatinib, an ErbB1-epidermal growth factor receptor (EGFR)/ErbB2 or human EGFR2 (HER2) tyrosine kinase inhibitor (TKI), in aggressive prolactinomas.
Design
A prospective, phase 2a multicenter trial was conducted.
Setting
This study took place at a tertiary referral pituitary center.
Patients
Study participants included adults with aggressive prolactinomas showing continued tumor growth despite maximally tolerated dopamine agonist therapy.
Intervention
Intervention included oral lapatinib 1250 mg/day for 6 months.
Main Outcome Measures
The primary end point was 40% reduction in any tumor dimension assessed by magnetic resonance imaging at study end; tumor response was assessed by Response Evaluation Criteria in Solid Tumors criteria. Secondary end points included prolactin (PRL) reduction, correlation of response with EGFR/HER2 expression, and safety.
Results
Owing to rigorous inclusion criteria, of 24 planned participants, only 7 consented and 4 were treated. None achieved the primary end point but 3 showed stable disease, including 2 with a 6% increase and 1 with a 16.8% decrease in tumor diameter. PRL response was not always concordant with tumor response, as 2 showed 28% and 59% increases in PRL. The fourth participant had a PRL-secreting carcinoma and withdrew after 3 months of lapatinib because of imaging and PRL progression. EGFR/HER2 expression did not correlate with treatment response. Lapatinib was well tolerated overall, with reversible grade 1 transaminitis in 2 patients, grade 2 rash in 2 patients, and grade 1 asymptomatic bradycardia in 2 patients.
Conclusions
An oral TKI such as lapatinib may be an effective option for a difficult-to-treat patient with an aggressive prolactinoma.
Pituitary Imaging Pressman, Barry D
Endocrinology and metabolism clinics of North America
46, Številka:
3
Journal Article
Recenzirano
Modern pituitary imaging is MRI. However, computed tomography (CT) still has limited usefulness. In addition, because CT offers much better bone detail and calcium detection, there are some cases in ...which such additional information is necessary. Before the advent of CT, plain radiography, pneumoencephalography, and angiography were used to diagnose pituitary masses. More recently, CT, and then especially MRI, made it possible to primarily delineate lesions within and around the pituitary gland rather than depend on secondary information that could only suggest their presence.
We sought to examine the association of epicardial adipose tissue (EAT) quantified on chest computed tomography (CT) with the extent of pneumonia and adverse outcomes in patients with coronavirus ...disease 2019 (COVID-19).
We performed a post-hoc analysis of a prospective international registry comprising 109 consecutive patients (age 64 ± 16 years; 62% male) with laboratory-confirmed COVID-19 and noncontrast chest CT imaging. Using semi-automated software, we quantified the burden (%) of lung abnormalities associated with COVID-19 pneumonia. EAT volume (mL) and attenuation (Hounsfield units) were measured using deep learning software. The primary outcome was clinical deterioration (intensive care unit admission, invasive mechanical ventilation, or vasopressor therapy) or in-hospital death.
In multivariable linear regression analysis adjusted for patient comorbidities, the total burden of COVID-19 pneumonia was associated with EAT volume (β = 10.6, p = 0.005) and EAT attenuation (β = 5.2, p = 0.004). EAT volume correlated with serum levels of lactate dehydrogenase (r = 0.361, p = 0.001) and C-reactive protein (r = 0.450, p < 0.001). Clinical deterioration or death occurred in 23 (21.1%) patients at a median of 3 days (IQR 1–13 days) following the chest CT. In multivariable logistic regression analysis, EAT volume (OR 5.1 95% CI 1.8–14.1 per doubling p = 0.011) and EAT attenuation (OR 3.4 95% CI 1.5–7.5 per 5 Hounsfield unit increase, p = 0.003) were independent predictors of clinical deterioration or death, as was total pneumonia burden (OR 2.5, 95% CI 1.4–4.6, p = 0.002), chronic lung disease (OR 1.3 95% CI 1.1–1.7, p = 0.011), and history of heart failure (OR 3.5 95% 1.1–8.2, p = 0.037).
EAT measures quantified from chest CT are independently associated with extent of pneumonia and adverse outcomes in patients with COVID-19, lending support to their use in clinical risk stratification.
•Epicardial adipose tissue (EAT) volume and attenuation associate with the quantitative burden of COVID-19 pneumonia.•An increasing EAT volume or attenuation independently predicts clinical deterioration or death.•EAT may contribute to the augmented systemic inflammatory response to COVID-19.•The integration of EAT measurements into COVID-19 risk scores has the potential to enhance outcome prediction.
The role of cervicomedullary decompression (CMD) in the care of hydrocephalic achondroplastic children who present with simultaneous foramen magnum stenosis is not well understood. We sought to ...determine the percentage of symptomatic achondroplastic children with foramen magnum stenosis who had stabilization or improvement in ventriculomegaly following CMD. The authors retrospectively reviewed the records of pediatric patients at Cedars‐Sinai Medical Center with achondroplasia and signs of progressive ventriculomegaly who underwent CMD for symptomatic foramen magnum stenosis between the years 2000 and 2018. Clinical outcomes included changes in fontanelle characteristics, head circumference (HC) percentile, and incidence of ventriculoperitoneal (VP) shunting. Radiographic outcomes measured included changes in Evans ratio. We excluded individuals who were shunted before CMD from our study. Sixteen children presented with symptomatic foramen magnum stenosis and full anterior fontanelle or jump in the HC percentiles. Two children underwent placement of a VP shunt before decompressive surgery and were excluded from further analysis. Of the remaining 14 children who underwent CMD, 13 (93%) showed softening or flattening of their fontanelles post‐operatively. Ten of these 14 children had both pre‐ and post‐operative HC percentile records available, with 8 showing increasing HC percentiles before surgery. Seven of those eight children (88%) showed a deceleration or stabilization of HC growth velocity following decompression of the foramen magnum. Among 10 children with available pre‐ and post‐operative brain imaging, ventricular size improved in 5 (50%), stabilized in 2 (20%), and slightly increased in 3 (30%) children after decompression. Two children (14%) required a shunt despite decompression of the foramen magnum. A significant proportion of children with concomitant signs of raised intracranial pressure or findings of progressive ventriculomegaly and foramen magnum stenosis may have improvement or stabilization of these findings following CMD. CMD may decrease the need for VP shunting and its associated complications in the select group of hydrocephalic children with achondroplasia presenting with symptomatic foramen magnum stenosis.
We aimed to evaluate the effectiveness of utilizing artificial intelligence (AI) to quantify the extent of pneumonia from chest CT scans, and to determine its ability to predict clinical ...deterioration or mortality in patients admitted to the hospital with COVID-19 in comparison to semi-quantitative visual scoring systems.
A deep-learning algorithm was utilized to quantify the pneumonia burden, while semi-quantitative pneumonia severity scores were estimated through visual means. The primary outcome was clinical deterioration, the composite end point including admission to the intensive care unit, need for invasive mechanical ventilation, or vasopressor therapy, as well as in-hospital death.
The final population comprised 743 patients (mean age 65 ± 17 years, 55% men), of whom 175 (23.5%) experienced clinical deterioration or death. The area under the receiver operating characteristic curve (AUC) for predicting the primary outcome was significantly higher for AI-assisted quantitative pneumonia burden (0.739,
= 0.021) compared with the visual lobar severity score (0.711,
< 0.001) and visual segmental severity score (0.722,
= 0.042). AI-assisted pneumonia assessment exhibited lower performance when applied for calculation of the lobar severity score (AUC of 0.723,
= 0.021). Time taken for AI-assisted quantification of pneumonia burden was lower (38 ± 10 s) compared to that of visual lobar (328 ± 54 s,
< 0.001) and segmental (698 ± 147 s,
< 0.001) severity scores.
Utilizing AI-assisted quantification of pneumonia burden from chest CT scans offers a more accurate prediction of clinical deterioration in patients with COVID-19 compared to semi-quantitative severity scores, while requiring only a fraction of the analysis time.
Quantitative pneumonia burden assessed using AI demonstrated higher performance for predicting clinical deterioration compared to current semi-quantitative scoring systems. Such an AI system has the potential to be applied for image-based triage of COVID-19 patients in clinical practice.
Pediatric victims of blunt trauma have developmental and anatomic characteristics that can make it difficult to assess their risk of cervical spine injury (CSI). Previous reports, all retrospective ...in nature, have not identified any cases of CSI in either children or adults in the absence of neck pain, neurologic symptoms, distracting injury, or altered mental status. The objective of this study was to examine the incidence and spectrum of spine injury in patients who are younger than 18 years and to evaluate the efficacy of the National Emergency X-Radiography Utilization Study (NEXUS) decision instrument for obtaining cervical spine radiography in pediatric trauma victims.
We performed a prospective, multicenter study to evaluate pediatric blunt trauma victims. All patients who presented to participating emergency departments underwent clinical evaluation before radiographic imaging. The presence or absence of the following criteria was noted: midline cervical tenderness, altered level of alertness, evidence of intoxication, neurologic abnormality, and presence of painful distracting injury. Presence or absence of each individual criterion was documented for each patient before radiographic imaging, unless the patient was judged to be too unstable to complete the clinical evaluation before radiographs. The decision to radiograph a patient was entirely at the physician's discretion and not driven by the NEXUS questionnaire. The presence or absence of CSI was based on the final interpretation of all radiographic studies. Data on all patients who were younger than 18 years were sequestered from the main database for separate analysis.
There were 3065 patients (9.0% of all NEXUS patients) who were younger than 18 years in this cohort, 30 of whom (0.98%) sustained a CSI. Included in the study were 88 children who were younger than 2, 817 who were between 2 and 8, and 2160 who were 8 to 17. Fractures of the lower cervical vertebrae (C5-C7) accounted for 45.9% of pediatric CSIs. No case of spinal cord injury without radiographic abnormality was reported in any child in this study, although 22 cases were reported in adults. Only 4 of the 30 injured children were younger than 9 years, and none was younger than 2 years. Tenderness and distracting injury were the 2 most common abnormalities noted in patients with and without CSI. The decision rule correctly identified all pediatric CSI victims (sensitivity: 100.0%; 95% confidence interval: 87.8%-100.0%) and correctly designated 603 patients as low risk for CSI (negative predictive value: 100.0%; 95% confidence interval: 99.4%-100.0%).
The lower cervical spine is the most common site of CSI in children, and fractures are the most common type of injury. CSI is rare among patients aged 8 years or younger. The NEXUS decision instrument performed well in children, and its use could reduce pediatric cervical spine imaging by nearly 20%. However, the small number of infants and toddlers in the study suggests caution in applying the NEXUS criteria to this particular age group.
Purpose
Parasellar plasmacytomas are rare tumors localized to the sellar region arising from plasma cells. Knowledge of clinical, imaging, surgical, and pathological characteristics is limited to ...single case reports.
Methods
A retrospective analysis of five primary cases was conducted, followed by systematic review of English language articles using PubMed in accordance with PRISMA guidelines.
Results
Five primary case patients include four men and one woman, ages 60–77, followed up to 3 years. A systematic review identified 65 additional patients, of whom 65% presented with cranial nerve palsies and 15% with hypopituitarism. Sixteen percent had history of known multiple myeloma (MM) while 37% were diagnosed concurrently with MM on presentation of parasellar plasmacytoma. Imaging showed median tumor size of 38 mm (range, 4–70 mm), with MRI intensity similar to that of other sellar masses. Surgical biopsy with immunohistochemical studies confirmed plasmacytoma diagnosis. Eighty-one percent underwent parasellar radiotherapy, and chemotherapy initiated in 59% of the 69 patients with MM. Overall survival rate was 74% at follow-up (median 12 months), with 18% having parasellar recurrences and 38% progressing to systemic MM after presentation of a solitary plasmacytoma (median 3 months).
Conclusions
Parasellar plasmacytomas are rare tumors that should be considered in the differential diagnosis for lesions involving the sella and arising from the clivus, especially when cranial nerve paresis is apparent, even in the absence of known MM. Although recurrence rates for parasellar plasmacytoma is low, patients should be monitored for progression to MM. Treatment depends on the presence of systemic disease at diagnosis.
Rebound high-pressure headaches may complicate treatment of spontaneous intracranial hypotension (SIH), but no comprehensive study of such patients has been reported and little is known about its ...frequency and risk factors. We therefore studied patients undergoing treatment for SIH and performed magnetic resonance venography (MRV) to assess for cerebral venous sinus stenosis, a risk factor for idiopathic intracranial hypertension.
We studied a consecutive group of patients who underwent treatment for SIH. Rebound high-pressure headache was defined as a reverse orthostatic headache responsive to acetazolamide. MRV was obtained in all patients and lateral sinus stenosis was scored according to the system published by Higgins et al., with 0 being normal and 4 signifying bilateral signal gaps.
The mean age of the 46 men and 67 women was 45.9 years (range 13-71 years) at the time of onset of SIH. Rebound high-pressure headache was diagnosed in 31 patients (27.4%); 14% of patients with an MRV score of 0, 24% with a score of 1, and 46% with a score of 2 or 3 (
= 0.0092). Also, compared to SIH patients who did not develop rebound high-pressure headaches (n = 82), those with rebound high-pressure headaches were younger, more often female, and more often had an extradural CSF collection on spinal imaging.
Rebound high-pressure headache occurs in about one-fourth of patients following treatment of SIH and is more common in those with restriction of cerebral venous outflow.
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