Sellar Remodeling after Surgery for Nonfunctioning Pituitary Adenoma: Intercarotid Distance as a Predictor of Recurrence

Introduction  As they grow, pituitary adenoma can remodel the sella turcica and alter anatomical relationships with adjacent structures. The intercarotid distance (ICD) at the level of the sella is a measure of sella width. The purpose of this study was to (1) assess how ICD changes after transsphenoidal surgery and (2) explore whether the extent of ICD change is associated with tumor recurrence. Methods  A retrospective analysis of preoperative and postoperative coronal magnetic resonance imaging (MRI) scans was carried out by two independent assessors on patients who underwent transsphenoidal surgery for nonfunctioning pituitary macroadenomas. Preoperative tumor volume and any change in ICD following surgery were recorded and compared between groups. Logistic regression models of recurrence were generated. Results  In 36 of 42 patients, ICD fell after surgery (mean = 1.8 mm) and six cases were static. At time of follow-up (mean = 77 months), 25 had not required further intervention and 17 had undergone second surgery or radiosurgery. In patients in whom no further intervention has yet been necessary, the postoperative reduction in ICD was significantly smaller than in those who required repeat intervention (1.1 vs. 2.7 mm respectively, p  < 0.01). ICD decrease was weakly correlated with tumor volume ( r  = 0.35). ICD decrease was a significant predictor of recurrence (odds ratio [OR] = 3.15; 95% confidence interval [CI]: 1.44–6.87), largely independent of tumor volume. Conclusion  For most patients, ICD falls following surgical excision of a nonfunctioning pituitary macroadenoma. A greater reduction in ICD postsurgery appears to predict recurrence. Change in ICD shows promise as a radiographic tool for prognosticating clinical course after surgery

Metformin does not reduce inflammation in diabetics with abdominal aortic aneurysm or at high risk of abdominal aortic aneurysm formation

Introduction The protective effect of diabetes mellitus on abdominal aortic aneurysm formation and growth has been repeatedly observed in population studies but continues to be poorly understood. However, recent investigations have suggested that metformin, a staple antihyperglycemic medication, may be independently protective against abdominal aortic aneurysm formation and growth. Therefore, we describe the effect of metformin in abdominal aortic aneurysm and at-risk patients on markers of inflammation, the driver of early abdominal aortic aneurysm formation and growth. Methods Peripheral blood was collected from patients previously diagnosed with abdominal aortic aneurysm or presenting for their U.S. Preventive Task Force-recommended abdominal aortic aneurysm screening. Plasma and circulating peripheral blood mononuclear cells were isolated using Ficoll density centrifugation. Circulating plasma inflammatory and regulatory cytokines were assessed with enzyme-linked immunosorbent assays. CD4+ cell phenotyping was performed using flow cytometric analysis and expressed as a proportion of total CD4+ cells. To determine the circulating antibody to self-antigen response, a modified enzyme-linked immunosorbent assay was performed against antibodies to collagen type V and elastin fragments. Results Peripheral blood was isolated from 266 patients without diabetes mellitus (n=182), with diabetes mellitus not treated with metformin (n=34), and with diabetes mellitus actively taking metformin (n=50) from 2015 to 2017. We found no differences in the expression of Tr1, Th17, and Treg CD4+ fractions within diabetics ± metformin. When comparing inflammatory cytokines, we detected no differences in IL-1β, IL-6, IL-17, IL-23, IFN-γ, and TNF-α. Conversely, no differences were observed pertaining to the expression to regulatory cytokines IL-4, IL-10, IL-13, TSG-6, or TGF-β. Lastly, no differences in expression of collagen type V and elastin fragment antigen and/or antibodies were detected with metformin use in diabetics. Conclusion Metformin in diabetics at-risk for abdominal aortic aneurysm or diagnosed with abdominal aortic aneurysm does not seem to alter the peripheral inflammatory environment

Monitoring blood pressure variability via chaotic global metrics using local field potential oscillations

The intention was to associate blood pressure (BP) variability (BPV) measurements to Local field potentials (LFPs). Thus, assessing how LFPs can co-vary with BPV to permit implantable brain devices (via LFPs) to control output. Elevated BPV is a considerable cardiovascular disease risk factor. Often patients are resistant to pharmacotherapies. An alternative treatment is Deep Brain Stimulation (DBS). Mathematical techniques based on nonlinear dynamics assessed their correlation of BPV chaotic global metrics to LFPs. Chaos Forward Parameter (CFP6) was computed for LFPs, at three electrode depths in the mid-brain and sensory thalamus. Mean, root mean square of the successive differences (RMSSD) and the chaotic global metrics (CFP1 to CFP7) were computed for the BP signal. The right ventroposterolateral (RVPL) nucleus provided a substantial correlation via CFP6 for BP with R-squared up to approximately 79% by means of LFP gamma oscillations. Investigation of BPV via LFPs as a proxy marker might allow therapies to be attuned in a closed-loop system. Whilst all patients were chronic pain patients the chaotic global relationship should be unperturbed. LFPs correlation does not unconditionally predict its causation. There is no certainty DBS in these locations would be therapeutic but can be used as an assessment tool

The involvement of the piriform cortex in non-lesional temporal lobe epilepsy: an uncommon component of the epileptogenic network

The piriform cortex is recognized as highly epileptogenic in rodents, yet its electrophysiological role in human epilepsy remains understudied. Recent surgical outcomes have suggested potential benefits in resecting the piriform cortex for cases of medial temporal lobe epilepsy. However, little is known about its electrophysiological activity in human epilepsy. This case-series study aimed to explore the electrophysiological role of the piriform cortex within the epileptogenic network among patients with suspected temporal lobe epilepsy. Participants were recruited from Emory University Hospital or Children's Healthcare of Atlanta, with non-lesional frontotemporal or temporal lobe hypotheses, undergoing stereoelectroencephalographic studies. Specifically, focus was placed on patients with one or more electrode contacts in the piriform cortex. Primary objectives included determining piriform cortex involvement within the electrophysiologically defined epileptogenic network and assessing the effects of electrical stimulation. Twenty-two patients were included in the study. Notably, only one patient exhibited piriform cortex involvement at seizure onset, associated with an olfactory aura. Two patients showed early piriform cortex involvement, while others displayed late or no involvement. Electrical stimulation of the piriform cortex induced after-discharges in three patients and replicated a habitual seizure in one. These findings present a contrast to surgical outcome studies, suggesting that the piriform cortex may not typically play a significant role in the epileptogenic network among patients with non-lesional temporal lobe epilepsy

Cryopreserved Homografts in Infected Infrainguinal Fields Are Associated with Frequent Reinterventions and Poor Amputation-Free Survival

Background Single-length saphenous vein continues to be the conduit of choice in infected-field critical limb ischemia. However, half of these individuals have inadequate vein secondary to previous use or chronic venous disease. We reviewed our outcomes of infected-field infrainguinal bypasses performed with cryopreserved homografts (CHs), a widely accepted alternative to autogenous vein in this setting. Methods This is a retrospective, institutional descriptive analysis of infected-field infrainguinal revascularizations between 2012 and 2015. Results Twenty-four operations were performed in the same number of patients for limb ischemia with signs of active infection. The mean age of the cohort examined was 62.5 ± 14.4 (standard deviation) years. Mean Society of Vascular Surgery risk score was 3.9 with a baseline Rutherford's chronic ischemia score of 4.3 at presentation. Emergent procedures constituted 29% of cases, and the remainder cases were urgent procedures. The CH bypass captured was a reoperative procedure in all but one of the patients. Culture positivity was present in 75% of cases with Staphylococcus aureus (29%), the most commonly isolated organism. Thirty-day mortality and major adverse cardiovascular events were both 4%. Amputation-free survival (AFS) was 75% at 30 days. Similarly, 30-day reintervention was 38% with debridement (43%) and bleeding (29%), the most common indications. Average duration of follow-up was 27.9 ± 20.4 months (range: 0.5–60.4). Mean length of stay was 14.8 days. Reinfection requiring an additional procedure or antibiotic regimen separate from the index antibiotic course was 13%. Primary patency and AFS at 1 year was 50% and 58%, respectively. Primary patency and AFS at 2 years was 38% and 52%, respectively. Limb salvage at 1 and 2 years was 70% and 65%, respectively. Fifteen patients (63%) required reintervention during the follow-up period with 40% of those subjects undergoing multiple procedures. Conclusions CHs remain a marginal salvage conduit in the setting of infection and no autogenous choices. Therefore, clinicians should individualize usage of this high-cost product in highly selected patients only

Perioperative Outcomes are Adversely Affected by Poor Pretransfer Adherence to Acute Limb Ischemia Practice Guidelines

Objectives The accepted treatment for acute limb ischemia (ALI) is immediate systemic anticoagulation and timely reperfusion to restore blood flow. In this study, we describe the retrospective assessment of pretransfer management decisions by referring hospitals to an academic tertiary care facility and its impact on perioperative adverse events. Methods A retrospective analysis of ALI patients transferred to us via our Level I Vascular Emergency program from 2010 to 2013 was performed. Patient demographics, comorbidities, Rutherford ischemia classification, time to anticoagulation, and time to reperfusion were tabulated and analyzed for correlation to incidence of major adverse limb events (MALE), mortality, and bypass patency in the perioperative period (30-day postoperative). All time intervals were calculated from the onset of symptoms and categorized into three subcohorts (48 hrs). Results Eighty-seven patients with an average age of 64.0 (± 16.2) years presented to outlying hospitals and was transferred to us with lower extremity ALI. The mean delay from symptom onset to initial referring physician evaluation was 18.3 hrs. At that time of evaluation, 53.8% had Rutherford class IIA ischemia and 36.3% had class IIB ischemia. Seventy-six (87.4%) patients were started on heparin previous to transfer. However, only 44 (57.9%) patients reached therapeutic levels as measured by activated partial thromboplastin time (aPTT) prior to definitive revascularization. A delay of anticoagulation initiation >48 hrs from symptom onset was associated with increased 30-day reintervention rates compared with the <6 hrs group (66.7% vs. 23.5%; p<0.05). However, time to reperfusion had no statistically significant impact on MALE, 30-day mortality, or 30-day interventional patency in our small cohorts. Additionally, patients with a previous revascularization had a higher 30-day reintervention rate (46.5%; p<0.05). Conclusions The practice of timely therapeutic anticoagulation of patients referred for ALI from community facilities occurs less frequently than expected and is associated with an increased perioperative reintervention rate

Cerebellar High-Grade Glioma: A Translationally Oriented Review of the Literature

World Health Organization (WHO) grade 4 gliomas of the cerebellum are rare entities whose understanding trails that of their supratentorial counterparts. Like supratentorial high-grade gliomas (sHGG), cerebellar high-grade gliomas (cHGG) preferentially affect males and prognosis is bleak; however, they are more common in a younger population. While current therapy for cerebellar and supratentorial HGG is the same, recent molecular analyses have identified features and subclasses of cerebellar tumors that may merit individualized targeting. One recent series of cHGG included the subclasses of (1) high-grade astrocytoma with piloid features (HGAP, ~31% of tumors); (2) H3K27M diffuse midline glioma (~8%); and (3) isocitrate dehydrogenase (IDH) wildtype glioblastoma (~43%). The latter had an unusually low-frequency of epidermal growth factor receptor (EGFR) and high-frequency of platelet-derived growth factor receptor alpha (PDGFRA) amplification, reflecting a different composition of methylation classes compared to supratentorial IDH-wildtype tumors. These new classifications have begun to reveal insights into the pathogenesis of HGG in the cerebellum and lead toward individualized treatment targeted toward the appropriate subclass of cHGG. Emerging therapeutic strategies include targeting the mitogen-activated protein kinases (MAPK) pathway and PDGFRA, oncolytic virotherapy, and immunotherapy. HGGs of the cerebellum exhibit biological differences compared to sHGG, and improved understanding of their molecular subclasses has the potential to advance treatment

Bumps and Babies Longitudinal Study (BABBLES): An independent evaluation of the Baby Buddy app

Introduction: Developments in information and communication technologies have enabled and supported the development and expansion of electronic health in the last decade. This has increased the possibility of self-management and care of health issues.Objectives: To assess the effectiveness of on maternal self-efficacy and mental wellbeing three months post-birth in a sample of mothers recruited during the antenatal period. In addition, to explore when, why and how mothers use the app and consider any benefits the app may offer them in relation to their parenting, health, relationships or communication with their child, friends, family members or health professionals.Design: A mixed methods approach, including a longitudinal cohort study, a qualitative study and detailed analysis and synthesis of data from the Baby Buddy app about the way in which mothers accessed and used the app content.Setting: The study was conducted in five geographically separate sites in England: Coventry, Lewisham, Bradford, Blackpool and Leicester. These areas were chosen as they were geographically, ethnically and socio-economically diverse and where the Baby Buddy app was reported to be well-embedded, both formally and informally, into the maternity and child health pathways by the relevant healthcare staff.Participants: Pregnant women who were aged 16 years and over, had no previous live child, were between 12-16 weeks and six days gestation and booked with the maternity services in each of the five study sites were invited to take part.Interventions: Self-reported use of the Baby Buddy app at one of the three data collection time-points: 12-16+6 weeks gestation, 35 weeks gestation and three months post-birth.Outcome measures: The primary outcome measure was parental self-efficacy at three months post-birth using the Tool to measure Parenting Self-Efficacy (TOPSE). The main secondary outcome was maternal mental well-being at three months post-birth using the Warwick and Edinburgh Mental Wellbeing Scale (WEMWBS).Results: Recruitment took place between September 2016 and February 2017. A total of 488 participants provided valid data at baseline (12-16 weeks gestation), 296 participants also provided valid data at 3 months post-birth, 114 (38.5%) of whom reported that they had used the Baby Buddy app at one or more of the data collection time-points (‘app user’). Seventeen first-time mothers participated in the qualitative arm via telephone interviews (n=9) and a focus group (n=8). Twenty healthcare professionals participated in interviews (n=5) and two focus groups (n=15). Consent was gained from 98 participants who gave permission for their in-app4data to be made accessible but just 61 participants could be identified from the database provided, of whom 51 were included in the analyses.At recruitment there were no differences between Baby Buddy app users and non-app users in respect to: age, IMD, ethnicity, highest education, employment, relationship status. Baby Buddy app users were more likely to use pregnancy or parenting apps (80.7% vs 69.6%, p=.035), more likely to have been introduced to the app by a healthcare professional (p=.005) and have a lower median score for perceived social support (81 vs 83, p=.034) than non-app users. The Baby Buddy app did not illicit a statistically significant change in TOPSE scores from baseline to 3 months post-birth (adjusted OR 1.12, 95%CI 0.59 to 2.13, p=.730). Finding out about the Baby Buddy app from a healthcare professional appeared to grant no additional benefit to app users compared to all other participants in terms of self-efficacy at three months post-birth (adjusted OR 1.16, 95%CI 0.60 to 2.23, p=.666).Apps were popular; Baby Buddy app users were more likely to use other pregnancy-related apps than non-Baby Buddy users and the most frequent source from which Baby Buddy app users found out about the app was a midwife. A post-hoc analysis found that Baby Buddy app users were more likely to breastfeed than non-Baby Buddy app users. This was a consistent pattern for both exclusive breastfeeding and any breast feeding: there was a 9% increase in exclusive breastfeeding at any time up to 3 months post-birth in Baby Buddy app users and a 12% increase in any breastfeeding up to three months post-birth, compared to non-app users. Whilst this is an important finding, this needs to be used with care due to the post-hoc element of the analysis.First-time mothers who participated in the qualitative arm of the study found that the Baby Buddy app worked well due to its accessibility and that the information was concise and easy to find. They liked that it followed the progress of pregnancy with appropriately-timed information and that different aspects could be accessed as and when needed. The app was designed to be an adjunct to service delivery not a replacement for healthcare. The importance of this was demonstrated by many first-time mothers reporting that they preferred in-practice support from a healthcare professional.The qualitative data indicated that the four preconditions of normalisation process theory: implementation, adoption, translation and stabilisation were met in regard to healthcare professionals’ use of the Baby Buddy app. This suggests that the healthcare professionals were actively integrating the Baby Buddy app into clinical practice with other professionals and first-time mothers, therefore embedding the Baby Buddy app into their service delivery.The in-app data from the sub-sample of participants (n=51) suggest that there was a difference in the amount of time participants spent accessing elements of the app; the median time spent using the app per session was 8.3 minutes (SD 5.8 minutes). The most popular features that5were used were ‘Today’s Information’, videos, ‘Bump/Baby Booth’, ‘Ask Me’ and ‘What does that mean?’. Participants used the app most often between 9-10am with another peak in the evening around 8-9pm. There were also a broad range of topics and issues that the participants searched for, of which the most searched words included: ‘labour’, ‘form’, ‘birth’, ‘pregnant’ and ‘developing’. In the sub-sample for whom we had in-app data, there was a large range for the number of times the app was used, from 0-593 times. The median number of times the app was opened was 146.5 but the data were positively skewed (LQ 52.5 – UQ 329). This indicates that the data are bunched towards the smaller number of times opened. Within this sub-sample, 21.6% of the engaged type of user used the app up to 25 times and 47% of this type of user used the app more than 100 times. This contrasts with the highly engaged type of user where 43% used the app 25 or less times and just 9.8% of this proactive type of user used it more than 100 times.We found no statistically significant difference in the TOPSE or the WEMWBS scores between the type of user who was engaged with the app and non-app users (adjusted OR 0.69, 95%CI 0.22 to 2.16, p=.519 and adjusted OR 1.54, 95%CI 0.57 to 4.16, p=.329, respectively). Similarly, we found no statistically significant difference between the type of users who were highly engaged users and non-app users (TOPSE: adjusted OR 0.48, 95%CI 0.14t o 1.68, p=.251; WEMWBS: adjusted OR 1.40, 95%CI 0.52 to 3.76, p=.509).Strengths and limitations: The primary objective was to explore the impact of the Baby Buddy app on parental self-efficacy and the Tool for Parenting Self-Efficacy (TOPSE website, Kendall, Bloomfield and Nash 2009), a validated measure, was selected to measure the primary outcome. The retention rate of 60.7% from baseline to three months post-birth demonstrates the difficulty of engaging new mothers during this demanding period of their lives. Nevertheless, in the initial and final samples, app users and non-users remained generally comparable and relevant confounders were adjusted for. Mothers were invited to take part in interviews and/or focus groups, the latter of which were held in a baby-friendly, welcoming environment for women and babies. Telephone interviews were offered for greater convenience for the women. Analysing the in-app data, we were able to compare outcomes for both the high versus low or non-user app groups and for those mothers who were the type of highly engaged users versus those who were a less engaged type. This was for a relatively small number of mothers but was a new method of analysing the in-app data.The Baby Buddy app was publicly available, meaning randomisation was not possible and therefore participants were only asked about their specific use of the app after the 35 weeks gestation data collection point to avoid directed app use. The participants were a self-selected group, especially those for whom we had in-app data and this is reflected in the higher than the national average for women who were degree holders (58.6% in final sample versus 42% nationally). The overall TOPSE scores were high at baseline which meant there was little room6for improvement. Nevertheless, there was no difference between the Baby Buddy app users and those participants who did not use the app.Conclusions: First-time mothers in the study found the app accessible and the information concise. The quantitative results, including those from the in-app data, found no evidence of impact from the Baby Buddy app on the primary outcome of parental self-efficacy or mental well-being (secondary outcome) at three months post-birth. The participant mothers had lower social support scale scores, which might suggest that the app attracted mothers who had a smaller social support network. Both mothers and healthcare professionals valued the fact that the Baby Buddy app was professionally endorsed which encouraged the women to trust the contents and the healthcare professionals to use it in their everyday practice. The most frequent source from which Baby Buddy app users found out about the app was a midwife, which suggests that the embedding of the app into service delivery by Best Beginnings was beneficial. A post-hoc finding was that women who used the Baby Buddy app were significantly more likely to exclusively breastfeed, or ever breastfeed, than those not using the app. The Baby Buddy app has gone some way to help to ‘Make Every Contact Count’ for both first-time mothers and healthcare professionals

Areas of normal pulmonary parenchyma on HRCT exhibit increased FDG PET signal in IPF patients

Purpose: Patients with idiopathic pulmonary fibrosis (IPF) show increased PET signal at sites of morphological abnormality on high-resolution computed tomography (HRCT). The purpose of this investigation was to investigate the PET signal at sites of normal-appearing lung on HRCT in IPF. Methods: Consecutive IPF patients (22 men, 3 women) were prospectively recruited. The patients underwent 18F-FDG PET/HRCT. The pulmonary imaging findings in the IPF patients were compared to the findings in a control population. Pulmonary uptake of 18F-FDG (mean SUV) was quantified at sites of morphologically normal parenchyma on HRCT. SUVs were also corrected for tissue fraction (TF). The mean SUV in IPF patients was compared with that in 25 controls (patients with lymphoma in remission or suspected paraneoplastic syndrome with normal PET/CT appearances). Results: The pulmonary SUV (mean ± SD) uncorrected for TF in the controls was 0.48 ± 0.14 and 0.78 ± 0.24 taken from normal lung regions in IPF patients (p < 0.001). The TF-corrected mean SUV in the controls was 2.24 ± 0.29 and 3.24 ± 0.84 in IPF patients (p < 0.001). Conclusion: IPF patients have increased pulmonary uptake of 18F-FDG on PET in areas of lung with a normal morphological appearance on HRCT. This may have implications for determining disease mechanisms and treatment monitoring. © 2013 The Author(s)