Real-time quantification of in vivo cerebrospinal fluid velocity using the functional magnetic resonance imaging inflow effect.

In vivo estimation of cerebrospinal fluid (CSF) velocity is crucial for understanding the glymphatic system and its potential role in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Current cardiac or respiratory-gated approaches, such as 4D flow magnetic resonance imaging (MRI), cannot capture CSF movement in real time because of limited temporal resolution and, in addition, deteriorate in accuracy at low fluid velocities. Other techniques like real-time phase-contrast-MRI or time-spatial labeling inversion pulse are not limited by temporal averaging but have limited availability, even in research settings. This study aims to quantify the inflow effect of dynamic CSF motion on functional MRI (fMRI) for in vivo, real-time measurement of CSF flow velocity. We considered linear and nonlinear models of velocity waveforms and empirically fit them to fMRI data from a controlled flow experiment. To assess the utility of this methodology in human data, CSF flow velocities were computed from fMRI data acquired in eight healthy volunteers. Breath-holding regimens were used to amplify CSF flow oscillations. Our experimental flow study revealed that CSF velocity is nonlinearly related to inflow effect-mediated signal increase and well estimated using an extension of a previous nonlinear framework. Using this relationship, we recovered velocity from in vivo fMRI signal, demonstrating the potential of our approach for estimating CSF flow velocity in the human brain. This novel method could serve as an alternative approach to quantifying slow flow velocities in real time, such as CSF flow in the ventricular system, thereby providing valuable insights into the glymphatic system's function and its implications for neurological disorders.

Shape-Sensing Robotic-Assisted Bronchoscopy in the Multiple Pulmonary Nodule Diagnosis during a Single Anesthetic Event.

INTRODUCTION: The widespread use of computed tomography as a screening tool for early lung cancer has increased detection of pulmonary lesions. It is common to encounter patients with more than one peripheral pulmonary nodule (PPN) of uncertain etiology. Shape-sensing robotic-assisted bronchoscopy (ssRAB) emerges as a potential alternative to biopsy multiple PPN, in addition to mediastinal staging in single anesthetic procedure. METHODS: This is a single-center, retrospective review of 22 patients who underwent ssRAB for evaluation of two or more PPN, between November 2021 and April 2023 at Mayo Clinic, FL, USA. RESULTS: A total of 46 PPNs were biopsied in 22 patients. All lesions were ≤2 cm with a median minimum and maximum cross-sectional lesion size of 1.40 cm and 1.05 cm, respectively. Diagnostic yield was 86.9% (n = 40), and target reach was 91.3% (n = 42). Most lesions were in the upper lobes, a solid pattern was found in 78.3% (n = 36), bronchus sign was present in 82.6% of cases (n = 38), 54.4% (n = 25) were malignant nodules, and 32.6% (n = 15) were benign. Fourteen patients had at least one malignant lesion out of two or more nodules sampled, and 10 patients had a malignant diagnosis for all sampled lesions. The complication rate was 9% (n = 2) with one case of bleeding and one of pneumothorax. CONCLUSION: This study is, to our knowledge, the first to assess the use and safety of ssRAB for diagnosis of multiple PPN in a single anesthetic event. This procedure will mainly impact management decisions and subsequently shorten the time from diagnosis to treatment.

Shape-Sensing Robotic-Assisted Bronchoscopy versus Computed Tomography-Guided Transthoracic Biopsy for the Evaluation of Subsolid Pulmonary Nodules.

INTRODUCTION: Lung cancer remains the leading cause of cancer death worldwide. Subsolid nodules (SSN), including ground-glass nodules (GGNs) and part-solid nodules (PSNs), are slow-growing but have a higher risk for malignancy. Therefore, timely diagnosis is imperative. Shape-sensing robotic-assisted bronchoscopy (ssRAB) has emerged as reliable diagnostic procedure, but data on SSN and how ssRAB compares to other diagnostic interventions such as CT-guided transthoracic biopsy (CTTB) are scarce. In this study, we compared diagnostic yield of ssRAB versus CTTB for evaluating SSN. METHODS: A retrospective study of consecutive patients who underwent either ssRAB or CTTB for evaluating GGN and PSN with a solid component less than 6 mm from February 2020 to April 2023 at Mayo Clinic Florida and Rochester. Clinicodemographic information, nodule characteristics, diagnostic yield, and complications were compared between ssRAB and CTTB. RESULTS: A total of 66 nodules from 65 patients were evaluated: 37 PSN and 29 GGN. Median size of PSN solid component was 5 mm (IQR: 4.5, 6). Patients were divided into two groups: 27 in the ssRAB group and 38 in the CTTB group. Diagnostic yield was 85.7% for ssRAB and 89.5% for CTTB (p = 0.646). Sensitivity for malignancy was similar between ssRAB and CTTB (86.4% vs. 88.5%; p = 0.828), with no statistical difference. Complications were more frequent in CTTB with no significant difference (8 vs. 2; p = 0.135). CONCLUSION: Diagnostic yield for SSN was similarly high for ssRAB and CTTB, with ssRAB presenting less complications and allowing mediastinal staging within the same procedure.

Acute Effects of Ketamine on Intracranial Pressure in Children With Severe Traumatic Brain Injury.

OBJECTIVES: The acute cerebral physiologic effects of ketamine in children have been incompletely described. We assessed the acute effects of ketamine on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in children with severe traumatic brain injury (TBI). DESIGN: In this retrospective observational study, patients received bolus doses of ketamine for sedation or as a treatment for ICP crisis (ICP > 20 mm Hg for > 5 min). Administration times were synchronized with ICP and CPP recordings at 1-minute intervals logged in an automated database within the electronic health record. ICP and CPP were each averaged in epochs following drug administration and compared with baseline values. Age-based CPP thresholds were subtracted from CPP recordings and compared with baseline values. Trends in ICP and CPP over time were assessed using generalized least squares regression. SETTING: A 30-bed tertiary care children's hospital PICU. PATIENTS: Children with severe TBI who underwent ICP monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data from 33 patients, ages 1 month to 16 years, 22 of whom received bolus doses of ketamine, with 127 doses analyzed. Demographics, patient, and injury characteristics were similar between patients who did versus did not receive ketamine boluses. In analysis of the subset of ketamine doses used only for sedation, there was no significant difference in ICP or CPP from baseline. Eighteen ketamine doses were given during ICP crises in 11 patients. ICP decreased following these doses and threshold-subtracted CPP rose. CONCLUSIONS: In this retrospective, exploratory study, ICP did not increase following ketamine administration. In the setting of a guidelines-based protocol, ketamine was associated with a reduction in ICP during ICP crises. If these findings are reproduced in a larger study, ketamine may warrant consideration as a treatment for intracranial hypertension in children with severe TBI.

Utility of Magnetic Resonance Imaging for Localizing Prostate Cancer Near the Urethra in Men Who Are Candidates for Focal Gland Ablation.

PURPOSE: Given that treatment near the urethra is often limited to reduce side effects, in this study we aim to determine whether prostate MRI can accurately identify the distance of prostate cancer to the urethra in a cohort of men who were potential candidates for focal gland ablation. MATERIALS AND METHODS: A single-institution analysis was performed of men who underwent MRI, targeted biopsy, and radical prostatectomy from July 2012 to April 2021. Men who were candidates for focal gland ablation were identified. The ability of MRI to identify prostate cancer within 5 mm of the prostatic urethra as confirmed on whole-mount pathology was assessed. Multivariate regression was utilized to determine characteristics associated with prostate cancer within 5 mm of the urethra on whole-mount pathology. RESULTS: In 48 out of 67 men (72%), the tumor was within 5 mm of the urethra on whole-mount pathology. MRI was concordant with whole-mount pathology in 49 out of 67 men (73%). The sensitivity of MRI for identifying cancer within 5 mm of the urethra was 77% (65%-89%) and the specificity was 63% (42%-89%). The positive predictive value was 84% (range 73%-95%) and negative predictive value was 52% (32%-73%). In adjusted analysis, PSA density and Prostate Imaging-Reporting and Data System were not significantly associated with having prostate cancer within close proximity of the urethra. CONCLUSIONS: A significant number of men who are potential candidates for focal gland ablation have cancer within close proximity to the urethra that could serve as a significant source of in-field recurrence. The sensitivity of MRI for identifying these lesions is 77% and can be used to further improve patient selection for focal gland ablation.

Robotic-assisted bronchoscopy versus CT-guided transthoracic biopsy for diagnosis of pulmonary nodules.

BACKGROUND AND OBJECTIVE: Currently, computed tomography-guided transthoracic biopsy (CTTB) is the most accurate diagnostic approach for pulmonary nodules suspected of malignancy. Traditional bronchoscopy has shown suboptimal diagnostic sensitivity, but the emergence of robotic-assisted bronchoscopy (RAB) has the potential to improve diagnostic accuracy, maximize diagnostic yield and complete mediastinal and hilar staging in a single procedure. We aim to assess the efficacy and diagnostic performance of RAB compared to CTTB for diagnosing pulmonary nodules suspected of lung cancer. METHODS: A multicenter retrospective review of consecutive patients who underwent RAB and CTTB for evaluating pulmonary nodules from January 2019 to March 2021 at Mayo Clinic Florida and Mayo Clinic Rochester, United States. Clinical and demographic information, nodule characteristics, outcomes and complications were compared between RAB and CTTB. RESULTS: A total of 225 patients were included: 113 in the RAB group and 112 in the CTTB group. Overall diagnostic yield was 87.6% for RAB and 88.4% for CTTB. For malignant disease, RAB had a sensitivity of 82.1% and a specificity of 100%, CTTB had a sensitivity of 88.5% and a specificity of 100%. Complication rate was significantly higher for CTTB compared to RAB (17% vs. 4.4%; p = 0.002). CONCLUSION: RAB, when available, can be as accurate as CTTB for sampling pulmonary nodules with similar or reduced complications and should be considered as a means for nodule biopsy, particularly when mediastinal staging is also clinically warranted.

Visualization of retinal breaks on ultra-widefield fundus imaging using a digital green filter.

PURPOSE: We compare the ability of resident physicians to identify retinal breaks on ultra-widefield color fundus photos using the traditional image compared to an image with a green filter overlay. METHODS: Residents were shown fundus photos of 10 eyes with either a retinal tear or hole. Participants were shown each photo twice-once with traditional color settings and once with a green filter overlay. Participants were scored on whether the break was correctly identified and timed on how long it took to identify the pathology. RESULTS: Residents were able to correctly identify more retinal breaks on fundus photos with a green filter overlay compared to photos with traditional settings (P = 0.02). Residents were also able to identify breaks on fundus photos more quickly on images with a green filter overlay compared to the traditional images (P < 0.001). CONCLUSIONS: The application of a green filter overlay may help in identifying retinal breaks.

Acute Mania and Psychosis in the Context of Primary Adrenal Insufficiency: A Systematic Review of the Literature.

BACKGROUND: Given the sparse nature of acute mania or psychosis in primary adrenal insufficiency (PAI), physicians may not be aware of the association of these two entities. OBJECTIVE: To conduct a systematic review of the literature for the purpose of identifying all studies reporting mania and/or psychosis in individuals with PAI. METHOD: We conducted a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the PubMed, Embase, and Web of Science databases from June 22, 1970 to June 22, 2021, for the purpose of identifying all studies reporting instances of mania or psychosis associated with PAI. RESULTS: We identified nine case reports featuring nine patients (M age = 43.3 years, male = 44.4%) over eight countries that fit our inclusion/exclusion criteria. Eight (89%) of the patients had experienced psychosis. Manic and/or psychotic symptom resolution was achieved in 100% of the cases, of which steroid replacement therapy was efficacious in seven (78%) cases and was sufficient in six (67%). CONCLUSION: Acute mania and psychosis in the context of PAI is a very rare presentation of an already uncommon disease. Resolution of acute psychiatric change is reliably achieved with the correction of underlying adrenal insufficiency.

Diagnostic Yield of Shape-Sensing Robotic-Assisted Bronchoscopy for Ground-Glass Nodules and Subsolid Nodules with a Solid Component Less than 6 mm.

BACKGROUND: Ground-glass pulmonary nodules (GGNs) are most commonly sampled by percutaneous transthoracic biopsy. Diagnostic yield for ground-glass nodules using robotic-assisted bronchoscopy has been scarcely described, with a reported yield of 70.6%. OBJECTIVES: The aim of this study is to assess diagnostic yield for GGNs using shape-sensing robotic-assisted bronchoscopy (ssRAB). METHOD: A retrospective study of patients who underwent ssRAB for evaluation of GGNs, from September 2021 to April 2023. Primary outcome was diagnostic yield of ssRAB for GGNs, secondary outcomes were sensitivity for malignancy, and complications that required admission or intervention. RESULTS: A total of 23 nodules were biopsied from 22 patients. Median age was 71 years (IQR 66-81), 63.6% were female, and 40.9% had a previous history of cancer. Forty-three percent of nodules were in the right upper lobes, and the median lesion size was 1.8 × 1.21. Twelve were subsolid nodules (SSNs), and 11 were pure GGNs. Overall diagnostic yield was 87%, with a sensitivity for malignancy of 88.9%. Adenocarcinoma was the most common malignancy diagnosed (70%). No procedure-related complications were reported. CONCLUSION: The use of ssRAB shows a high diagnostic yield for diagnosing GGN and SSN with less than 6 mm solid component with a low risk for complications.

Developing Predictive Models to Anticipate Shunt Complications in 33,248 Pediatric Patients with Shunted Hydrocephalus Utilizing Machine Learning.

INTRODUCTION: Hydrocephalus is a common pediatric neurosurgical pathology, typically treated with a ventricular shunt, yet approximately 30% of patients experience shunt failure within the first year after surgery. As a result, the objective of the present study was to validate a predictive model of pediatric shunt complications with data retrieved from the Healthcare Cost and Utilization Project (HCUP) National Readmissions Database (NRD). METHODS: The HCUP NRD was queried from 2016 to 2017 for pediatric patients undergoing shunt placement using ICD-10 codes. Comorbidities present upon initial admission resulting in shunt placement, Johns Hopkins Adjusted Clinical Groups (JHACG) frailty-defining criteria, and Major Diagnostic Category (MDC) at admission classifications were obtained. The database was divided into training (n = 19,948), validation (n = 6,650), and testing (n = 6,650) datasets. Multivariable analysis was performed to identify significant predictors of shunt complications which were used to develop logistic regression models. Post hoc receiver operating characteristic (ROC) curves were created. RESULTS: A total of 33,248 pediatric patients aged 6.9 ± 5.7 years were included. Number of diagnoses during primary admission (OR: 1.05, 95% CI: 1.04-1.07) and initial neurological admission diagnoses (OR: 3.83, 95% CI: 3.33-4.42) positively correlated with shunt complications. Female sex (OR: 0.87, 95% CI: 0.76-0.99) and elective admissions (OR: 0.62, 95% CI: 0.53-0.72) negatively correlated with shunt complications. ROC curve for the regression model utilizing all significant predictors of readmission demonstrated area under the curve of 0.733, suggesting these factors are possible predictors of shunt complications in pediatric hydrocephalus. CONCLUSION: Efficacious and safe treatment of pediatric hydrocephalus is of paramount importance. Our machine learning algorithm delineated possible variables predictive of shunt complications with good predictive value.

A Retrospective Cohort Study of Implantable Pulse Generator Surgical Site Infections After Deep Brain Stimulation Surgery With an Antibacterial Envelope.

INTRODUCTION: Deep brain stimulation (DBS) surgery is an established treatment for many patients with neurologic disease, and a common complication of DBS is surgical site infection (SSI). In 2016, neurosurgeons at our institution began enclosing implantable pulse generators (IPGs) within fully absorbable, antibacterial envelopes in patients who underwent initial DBS implantation. We sought to determine whether the use of antibacterial envelopes reduced IPG-related SSIs. MATERIALS AND METHODS: We performed a retrospective chart review of all adult patients who underwent initial DBS implantation at Stanford Hospital between November 14, 2012, and November 9, 2020. Operative details, perioperative antibiotics, comorbidities, and postoperative complications were extracted for all patients. Univariate and multivariate logistic regression were used to identify factors associated with SSIs within three months of surgery, and interrupted time-series analysis was performed to assess whether the departmental adoption of the antibacterial envelope led to a reduction in IPG SSIs. RESULTS: Of 344 patients who underwent initial IPG implantation with the antibacterial envelope, one developed an SSI within three months of surgery (0.3%), compared with six of 204 patients (2.9%) who underwent the same procedure without the antibacterial envelope (odds ratio: 0.10, 95% CI: 0.01-0.80, p = 0.031). Univariate logistic regression revealed that the antibacterial envelope and 2000-mg intravenous cefazolin perioperatively were associated with reduced SSI risk, whereas no other factors reached statistical significance. After adjusting for comorbidities, no association remained statistically significant. Interrupted time-series analysis showed a reduction in SSIs after 2016, but the effect was not significant. CONCLUSIONS: The adoption of antibacterial envelopes was found to reduce IPG SSIs at the univariate level, but this association did not remain significant after controlling for confounding variables including perioperative antibiotic administration. Although encouraging, this study does not conclusively establish that the use of antibacterial pouches in patients who underwent initial DBS implantation reduces the incidence of IPG SSIs. Future prospective studies that control for confounding variables are necessary to determine the efficacy of antibacterial envelopes in reducing post-DBS infections at the IPG site before clear recommendations can be made.

Staphylococcus Aureus Swabbing and Decolonization Before Neuromodulation Procedures: A Systematic Review and Meta-Analysis.

INTRODUCTION: Staphylococcus aureus (S aureus) is the foremost bacterial cause of surgical-site infection (SSI) and is a common source of neuromodulation SSI. Endogenous colonization is an independent risk factor for SSI; however, this risk has been shown to diminish with screening and decolonization. MATERIALS AND METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, Cochrane Library, and Embase data bases from inception to January 1, 2022, for the purposes of identifying all studies reporting on the use of S aureus swabbing and/or decolonization before neuromodulation procedures. A random-effects meta-analysis was performed using the metaphor package in R to calculate odds ratios (OR). RESULTS: Five observational cohort studies were included after applying the inclusion and exclusion criteria. The average study duration was 6.6 ± 3.8 years. Three studies included nasal screening as a prerequisite for subsequent decolonization. Type of neuromodulation included spinal cord stimulation in two studies, deep brain stimulation in two studies, intrathecal baclofen in one study, and sacral neuromodulation in one study. Overall, 860 and 1054 patients were included in a control or intervention (ie, screening and/or decolonization) group, respectively. A combination of nasal mupirocin ointment and a body wash, most commonly chlorhexidine gluconate soap, was used to decolonize throughout. Overall infection rates were observed at 59 of 860 (6.86%) and ten of 1054 (0.95%) in the control and intervention groups, respectively. Four studies reported a significant difference. The OR for intervention (screen and/or decolonization) vs no intervention was 0.19 (95% CI, 0.09-0.37; p < 0.001). Heterogeneity between studies was nonsignificant (I2 = 0.43%, τ2 = 0.00). CONCLUSIONS: Preoperative S aureus swabbing and decolonization resulted in significantly decreased odds of infection in neuromodulation procedures. This measure may represent a worthwhile tool to reduce neuromodulation SSI, warranting further investigation.

Investigating Deep Brain Stimulation of the Habenula: A Review of Clinical Studies.

OBJECTIVES: The aim of this study was to examine the current scientific literature on deep brain stimulation (DBS) targeting the habenula for the treatment of neuropsychiatric disorders including schizophrenia, major depressive disorder, and obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: Two authors performed independent data base searches using the PubMed, Cochrane, PsycINFO, and Web of Science search engines. The data bases were searched for the query ("deep brain stimulation" and "habenula"). The inclusion criteria involved screening for human clinical trials written in English and published from 2007 to 2020. From the eligible studies, data were collected on the mean age, sex, number of patients included, and disorder treated. Patient outcomes of each study were summarized. RESULTS: The search yielded six studies, which included 11 patients in the final analysis. Treated conditions included refractory depression, bipolar disorder, OCD, schizophrenia, and major depressive disorder. Patients with bipolar disorder unmedicated for at least two months had smaller habenula volumes than healthy controls. High-frequency stimulation of the lateral habenula attenuated the rise of serotonin in the dorsal raphe nucleus for treating depression. Bilateral habenula DBS and patient OCD symptoms were reduced and maintained at one-year follow up. Low- and high-frequency stimulation DBS can simulate input paths to the lateral habenula to treat addiction, including cocaine addiction. More data are needed to draw conclusions as to the impact of DBS for schizophrenia and obesity. CONCLUSIONS: The habenula is a novel target that could aid in reducing neuropsychiatric symptoms and should be considered in circuit-specific investigation of neuromodulation for psychiatric disorders. More information needs to be gathered and assessed before this treatment is fully approved for treatment of neuropsychiatric conditions.

Immune Deficiency Does Not Increase Inflatable Penile Prosthesis Reoperation Rates.

INTRODUCTION: Immunocompromised patients are postulated to have higher rates of post-operative infection. We sought to determine if inflatable penile prosthesis (IPP) reoperation rates (due to infection, erosion, device malfunction or patient dissatisfaction) are higher among immunocompromised men. METHODS: We analyzed men who underwent initial IPP insertion from 2000 to 2016 in the New York Statewide Planning and Research Cooperative System database. Immunocompromised patients were propensity-score matched in a 1:3 fashion with immunocompetent patients. We estimated and compared reoperation rates (including removal, reoperation due to infection, revision, or replacement of an IPP after an index procedure) at 30 days, 90 days, 1 year and 3 years of follow up between immunocompromised men and controls by performing a Kaplan Meier analysis and Log-rank tests. Cox proportional hazards models were built to examine the overall association between immune deficient status and the risk of reoperation. MAIN OUTCOME MEASURE: Reoperation rate and time to reoperation after index IPP placement. RESULTS: A total of 245 immunocompromised patients who received an initial IPP between 2000 and 2016 were identified. After propensity score matching, we analyzed 235 immunocompromised men and 705 controls. There was no difference in overall reoperation rates between immunocompromised men and controls within any time period assessed (30 days, 90 days, 1 year, or 3 years). In our Cox proportional hazards model, the hazards of overall reoperation, removal, or revision/replacement (HR 1.11 [95% CI 0.74-1.67], HR 1.58 [95% CI 0.90-2.79)], and HR 0.83 [95% CI 0.47-1.45], respectively) were not significant different between immunocompromised men and controls. Reoperation due to infection was also not significantly different between immunocompromised and immunocompetent men (HR 2.06 [95% CI 0.97-4.40]). STRENGTHS & LIMITATIONS: This study is strengthened by its size as the largest cohort of immunocompromised men treated with IPP to date in the literature, but is limited by the retrospective nature of the database which may introduce selection bias and by the low event rate for IPP reoperation. CONCLUSIONS: Reoperation rates, including those due to infection, are not significantly different between immunocompromised men and immunocompetent controls. Therefore, immune status in appropriately selected candidates does not appear to place patients at substantially higher risk of explant or revision. Gaffney CD, Fainberg J, Aboukhshaba A, et al. Immune Deficiency Does Not Increase Inflatable Penile Prosthesis Reoperation Rates. J Sex Med 2021;18:1427-1433.

Distressed Communities Index in Patients Undergoing Transcatheter Aortic Valve Implantation in an Affluent County in New York.

BACKGROUND: The clinical impact of the distressed communities index (DCI), a composite measure of economic well-being based on the U.S. zip code, is becoming increasingly recognized. Ranging from 0 (prosperous) to 100 (distressed), DCI's association with cardiovascular outcomes remains unknown. We aimed to study the association of the DCI with presentation and outcomes in adults with severe symptomatic aortic stenosis (AS) undergoing transcatheter aortic valve intervention (TAVR) in an affluent county in New York. METHODS: The study population included 286 patients with severe symptomatic AS or degeneration of a bioprosthetic valve who underwent TAVR with a newer generation transcatheter heart valve (THV) from December 2015 to June 2018 at an academic tertiary medical center. DCI for each patient was derived from their primary residence zip code. Patients were classified into DCI deciles and then categorized into 4 groups. The primary and secondary outcomes of interest were 30-day, 1-year, and 3-year mortality, respectively. RESULTS: Among 286 patients studied, 26%, 28%, 28%, and 18% were categorized into DCI groups 1-4, respectively (DCI <10: n = 73; DCI 10-20: n = 81; DCI 20-30: n = 80; DCI >30: n = 52). Patients in group 4 were younger with worse kidney function compared to patients in groups 1 and 2. They also had smaller aortic annuli and were more likely to receive a smaller THV. No significant difference in hospital length of stay or distribution of in-hospital, 30-day, 1-year, and 3-year mortality was demonstrated. CONCLUSIONS: While the DCI was associated with differences in the clinical and anatomic profile, it was not associated with differences in clinical outcomes in this prospective observational study of adults undergoing TAVR suggesting that access to care is the likely discriminator.

Management of Significant Airway Bleeding during Robotic Assisted Bronchoscopy: A Tailored Approach.

Robotic assisted bronchoscopy represents a major turning point in bronchoscopic history. The management strategies to address significant airway bleeding in this "robotic era" are not well documented, and further guidance is required. We present a case report that exemplifies our approach and management strategy using a combined and simultaneous flexible/robotic bronchoscopy if this complication is encountered.

Interventional Bronchoscopy.

For over 150 years, bronchoscopy, especially flexible bronchoscopy, has been a mainstay for airway inspection, the diagnosis of airway lesions, therapeutic aspiration of airway secretions, and transbronchial biopsy to diagnose parenchymal lung disorders. Its utility for the diagnosis of peripheral pulmonary nodules and therapeutic treatments besides aspiration of airway secretions, however, has been limited. Challenges to the wider use of flexible bronchoscopy have included difficulty in navigating to the lung periphery, the avoidance of vasculature structures when performing diagnostic biopsies, and the ability to biopsy a lesion under direct visualization. The last 10-15 years have seen major advances in thoracic imaging, navigational platforms to direct the bronchoscopist to lung lesions, and the ability to visualize lesions during biopsy. Moreover, multiple new techniques have either become recently available or are currently being investigated to treat a broad range of airway and lung parenchymal diseases, such as asthma, emphysema, and chronic bronchitis, or to alleviate recurrent exacerbations. New bronchoscopic therapies are also being investigated to not only diagnose, but possibly treat, malignant peripheral lung nodules. As a result, flexible bronchoscopy is now able to provide a new and expanding armamentarium of diagnostic and therapeutic tools to treat patients with a variety of lung diseases. This State-of-the-Art review succinctly reviews these techniques and provides clinicians an organized approach to their role in the diagnosis and treatment of a range of lung diseases.

Intrathecal baclofen, selective dorsal rhizotomy, and extracorporeal shockwave therapy for the treatment of spasticity in cerebral palsy: a systematic review.

Cerebral palsy (CP) is a chronic congenital disorder as the result of abnormal brain development. Children suffering from CP often battle debilitating chronic spasticity, which has been the focus of recent academic literature. In this systematic review, the authors aim to update the current neuromodulation procedures for the treatment of spasticity associated with CP in all age groups. A systematic review following was conducted using PubMed from inception to 2020. After initial title and abstract screening, 489 articles were identified, and 48 studies met the inclusion criteria for this review. In total, a majority of the published articles of treatments for CP were reporting the use of selective dorsal rhizotomy (SDR) (54%), and the remainder were of intrathecal baclofen (ITB) pumps (29%) and extracorporeal shockwave therapy (ESWT) (17%). Each method was found to have improvement of spasticity at a rate that achieved statistical significance. ITB pump therapy is an all-encompassing method of treating spasticity in children from CP, as it allows for a less invasive treatment that can be titrated to individual patient needs; however, its disadvantages include its long-term maintenance requirements. SDR appears to be an effective method for permanent spasticity relief in young patients. ESWT is a more recent and innovative technique for offering relief of spasticity while being minimally invasiveness. Further studies are needed to establish optimal frequencies and sites of application for ESWT.

Association between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Lung Cancer.

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed antihypertensives, with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated this potential association in a large population using propensity matching. METHODS: This was a population-based cohort study in a large healthcare system in three regions of the United States. Pairwise propensity score matching was performed using demographics and comorbidities. All of the adult patients in the healthcare system from January 1, 2000 to April 30, 2018 with at least 1 year of follow-up were included. RESULTS: In total, 3,253,811 patients with a median age of 59 (range 18-103) years were included. The ACEI group had a higher freedom from lung cancer versus controls at 15 years (98.47%, 95% confidence interval [CI] 98.41-98.54) versus 98.26%, (95% CI 98.20-98.33), whereas ARBs had similar rates versus controls at all time points. For patients diagnosed as having lung cancer, median all-cause survival was significantly higher in the ACEI (34.7 months, 95% CI 32.8-36.6) and ARB (30.9 months, 95% CI 28.1-33.8) groups than the control group (20.6 months, 95% CI 20.1-21.1). CONCLUSIONS: This study showed lower rates of lung cancer with ACEI use and no difference in risk with ARBs. In addition, use of these medications was found to be associated with increased survival in those diagnosed as having lung cancer. This study supports the continued use of these medications without concern for increasing the risk of lung cancer.

A multi-state model of the CaMKII dodecamer suggests a role for calmodulin in maintenance of autophosphorylation.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) accounts for up to 2 percent of all brain protein and is essential to memory function. CaMKII activity is known to regulate dynamic shifts in the size and signaling strength of neuronal connections, a process known as synaptic plasticity. Increasingly, computational models are used to explore synaptic plasticity and the mechanisms regulating CaMKII activity. Conventional modeling approaches may exclude biophysical detail due to the impractical number of state combinations that arise when explicitly monitoring the conformational changes, ligand binding, and phosphorylation events that occur on each of the CaMKII holoenzyme's subunits. To manage the combinatorial explosion without necessitating bias or loss in biological accuracy, we use a specialized syntax in the software MCell to create a rule-based model of a twelve-subunit CaMKII holoenzyme. Here we validate the rule-based model against previous experimental measures of CaMKII activity and investigate molecular mechanisms of CaMKII regulation. Specifically, we explore how Ca2+/CaM-binding may both stabilize CaMKII subunit activation and regulate maintenance of CaMKII autophosphorylation. Noting that Ca2+/CaM and protein phosphatases bind CaMKII at nearby or overlapping sites, we compare model scenarios in which Ca2+/CaM and protein phosphatase do or do not structurally exclude each other's binding to CaMKII. Our results suggest a functional mechanism for the so-called "CaM trapping" phenomenon, wherein Ca2+/CaM may structurally exclude phosphatase binding and thereby prolong CaMKII autophosphorylation. We conclude that structural protection of autophosphorylated CaMKII by Ca2+/CaM may be an important mechanism for regulation of synaptic plasticity.