Mucus clears from the trachea in a helix: a new twist to understanding airway diseases.

BACKGROUND: Mucociliary clearance (MCC) is critical to lung health and is impaired in many diseases. The path of MCC may have an important impact on clearance but has never been rigorously studied. The objective of this study is to assess the three-dimensional path of human tracheal MCC in disease and health. METHODS: Tracheal MCC was imaged in 12 ex-smokers, 3 non-smokers (1 opportunistically imaged during acute influenza and repeated after recovery) and 5 individuals with primary ciliary dyskinesia (PCD). Radiolabelled macroaggregated albumin droplets were injected into the trachea via the cricothyroid membrane. Droplet movement was tracked via scintigraphy, the path of movement mapped and helical and axial models of tracheal MCC were compared. MEASUREMENTS AND MAIN RESULTS: In 5/5 participants with PCD and 1 healthy participant with acute influenza, radiolabelled albumin coated the trachea and did not move. In all others (15/15), mucus coalesced into globules. Globule movement was negligible in 3 ex-smokers, but in all others (12/15) ascended the trachea in a helical path. Median cephalad tracheal MCC was 2.7 mm/min ex-smokers vs 8.4 mm/min non-smokers (p=0.02) and correlated strongly to helical angle (r=0.92 (p=0.00002); median 18o ex-smokers, 47o non-smokers (p=0.036)), but not to actual speed on helical path (r=0.26 (p=0.46); median 13.6 mm/min ex-smokers vs 13.9 mm/min non-smokers (p=1.0)). CONCLUSION: For the first time, we show that human tracheal MCC is helical, and impairment in ex-smokers is often caused by flattened helical transit, not slower movement. Our methodology provides a simple method to map tracheal MCC and speed in vivo.

Reflux scintigraphy in gastro-esophageal reflux disease: a comparison study with 24 hour pH-impedance monitoring.

OBJECTIVE: Reflux scintigraphy is often used to diagnose gastro-esophageal reflux disease (GERD). However, the efficacy of this study remains controversial. Our aim was to determine the role of reflux scintigraphy in diagnosing GERD by comparing it to 24 h combined pH-impedance study as the gold standard. MATERIALS AND METHODS: Adult patients who presented for investigations of reflux symptoms were prospectively recruited into the study. All patients underwent high resolution esophageal manometry and those with major motor disorders of the esophagus were excluded. Eligible patients immediately underwent reflux scintigraphy following insertion of the pH-impedance catheter. RESULTS: Thirty patients were included in the study. Using a total acid exposure time (AET) of >4.2% as the reference for abnormal acid reflux, reflux scintigraphy had a sensitivity and specificity of 62.5 and 68.2%, respectively, in detecting acid reflux. When compared to AET >6%, reflux scintigraphy had a sensitivity and specificity of 66.7 and 62.5%, respectively, and a positive predictive value of 30.8% and a negative predictive value of 88.2%. There were no associations between outcomes of reflux scintigraphy and total AET (p = .46), total (acid or non-acid) reflux events (p = 0.11), proximal AET (p = .33) or the number of proximal reflux episodes (p = .75) on 24 h pH-impedance study. CONCLUSIONS: Reflux scintigraphy has limited role in diagnosing GERD when compared to 24 h combined pH-impedance monitoring.

Assessing the Risks Associated with MRI in Patients with a Pacemaker or Defibrillator.

BACKGROUND: The presence of a cardiovascular implantable electronic device has long been a contraindication for the performance of magnetic resonance imaging (MRI). We established a prospective registry to determine the risks associated with MRI at a magnetic field strength of 1.5 tesla for patients who had a pacemaker or implantable cardioverter-defibrillator (ICD) that was "non-MRI-conditional" (i.e., not approved by the Food and Drug Administration for MRI scanning). METHODS: Patients in the registry were referred for clinically indicated nonthoracic MRI at a field strength of 1.5 tesla. Devices were interrogated before and after MRI with the use of a standardized protocol and were appropriately reprogrammed before the scanning. The primary end points were death, generator or lead failure, induced arrhythmia, loss of capture, or electrical reset during the scanning. The secondary end points were changes in device settings. RESULTS: MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD. No deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI. We observed six cases of self-terminating atrial fibrillation or flutter and six cases of partial electrical reset. Changes in lead impedance, pacing threshold, battery voltage, and P-wave and R-wave amplitude exceeded prespecified thresholds in a small number of cases. Repeat MRI was not associated with an increase in adverse events. CONCLUSIONS: In this study, device or lead failure did not occur in any patient with a non-MRI-conditional pacemaker or ICD who underwent clinically indicated nonthoracic MRI at 1.5 tesla, was appropriately screened, and had the device reprogrammed in accordance with the prespecified protocol. (Funded by St. Jude Medical and others; MagnaSafe ClinicalTrials.gov number, NCT00907361 .).

In vivo administration of a JAK3 inhibitor during acute SIV infection leads to significant increases in viral load during chronic infection.

The studies reported herein are the first to document the effect of the in vivo administration of a JAK3 inhibitor for defining the potential role of NK cells during acute SIV infection of a group of 15 rhesus macaques (RM). An additional group of 16 MHC/KIR typed RM was included as controls. The previously optimized in vivo dose regimen (20 mg/kg daily for 35 days) led to a marked depletion of each of the major NK cell subsets both in the blood and gastro-intestinal tissues (GIT) during acute infection. While such depletion had no detectable effects on plasma viral loads during acute infection, there was a significant sustained increase in plasma viral loads during chronic infection. While the potential mechanisms that lead to such increased plasma viral loads during chronic infection remain unclear, several correlates were documented. Thus, during acute infection, the administration of the JAK3 inhibitor besides depleting all NK cell subsets also decreased some CD8⁺ T cells and inhibited the mobilization of the plasmacytoid dendritic cells in the blood and their localization to the GIT. Of interest is the finding that the administration of the JAK3 inhibitor during acute infection also resulted in the sustained maintenance during chronic infection of a high number of naïve and central memory CD4⁺ T cells, increases in B cells in the blood, but decreases in the frequencies and function of NKG2a⁺ NK cells within the GIT and blood, respectively. These data identify a unique role for JAK3 inhibitor sensitive cells, that includes NK cells during acute infection that in concert lead to high viral loads in SIV infected RM during chronic infection without affecting detectable changes in antiviral humoral/cellular responses. Identifying the precise mechanisms by which JAK3 sensitive cells exert their influence is critical with important implications for vaccine design against lentiviruses.

False positive metastatic disease due to combined thoracic and subcutaneous splenosis.

A 56-year-old man presented with dyspnea secondary to pulmonary emboli and dilated cardiomyopathy. His past medical history included a history of emergency laparotomy, splenectomy, and splenic flexure resection following a gunshot injury 30 years ago. CT and MRI imaging demonstrated multiple homogeneously enhancing lobulated lesions at the left-sided pleura and chest wall with an irregular calcified spleen. The aforementioned lesions demonstrated a similar level of tracer uptake to the splenic activity with no evidence of other FDG avid malignancy on the follow-up 18F-FDG PET study. All the above-mentioned pleural and chest wall lesions demonstrated intense tracer accumulation on technetium-99m labeled heat-damaged red cell scintigraphy, consistent with combined thoracic and subcutaneous splenosis.

Determining the risks of clinically indicated nonthoracic magnetic resonance imaging at 1.5 T for patients with pacemakers and implantable cardioverter-defibrillators: rationale and design of the MagnaSafe Registry.

BACKGROUND: Until recently, the presence of a permanent pacemaker or an implantable cardioverter-defibrillator has been a relative contraindication for the performance of magnetic resonance imaging (MRI). A number of small studies have shown that MRI can be performed with minimal risk when patients are properly monitored and device programming is modified appropriately for the procedure. However, the risk of performing MRI for patients with implanted cardiac devices has not been sufficiently evaluated to advocate routine clinical use. The aim of the present protocol is to prospectively determine the rate of adverse clinical events and device parameter changes in patients with implanted non-MRI-conditional cardiac devices undergoing clinically indicated nonthoracic MRI at 1.5 T. METHODS: The MagnaSafe Registry is a multicenter, prospective cohort study of up to 1500 MRI examinations in patients with pacemakers or implantable cardioverter-defibrillators implanted after 2001 who undergo clinically indicated nonthoracic MRI following a specific protocol to ensure that preventable potential adverse events are mitigated. Adverse events and changes in device parameter measurements that may be associated with the imaging procedure will be documented. RESULTS: Through August 2012, 701 MRI studies have been performed, representing 47% of the total target enrollment. CONCLUSIONS: The results of this registry will provide additional documentation of the risk of MRI and will further validate a clinical protocol for screening and the performance of clinically indicated MRI for patients with implanted cardiac devices.

Comparative assessment of rest and post-stress left ventricular volumes and left ventricular ejection fraction on gated myocardial perfusion imaging (MPI) and echocardiography in patients with transient ischaemic dilation on adenosine MPI: myocardial stunning or subendocardial hypoperfusion?

BACKGROUND: Transient ischaemic dilation (TID) on myocardial perfusion imaging (MPI) is an important finding, conveying a high risk of subsequent cardiac events. However, the mechanism leading to TID on MPI is not well elucidated. This study aimed to determine if TID is due to true LV cavity dilation and ventricular stunning, or is due to relative subendocardial hypoperfusion. METHODS: 31 patients undergoing single-day Tc-99m adenosine sestamibi MPI were recruited. All had routine ECG-gated single-day rest-stress adenosine MPI, with transthoracic echocardiograms (echo) acquired concurrently at rest, and both immediately, and 2 hours, post-stress. Echocardiography was performed using a Vivid-7 (GE). LV volumes and LVEF were quantified blinded to MPI results, using biplane Simpson method on echo, and quantitatively (including TID) with QGS(®), on MPI. RESULTS: Patients were divided into quartiles for TID, with the top quartile considered TID positive [TID+ 9/31 (TID ratio 1.3 ± 0.09)], and TID negative [TID- 22/31 (TID ratio 1.01 ± 0.04)]. There was good correlation between resting echo and MPI physical measurements (LVEDV r(2) = 0.79, LVESV r(2) = 0.9, and LVEF r(2) = 0.75). On MPI, a significant drop in LVEF was observed between rest and early stress in the TID+ group (56.6% vs 46.5%, P < .002), as well as an increase in both LVESV (62 vs 79 mls, P < .0001) and LVEDV (113 vs 131 mls, P < .0001). However, no statistically significant change in LVEF, LVESV or LVEDV was identified on concurrent echo imaging (LVEF 57% vs 56%, P < .66; LVESV 48 vs 54 mls, P < .26; LVEDV 87 vs 97 mls, P < .299). No significant change in LVEF or ventricular volumes was noted in the TID- group by either echo or MPI. CONCLUSION: Transient dilation of the left ventricle on adenosine MPI is not related to chamber enlargement and myocardial stunning, but is more likely a function of subendocardial hypoperfusion and impaired coronary flow reserve.

Accessory Thyroid Tissue Detected Using 131 I SPECT/CT Imaging.

ABSTRACT: Thyroid ectopia has been described as a rare congenital anomaly, characterized by the presence of a thyroid gland in locations other than the orthotopic pretracheal location. The prevalence of accessory thyroid tissue in patients undergoing postablative radioiodine therapy in a 12-month period at a tertiary hospital nuclear medicine department was assessed. Fifty-seven patients were treated between September 2020 and September 2021. Retrospective analysis identified the presence and location of all accessory thyroid tissue separate from the orthotopic pretracheal thyroid gland. Accessory thyroid tissue was present in 21.1% (12/57) of the patients. Accessory thyroid tissue was most commonly located in the lingual region.

Dissecting Mycotic RCA Aneurysm Detected on 67Ga Scintigraphy.

ABSTRACT: A 61-year-old man presented with pneumonia and myocardial infarction on a background of diabetes and end-stage renal failure. Methicillin-resistant Staphylococcus aureus bacteremia was confirmed in the setting of ongoing pyrexia. The patient was referred for a 67Ga study, which revealed Ga-avid active disease in the pericardial effusion. This was localized further on CT/MRI and coronary angiography to a dissecting right coronary artery aneurysm, which was treated with surgical repair and long-term antibiotic treatment.

131I Ablation of an Entire Thyroid Gland in Locally Invasive Differentiated Thyroid Cancer Without Surgery.

ABSTRACT: A 79-year-old man with locally metastatic papillary thyroid cancer to left-sided cervical lymph nodes was referred for radioiodine therapy. He was considered unfit for thyroidectomy due to extensive local involvement and severe interstitial lung disease requiring continuous oxygen. The patient was treated with low doses of radioiodine (approximately 30 mCi) every 6 months with corticosteroid cover for 3 years with good effect. Sequential 131I scanning and serum thyroglobulin levels confirmed virtual complete ablation of the thyroid gland. The patient remained well on thyroid hormone replacement.

A novel technique for ultra-low contrast administration during angiography or intervention.

Contrast-induced nephropathy (CIN) after coronary angiography or intervention is associated with substantial morbidity. The data supporting various prophylactic measures and adjunctive therapies to prevent this complication are conflicting. However, contrast volume is clearly related to CIN after percutaneous coronary intervention (PCI), and the risk of CIN has been shown to be directly related to contrast dose. Therefore, minimizing contrast exposure is a primary method to reduce the risk of CIN, especially in at-risk patients. We report a novel technique designed to deliver ultra-low (<15 cm(3)) volume contrast to patients with chronic kidney disease undergoing coronary angiography and PCI.

Biopsy diagnosis of early myositis ossificans without radiologic evidence of calcification: success of early surgical resection.

Myositis ossificans is an uncommon disorder, which is commonly mistaken for a malignant muscle disease before histologic examination. Trauma is the most common cause of the acquired form of the disease; however, atraumatic cases have been described. The factors responsible for extraosseous ossification, such as the role of bone morphogenic protein 4, are becoming better understood. However, treatment of the disorder is not well defined. We present a case of atraumatic myositis ossificans in a 16-year-old girl that was associated with severe pain and lacked radiologic evidence of calcification. She underwent early surgical excision, resulting in immediate resolution of her symptoms. This case demonstrates that waiting for complete maturation of the lesion may not be necessary.