Novel insights into the composition and function of the Toxoplasma IMC sutures.

The Toxoplasma inner membrane complex (IMC) is a specialized organelle underlying the parasite's plasma membrane that consists of flattened rectangular membrane sacs that are sutured together and positioned atop a supportive cytoskeleton. We have previously identified a novel class of proteins localizing to the transverse and longitudinal sutures of the IMC, which we named IMC sutures components (ISCs). Here, we have used proximity-dependent biotin identification at the sutures to better define the composition of this IMC subcompartment. Using ISC4 as bait, we demonstrate biotin-dependent labeling of the sutures and have uncovered two new ISCs. We also identified five new proteins that exclusively localize to the transverse sutures that we named transverse sutures components (TSCs), demonstrating that components of the IMC sutures consist of two groups: those that localize to the transverse and longitudinal sutures (ISCs) and those residing only in the transverse sutures (TSCs). In addition, we functionally analyze the ISC protein ISC3 and demonstrate that ISC3-null parasites have morphological defects and reduced fitness in vitro. Most importantly, Δisc3 parasites exhibit a complete loss of virulence in vivo. These studies expand the known composition of the IMC sutures and highlight the contribution of ISCs to the ability of the parasite to proliferate and cause disease.

Association of Atrial Fibrillation and/or Flutter With Adverse Cardiac Outcomes and Mortality in Patients With Wolff-Parkinson-White Syndrome.

Background: Wolff-Parkinson-White (WPW) syndrome is characterized by the presence of accessory pathways and development of potentially malignant arrhythmias that can lead to sudden cardiac death. We aimed to determine the impact of atrial fibrillation and/or flutter (AF/AFL) on adverse cardiac outcomes and mortality in patients with WPW syndrome. Methods: This study identified a cohort of Military Health System patients with WPW syndrome from January 1, 2014, to December 31, 2019. The cohort was divided into 2 subgroups by the presence or absence of AF/AFL. Cardiac composite outcome and mortality were assessed. Kaplan-Meier curves were constructed to assess the bivariate association between exposure and these 2 study outcomes. Cox proportional models were used to estimate the hazard ratios and 95% CIs associated with the cardiac composite outcome and mortality. Results: Of 35,539 patients included in the study, 19,961 were female (56.2%), the mean (SD) age was 62.9 (18.0) years, and 5291 patients (14.9%) had AF/AFL. The cardiac composite outcome and mortality incidence rates per 100 person-years in the AF/AFL vs non-AF/AFL subgroups were 8.18 vs 4.90, and 4.09 vs 2.13, respectively (P < .001). There were 3130 (8.8%) deaths. After adjusting for confounding variables, the AF/AFL subgroup maintained a 12% and 16% higher association with the composite outcome and mortality, respectively. Conclusions: Patients with WPW syndrome and AF/AFL have a higher association with adverse cardiac outcomes and death. Consideration for more aggressive electrophysiology screening and ablation strategies may be warranted in this population.

Myopericarditis and pericarditis in the deployed military member: a retrospective series.

In this study, we investigated the incidence and etiology of pericarditis and myopericarditis of military members deployed to Iraq and Kuwait from 2004 through 2008. The importance of acute pericarditis and myopericarditis in the deployed military service member has resurfaced with the reintroduction of the smallpox vaccination by the U.S. Department of Defense in 2002. There are limited epidemiologic data on acute pericarditis and myopericarditis in the general population. As a primary evacuation node for cardiology patients between 2004 and 2008, the United States Military Hospital Kuwait cardiology clinic was uniquely situated to reliably extrapolate epidemiologic data for U.S. Armed Service Members serving in the Middle East. Between these years, approximately 721,600 service members served in Kuwait and Iraq. A total of 70 cases of pericarditis and 9 cases of myopericarditis were diagnosed. This yields an estimated incidence of 7.4 and 0.95 cases per 100,000 per year for pericarditis and myopericarditis, respectively. A total of eleven patients had received the smallpox vaccine 4 to 30 days before being diagnosed with pericarditis or myopericarditis. Four of the eleven patients (36.3%) had pericarditis, with a mean duration of 28.3 days since vaccination. Seven of these eleven (63.6%) patients had myopericarditis, with a mean duration of 13.7 days since smallpox vaccination. The incidence of pericarditis and myopericarditis was lower than previously reported incidence rates in the population. In all cases of myopericarditis and pericarditis, smallpox vaccination was preferentially related to myopericarditis versus pericarditis.

Management Consideration for Anterior Mediastinal Mass in a Patient With Grave's Disease.

A 36-year-old active duty female presented to an outside hospital emergency department for the evaluation of chest pain and weakness. Per report, comprehensive evaluation ruled out acute cardiopulmonary conditions. A computerized tomography scan revealed a large homogeneous anterior mediastinal mass. The patient was referred to a cardiothoracic surgeon who discussed treatment options, including surgery. She was subsequently referred to an interventional radiologist, who performed a biopsy. Findings were consistent with thymic hyperplasia without evidence of malignant cells. Follow-up with her primary care physician revealed an undetectable thyroid-stimulating hormone (TSH) level, and she was subsequently diagnosed with Graves' disease (GD). The primary care physician referred her to an endocrinologist who initiated treatment with methimazole. The patient's GD responded well to medication therapy; the thymic mass size decreased and her exercise tolerance increased. Notably, testing for TSH levels upon initial presentation could have avoided the need for biopsy.

Reporting Coronary Artery Calcium on Low-Dose Computed Tomography Impacts Statin Management in a Lung Cancer Screening Population.

Background: Cigarette smoking is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Concomitant use of low-dose computed tomography (LDCT) for coronary artery calcium (CAC) scoring with lung cancer screening (LCS) has been proposed to further determine ASCVD risk and mortality. We aimed to determine the validity of LDCT in identifying CAC and its impact on statin management. Methods: We conducted a retrospective review from November 2020 to May 2021 of Military Health System (MHS) beneficiaries who received LCS with LDCT and were referred for CAC scoring with electrocardiogram-gated CT. Of the 190 participants initially identified, 170 met study eligibility. The Agatston method was used to score CAC on both scan types. Results: Participants had a mean (SD) age of 62.1 (4.6) years and were 70.6% male. CAC was seen more on ECG-gated CT compared with LDCT (88% vs 74%, P < .001). The Spearman correlation and Kendall W coefficient of concordance of CAC scores between the 2 scan types was 0.945 (P < .001) and 0.643, respectively. The κ statistic between CAC scores on the 2 different scans was 0.49 (SEκ = 0.048; 95% CI, -0.726-1.706), and the weighted κ statistic was 0.711. Bland-Altman analysis demonstrated a mean bias of 111.45 Agatston units, with limits of agreement between -268.64 and 491.54, suggesting CAC scores on electrocardiogram-gated CT were on average about 111 units higher than those on LDCT. There was a statistically significant proportion of nonstatin participants who met statin criteria based on additional CAC reporting (P < .001). Conclusions: CAC scores are highly correlated and concordant between LDCT and electrocardiogram-gated CT. Smokers undergoing annual LDCT may benefit from concomitant CAC scoring to help stratify ASCVD risk.

An overview of Afghan National Army critical care capabilities.

BACKGROUND: The North Atlantic Treaty Organization created the International Security Assistance Force to help support the growth in capacity and capability of Afghan National Army (ANA). OBJECTIVE: This article describes the current critical care capabilities of the ANA, which was supported by embedded medical mentors to help build up Afghanistan's medical infrastructure after the fall of the Taliban. DESIGN: We reviewed the experiences of deployed medical mentors in ANA hospitals to report the progress and limitations of the North Atlantic Treaty Organization medical mentoring mission. RESULTS: From October 2008 through November 2009, the continued development of ANA Intensive Care Unit capabilities has decreased mortality from 26.3% to 5.1% despite an increase in admissions from 19 to 78 per month. CONCLUSIONS: Significant progress was made in the critical care capabilities of the ANA critical care physicians. The medical mentoring mission is an effective weapon in building the health care capacity of the ANA medical system.

Prolonged Stabilization During a Mass Casualty Incident at Sea in the Era of Distributed Maritime Operations.

In August 2017, the USS Bataan received a mass casualty incident (MCI) of 6 foreign special forces operators after a helicopter crash. All 6 patients were medically evacuated successfully to the USS Bataan, and all patients survived and were successfully returned to their allied country. Four of the patients received whole blood with 2 receiving over 10 units of blood or massive transfusions. One patient required 44 units of blood, and at 1 point in his resuscitation, he received 12 units of whole blood every 30 minutes. Due to administrative factors outside of the ship's control, these 6 patients had prolonged stabilization during the MCI. This factor differentiates this MCI on the USS Bataan from previous cases. Internal medicine trained physicians with their expertise in inpatient care, postsurgical management, and critical care were instrumental in sustaining these casualties in this prolonged stabilization environment. In the era of distributed maritime operations, where casualty-receiving ships will experience more geographic and resource isolation, there is a potential for the need for prolonged stabilization above the 6 to 12-hour window typical of role II platforms. The known increase in cardiac and pulmonary morbidity and mortality with medical evacuation delay highlights the importance of internal medicine physicians in the role II setting. It is critical that we emphasize the inpatient and critical care principles of these patients in the prolonged field care environment.

Postpartum dyspnea in a breast cancer survivor.

: Breast cancer is the most common cancer among women and the second leading cause of cancer death in the world. As treatments advance and survival increases among breast cancer survivors, we will continue to see more obstetric patients exposed to anthracycline drugs. Anthracycline toxicity risk is dose dependent, and any exposure to anthracyclines places obstetric patients at risk to cardiotoxicity. In this case report, we explore the potential chemotherapy toxicities of anthracycline exposure.

Limited Use of Outpatient Stress Testing in Young Patients With Atypical Chest Pain.

Low prevalence of coronary artery disease within this population suggests that younger patients may not require stress testing for chest pain evaluations as long as pretest likelihood is low.

Red tides: Mass casualty and whole blood at sea.

BACKGROUND: The U.S. Navy's casualty-receiving ships provide remote damage control resuscitation platforms to treat injured combatants deployed afloat and ashore. We report a significant mass casualty incident aboard the USS Bataan, and the most warm fresh whole blood (WFWB) transfused at sea for traumatic hemorrhagic shock since the Vietnam War. METHODS: Casualty-receiving ships have robust medical capabilities, including a frozen blood bank with packed red blood cells (pRBC) and fresh frozen plasma (FFP). The blood supply can be augmented with WFWB collected from a "walking blood bank." RESULTS: Following a helicopter crash, six patients were transported by MV-22 Osprey to the USS Bataan. Patient 1 had a pelvic fracture, was managed with a pelvic binder, and received 4 units of pRBC, 2 units of FFP, and 6 units of WFWB. Patient 2, with a comminuted tibia and fibula fracture, underwent lower extremity four-compartment fasciotomy, and received 4 units of WFWB. Patient 3 underwent several procedures, including left anterior thoracotomy, aortic cross-clamping, exploratory laparotomy, small bowel resection, and tracheostomy. He received 8 units of pRBC, 8 units of FFP, and 28 units of WFWB. Patients 4 and 5 had suspected spine injuries and were managed nonoperatively. Patient 6, with open tibia and fibula fractures, underwent lower extremity four-compartment fasciotomy with tibia external fixation and received 1 unit of WFWB. All patients survived aeromedical evacuation to a role 4 medical facility and subsequent transfer to local hospitals. CONCLUSION: Maritime military mass casualty incidents are challenging, but the U.S. Navy's casualty-receiving ships are ready to perform remote damage control resuscitation at sea. Activation of the ship's walking blood bank to transfuse WFWB is essential for hemostatic resuscitations afloat. LEVEL OF EVIDENCE: Study type: case series, level V.

Rates of symptom reoccurrence after endovascular therapy in subclavian artery stenosis and prevalence of subclavian artery stenosis prior to coronary artery bypass grafting.

Percutaneous transluminal angioplasty (PTA) and stenting is commonly used to treat subclavian artery stenosis (SAS). In this study, the outcomes of 43 consecutive cases, performed at one institution from October 1997 to October 2005, were analyzed. Mean stenosis was 84.41% pre-intervention and 6.83% post-intervention. Five of the procedures were angioplasty alone; 38 were angioplasty with stenting. Technical success was achieved in 42 out of 43 patients. The 30-day mortality rate was 0%. At one-month post intervention, all patients were symptom free. Ten patients redeveloped symptoms by one year. Demographic data, patient comorbidities, and indication to treat were analyzed. It was found that prior coronary intervention led to a statistically significant higher rate of symptom reoccurrence (p = 0.036). Additionally, a divergence in the rate of symptom reoccurrence based on indication to treat SAS was noted with the highest rate of symptom reoccurrence in the pre-coronary artery bypass grafting (CABG) group and the lowest rate of symptom reoccurrence in the subclavian steal syndrome (SSS) group. The coronary subclavian steal (CSS) group had an intermediate rate of symptom reoccurrence. During this time period, 1154 CABGs were performed. Flow-limiting stenosis was noted on angiography in 17 of these patients, giving pre-CABG prevalence of 1.46%.

Repeat Hospitalizations Predict Mortality in Patients With Heart Failure.

INTRODUCTION: Heart failure (HF) affects more than 5.1 million Americans and is projected to increase. Understanding the relationship between hospitalization and mortality can help to guide clinical management. The aim of the study is to evaluate the impact of repeat HF hospitalizations on all-cause mortality and to determine risk variables related to patient mortality. MATERIALS AND METHODS: Using administrative data from the Military Health System, a cohort of patients with an index admission for HF between 2007 and 2011 was identified. HF hospitalizations were defined as any hospital claim with an International Classification of Diseases, Ninth Revision diagnosis of 428.xx in the primary diagnosis field over the 7-year study period (2007-2013). Patients were subsequently categorized based on total number of HF hospitalizations. A multivariate Cox regression model, adjusting for age, sex, and comorbidities, was used to estimate hazard ratios. Kaplan-Meier survival curves were constructed based on the frequency of HF hospitalizations. RESULTS: Of the 51,286 patients admitted for HF, 54.7% were male with a mean (SD) age of 76.3 (10.8) years, and 29,714 died during 135,211 person-years of follow-up. Mean survival time was 2.6, 1.8, 1.5, and 1.3 years after the first, second, third, and fourth hospitalization, respectively. The mortality rate of patients at 30 days and 1 year postindex HF hospitalization was 7.4% and 27.3%, respectively. A history of dementia and chronic kidney disease without dialysis decreased overall survival. CONCLUSIONS: Repeat HF hospitalizations remain a strong predictor of mortality for existing patients with HF. As a result, clinicians and patients can individualize the optimal treatment strategy and resources on the basis of the suspected prognosis.

Return on Investment Analysis of Health Experts onLine at Portsmouth: A 2-Year Review of the Navy's Newest Teleconsultation System.

BACKGROUND: Health Experts onLine at Portsmouth (HELP) is a web-based teleconsultation system launched in June 2014 to facilitate communication between specialists at Naval Medical Center Portsmouth and providers assigned to both the fleet forces and primary care clinics across the eastern United States, Europe, and the Middle East. Specialist consultations through the HELP system purport to improve access to care for patients who otherwise might be referred to the civilian network or medically evacuated (MEDEVACed) to Naval Medical Center Portsmouth for specialized care. If HELP-facilitated communications help avoid civilian referrals or MEDEVACs, the associated costs of that care should be reduced. METHODS: We evaluated cost savings associated with prevented MEDEVACs by analyzing both tangible savings (prevented costs of flights, per diems, and consults) and intangible savings (reduced lost productivity time). We compared these savings to the costs of maintaining and utilizing the HELP system: startup costs, administrative costs, and provider time costs. We used patient and provider data from the HELP database to evaluate clinical consult cases. Before this analysis, a panel of 3 physicians associated with HELP reviewed each consult to determine whether a case qualified as a prevented MEDEVAC. Data from the Military Health System (MHS) Management and Analysis Reporting Tool and the MHS Data Repository were used to estimate costs associated with provider time, patient time, and direct care medical encounters. FINDINGS: The HELP program delivered measurable, positive returns on investment (ROIs) between June 2014 and December 2015. In that time frame, 559 consult cases occurred in the HELP system. Of the 559 total consult cases, 50 consults prevented MEDEVACs. Incorporating only tangible savings, HELP produced an 80% ROI on the basis of prevented medical evacuations; the addition of intangible savings such as reduced lost productivity increased the ROI to 250%. The dollar values of these savings were $693,461 and $1,337,628, respectively. IMPACT: The HELP program produces considerable savings (both tangible and intangible) to the Military Healthcare System for small costs. It does this both by increasing access to care at previously inaccessibly remote medical treatment facilities and by consequently decreasing the forward provider's reliance on medical evacuation in questionable cases. This positive ROI was potentially underestimated as this analysis did not account for recapture of care that would otherwise have been sent to the civilian market. On the basis of this analysis, a low bandwidth, asynchronous, and internet accessible teleconsultation system is both a feasible and effective means of projecting quality care forward into the deployed setting. Future implementation of similar initiatives throughout the MHS can be expected, and will likely draw from the lessons learned during the successful implementation and execution of the HELP system.

The Health Experts onLine at Portsmouth (HELP) system: One-year review of adult and Pediatric Asynchronous Telehealth Consultations.

INTRODUCTION: The Health Experts onLine at Portsmouth teleconsultation system is designed to connect health providers in the Navy Medicine East Region to specialists at Naval Medical Center Portsmouth. METHODS: A review of the first year of the Health Experts onLine at Portsmouth system was performed. Data on each teleconsultation were extracted from the Health Experts onLine at Portsmouth system database and analyzed. RESULTS: From June 2014 to May 2015 there have been 585 teleconsultations. Providers stationed on 36 ships/submarines and at 28 remote military treatment facilities have utilized the Health Experts onLine at Portsmouth system. Over 280 specialists in 34 different specialties were consulted. The median time to first response from a specialist was 6 h and 8 min, with 75% of all consults being addressed within 24 h. Eighteen medevacs were recommended. Thirty-nine potential medevacs were prevented, and 100 potential civilian network deferrals were prevented, resulting in an estimated savings of over US$580,000. DISCUSSION: Based on the 1-year metrics, Health Experts onLine at Portsmouth has provided improved access and quality of care to service members and their families throughout the Navy Medicine East Region. It has helped avoid over US$580,000 in unnecessary cost burden. Further review at the 2-year time interval will demonstrate the continued growth and effectiveness of the Health Experts onLine at Portsmouth system.

In Vivo Biotinylation of the Toxoplasma Parasitophorous Vacuole Reveals Novel Dense Granule Proteins Important for Parasite Growth and Pathogenesis.

UNLABELLED: Toxoplasma gondii is an obligate intracellular parasite that invades host cells and replicates within a unique parasitophorous vacuole. To maintain this intracellular niche, the parasite secretes an array of dense granule proteins (GRAs) into the nascent parasitophorous vacuole. These GRAs are believed to play key roles in vacuolar remodeling, nutrient uptake, and immune evasion while the parasite is replicating within the host cell. Despite the central role of GRAs in the Toxoplasma life cycle, only a subset of these proteins have been identified, and many of their roles have not been fully elucidated. In this report, we utilize the promiscuous biotin ligase BirA* to biotinylate GRA proteins secreted into the vacuole and then identify those proteins by affinity purification and mass spectrometry. Using GRA-BirA* fusion proteins as bait, we have identified a large number of known and candidate GRAs and verified localization of 13 novel GRA proteins by endogenous gene tagging. We proceeded to functionally characterize three related GRAs from this group (GRA38, GRA39, and GRA40) by gene knockout. While Δgra38 and Δgra40 parasites showed no altered phenotype, disruption of GRA39 results in slow-growing parasites that contain striking lipid deposits in the parasitophorous vacuole, suggesting a role in lipid regulation that is important for parasite growth. In addition, parasites lacking GRA39 showed dramatically reduced virulence and a lower tissue cyst burden in vivo Together, the findings from this work reveal a partial vacuolar proteome of T. gondii and identify a novel GRA that plays a key role in parasite replication and pathogenesis. IMPORTANCE: Most intracellular pathogens reside inside a membrane-bound vacuole within their host cell that is extensively modified by the pathogen to optimize intracellular growth and avoid host defenses. In Toxoplasma, this vacuole is modified by a host of secretory GRA proteins, many of which remain unidentified. Here we demonstrate that in vivo biotinylation of proximal and interacting proteins using the promiscuous biotin ligase BirA* is a powerful approach to rapidly identify vacuolar GRA proteins. We further demonstrate that one factor identified by this approach, GRA39, plays an important role in the ability of the parasite to replicate within its host cell and cause disease.

Prevalence of stroke and the need for thromboprophylaxis in young patients with atrial fibrillation: a cohort study.

Atrial fibrillation is the most common cardiac arrhythmia, and age is a well-established independent risk factor for stroke in these patients. Whereas high-risk patients clearly benefit from anticoagulation to prevent stroke, less is known about how to treat low-risk patients. Despite the recent guidelines and studies demonstrating no benefit and excess bleeding risk with aspirin, many low-risk patients still receive this medication. Our objective was to determine the stroke rate in young patients with atrial fibrillation, a group of previously unstudied and predominantly low-risk patients. We hypothesized that the event rate would be so low as to preclude benefit from antithrombotic medications. A retrospective chart review identified patients with atrial fibrillation between the age of 18 and 35. Exclusion criteria included no ECG documentation of atrial fibrillation, anticoagulation, except around the time of cardioversion, and surgical valve disease. The primary outcome was stroke during the period of observation. The final cohort included 99 patients, mean age 27.6 years, followed for a mean of 4.3 years. Mean CHADS2 and CHA2DS2-VASc scores were 0.26 and 0.4, respectively. A total of 42.4% were taking aspirin for over 50% of the time. There was one event identified, a transient ischemic attack in a man not on aspirin with CHADS2 and CHADS2-VASc scores of 1, resulting in event rates of 0.234 per 100 patient-years overall or 0.392 among those not on aspirin. Patients with nonvalvular atrial fibrillation under age 35 have an exceedingly low stroke risk. We assert that aspirin may be unnecessary for most patients in this population, especially those with a CHA2DS2-VASc score of 0.

Overdrive pacing in a patient with incessant torsades de pointes.

A 75-year-old man presented to the emergency department (ED) for syncope and was found to have intermittent runs of torsades de pointes (TdP). The patient had a medical history significant for disseminated coccidiomycosis and was on prophylactic fluconazole. Forty-eight hours prior to presentation, the patient had intractable nausea and vomiting and was unable to take anything orally. He eventually presented to the ED with severe hypokalaemia and hypomagnesaemia with repeat symptomatic runs of TdP, which required overdrive transvenous pacing. During the patient''s admission, his electrolytes were aggressively replete. Fluconazole was discontinued, and prior to discharge, the patient recovered fully with ECGs showing a normalisation of the QT interval.

Pericarditis, thymic hyperplasia, and Graves' thyrotoxicosis: case report and review of the literature.

Graves' thyrotoxicosis with thymic hyperplasia and pericarditis has never been described in the literature. In this case report, we present the clinical, laboratory, and radiographic findings of a 24-year-old active duty male who was admitted for management of nonexertional, positional, pleuritic chest pain. Electrocardiography confirmed pericarditis as the presenting diagnosis. Laboratory findings revealed an undetectable serum thyrotropin level and further evaluation with a contrast chest computed tomography confirmed the presence of a goiter and an anterior mediastinal mass. The patient's pericarditis and thymic hyperplasia resolved with treatment of his Graves' disease.

Multivessel spontaneous coronary artery dissection treated with staged percutanous coronary intervention in a non-postpartum female.

We present a case of a 43-year-old woman who presented with a non-ST elevation myocardial infarction. During her first cardiac catheterisation, she was diagnosed with a chronic total occlusion of the right coronary artery and a flow limiting dissection of her middle left anterior descending artery. The dissection of the left anterior descending artery was stented with two overlapping everolimus-eluting stents. There were no complications from this percutaneous coronary intervention. On the following day, the patient continued to have persistent chest pain and returned to the catheterisation laboratory. It was then found that the patient had a total occlusion of the right coronary artery secondary to dissection. This was also stented with three everolimus-eluting stents with excellent clinical and angiographic results. It is important to consider spontaneous multivessel coronary dissections which can be treated successfully with percutaneous coronary intervention.