Axillary mechanical circulatory support improves renal function prior to heart transplantation in patients with chronic kidney disease.

Impaired kidney function is often associated with acute decompensation of chronic heart failure and portends a poor prognosis. Unfortunately, current data have demonstrated worse survival in patients with acute kidney injury than in patients with chronic kidney disease during durable LVAD placement as bridge therapy. Furthermore, end-stage heart failure patients undergoing combined heart-kidney transplantation have poorer short- and long-term survival than heart transplants alone. We evaluated the kidney function recovery in our heart failure population awaiting heart transplantation at our institution, supported by temporary Mechanical Circulatory Support (tMCS) with Impella 5.5. The protocol (#22004000) was approved by the Mayo Clinic institutional review board, after which we performed a retrospective review of all patients with acute on chronic heart failure and kidney disease in patients considered for only heart and kidney combined organ transplant and supported by tMCS between January 2020 and February 2021. Hemodynamic and kidney function trends were recorded and analyzed before and after tMCS placement and transplantation. After placement of tMCS, we observed a trend towards improvement in creatinine, Fick cardiac index, mixed venous saturation, and glomerular filtration rate (GFR), which persisted through transplantation and discharge. The average duration of support with tMCS was 16.5 days before organ transplantation. The median pre-tMCS creatinine was 2.1 mg/dL (IQR 1.75-2.3). Median hematocrit at the time of tMCS placement was 32% (IQR 32-34), and the median estimated glomerular filtration rate was 34 mL/min/BSA (34-40). The median GFR improved to 44 mL/min/BSA (IQR 45-51), and serum creatinine improved to 1.5 mg/dL (1.5-1.8) after tMCS. Median discharge creatinine was 1.1 mg/dL (1.19-1.25) with a GFR of 72 (65-74). None of these six patients supported with tMCS required renal replacement therapy after heart transplantation. Early adoption of Impella 5.5 in this patient population resulted in renal recovery without needing renal replacement therapies or dual organ transplantation and should be further evaluated.

2022 ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. STRUCTURE: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.

Aortoiliac: Covered, Uncovered, CERAB as It Relates to Peripheral Arterial Disease.

Peripheral arterial disease (PAD) affects over 200 million worldwide and is the leading cause of major limb amputation, with individuals suffering from PAD being at three times greater risk of dying compared with matched controls. TASC-II guidelines provide a consensus on the management of PAD based on the collaboration between international vascular specialties. These guidelines previously outlined open surgery as the gold standard for treatment of aortoiliac disease and PAD as it has demonstrated consistent long-term results. However, this approach is also associated with high perioperative mortality, especially when compared with endovascular techniques. With recent developments in endovascular technology, user technique, and experience, this approach has become more widely used as primary intervention for aortoiliac disease. One of these novel techniques includes covered endovascular reconstruction of the aortic bifurcation, which has demonstrated excellent technical success and improved primary and secondary patency rates with follow-up. The aim of this review is to compare the efficacy of these approaches to the treatment of aortoiliac disease and demonstrate the benefits of the shift toward an endovascular-first approach to treatment of this disease, regardless of lesion complexity or severity.

ACR Appropriateness Criteria® Central Venous Access Device and Site Selection.

The use of central venous access devices is ubiquitous in both inpatient and outpatient settings, whether for critical care, oncology, hemodialysis, parenteral nutrition, or diagnostic purposes. Radiology has a well-established role in the placement of these devices due to demonstrated benefits of radiologic placement in multiple clinical settings. A wide variety of devices are available for central venous access and optimal device selection is a common clinical challenge. Central venous access devices may be nontunneled, tunneled, or implantable. They may be centrally or peripherally inserted by way of veins in the neck, extremities, or elsewhere. Each device and access site presents specific risks that should be considered in each clinical scenario to minimize the risk of harm. The risk of infection and mechanical injury should be minimized in all patients. In hemodialysis patients, preservation of future access is an additional important consideration. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

A case of spontaneous pneumothorax due to paragonimiasis in North America with literature review.

The species, Paragonimus kellicotti , causes human paragonimiasis in North America. As a foodborne disease, human infection with P. kellicotti occurs after eating raw or undercooked crayfish containing metacercariae. Many risk factors have been described in the literature, including young adult age, male, alcohol consumption, outdoor activities involving rivers within Missouri, and ingesting raw or partially cooked crayfish. Here, we report a case of a 41-year-old male with a 5-year history of cough who presented with acute shortness of breath. Further workup showed mild eosinophilia and spontaneous pneumothorax. A definitive diagnosis was made with a lung biopsy, which showed P. kellicotti eggs. Further questioning revealed that the patient took a hunting and river rafting trip on a river in Missouri 5 years ago, though the history was negative for any crayfish consumption. Paragonimiasis should be considered in those with associated clinical features, including cough and eosinophilia, with a history of a river raft float trip in Missouri, even if the history is negative for crayfish ingestion or travel.

Non-invasive detection of cardiac allograft rejection among heart transplant recipients using an electrocardiogram based deep learning model.

Aims: Current non-invasive screening methods for cardiac allograft rejection have shown limited discrimination and are yet to be broadly integrated into heart transplant care. Given electrocardiogram (ECG) changes have been reported with severe cardiac allograft rejection, this study aimed to develop a deep-learning model, a form of artificial intelligence, to detect allograft rejection using the 12-lead ECG (AI-ECG). Methods and results: Heart transplant recipients were identified across three Mayo Clinic sites between 1998 and 2021. Twelve-lead digital ECG data and endomyocardial biopsy results were extracted from medical records. Allograft rejection was defined as moderate or severe acute cellular rejection (ACR) based on International Society for Heart and Lung Transplantation guidelines. The extracted data (7590 unique ECG-biopsy pairs, belonging to 1427 patients) was partitioned into training (80%), validation (10%), and test sets (10%) such that each patient was included in only one partition. Model performance metrics were based on the test set (n = 140 patients; 758 ECG-biopsy pairs). The AI-ECG detected ACR with an area under the receiver operating curve (AUC) of 0.84 [95% confidence interval (CI): 0.78-0.90] and 95% (19/20; 95% CI: 75-100%) sensitivity. A prospective proof-of-concept screening study (n = 56; 97 ECG-biopsy pairs) showed the AI-ECG detected ACR with AUC = 0.78 (95% CI: 0.61-0.96) and 100% (2/2; 95% CI: 16-100%) sensitivity. Conclusion: An AI-ECG model is effective for detection of moderate-to-severe ACR in heart transplant recipients. Our findings could improve transplant care by providing a rapid, non-invasive, and potentially remote screening option for cardiac allograft function.

Sphenoid mucopyocele causing bilateral sixth nerve palsy.

Sphenoid mucoceles, although rare, should be considered in patients with headache, visual disorders and eye paralysis. Due to close relationships with the orbit and neuromeningeal structures, early recognition is vital. We report the case of a patient who presented with bilateral abducens nerve palsies. At surgery, she was found to have a mucopyocele; this was drained and she required prolonged intravenous antibiotic therapy due to ongoing symptoms and persistent dural enhancement on imaging. A lesion of sufficient size in the clival area has the potential to cause bilateral abducens nerve palsies, though we believe this is the first time it has been described in relation to a sphenoid mucocele. Imaging plays a crucial role in diagnosis, and prompt surgical intervention is essential to avoid serious and permanent complications. The multi-disciplinary team approach is vital-these cases requiring input from ophthalmology, ear nose and throat, microbiology, radiology, neurology and neurosurgery.

Controlled temperatures in cold preservation provides safe heart transplantation results.

BACKGROUND: We aimed to investigate the short-term outcomes of heart transplant patients who underwent SherpaPak™ donor organ preservation. METHOD: We prospectively collected the data of patients who underwent heart transplantation using SherpaPak™ system for donor organ transportation from February 2020 to March 2021. Donor and recipient demographic data, preoperative and postoperative echocardiographic and hemodynamic parameters, total ischemic time and SherpaPak temperatures, vasoactive inotropic scores (VIS), primary graft dysfunction (PGD) status, intensive care unit stay, complications, and mortality during follow-up were assessed. RESULTS: A total of 39 consecutive heart transplant patients with SherpaPak system were included in the study. The mean donor age was 32.2 ± 6.7 (range: 16-46). The mean recipient age was 57.5 ± 12 (range: 19-73). The mean preoperative ejection fraction (EF) was 23.7 ± 15.4 (range: 5-75). All recipients underwent a standard bicaval technique for orthotopic heart implantation. The mean total ischemic time was 230.1 ± 41 (range: 149-342) min. The mean Sherpa temperature was 5.6 ± 0.8°C (range: 3.7-7.5). The mean VIS was 10.2 ± 6.5 (range: 2-32). The number of mild PGD was 5 (14.7%), and moderate PGD was 4 (11.8%). There was no severe PGD. The postoperative EF was 64.3 ± 5.5 (range: 50-78). Mean intubation time was 47.4 ± 64 (range: 8-312, median: 22) h. The mean time of intensive care unit stay was 6.3 ± 5 (range: 2-31, median: 5) days. Two patients required chest revision (5.8%), two patients had lung infection (5.8%). Two patients had a stroke (5.8%). There was no mortality. CONCLUSION: Using the SherpaPak system during heart transplantation is safe and not associated with significant recipient morbidity. None of the recipients experienced significant PGD and mortality.

A challenging case of tracheal foreign body retrieval following COVID-19 swabbing.

The COVID-19 pandemic has resulted in a significant increase in the number of tracheostomised patients in hospitals requiring ventilatory support. These patients require highly specialist care, but overwhelmed hospital systems with stretched human resources potentially leave these patients cared for by undertrained healthcare professionals. We describe a rare complication where a routine COVID-19 swab done incorrectly via a tracheostomy tube, resulted in a snapped-off swab in the trachea. We outline the events and our method of removal using rigid bronchoscopy through the tracheostomy stoma as endo-tracheal bronchoscopy was impossible due to significant sub-glottic stenosis. This case highlights the paramount importance of the unique care needed to safely manage tracheostomies during this ongoing pandemic.

Impact of COVID-19 pandemic on bariatric surgery in India: An obesity and metabolic surgery society of India survey of 1307 patients.

BACKGROUND: Although safe practice guidelines were issued by the Obesity and Metabolic Surgery Society of India (OSSI) in the end of May 2020, surgeons have been in a dilemma about risk of subjecting patients to hospitalisation and bariatric surgery. This survey was conducted with the objective to evaluate the risk of coronavirus disease-19 (COVID-19) infection in peri- and post-operative period after bariatric and metabolic surgery (BMS). METHODS: A survey with OSSI members was conducted from 20 July 2020 to 31 August 2020 in accordance with EQUATOR guidelines. Google Form was circulated to all surgeon members through E-mail and WhatsAppTM. In the second phase, clinical details were captured from surgeons who reported positive cases. RESULTS: One thousand three hundred and seven BMS were reported from 1 January 2020 to 15 July 2020. Seventy-eight per cent were performed prior to 31 March 2020 and 276 were performed after 1 April 2020. Of these, 13 (0.99%) patients were reported positive for COVID-19 in the post-operative period. All suffered from a mild disease and there was no mortality. Eighty-seven positive cases were reported from patients who underwent BMS prior to 31 December 2019. Of these, 82.7% of patients had mild disease, 13.7% of patients had moderate symptoms and four patients succumbed to COVID-19. CONCLUSION: BMS may be considered as a safe treatment option for patients suffering from clinically severe obesity during the COVID-19 pandemic. Due care must be taken to protect patients and healthcare workers and all procedures must be conducted in line with the safe practice guidelines.

ACR Appropriateness Criteria® Radiologic Management of Lower Gastrointestinal Tract Bleeding: 2021 Update.

Diverticulosis remains the commonest cause for acute lower gastrointestinal tract bleeding (GIB). Conservative management is initially sufficient for most patients, followed by elective diagnostic tests. However, if acute lower GIB persists, it can be investigated with colonoscopy, CT angiography (CTA), or red blood cell (RBC) scan. Colonoscopy can identify the site and cause of bleeding and provide effective treatment. CTA is a noninvasive diagnostic tool that is better tolerated by patients, can identify actively bleeding site or a potential bleeding lesion in vast majority of patients. RBC scan can identify intermittent bleeding, and with single-photon emission computed tomography, can more accurately localize it to a small segment of bowel. If patients are hemodynamically unstable, CTA and transcatheter arteriography/embolization can be performed. Colonoscopy can also be considered in these patients if rapid bowel preparation is feasible. Transcatheter arteriography has a low rate of major complications; however, targeted transcatheter embolization is only feasible if extravasation is seen, which is more likely in hemodynamically unstable patients. If bleeding site has been previously localized but the intervention by colonoscopy and transcatheter embolization have failed to achieve hemostasis, surgery may be required. Among patients with obscure (nonlocalized) recurrent bleeding, capsule endoscopy and CT enterography can be considered to identify culprit mucosal lesion(s). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Left ventricular assist devices in the elderly: Marching forward with cautions.

Congestive heart failure is highly prevalent in the elderly population and left ventricular assist device (LVAD) has been increasingly used in this population. LVAD therapy is more costly than medical treatment but it increases the survival and quality of life of the elderly patients with low disease acuity. Therefore careful selection of candidates and implementation of LVAD therapy earlier in the course of the disease is crucial to improve outcomes. With the technical advances and improvement in clinical management, the financial burden of LVAD therapy in the elderly will become less, making this therapy more economically feasible.

Aortic Remodeling and Clinical Outcomes Following Thoracic Endovascular Aortic Repair for Blunt Thoracic Aortic Injury.

BACKGROUND: There is currently limited data assessing the long-term consequences of thoracic endovascular aortic repair (TEVAR) in otherwise healthy aortic segments remote from the site of endograft coverage. The aim of this study is to retrospectively evaluate aortic remodeling and long-term outcomes of blunt thoracic aortic injury (BTAI) patients treated with TEVAR. Our hypothesis is that significant changes to the aorta proximal to the graft-covered segment are suspected following TEVAR. METHODS: An institutional review board-approved retrospective review of patients who underwent TEVAR for BTAI at a level I trauma center from 2004 to 2018 was performed. Forty-six patients were identified and of these, 32 patients with high-resolution computed tomographic angiography imaging follow-up were included in the study. Computed tomographic angiography measurements of aortic dimensions and branch vessels proximal, distal, and adjacent to the stent grafted segment were recorded preprocedure and postprocedure and analyzed. Primary device-related outcomes such as birdbeaking, mural thrombus, stent migration, and persistent endoleak were assessed. Patient outcomes including mortality, graft-related morbidity, and need for secondary interventions were also analyzed. RESULTS: Mean follow-up of the selected patients in the study was 1.52 y (range, 0.06-8.0 y). Following TEVAR, the ascending aortic length increased significantly (mean 5.7 ± 4.6 mm, P < 0.001). The mean diameters of the ascending aorta (1.5 ± 1.5, P < 0.001 mm), the midaortic arch (1.3 ± 1.7 mm, P < 0.001), and proximal and the distal endograft landing zones (1.9 ± 2.1 mm and 2.2 ± 1.6 mm, respectively, P < 0.001) also increased significantly following TEVAR. Clinically relevant device-related outcomes occurred with the presence of endograft infolding and subsequent development of endograft mural thrombus (P < 0.001). The need for secondary intervention following TEVAR for BTAI was associated with endograft mural thrombus (P < 0.05). CONCLUSIONS: TEVAR for BTAI causes significant geometric changes in the aorta proximal to the stented grafted segment of the aorta. Direct consequences of the graft at the stented segment includes mural thrombus development within the endograft which was associated with the need for secondary intervention. Although clinical significance is yet to be determined, post-TEVAR changes in aortic architecture warrant continued aortic surveillance following BTAI.

Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients With Peripheral Artery Disease (STOP-PAD) Trial: Six-Month Results.

Purpose: To present the 6-month results of the Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Peripheral Artery Disease (STOP-PAD) trial. The trial was an attempt to alter the course of chronic limb-threatening ischemia (CLTI) with a biological agent vs placebo after successful arterial revascularization at or below the knee. Materials and Methods: The multicenter, randomized, double-blinded, placebo-controlled, phase 2B STOP-PAD trial (ClinicalTrials.gov identifier NCT02544204) randomized 109 patients (mean age 71 years; 68 men) with Rutherford category 5 or 6 CLTI and evidence of persistent impaired forefoot perfusion following recent successful revascularization to 8- (n=34) or 16-mg (n=36) intramuscular injections of a non-viral DNA plasmid-based treatment vs placebo (n=34). The primary efficacy outcome was the 6-month wound healing score evaluated by an independent wound core laboratory; the primary safety endpoint was major adverse limb events (MALE), a composite of major amputation plus clinically-driven target lesion revascularization at 6 months. Results: Only one-third of the patients had complete wound healing at 6 months in the placebo (31%), 8-mg injection (33%), and 16-mg injection (33%) groups. In addition, the observed increase in the toe-brachial index from baseline to 6 months was statistically significant in each group; however, this did not result in lower rates of MALE at 6 months (24% in the placebo, 29% in the 8-mg injection, and 11% in the 16-mg injection groups). During the 6-month period, 6 patients (6%) died, and 24 patients (23%) had an amputation [only 4 (4%) major]. Conclusion: Combining revascularization and biological therapy failed to improve outcomes in CLTI at 6 months. STOP-PAD has provided insights for future trials to evaluate biological therapy.

Recent Trends in Clinical Setting and Provider Specialty for Endovascular Peripheral Artery Disease Interventions for the Medicare Population.

PURPOSE: To describe national trends in peripheral endovascular interventions by physician specialty, anatomic segment of disease, and clinical location of service. MATERIALS AND METHODS: Current Procedural Terminology codes were used to identify claims for peripheral vascular interventions (PVIs) in 2011-2017 Physician Supplier Procedure Summary master files, which contain 100% Part B Medicare billing. Market share was defined as enrollment-adjusted proportion of billed PVI services for each specialty. Annual volume of billed services was additionally evaluated by clinical location (inpatient, outpatient, office-based laboratories) and anatomic segment of disease (iliac, femoral/popliteal, infrapopliteal). RESULTS: Aggregate PVI claims increased 31.3%, from 227,091 in 2011 to 298,127 in 2017. Annual market share remained relatively stable for all specialties: surgery, 48.3%-49.6%; cardiology, 37.2%-35.1%; radiology, 12.8%-13.3%. Accounting for Medicare enrollment, the volume of iliac interventions decreased by 18% over the study period, while femoral/popliteal interventions increased modestly (+7.5%) and infrapopliteal interventions increased (+46%). The greatest proportional increase in infrapopliteal claims occurred among radiologists (surgeons +40.4%, cardiologists +32.1%, radiologists +106.6%). Adjusting for enrollment, claims from office-based laboratories increased substantially (+305.7%), while hospital-based billing decreased (inpatient -25.7%, outpatient -12.9%). Office-based laboratory utilization increased dramatically with all specialties (surgery +331.8%, cardiology +256.0%, radiology +475.7%). CONCLUSIONS: Utilization of PVIs continues to increase, while specialty market shares have stabilized since 2011, leaving surgeons and cardiologists as the major providers of endovascular peripheral artery disease care. The greatest relative increases are occurring in infrapopliteal interventions and office-based laboratory procedures, where radiologist involvement has increased dramatically.

Kidney transplantation on extracorporeal life support for primary cardiac allograft dysfunction.

Patients undergoing heart-kidney transplants who have primary graft dysfunction (PGD) of the heart are at risk of losing both organs, which may cause reluctance on the part of the transplant team to proceed with transplanting the kidney while the transplanted heart is being supported by mechanical device. We describe a case series in which 2 patients received kidney transplants while on veno-arterial ECMO support for PGD after heart transplant. Both patients are alive more than 1 year following transplant, with good cardiac and renal function and no signs of cardiac rejection. Kidney transplant surgery is safe for patients on veno-arterial ECMO support for cardiac PGD. It allows the heart recipient to receive a kidney from the same donor with both immunologic and survival advantages.

Endovascular repair of delayed traumatic aortocaval fistula.

Aortocaval fistula (ACF) is an uncommon condition that can result in a number of adverse clinical sequelae. We describe a case of an ACF that occurred several years after open repair of a penetrating injury of the abdominal aorta and inferior vena cava. Whereas ACF can have sudden and catastrophic presentations, our patient had a subacute presentation of high-output heart failure. We were able to fully correct the vascular injury and heart failure physiology and symptoms with endovascular therapy.

Outcomes and Cost Comparison of Percutaneous Endovascular Aortic Repair versus Endovascular Aortic Repair With Open Femoral Exposure.

BACKGROUND: The objective of this study was to assess cost differences between patients who underwent percutaneous endovascular aortic repair (PEVAR) and open surgical femoral exposure in elective endovascular aortic repair (EVAR) of abdominal aortic aneurysms. MATERIALS AND METHODS: An IRB-approved single center retrospective analysis of patients who underwent elective EVAR for abdominal aortic aneurysms from 2009 to 2016 was performed. One hundred patients were selected with 50 patients who underwent PEVAR and 50 patients who underwent open surgical femoral exposure. Patient demographics, procedural variables, and hospital outcomes were collected and compared. Primary outcomes assessed used in cost calculations included operating time (OR time), hospital length of stay (LOS), and intensive care unit stay (ICU LOS). Extrapolated cost differences were based on known, published cost multipliers for the primary outcomes observed. RESULTS: Patients undergoing PEVAR had significant reduction in mean OR time (113.9 min versus 144.9 min, P < 0.001), mean ICU LOS (19.7 h versus 28.9 h, P = 0.094), and overall LOS (28.3 h versus 33.1 h, P = 0.020). There was no statistically significant difference in access related complications, although there was a trend toward less complication rates with PEVAR (0% versus 5%, P = 0.056). Calculated cost of procedures based on mean ICU LOS, hospital LOS, and OR time, showed significant reduction in mean hospital costs with PEVAR ($16,628.5 versus $21,705.8, P < 0.001). Multiple linear regression analysis demonstrated an overall 23% cost reduction with PEVAR. CONCLUSIONS: Prior reports comparing PEVAR versus EVAR with open femoral exposures have shown improvement in overall patient time to ambulation and other hospital metrics such as LOS with PEVAR. There is, however, a paucity of overall cost comparison data regarding PEVAR. In this study, adoption of PEVAR was seen to significantly reduce OR times (19%) and overall hospital LOS (50%). The outcomes observed ultimately translated into significant reduction in hospital costs.