Antimicrobial use and appropriateness in neutropenic fever: a study of the Hospital National Antimicrobial Prescribing Survey data.

BACKGROUND: Neutropenic fever (NF) is a common complication in patients receiving chemotherapy. Judicious antimicrobial use is paramount to minimize morbidity and mortality and to avoid antimicrobial-related harms. OBJECTIVES: To use an Australian national dataset of antimicrobial prescriptions for the treatment of NF to describe antimicrobial use, prescription guideline compliance and appropriateness; and to compare these findings across different healthcare settings and patient demographics. We also aimed to identify trends and practice changes over time. METHODS: Data were extracted from the Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) database from August 2013 to May 2022. Antimicrobial prescriptions with a NF indication were analysed for antimicrobial use, guideline compliance and appropriateness according to the Hospital NAPS methodology. Demographic factors, hospital classifications and disease characteristics were compared. RESULTS: A total of 2887 (n = 2441 adults, n = 441 paediatric) NF prescriptions from 254 health facilities were included. Piperacillin-tazobactam was the most prescribed antimicrobial. Overall, 87.4% of prescriptions were appropriate. Piperacillin-tazobactam and cefepime had the highest appropriateness though incorrect piperacillin-tazobactam dosing was observed. Lower appropriateness was identified for meropenem, vancomycin, and gentamicin prescribing particularly in the private hospital and paediatric cohorts. The most common reasons for inappropriate prescribing were spectrum too broad, incorrect dosing or frequency, and incorrect duration. CONCLUSIONS: This study provides insights into antimicrobial prescribing practices for NF in Australia. We have identified three key areas for improvement: piperacillin-tazobactam dosing, paediatric NF prescribing and private hospital NF prescribing. Findings from this study will inform the updated Australian and New Zealand consensus guidelines for the management of neutropenic fever in patients with cancer.

Approach to diagnostic evaluation and prevention of invasive fungal disease in patients prior to allogeneic hematopoietic stem cell transplant.

In recent years, advancements in the treatment landscape for hematological malignancies, such as acute myeloid leukemia and acute lymphoblastic leukemia, have significantly improved disease prognosis and overall survival. However, the treatment landscape is changing and the emergence of targeted oral therapies and immune-based treatments has brought forth new challenges in evaluating and preventing invasive fungal diseases (IFDs). IFD disproportionately affects immunocompromised hosts, particularly those undergoing therapy for acute leukemia and allogeneic hematopoietic stem cell transplant. This review aims to provide a comprehensive overview of the pretransplant workup, identification, and prevention of IFD in patients with hematological malignancy. The pretransplant period offers a critical window to assess each patient's risk factors and implement appropriate prophylactic measures. Risk assessment includes evaluation of disease, host, prior treatments, and environmental factors, allowing a dynamic evaluation that considers disease progression and treatment course. Diagnostic screening, involving various biomarkers and radiological modalities, plays a crucial role in early detection of IFD. Antifungal prophylaxis choice is based on available evidence as well as individual risk assessment, potential for drug-drug interactions, toxicity, and patient adherence. Therapeutic drug monitoring ensures effective antifungal stewardship and optimal treatment. Patient education and counselling are vital in minimizing environmental exposures to fungal pathogens and promoting medication adherence. A well-structured and individualized approach, encompassing risk assessment, prophylaxis, surveillance, and patient education, is essential for effectively preventing IFD in hematological malignancies, ultimately leading to improved patient outcomes and overall survival.

Fluoroquinolone prophylaxis in patients with neutropenia at high risk of serious infections: Exploring pros and cons.

BACKGROUND: The use of fluoroquinolones to prevent infections in neutropenic patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT) is a controversial issue, with international guidelines providing conflicting recommendations. Although potential benefits are clear, concerns revolve around efficacy, potential harms, and antimicrobial resistance (AMR) implications. DISCUSSION: Fluoroquinolone prophylaxis reduces neutropenic fever (NF) bloodstream infections and other serious bacterial infections, based on evidence from systematic reviews, randomized controlled trials, and observational studies in adults and children. Fluoroquinolone prophylaxis may also reduce infection-related morbidity and healthcare costs; however, evidence is conflicting. Adverse effects of fluoroquinolones are well recognized in the general population; however, studies in the cancer cohort where it is used for a defined period of neutropenia have not reflected this. The largest concern for routine use of fluoroquinolone prophylaxis remains AMR, as many, but not all, observational studies have found that fluoroquinolone prophylaxis might increase the risk of AMR, and some studies have suggested negative impacts on patient outcomes as a result. CONCLUSIONS: The debate surrounding fluoroquinolone prophylaxis calls for individualized risk assessment based on patient characteristics and local AMR patterns, and prophylaxis should be restricted to patients at the highest risk of serious infection during the highest risk periods to ensure that the risk-benefit analysis is in favor of individual and community benefit. More research is needed to address important unanswered questions about fluoroquinolone prophylaxis in neutropenic patients with cancer or receiving HSCT.

Comparing the Efficacy of Postoperative Antibiotic Regimens in the Treatment of Maxillofacial Fractures: A Prospective Study.

AIM: The present study was designed to investigate the difference in the effectiveness of a 3 day postoperative course and a single perioperative dose of antibiotics on the incidence of postoperative infection in the management of maxillofacial trauma patients. MATERIALS AND METHODS: About 183 maxillofacial trauma patients requiring open reduction and internal fixation (ORIF) under general anesthesia were divided based on the type of fracture sustained, i.e., mandibular fractures, Le Fort fractures, and zygomaticomaxillary complex fractures. Patients from each fracture type were randomized into two groups, A and B. All patients were administered amoxicillin/clavulanate 1.2 grams intravenously 8 hours from the time of admission till the patient was taken up for surgery. Once the patients were taken up for surgery, a perioperative dose was administered. No antibiotics beyond this point were given to patients in Group A. Patients in Group B were administered the same antibiotic for 3 postoperative days additionally. Outcomes in terms of purulent discharge from the surgical site, an abscess or any other sign of infection, and wound dehiscence requiring reopening of the surgical site were considered. Patients were reviewed at 1 week, 2 weeks, 1 month, 2 months, and 3 months. RESULTS: No statistically significant difference was found between the two groups across all three fracture types in terms of postoperative outcomes. However, increased numbers of complications were noted in the patients treated with an intra-oral approach in each fracture type irrespective of group. All complications were managed with local measures. CONCLUSION: A single perioperative dose of antibiotics is effective in minimizing postoperative complications following ORIF of maxillofacial fractures and there is no significant benefit in prolonging the course of antibiotics postoperatively with the need for further studies to be conducted considering comminuted, complex fractures and old fractures. CLINICAL SIGNIFICANCE: In maxillofacial trauma, fractures frequently communicate with contaminated indigenous flora on the skin surface, oral cavities, or sinus cavities. Surgery is frequently performed using an approach across a contaminated area, even in closed fractures. Postoperative infections can be significantly decreased by using antibiotics in surgical procedures to treat facial fractures.

Skin Cancer: An Insight On Its Association With Aging, Pathogenesis And Treatment Strategies.

Skin cancer is one of the deadly diseases of the skin characterized by pain and uncontrolled growth of cells. The pathogenesis of skin cancer involves the uncontrolled division of abnormal cells in the part of the body affected by an accumulation of genome variation over the course of a lifetime. The incidence of skin cancer has been increasing all over the world and has been reported more in old-aged persons. Furthermore, aging plays a vital role in promoting malignancy. Cancer necessitates lifelong administration of drugs to maintain the quality of life. The major challenge of treatment is the side effects associated with these drugs. Novel and targeted approaches are now formulated to explore as an alternative measure to treat cancer. The current review summarizes the pathogenesis of cancer and its treatment strategies. These approaches are discussed with regard to the drugs, mechanism of action, causative factors, distribution of cancer, mortality rate, and treatment strategies.

Comparative study of intubating conditions and hemodynamic changes during awake fiber-optic intubation using midazolam with fentanyl versus dexmedetomidine in cases of difficult airway.

Background: The aim of the study is to compare intubating conditions and hemodynamic changes during awake fiber-optic intubation (AFOI) using midazolam and fentanyl versus dexmedetomidine in cases of difficult airway. Materials and Methods: A randomized prospective study was conducted in the department of oral and maxillofacial surgery, with a total of 60 patients, 18-55 years of age, ASA class I-II, of either sex with anticipated difficult airway planned for elective surgery. They were divided into two groups; group I patients received 1 µg/kg of dexmedetomidine and then an infusion of 0.5 to 0.7 µg/kg/hr of dexmedetomidine, whereas group II patients received 1 µg/kg of intra-venous (iv) fentanyl and 0.05 mg/kg of iv midazolam with additional doses of 0.02 mg/kg to achieve a Ramsay Sedation Scale score of ≥2. The ease of placement of the fiber-optic scope and the endotracheal tube and the patient's reaction to placement of the fiber-optic scope were assessed on a scale of 1-4 and were recorded as endoscopist satisfaction score and patient discomfort score, respectively. Results: The endoscopy time ranged from 2.66 ± 1.00 (group I) to 3.90 ± 0.96 (group II) minutes and was found to be statistically significant (p < 0.05). Also, the patient discomfort score was recorded during endoscopy (1-4) and ranged from 1.3 ± 0.53 (group I) and 2.33 ± 0.66 (group II) and was found to be statistically significant (p value < 0.05). Patients undergoing the procedure who received dexmedetomidine were thus more comfortable than those who received fentanyl and midazolam combination. Conclusion: Dexmedetomidine provided better intubating conditions, patient tolerance, higher endoscopist satisfaction, and reduced hemodynamic responses compared to fentanyl and midazolam combinations. Also, the major advantage of dexmeditomidine for preservation of airway with a lesser degree of respiratory depression allows for safer use of AFOI in cases of difficult airway.

Recurrent ST-elevation myocardial infarction: a case report of a rare complication of caseous mitral annular calcification.

BACKGROUND: Caseous mitral annular calcification (MAC) is an under-diagnosed division of calcific mitral valve disease that has recently been reported to have increased propensity for embolic disease. Early recognition of this entity as a cause of embolic disease can lead to prevention of occlusive vascular disease and long-standing complications. CASE SUMMARY: We present the case of a patient with end-stage renal disease who presented for evaluation of chest pain and was found to have ST-segment myocardial infarction. Despite thrombectomy and stenting, he had multiple recurrent events, and imaging evaluation demonstrated caseous MAC with mobile components. He was taken for surgical replacement of the mitral valve, with pathology confirming diagnosis. DISCUSSION: Caseous MAC may represent an increased risk of embolic disease. Better understanding of this pathology and it's propensity for embolic disease will be important to best determine treatment plans and timing of operative intervention.

Functional performance status and risk of cardiovascular events and mortality following endovascular repair of thoracic and abdominal aortic pathology.

OBJECTIVE: To characterize the association of preoperative functional performance status based on Eastern Cooperative Oncology Group (ECOG) scoring with the risk of adverse cardiovascular events, vascular events, and mortality in patients undergoing EVAR and TEVAR. METHODS: Retrospective review of the Society for Vascular Surgery Vascular Quality Initiative, a large, multi-center, registry database was performed. All individuals undergoing EVAR (n = 18,730) and TEVAR (n = 6595) for non-ruptured aortic pathologies between 2014 and 2018 were eligible for analysis. Multivariable logistic regression was used to determine the association of pre-procedure ECOG functional performance status on risk of in-hospital adverse cardiovascular events, vascular events, and mortality. RESULTS: The number of operations complicated by adverse cardiovascular and vascular events was 480 (2.6%) and 190 (1.0%) for EVAR and 733 (11.1%) and 219 (3.3%) for TEVAR, respectively. There were 118 (0.6%) and 240 (3.6%) in-hospital deaths following EVAR and TEVAR, respectively. Patients with ECOG grades 3 or 4 undergoing EVAR were at increased risk of cardiovascular events (OR = 1.62; 95% CI = 1.09, 2.41) and one-year mortality (HR = 2.62; 95% CI = 1.92, 3.57) compared to those with ECOG grade 0. Patients undergoing TEVAR with ECOG grade 3 or 4 were at increased risk for both inpatient death (OR = 2.77; 95% CI = 1.56, 4.9) and one-year mortality (HR = 3.27, 95% CI = 2.06, 5.21). ECOG status was not associated with an increased risk of adverse vascular events following either EVAR or TEVAR. CONCLUSIONS: Poor preoperative functional status as assessed by ECOG score is associated with an increased risk of adverse postoperative cardiovascular events following EVAR and a higher mortality risk following both EVAR and TEVAR. Functional status assessment may be useful for risk stratification and determining procedural candidacy prior to EVAR and TEVAR.

Prescribing of Statins After Lower Extremity Revascularization Procedures in the US.

Importance: The use of statins in patients with symptomatic peripheral artery disease remains suboptimal despite strong clinical practice guideline recommendations; however, it is unknown whether rates are associated with substantial improvements after lower extremity revascularization. Objective: To report longitudinal trends of statin use in patients with peripheral artery disease undergoing lower extremity revascularization and to identify the clinical and procedural characteristics associated with prescriptions for new statin therapy at discharge. Design, Setting, and Participants: This was a retrospective cross-sectional study using data from the Vascular Quality Initiative registry of patients who underwent lower extremity peripheral artery disease revascularization from January 1, 2014, through December 31, 2019. The Vascular Quality Initiative is a multicenter registry database including academic and community-based hospitals throughout the US. Patients aged 18 years or older undergoing lower extremity revascularization with available statin data (preprocedure and postprocedure) were included. Those not receiving statin therapy for medical reasons were excluded from final analyses. Exposures: Patients undergoing lower extremity revascularization for whom statin therapy is indicated. Main Outcomes and Measures: Multivariate logistic regression was used to determine the clinical and procedural characteristics associated with new statin prescription for patients not already taking a statin preprocedure. The overall rates of statin prescription as well as rates of new statin prescription at discharge were determined. In addition, the clinical, demographic, and procedural characteristics associated with new statin prescription were analyzed. Results: There were 172 025 procedures corresponding to 125 791 patients (mean [SD] age, 67.7 [11.0] years; 107 800 men [62.7%]; and 135 405 White [78.7%]) included in the analysis. Overall rates of statin prescription at discharge improved from 17 299 of 23 093 (75%) in 2014 to 29 804 of 34 231 (87%) in 2019. However, only 12 790 of 42 020 patients (30%) not already taking a statin at the time of revascularization during the study period were newly discharged with a statin medication. New statin prescription rates were substantially lower after endovascular intervention (7745 of 29 581 [26%]) than after lower extremity bypass (5045 of 12 439 [41%]). Body mass index of 30 or greater (odds ratio [OR], 1.13; 95% CI, 1.04-1.24; P < .001), diabetes (diet-controlled vs no diabetes, OR, 1.22; 95% CI, 1.05-1.41; P = .01), smoking (current vs never, OR, 1.32; 95% CI, 1.21-1.45; P < .001), hypertension (OR, 1.19; 95% CI, 1.09-1.29; P < .001), and coronary heart disease (OR, 1.26; 95% CI, 1.17-1.35; P < .001) were associated with an increased likelihood of new statin prescription after endovascular intervention, whereas female sex, older age, antiplatelet use, and prior peripheral revascularization were associated with a decreased likelihood. Conclusions and Relevance: In this cross-sectional study, although statin use was associated with a substantial improvement after lower extremity revascularization, more than two-thirds of patients not already taking a statin preprocedure remained not taking a statin at discharge. Further investigations to understand the clinical implications of these findings and develop clinician- and system-based interventions are needed.

Perianeurysmal retroperitoneal fibrosis presenting as acute kidney injury: A case report.

Retroperitoneal fibrosis and chronic periaortitis describe overlapping groups of rare diseases characterized by inflammation and fibrosis involving the aorta. The presentation is often non-specific, and while obstructive nephropathy is a common complication, these entities are an uncommon cause of renal failure necessitating dialysis. A 57-year-old man presented multiple times with acute kidney injury, even requiring hemodialysis, with repeated abrupt resolution. Renal ultrasound repeatedly did not reveal acute hydronephrosis. Renal biopsy on his first admission showed acute tubular injury attributed to hypovolemia. Computed tomography finally revealed a retroperitoneal soft tissue mass encasing the infrarenal abdominal aorta and partially encasing the bilateral ureters. Bilateral nephrostomy tubes were placed, steroids were initiated, and the patient experienced rapid and remarkable improvement in renal function. Chronic periaortitis should be considered in older patients with acute kidney injury, even in the absence of ultrasonographic evidence of obstruction. Additional studies are needed to describe the test characteristics of renal sonography for periaortitis, the long-term sequelae of acute kidney injury secondary to periaortitis, and the optimal management to preserve long-term renal function.

Echocardiographic predictors of new-onset atrial arrhythmias in patients undergoing hematopoietic stem cell transplantation.

BACKGROUND: Atrial arrhythmias following hematopoietic stem cell transplantation (HSCT) have been associated with increased length of stay, need for intensive care, and increased mortality within one-year post-transplant. We sought to identify echocardiographic parameters that may predict the development of new atrial arrhythmias post-HSCT. METHODS: We performed a retrospective chart review of 753 consecutive patients who underwent HSCT at the University of Chicago from January 2015 through December 2019. Patients with baseline echocardiogram within 6 months prior to transplantation were included. Those with prior transplants, history of atrial arrhythmias, or unavailable echocardiographic images were excluded, resulting in 187 patients included for final analysis. Baseline clinical and demographic variables, as well as echocardiographic parameters, were compared between patients who developed new atrial arrhythmias post-HSCT versus those who did not. RESULTS: Of the 187 patients included for analysis, 25 (13%) developed new atrial arrhythmias, with 13 of these occurring within 30 days of transplantation. Despite no significant difference in left atrial (LA) end-systolic volume between those with and without new arrhythmia following HSCT (OR 1.04; 95% CI 0.91-1.09, p = 0.233), univariable analysis demonstrated that patients who developed atrial arrhythmias had reduced LA function, as reflected by lower LA emptying fraction (OR 0.94; 95% CI 0.91-0.98, p = 0.003) and lower LA reservoir strain (OR 0.95; 95% CI 0.92-0.99, p = 0.009). CONCLUSIONS: Echocardiographic indices of LA function, namely LA emptying fraction and LA reservoir strain, can identify patients at risk for developing new atrial arrhythmias post-HSCT, prior to the development of morphologic changes in the LA.

The complex genomic basis of rapid convergent adaptation to pesticides across continents in a fungal plant pathogen.

Convergent evolution leads to identical phenotypic traits in different species or populations. Convergence can be driven by standing variation allowing selection to favour identical alleles in parallel or the same mutations can arise independently. However, the molecular basis of such convergent adaptation remains often poorly resolved. Pesticide resistance in agricultural ecosystems is a hallmark of convergence in phenotypic traits. Here, we analyse the major fungal pathogen Zymoseptoria tritici causing serious losses on wheat and with fungicide resistance emergence across several continents. We sampled three population pairs each from a different continent spanning periods early and late in the application of fungicides. To identify causal loci for resistance, we combined knowledge from molecular genetics work and performed genome-wide association studies (GWAS) on a global set of isolates. We discovered yet unknown factors in azole resistance including a gene encoding membrane associated functions. We found strong support for the "hotspot" model of resistance evolution with convergent changes in a small set of loci but additional loci showed more population-specific allele frequency changes. Genome-wide scans of selection showed that half of all known resistance loci were overlapping a selective sweep region. Hence, the application of fungicides was one of the major selective agents acting on the pathogen over the past decades. Furthermore, loci identified through GWAS showed the highest overlap with selective sweep regions underlining the importance to map phenotypic trait variation in evolving populations. Our population genomic analyses highlighted that both de novo mutations and gene flow contributed to convergent pesticide adaptation.

Suprasellar Tension Pneumatocele after Endoscopic Transsphenoidal Surgery for Pituitary Macroadenoma.

Tension pneumatocele is a very rare but potentially fatal complication of transsphenoidal surgery that can result from an influx of air into the intracranial cavity through the cerebrospinal fluid fistula. Although transsphenoidal surgeries for pituitary adenomas are very commonly performed procedures, this complication is extremely rare. We report a case of tension pneumatocele after transsphenoidal resection of a pituitary macroadenoma. After a second endoscopic transsphenoidal procedure to remove the air and repair of the sella floor, visual acuity recovered dramatically. Tension pneumatocele is an uncommon but potentially lethal complication of transsphenoidal pituitary surgery, which can present anytime, even after years postoperatively. It is important for all skull base surgeons to be aware of this condition so that prompt treatment can be instituted.

Discharge Prescription Patterns for Antiplatelet Therapy Following Lower Extremity Peripheral Vascular Intervention.

BACKGROUND: Despite current guidelines suggesting a benefit for dual antiplatelet therapy (DAPT) following peripheral vascular intervention (PVI), there are limited data on antiplatelet prescribing patterns post-procedure. We attempted to determine variables associated with DAPT prescription following lower extremity PVI. METHODS: Retrospective analysis of patients undergoing lower extremity PVI in the Vascular Quality Initiative (2017-2018) was performed. Participants not on anticoagulation or DAPT before the procedure were considered for the final analysis. Postdischarge antiplatelet therapy regimen rates were determined (none, aspirin only, P2Y12 inhibitor only, and DAPT). Multivariate logistic regression was performed to determine variables associated with DAPT initiation compared with those discharged on single-agent or no antiplatelet therapy. RESULTS: A total of 16 597 procedures were included for analysis, with 49% initiated on DAPT post-PVI. Male sex (odds ratio [OR], 1.12 [95% CI, 1.05-1.20]), smoking (OR, 1.20 [95% CI, 1.09-1.32]), and coronary artery disease (OR, 1.19 [95% CI, 1.11-1.27]) were associated with an increased likelihood of post-PVI DAPT prescription. Procedures requiring multiple types of interventions (OR, 1.28 [95% CI, 1.15-1.42]), stent placement (OR, 1.16 [95% CI, 1.06-1.27]), and with complications (OR, 1.31 [95% CI, 1.14-1.52]) were also positively associated with DAPT prescription. CONCLUSIONS: In patients not already receiving anticoagulation or on DAPT at the time of lower extremity PVI, prescription of DAPT following intervention is ≈50%. Multiple factors were associated with the decision for DAPT versus single antiplatelet therapy, and further study is required to understand how this affects postintervention adverse limb and cardiovascular events.

Development of a 2-dimensional atlas of the human kidney with imaging mass cytometry.

An incomplete understanding of the biology of the human kidney, including the relative abundances of and interactions between intrinsic and immune cells, has long constrained the development of therapies for kidney disease. The small amount of tissue obtained by renal biopsy has previously limited the ability to use patient samples for discovery purposes. Imaging mass cytometry (IMC) is an ideal technology for quantitative interrogation of scarce samples, permitting concurrent analysis of more than 40 markers on a single tissue section. Using a validated panel of metal-conjugated antibodies designed to confer unique signatures on the structural and infiltrating cells comprising the human kidney, we performed simultaneous multiplexed imaging with IMC in 23 channels on 16 histopathologically normal human samples. We devised a machine-learning pipeline (Kidney-MAPPS) to perform single-cell segmentation, phenotyping, and quantification, thus creating a spatially preserved quantitative atlas of the normal human kidney. These data define selected baseline renal cell types, respective numbers, organization, and variability. We demonstrate the utility of IMC coupled to Kidney-MAPPS to qualitatively and quantitatively distinguish individual cell types and reveal expected as well as potentially novel abnormalities in diseased versus normal tissue. Our studies define a critical baseline data set for future quantitative analysis of human kidney disease.

Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis.

BACKGROUNDClinical diagnosis of acute interstitial nephritis (AIN) is challenging because of lack of a diagnostic biomarker and requires a kidney biopsy. We hypothesized that AIN is mediated by specific T cell subsets such that specific T cell cytokine levels could serve as biomarkers to distinguish AIN from other causes of acute kidney disease (AKD).METHODSWe enrolled consecutive sampling participants who underwent a kidney biopsy for AKD evaluation at 2 centers between 2015 and 2018. Three pathologists independently established AIN diagnosis through review of kidney biopsies. Through univariable and multivariable analysis of 12 selected urine and plasma cytokines, we identified 2 that were diagnostic of AIN.RESULTSOf the 218 participants, 32 (15%) were diagnosed with AIN by all 3 pathologists. Participants with AIN had consistently higher levels of urine TNF-α and IL-9 than those with other diagnoses, including acute tubular injury, glomerular diseases, and diabetic kidney disease, and those without any kidney disease. As compared with participants in the lowest quartile, we noted higher odds of AIN in participants in the highest quartiles of TNF-α levels (adjusted odds ratio, 10.9 [1.8, 65.9]) and IL-9 levels (7.5 [1.2, 45.7]) when controlling for blood eosinophils, leukocyturia, and proteinuria. Addition of biomarkers improved area under receiver operating characteristic curve over clinicians' prebiopsy diagnosis (0.84 [0.78, 0.91]) vs. 0.62 [(0.53, 0.71]) and a model of current tests (0.84 [0.76, 0.91] vs. 0.69 [0.58, 0.80]).CONCLUSIONSInclusion of urinary TNF-α and IL-9 improves discrimination over clinicians' prebiopsy diagnosis and currently available tests for AIN diagnosis.FUNDINGSupported by NIH awards K23DK117065, T32DK007276, K24DK090203, K23DK097201, R01DK113191, UG3-DK114866, P30DK079310; the Robert E. Leet and Clara Guthrie Patterson Trust; and American Heart Association award 18CDA34060118.

Preoperative hemoglobin A1c levels and increased risk of adverse limb events in diabetic patients undergoing infrainguinal lower extremity bypass surgery in the Vascular Quality Initiative.

BACKGROUND: The impact of preoperative glycemic control on the risk of adverse perioperative outcomes in diabetic patients undergoing lower extremity bypass (LEB) surgery is not well-understood. We determined whether higher preoperative hemoglobin A1c (HbA1c) levels are associated with an increased risk of major adverse limb events, major adverse cardiovascular events, and mortality in diabetic patients undergoing infrainguinal LEB. METHODS: A retrospective review of all infrainguinal LEB surgeries in the Vascular Quality Initiative registry from January 2012 to February 2017 was performed. Only surgeries performed on diabetic patients with complete demographic and clinical data, including HbA1c value at the time of LEB, were included for analysis (n = 7727). Entries were stratified according to the following HbA1c levels: 6 or less (n = 1087), greater than 6 to 7 or less (n = 2137), greater than 7 to 8 or less (n = 1657), and greater than 8 (n = 2846). Multivariate logistic regression was used to determine the association of preoperative HbA1c levels on the risk of in-hospital major adverse limb events (above ankle amputation, loss of primary graft patency), major adverse cardiovascular events (myocardial infarction, stroke, congestive heart failure, cardiac arrhythmia), and mortality. RESULTS: The number of surgeries complicated by adverse limb and cardiovascular events were 356 (4.6%) and 1314 (17.0%), respectively. There were 72 in-hospital deaths (0.9%). After adjustment for clinical and demographic variables, patients with high HbA1c values (≥8%) were at an increased risk of adverse limb events (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.01-1.86) compared with those with a normal HbA1c (>6% to ≤7%). High HbA1c values were not associated with an increased risk of cardiovascular events (OR, 1.07; 95% CI, 0.81-1.43) or mortality (OR, 1.57; 95% CI, 0.83-3.03). Patients with low HbA1c values (≤6%) did not experience a significantly higher risk for any of the three outcomes. In a stratified analysis, the association of high HbA1c values with adverse limb events was only present in those presenting without critical limb ischemia (OR 1.82; 95% CI, 1.05-3.16). CONCLUSIONS: Poor preoperative glycemic control in diabetic individuals undergoing infrainguinal LEB, particularly in those without critical limb ischemia, is associated with an increased risk of in-hospital limb events. Further study should evaluate whether improved efforts to identify individuals with poorly controlled diabetes and subsequent interventions to better optimize glycemic control during the preoperative period improve limb outcomes after LEB.

Clinical Implications of Technological Advances in Screening for Atrial Fibrillation.

The incidence of atrial fibrillation (AF) continues to increase worldwide as people live longer. AF is the leading cause of stroke among patients older than 75 years and is responsible for at least 15% of all strokes. Industry has responded to this problem with a plethora of monitoring devices. These include single lead ECG adhesive sensors, implantable loop recorders, smartphone attachments and wearables. This review will concentrate on clinical studies using these technologies. There are wearables including watches and watch-like devices that will be mentioned but these have not been validated for clinical use. This review will begin with a background regarding screening for AF and at the end present findings from Cardiac Implantable devices that could influence use of the new mobile health technologies.

Low-Rank Atlas Image Analyses in the Presence of Pathologies.

We present a common framework, for registering images to an atlas and for forming an unbiased atlas, that tolerates the presence of pathologies such as tumors and traumatic brain injury lesions. This common framework is particularly useful when a sufficient number of protocol-matched scans from healthy subjects cannot be easily acquired for atlas formation and when the pathologies in a patient cause large appearance changes. Our framework combines a low-rank-plus-sparse image decomposition technique with an iterative, diffeomorphic, group-wise image registration method. At each iteration of image registration, the decomposition technique estimates a "healthy" version of each image as its low-rank component and estimates the pathologies in each image as its sparse component. The healthy version of each image is used for the next iteration of image registration. The low-rank and sparse estimates are refined as the image registrations iteratively improve. For unbiased atlas formation, at each iteration, the average of the low-rank images from the patients is used as the atlas image for the next iteration, until convergence. Since each iteration's atlas is comprised of low-rank components, it provides a population-consistent, pathology-free appearance. Evaluations of the proposed methodology are presented using synthetic data as well as simulated and clinical tumor MRI images from the brain tumor segmentation (BRATS) challenge from MICCAI 2012.

Statistical atlas construction via weighted functional boxplots.

Atlas-building from population data is widely used in medical imaging. However, the emphasis of atlas-building approaches is typically to estimate a spatial alignment to compute a mean/median shape or image based on population data. In this work, we focus on the statistical characterization of the population data, once spatial alignment has been achieved. We introduce and propose the use of the weighted functional boxplot. This allows the generalization of concepts such as the median, percentiles, or outliers to spaces where the data objects are functions, shapes, or images, and allows spatio-temporal atlas-building based on kernel regression. In our experiments, we demonstrate the utility of the approach to construct statistical atlases for pediatric upper airways and corpora callosa revealing their growth patterns. We also define a score system based on the pediatric airway atlas to quantitatively measure the severity of subglottic stenosis (SGS) in the airway. This scoring allows the classification of pre- and post-surgery SGS subjects and radiographically normal controls. Experimental results show the utility of atlas information to assess the effect of airway surgery in children.