Citations

AbstractEculizumab is effective for complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome. Although lifelong therapy had been suggested, discontinuation does not universally lead to relapse. Comprehensive data evaluating risk factors for recurrence following discontinuation are limited. Our aim was to systematically review available literature assessing the role of complement genetic variants in this setting. Reports on CM-TMA and eculizumab withdrawal published before 1 January 2021, were included. Key reasons for patient exclusion were no follow-up after drug withdrawal and patients lacking complement genetic testing. Two-hundred eighty patients from 40 publications were included. Median age was 28 years, and 25 patients had a known history of renal transplant. Complement genetic variants were identified in 60%, most commonly in CFH (n = 59) and MCP/CD46 (n = 38). Of patients with a complement gene variant, 51.3% had ≥1 likely pathogenic/pathogenic variant whereas the remaining had variants of uncertain significance (VUS). Overall relapse rate after therapy discontinuation was 29.6%. Relapse rate was highest among patients with CFH variants and MCP/CD46 variants in canonical splice regions. VUS (P < .001) and likely pathogenic/pathogenic variants (P < .001) were associated with increased relapse. Presence of a renal allograft (P = .009); decreasing age (P = .029); and detection of variants in CFH (P < .001), MCP/CD46 (P < .001), or C3 (P < .001) were all independently associated with relapse after eculizumab discontinuation. Eculizumab discontinuation is appropriate in specific patients with CM-TMA. Caution should be exerted when attempting such a strategy in patients with high risk of recurrence, including a subgroup of patients with MCP/CD46 variants.

The evidence base supporting the management of patients with acute stroke is evolving at a rapid rate, as new methods that aim to reduce disability and death from stroke are explored. Intravenous tissue plasminogen activator remains the only treatment shown in numerous studies to reduce disability 3 months after stroke with no increase in the risk of death and a relatively minor rate of symptomatic intracerebral hemorrhage complications. Despite these findings, health care providers have been slow to adopt this evidence-based treatment, which results in many patients experiencing disability caused by stroke. Numerous controversies exist related to the management of patients with acute stroke, including the use of tissue plasminogen activator, positioning and early mobility, blood pressure lowering in acute intracerebral hemorrhage, and even the use of innovative advanced practice nurse–led stroke treatment teams, with varying amounts of evidence available to provide direction. This article explores controversies associated with both approved and evolving treatments for ischemic and hemorrhagic stroke and makes recommendations for practice on the basis of the body of existing evidence, with an aim to improve the delivery of acute stroke treatment.

Abstract Purpose To examine associations of social support and social isolation with burnout, program satisfaction, and organization satisfaction among a large population of U.S. residents and fellows and to identify correlates of social support and social isolation. Method All residents and fellows enrolled in graduate medical education programs at Mayo Clinic sites were surveyed in February 2019. Survey items measured social support (emotional and tangible), social isolation, burnout, program satisfaction, and organization satisfaction. Factors of potential relevance to social support were collected (via the survey, institutional administrative records, and interviews with program coordinators and/or program directors) and categorized as individual, interpersonal, program, or work-related factors (duty hours, call burden, elective time, vacation days used before survey administration, required away rotations, etc.). Multivariable regression analyses were conducted to examine relationships between variables. Results Of 1,146 residents surveyed, 762 (66%) from 58 programs responded. In adjusted models, higher emotional and tangible support were associated with lower odds of burnout and higher odds of program and organization satisfaction, while higher social isolation scores were associated with higher odds of burnout and lower odds of program satisfaction and organization satisfaction. Independent predictors of social support and/or social isolation included age, gender, relationship status, parental status, postgraduate year, site, ratings of the program leadership team, ratings of faculty relationships and faculty professional behaviors, satisfaction with autonomy, and vacation days used before survey administration. Conclusions This study demonstrates that social support and social isolation are strongly related to burnout and satisfaction among residents and fellows. Personal and professional relationships, satisfaction with autonomy, and vacation days are independently associated with social support and/or social isolation, whereas most program and work-related factors are not. Additional studies are needed to determine if social support interventions targeting these factors can improve well-being and enhance satisfaction with training.

The combination of endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitors is currently one of the preferred first-line regimens for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. CDK 4/6 inhibitors can cause serum creatinine (SCr) elevation and corresponding estimated glomerular filtration rate (eGFR) reduction without affecting kidney function by inhibiting tubular secretory transporters in the kidneys—a phenomenon called pseudo-acute kidney injury (pseudo-AKI). We report a case of a 69-year old woman found to have elevated SCr while on ribociclib for treatment of metastatic breast cancer. Further evaluation with cystatin C-based eGFR and measured GFR by urinary iothalamate clearance revealed values close to her baseline Cr-based eGFR prior to initiation of treatment with ribociclib. She was therefore diagnosed with ribociclib-induced pseudo-AKI. Treatment with ribociclib was continued with steady favorable response. This case highlights that, in addition to true AKI, ribociclib can cause pseudo-AKI. Alternative methods of kidney function assessment may be necessary in patients who develop elevated SCr while on this medication to help discriminate between artifactual and true kidney function impairment. Doing so can help avoid unnecessary work-up and/or premature discontinuation of the treatment.

Abstract Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2022 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2022 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2022 were based on a combination of quantitative analyses and expert opinion. Results In 2021, overall pharmaceutical expenditures in the US grew 7.7% compared to 2020, for a total of $576.9 billion. Utilization (a 4.8% increase), price (a 1.9% increase) and new drugs (a 1.1% increase) drove this increase. Adalimumab was the top drug in terms of overall expenditures in 2021, followed by apixaban and dulaglutide. Drug expenditures were $39.6 billion (a 8.4% increase) and $105.0 billion (a 7.7% increase) in nonfederal hospitals and in clinics, respectively. In clinics and hospitals, new products and increased utilization growth drove growth, with decreasing prices for both sectors acting as an expense restraint. Several new drugs that are likely to influence spending are expected to be approved in 2022. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. Conclusion For 2022, we expect overall prescription drug spending to rise by 4.0% to 6.0%, whereas in clinics and hospitals we anticipate increases of 7.0% to 9.0% and 3.0% to 5.0%, respectively, compared to 2021. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

Abstract Background: The use of cold whole blood (WB) is rapidly resurging as one of the treatment modalities of choice for the initial resuscitation of civilian trauma patients across the United States. The purpose of our study was to evaluate the effectiveness and safety of cold whole blood (WB) as compared to blood component therapy (BCT) in resuscitation of civilian trauma patients. Methods: This was a retrospective cohort study of trauma patients who received at least one unit of WB transfusion during emergent resuscitation between November 2015 and October 2019 at a level I trauma center. Primary outcome was mortality up to 30 days after trauma. Secondary outcomes included overall blood product utilization and incidence of transfusion reactions. Outcomes were compared between patients who received WB and a cohort receiving BCT who did not receive WB matched for age, sex, mechanism of injury, heart rate, systolic blood pressure, Glasgow Coma Scale, injury severity score, and FAST results. Results: We included 78 patients who received WB transfusion and 78 matched controls. Within 30 days of injury, there were 19 deaths (24.4%) in the WB cohort and 28 (35.9%) deaths in controls (hazard ratio 0.62, 95% CI 0.33 to 1.15, p = 0.086). Patients in the WB cohort received as many units of blood products as controls (median number of units was 10 (IQR 6, 20) vs. 12 (IQR 6, 23), p = 0.43). The incidence of any transfusion reactions was similar between groups (7.7% in WB vs 9.0% in controls, p = 0.78). Life-threatening reactions did not occur in any of the groups. Conclusions: There was no mortality difference between patients receiving cold WB and BCT. Cold WB was safe in this cohort with no life-threatening transfusion reactions.

Carbapenem-resistant Acinetobacter baumannii (CR Ab ) constitutes a major threat to public health. To elucidate the molecular and clinical epidemiology of CR Ab in the United States, clinical CR Ab isolates were collected along with data on patient characteristics and outcomes, and bacterial isolates underwent whole-genome sequencing and antibiotic susceptibility phenotyping.

Determinants of Intra-renal oxygenation in human RVD are poorly understood. Blood oxygen level-dependent (BOLD) MRI measures deoxyhemoglobin (R2*) to determine cortical and medullary R2* which have focal variations and gradients. We hypothesized that tissue fractional hypoxia (% of axial kidney area with R2*>30s -1 ) would correlate better with tissue perfusion, renal blood flow (RBF), and O2 consumption than using regions of interest (ROI). METHODS: Inpatient studies were performed in EH (n=68 kidneys), and high-grade RVD (n=18 kidneys, 71±5.5% occlusion) before and 3 months after stents. All were treated with ACE/ARB Rx and thiazides during 150 mEq/d Na+ intake. BOLD MR images were obtained at 3T before and after furosemide (20mg IV), and axial images analyzed to estimate R2* levels above 30s -1 (fractional hypoxia) over the entire kidney section. Maximal R2* levels using regions of interest (ROIs) also were determined. Single-kidney cortical and medullary RBF (ml/min) perfusion (ml/min/cc) were determined by MDCT. Results: RBF was lower in kidneys with untreated RVD than EH (285.6±141 vs. 399±159 ml/min p<0.05), as was cortical perfusion (2.58±.63 vs. 3.50±1.05, p<.05 ). Cortical and medullary R2* did not differ, but fractional hypoxia was greater in RVD as compared to EH (18.3±12 vs. 11.5±8.5%, p<.05). Fractional hypoxia was inversely correlated with blood flow (R=-.29, p<.01) and perfusion (R=-.26, p<.01). R2* fell after furosemide (p<0.01) indicating a role for O2 consumption in determining tissue hypoxia. RBF and cortical perfusion increased after stenting (285±141 vs. 318±178 ml/min and 2.58±0.6 vs. 2.9±0.7ml/min/cc, p<0.05) respectively. Fractional hypoxia, but not cortical or medullary R2* based on ROI-methods, decreased in patients 3 months after renal revascularization (18.3 ±12 vs. 10.52%, p<0.05) Conclusions: These data demonstrate for the first time that fractional hypoxia in the kidney is directly related to chronically reduced blood flow and cortical perfusion in human RVD, whereas selective ROI-based measures identified only minor changes in peak R2* gradients between cortex and medulla. The reversibility of fractional hypoxia after stenting supports the use of this new method to identify critical renovascular lesions.