Sepsis outcomes in solid organ transplant recipients.

BACKGROUND: We present data on a cohort of patients diagnosed with sepsis over a 10-year period comparing outcomes in solid organ transplant (SOT) and non-solid organ transplant (non-SOT) recipients. METHODS: This is a retrospective single-center study of patients with diagnosis of sepsis from 1/1/06 to 6/30/16. Cases and controls were matched by year of sepsis diagnosis with propensity score matching. Conditional logistic regression and repeated measurement models were performed for binary outcomes. Trends over time for in-hospital mortality were determined using the Cochran-Armitage test. A gamma-distributed model was performed on the continuous variables. RESULTS: Overall, there were 18 632 admission encounters with a discharge diagnosis of sepsis in 14 780 unique patients. Of those admissions, 1689 were SOT recipients. After 1:1 matching by year, there were three thousand three hundred and forty patients (1670 cases; 1670 controls) diagnosed with sepsis. There was a decreasing trend for in-hospital mortality for sepsis over time in SOT patients and non-SOT patients (P < .05) due to early sepsis recognition and improved standard of care. Despite higher comorbidities in the SOT group, conditional logistic regression showed that in-hospital mortality for sepsis in SOT patients was similar compared with non-SOT patients (odds ratio [OR] =1.14 [95% confidence interval {CI}, 0.95-1.37], P = .161). However, heart and lung SOT subgroups had higher odds of dying compared with the non-SOT group (OR = 1.83 [95% CI, 1.30-2.57], P < .001 and OR = 1.77 [95% CI, 1.34-2.34], P < .001). On average, SOT patients had 2 days longer hospital length of stay compared with non-SOT admissions (17.00 ± 19.54 vs 15.23 ± 17.07, P < .05). Additionally, SOT patients had higher odds of hospital readmission within 30 days (OR = 1.25 [95% CI, 1.06-1.51], P = .020), and higher odds for DIC compared with non-SOT patients (OR = 1.76 [95% CI, 1.10-2.86], P = .021). CONCLUSION: Sepsis in solid organ transplants and non-solid organ transplant patients have similar mortality; however, the subset of heart and lung transplant recipients with sepsis has a higher rate of mortality compared with the non-solid organ transplant recipients. SOT with sepsis as a group has a higher hospital readmission rate compared with non-transplant sepsis patients.

Analysis of Rothman Index Data to Predict Postdischarge Adverse Events in a Medical Intensive Care Unit.

OBJECTIVE: Currently, there are no objective metrics included in the intensive care unit (ICU) discharge decision making process. In this study, we evaluate Rothman Index(RI) data for a possible metric as part of a quality improvement project. Our objectives were to determine whether RI could predict adverse events occurring within 72 hours of ICU discharge decision, the optimal clinical cutoff value for this metric, and to determine whether there is a relation between the RI warning alert 24 hours prior to discharge and adverse events postdischarge. DESIGN: Retrospective observational study. SETTING: Single center tertiary hospital. PATIENTS: Adult medical ICU patients discharged from the ICU between January 20, 2015 and March 14, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 194 patients were studied with mean age of 62.74 (18.37) years. Data collection included RI at the time of decision-making for ICU discharge and the presence of any warning signals in the previous 24 hours. A 72-hour follow-up chart review recorded any adverse events, including readmission to a higher level of care, discontinuation of discharge due to clinical status change, emergency department visit if discharged home, rapid response activation, or cardiopulmonary arrest postdischarge. Adverse events after ICU discharge were observed in 31 (16%) patients with 9 events being ICU readmission (4.6%). Based on an age-adjusted multivariate model, a higher RI was associated with lower odds of an adverse event (odds ratio [OR] = 0.969, P = .006, confidence interval [CI]: 0.9487-0.9911). An RI value ≥ 50 was associated with 72% lower odds of an adverse event (OR = 0.2887, 95% CI = 0.1278-0.6517 and P = .003) compared to RI < 50. This RI cutoff value was associated with the largest decrease in odds of events. As expected, patients with a very high-risk warning alert had a higher proportion of adverse events compared to patients who did not. (31.75% vs 12.65%, P = < .02). CONCLUSIONS: Patients who have an RI < 50 or a very high-risk warning alert have a higher risk of adverse events postdischarge from the ICU. Rothman Index may be a useful metric for ICU discharge decision-making.

Both the Observer's Expertise and the Subject's Facial Symmetry Can Affect Anatomical Position of the Head.

PURPOSE: It is easier to judge facial deformity when the patient's head is in anatomic position. The purposes of this study were to determine 1) whether a group of expert observers would agree more than a group of nonexperts on what is the correct anatomic position of the head, 2) whether there would be more variation in the alignment of an asymmetrical face compared with a symmetrical one, and 3) whether the alignments of experts would be more repeatable than those of nonexperts. MATERIALS AND METHODS: Thirty-one orthodontists (experts) and 31 dental students (nonexperts) were recruited for this mixed-model study. They were shown randomly oriented 3-dimensional head photographs of an adult with a symmetrical face and an adolescent with an asymmetrical face. In viewing software, the observers oriented the images into anatomic position. They repeated the orientations 4 weeks later. Data were analyzed using a generalized linear model and Bland-Altman plots. The primary predictor variables were experience and symmetry status. The outcome variable was the anatomic position of the head. The other variables of interest included time and orientation direction. RESULTS: There was a statistically significant difference between measurements completed by experts and nonexperts (F1,60 = 14.83; P < .01). The interaction between expertise and symmetrical status showed a statistically significant difference between symmetrical and asymmetrical faces in the expert and nonexpert groups (F1,60 = 9.93; P = .003). The interaction between expertise and time showed a statistically significant difference in measurement over time in the expert and nonexpert groups (F1,60 = 4.66; P = .03). CONCLUSIONS: The study shows that experts can set a head into anatomic position better than nonexperts. In addition, facial asymmetry has a profound effect on the ability of an observer to align a head in the correct anatomic position. Moreover, observer-guided alignment is not reproducible.

Cup-to-Disc Ratio in Idiopathic Intracranial Hypertension without Papilloedema.

This study seeks to characterise potential differences in the cup-to-disc ratio (CDR) of patients with idiopathic intracranial hypertension (IIH) with papilloedema (IIHWP) compared with IIH without papilloedema (IIHWOP). The medical charts, optical coherence tomography (OCT), and digital optic disc photos of 30 patients (59 eyes) with IIHWP and 4 patients (8 eyes) with IIHWOP were reviewed retrospectively. The CDR values of the two groups were analysed using the Wilcoxon-Mann-Whitney test. Results showed a statistically significant smaller CDR in patients with IIHWP as compared with IIHWOP. These findings suggest that structural factors of the optic disc may play a role in the development of or lack thereof of papilloedema in patients with IIH.

Delphi Panel Consensus Statement Generation: COVID-19 Vaccination Recommendations for Immunocompromised Populations in the European Union.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare systems globally. The lack of quality guidelines on the management of COVID-19 in rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients has resulted in a wide variation in clinical practice. METHODS: Using a Delphi process, a panel of 16 key opinion leaders developed clinical practice statements regarding vaccine recommendations in areas where standards are absent or limited. Agreement among practicing physicians with consensus statements was also assessed via an online physician survey. The strength of the consensus was determined by the following rating system: a strong rating was defined as all four key opinion leaders (KOLs) rating the statement ≥ 8, a moderate rating was defined as three out of four KOLs rating the statement ≥ 8, and no consensus was defined as less than three out of four KOLs provided a rating of ≤ 8. Specialists voted on agreement with each consensus statement for their disease area using the same ten-point scoring system. RESULTS: Key opinion leaders in rheumatology, nephrology, and hematology achieved consensuses for all nine statements pertaining to the primary and booster series with transplant physicians reaching consensus on eight of nine statements. Experts agreed that COVID-19 vaccines are safe, effective, and well tolerated by patients with rheumatological conditions, renal disease, hematologic malignancy, and recipients of solid organ transplants. The Delphi process yielded strong to moderate suggestions for the use of COVID-19 messenger ribonucleic acid (mRNA) vaccines and the necessity of the COVID-19 booster for the immunocompromised population. The expert panel had mixed feelings concerning the measurement of antibody titers, higher-dose mRNA vaccines, and the development of disease-specific COVID-19 guidance. CONCLUSIONS: These results confirmed the necessity of COVID-19 vaccines and boosters in immunocompromised patients with rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients. Statements where consensus was not achieved were due to absent or limited evidence.

Red cell distribution width is a predictor of mortality in patients undergoing percutaneous coronary intervention.

Red cell distribution width (RDW), a measure of the variability in size of circulating erythrocytes, is an independent predictor of mortality in patients with cardiovascular disease. We hypothesized that RDW is a prognostic marker of death, myocardial infarction and unplanned revascularization in a broad population undergoing percutaneous coronary intervention (PCI). We investigated the prognostic value of RDW derived from a complete blood count drawn ≤24 h of PCI in 1,689 patients at four centers who underwent PCI between 2004 and 2007 in the evaluation of drug eluting stents and ischemic events registry. Patients who underwent blood transfusions were excluded. Multivariable analyses of death, MI, unplanned revascularization, and the combined occurrence of these events at 1 year were performed using methods from survival analysis. The analysis was adjusted for creatinine ≥1.5 mg/dL, hemoglobin, congestive heart failure, coronary artery bypass grafting history, male sex, BMI, atherosclerosis of ≥2 coronary vessels, and hypertension. In univariate analysis of RDW stratified by quartiles, membership in the highest quartile was a predictor of mortality as compared to the lowest quartile (HR 5.07, CI 2.07-12.40, p < 0.001). In multivariate analysis, RDW was not an independent predictor of unplanned revascularization after PCI; however, RDW remained an independent correlate of 1 year mortality (HR 1.65, CI 1.22-2.23, p = 0.001); with a continuous net reclassification improvement of 46.5% (95% CI 15.1-76.4%) and a relative integrated discrimination improvement of 57.8% (95% CI 22.1-94.9%) after PCI. RDW is a widely available independent correlate of 1-year mortality after PCI that increases the discriminative value of risk prediction in these patients.

Coronary artery calcium scoring in the emergency department: identifying which patients with chest pain can be safely discharged home.

STUDY OBJECTIVE: Coronary artery calcium scoring (CACS) is a simple and readily available test for identifying coronary artery disease. Our objective is to evaluate whether a CACS of zero will identify chest pain patients who can be safely discharged home, without need for further cardiac testing. METHODS: This was a prospective observational cohort study conducted at an urban tertiary care hospital of stable patients presenting to the emergency department (ED) with chest pain of uncertain cardiac cause. Patients with a normal initial troponin level, nonischemic ECG, and no history of coronary artery disease had stress myocardial perfusion imaging (SPECT) and CACS within 24 hours of ED admission. Cardiac events were defined as an acute coronary syndrome during the index hospitalization or in follow-up. CACS results were assessed in relation to SPECT findings and cardiac events. RESULTS: The 1,031 patients enrolled (mean [SD] age 54 [13] years) had a median CACS of 0 (61% with CACS of 0). The frequency of an abnormal SPECT ranged from 0.8% (CACS of 0) to17% (CACS>400). Cardiac events occurred in 32 patients (3.1%) during the index hospitalization (N=28) or after hospital discharge (N=4) (mean 7.4 [3.3] months). Only 2 events occurred in 625 patients with a CACS of 0 (0.3%; 95% confidence interval 0.04% to 1.1%). Thus, 2 of 32 patients with a cardiac event had a CACS of 0 (6%; 95% confidence interval 0.8% to 21%). Both of these patients developed increased troponin levels during their index visit but had normal serial ECG and SPECT study results and no cardiac events at 6-month follow-up. CONCLUSION: A majority of patients (61% in our sample) evaluated for chest pain of uncertain cardiac cause have a CACS of 0, which predicts both a normal SPECT result and an excellent short-term outcome. Our results suggest that patients with a CACS of 0 can be discharged home, without further cardiac testing.

How Leading Hospitals Operationalize Evidence-Based Readmission Reduction Strategies: A Mixed-Methods Comparative Study Using Systematic Review and Survey Design.

Although various interventions targeted at reducing hospital readmissions have been identified in the literature, little is known about actual operationalization of such evidence-based interventions. This study conducted a systematic review and a survey of key informants in 2 leading hospitals, Houston Methodist (HM) and MD Anderson Cancer Center (MDACC), to compare and contrast the most cited evidence-based interventions in the current literature with interventions reported by those hospitals. The authors found that both hospitals followed evidence-based practices reported as successful in the literature. Both hospitals have implemented interventions for inpatient settings, and the timing of interventions was very similar. Major implementation differences observed for post-discharge interventions focused on collaboration. It also was found that HM was more likely than MDACC to use medication reconciliation in outpatient (P = .018) and discharge planning for community/home patients (P = .032). Results will provide hospital professionals with insights for implementing the most effective interventions to reduce readmissions.

Eighty-six Percent Failure Rate of a Modular-Neck Femoral Stem Design at 3 to 5 Years: Lessons Learned.

BACKGROUND: While innovation drives advancement, it is not immune to failure. Previously, we reported a corrosion-related revision rate of 28% (23 of 81 total hip arthroplasties) among patients who received the Rejuvenate modular-neck stem implant with short-term follow-up. Because we observed a dramatic interval failure rate after our initial report, we undertook this study. METHODS: We prospectively followed a cohort of patients who had undergone implantation of the Rejuvenate modular-neck stem, as previously reported. At a minimum of 3 years of follow-up (range, 3.0 to 5.5 years), 73 hips in 63 patients (90% of the original group) were available for analysis. The mean serum cobalt and chromium ion levels were obtained preoperatively and postoperatively. Elevated serum cobalt ion levels (>4 µg/L), pain, or abnormal magnetic resonance imaging (MRI) findings were indications for revision surgery. Patient factors and serum metal ion levels were correlated to revision surgery. Additionally, post-revision serum cobalt and chromium ion level trends were assessed. RESULTS: An 86% clinical failure rate (63 of the 73 hips) was observed at a mean follow-up of 4.2 ± 0.6 years (range, 3.0 to 5.5 years); 57 (78%) of the hips underwent revision at a mean of 3.2 ± 1.0 years (range, 1.0 to 5.5 years), and 6 (8%) of the hips were scheduled for revision. Patients who underwent revision surgery were younger and had greater serum metal ion levels and greater pain compared with patients who did not undergo revision. An elevated serum cobalt ion level was the most important independent factor associated with revision surgery. Cobalt ion levels decreased sharply after revision; however, some patients demonstrated persistent elevation with more gradual decline. CONCLUSIONS: Emphasizing the reporting of positive results may leave orthopaedic surgeons reticent to publicize negative results; however, the high failure rate of this implant design within 5 years prompted this report. We believe that patients and orthopaedic surgeons should be made aware of this implant's clinical problems and patients should be followed closely. Expedient revision is necessary when failure is identified, to minimize potentially severe tissue damage and metal toxicity. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors.

PURPOSE: Accumulating evidence supports the existence of breast cancer stem cells (BCSC), which are characterized by their capacity to self-renew and divide indefinitely and resistance to conventional therapies. The Notch pathway is important for stem cell renewal and is a potential target for BCSC-directed therapy. EXPERIMENTAL DESIGN: Using human breast tumorgraft studies, we evaluated the impact of gamma secretase inhibitors (GSI) on the BCSC population and the efficacy of combining GSI with docetaxel treatment. The mouse experimental therapy paralleled a concurrent clinical trial in patients with advanced breast cancer, designed to determine the maximum-tolerated dose of the GSI, MK-0752, administered sequentially with docetaxel, and to evaluate BCSC markers in serial tumor biopsies. RESULTS: Treatment with GSI reduced BCSCs in MC1 and BCM-2147 tumorgrafts by inhibition of the Notch pathway. GSI enhanced the efficacy of docetaxel in preclinical studies. In the clinical trial, 30 patients with advanced breast cancer were treated with escalating doses of MK-0752 plus docetaxel. Clinically, meaningful doses of both drugs were possible with manageable toxicity and preliminary evidence of efficacy. A decrease in CD44(+)/CD24(-), ALDH(+), and mammosphere-forming efficiency were observed in tumors of patients undergoing serial biopsies. CONCLUSIONS: These preclinical data show that pharmacologic inhibition of the Notch pathway can reduce BCSCs in breast tumorgraft models. The clinical trial shows feasibility of combination GSI and chemotherapy, and together these results encourage further study of Notch pathway inhibitors in combination with chemotherapy in breast cancer.

Leptin replacement therapy does not improve the abnormal lipid kinetics of hypoleptinemic patients with HIV-associated lipodystrophy syndrome.

Patients with HIV-associated dyslipidemic lipodystrophy (HADL) have characteristic lipid kinetic defects: accelerated lipolysis, blunted fat oxidation and increased hepatic fatty acid reesterification. HADL patients with lipoatrophy also have leptin deficiency. Small or non-randomized studies have suggested that leptin replacement improves glucose metabolism in HADL, with very limited data regarding its effects on the lipid kinetic abnormalities. We performed a randomized, double-blind, placebo-controlled, dose-escalating (0.02 mg/kg/d for two months; 0.04 mg/kg/d for a further two months) study of the effects of metreleptin on lipid kinetics in 17 adults with HADL, hypertriglyceridemia and hypoleptinemia. Rates of lipolysis, intra-adipocyte and intrahepatic reesterification and fatty acid oxidation were measured using infusions of (13)C(1)-palmitate and (2)H(5)-glycerol, and indirect calorimetry. Fasting lipid profiles and glucose and insulin responses to oral glucose challenge were also measured. Metreleptin treatment induced significant, dose-dependent increases in fasting plasma leptin levels. There was no significant change in total lipolysis, net lipolysis, adipocyte or hepatic re-esterification or fatty acid oxidation, or in fasting triglyceride or HDL-C concentrations, with metreleptin treatment. Metreleptin decreased fasting non-HDL-C levels (P<.01) and area-under-the-curve for glucose (P<.05). In hypoleptinemic HADL patients, treatment with metreleptin at 0.02 or 0.04 mg/kg/d does not improve abnormal fasting lipid kinetics, or triglyceride or HDL-C levels. Metreleptin does, however, improve glycemia and non-HDL-C in these patients. These results suggest a dissociation between leptin's effects on glucose metabolism compared to those on lipid kinetics in HADL.

Differences in risk factors for coronary heart disease among diabetic and nondiabetic individuals from a population with high rates of diabetes: the Strong Heart Study.

CONTEXT: Coronary heart disease (CHD) is the leading cause of death in the United States. OBJECTIVE: This study compares differences in risk factors for CHD in diabetic vs. nondiabetic Strong Heart Study participants. DESIGN: This was an observational study. SETTING: The study was conducted at three centers in Arizona, Oklahoma, and North and South Dakota. PARTICIPANTS: Data were obtained from 3563 of 4549 American Indians free of cardiovascular disease at baseline. INTERVENTION(S): CHD events were ascertained during follow-up. MAIN OUTCOME MEASURE: CHD events were classified using standardized criteria. RESULTS: In diabetic and nondiabetic participants, 545 and 216 CHD events, respectively, were ascertained during follow-up (21,194 and 22,990 person-years); age- and sex-adjusted incidence rates of CHD were higher for the diabetic group (27.5 vs. 12.1 per 1,000 person-years). Risk factors for incident CHD common to both groups included older age, male sex, prehypertension or hypertension, and elevated low-density lipoprotein cholesterol. Risk factors specific to the diabetic group were lower high-density lipoprotein cholesterol, current smoking, macroalbuminuria, lower estimated glomerular filtration rate, use of diabetes medication, and longer duration of diabetes. Higher body mass index was a risk factor only for the nondiabetic group. The association of male sex and CHD was greater in those without diabetes than in those with diabetes. CONCLUSIONS: In addition to higher incidence rates of CHD events in persons with diabetes compared with those without, the two groups differed in CHD risk factors. These differences must be recognized in estimating CHD risk and managing risk factors.