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Background: Immediate extubation is becoming more common in liver transplantation. However, limited data exist on how to identify pediatric patients with potential for successful immediate extubation and how this intervention may affect recovery. Methods: This retrospective review evaluated patients who underwent liver transplantation from 2015 to 2021 at Children's Healthcare of Atlanta. Preoperative status and intraoperative management were evaluated and compared. Outcomes comprised thrombosis, surgical reexploration, retransplantation, as well as reintubation, high flow nasal cannula (HFNC) usage, postoperative infection, the length of stay (LOS), and mortality. Results: A total of 173 patients were analyzed, with 121 patients (69.9%) extubated immediately. The extubation group had older age (median 4.0 vs 1.25 years, p =.048), lower PELD/MELD (28 vs. 34, p =.03), decreased transfusion (10.2 vs. 41.7 mL/kg, p <.001), shorter surgical time (332 vs. 392 min, p <.001), and primary abdominal closure (81% vs. 40.4%, p <.001). Immediate extubation was associated with decreased HFNC (0.21 vs. 0.71 days, p =.02), postoperative infection (9.9% vs. 26.9%, p =.007), mortality (0% vs. 5.8%, p =.036), and pediatric intensive care unit LOS (4.7 vs. 11.4 days, p <.001). The complication rate was lower in the extubation group (24.8% vs. 36.5%), but not statistically significant. Conclusions: Approximately 70% of patients were able to be successfully extubated immediately, with only 2.5% requiring reintubation. Those immediately extubated had decreased need for HFNC, lower infection rates, shorter LOS, and decreased mortality. Our results show that with proper patient selection and a multidisciplinary approach, immediate extubation allows for improved recovery without increased respiratory complications after pediatric liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Children admitted to the pediatric intensive care unit (PICU), after liver transplantation, frequently require analgesia and sedation in the immediate postoperative period. Our objective was to assess trends and variations in sedation and analgesia used in this cohort. Methods: Multicenter retrospective cohort study using the Pediatric Health Information System from 2012 to 2022. Results: During the study period, 3963 patients with liver transplantation were admitted to the PICU from 32 US children's hospitals with a median age of 2 years [IQR: 0.00, 10.00]. 54 percent of patients received mechanical ventilation (MV). Compared with patients without MV, those with MV were more likely to receive morphine (57% vs 49%, p <.001), fentanyl (57% vs 44%), midazolam (45% vs 31%), lorazepam (39% vs. 24%), dexmedetomidine (38% vs 30%), and ketamine (25% vs 12%), all p <.001. Vasopressor usage was also higher in MV patients (22% vs. 35%, p <.001). During the study period, there was an increasing trend in the utilization of dexmedetomidine and ketamine, but the use of benzodiazepine decreased (p <.001). Conclusion: About 50% of patients who undergo liver transplant are placed on MV in the PICU postoperatively and receive a greater amount of benzodiazepines in comparison with those without MV. The overall utilization of dexmedetomidine and ketamine was more frequent, whereas the administration of benzodiazepines was less during the study period. Pediatric intensivists have a distinctive opportunity to collaborate with the liver transplant team to develop comprehensive guidelines for sedation and analgesia, aimed at enhancing the quality of care provided to these patients. [ABSTRACT FROM AUTHOR]

Many targeted therapies are administered at or near the maximum tolerated dose (MTD). With the advent of precision medicine, a larger therapeutic window is expected. Therefore, dose optimization will require a new approach to early clinical trial design. We analyzed publicly available data for 21 therapies targeting six kinases, and four poly (ADP‐ribose) polymerase inhibitors, focusing on potency and exposure to gain insight into dose selection. The free average steady‐state concentration (Css) at the approved dose was compared to the in vitro cell potency (half‐maximal inhibitory concentration (IC50)). Average steady‐state area under the plasma concentration‐time curve, the fraction unbound drug in plasma, and the cell potency were taken from the US drug labels, US and European regulatory reviews, and peer‐reviewed journal articles. The Css was remarkably similar to the IC50. The median Css/IC50 value was 1.2, and 76% of the values were within 3‐fold of unity. However, three drugs (encorafenib, erlotinib, and ribociclib) had a Css/IC50 value > 25. Seven other therapies targeting the same 3 kinases had much lower Css/IC50 values ranging from 0.5 to 4. These data suggest that these kinase inhibitors have a large therapeutic window that is not fully exploited; lower doses may be similarly efficacious with improved tolerability. We propose a revised first‐in‐human trial design in which dose cohort expansion is initiated at doses less than the MTD when there is evidence of clinical activity and Css exceeds a potency threshold. This potency‐guided approach is expected to maximize the therapeutic window thereby improving patient outcomes. [ABSTRACT FROM AUTHOR]

Sexual assault evidence often contains sperm cells, which are typically separated from nonsperm cells using manual differential lysis procedures. The goal of this study was to evaluate the automated QIAGEN QIAcube for this purpose and to compare it to manual QIAGEN and manual organic differential methods using DNA yields and STR profile data for assessment. DNA yields were determined by qPCR, followed by multiplex STR amplification, CE analysis, and mixture interpretation. The automated method was capable of effective cell separation, producing DNA yields sufficient for STR amplification. Further, sperm fraction human:male DNA ratios from the QIAcube samples were consistently closer to the desired 1:1 and STR profiles were less likely to result in mixtures, with 6–8× fewer female alleles detected (median 1.5 alleles). Ultimately, using the QIAcube for automated differential processing of semen-containing mixtures reduces the need for downstream mixture interpretation and improves STR profile quality with substantially less hands-on time. [ABSTRACT FROM AUTHOR]

Semaphorins (Semas) are a family of secreted and transmembrane proteins that play critical roles in development. Interestingly, several vertebrate transmembrane Sema classes are capable of producing functional soluble ectodomains. However, little is known of soluble Sema6 ectodomains in the nervous system. Herein, we show that the soluble Sema6A ectodomain, sSema6A, exhibits natural and protein kinase C (PKC)‐induced release. We show that PKC mediates Sema6A phosphorylation at specific sites and while this phosphorylation is not the primary mechanism regulating sSema6A production, we found that the intracellular domain confers resistance to ectodomain release. Finally, sSema6A is functional as it promotes the cohesion of zebrafish early eye field explants. This suggests that in addition to its canonical contact‐mediated functions, Sema6A may have regulated, long‐range, forward‐signaling capacity. [ABSTRACT FROM AUTHOR]

Background: Metformin is the most commonly used drug for type 2 diabetes. Research has shown that metformin also has a protective effect on endothelium by decreasing endothelial vascular reactivity. We hypothesize that metformin will decrease restenosis/reintervention rates in patients receiving lower extremity non–drug-eluting stents (nDESs) in the superficial femoral artery(SFA) and/or popliteal artery. Materials/Methods: Retrospective study was performed on 187 patients from October 2012 to December 2015 who received an nDES in the SFA and/or popliteal artery. Patients were divided into 3 groups (Table 1) and compared against for duplex based restenosis (>60%) rates, limb loss rates, and reintervention rates. Each patient's Trans-Atlantic-Inter-Society-Consensus II (TASC-II) class was collected. Postoperative duplex was performed 1 week after the procedure, then every 3 months for the first year, then, every 6 months to check for patency. IBM-SPSS-22 was used for all analyses. Results: Average age of the patients was 64.65 ± 73.4 years. 101 patients had 101 procedures performed on the left lower extremity; 86 patients had 86 procedures performed on the right lower extremity; 123 patients were male and 64 were female. Average length of follow-up was 13.1±9.7 months. Most common indication for intervention was claudication, followed by critical limb threatening ischemia. Restenosis and reintervention by groups can be seen in Table 1. No patients experienced limb loss. There were no statistically significant differences between any of the 3 groups and their limb loss, restenosis, or reintervention rates. Conclusions: Despite having multiple proven effects in improving certain clinical outcomes and a proven protective effect on endothelium by decreasing endothelial vascular reactivity, metformin does not appear to reduce restenosis or reintervention rates in patients receiving lower extremity nDESs in the SFA and/or popliteal artery. [ABSTRACT FROM AUTHOR]

The marketing manager faces several dilemmas when analyzing multivariate frequency data. If the choice is to analyze a series of two-dimensional condensed tables, the interrelationships between those factors not in the table will be lost and biased inferences can result. If the decision is to analyze the complete multiway table, many of the cells may be sparse. The authors address the issue of how best to handle sparse-cell values in the context of a marketing data set relating store choice behavior to a number of shopper-specific variables. A simple new approach to this problem, which utilizes loglinear modeling techniques, is developed and contrasted with alternative remedies. The results of the comparative analysis show the proposed approach performs well, especially in the correct classification of seemingly unclassifiable shoppers. [ABSTRACT FROM AUTHOR]

Buyer usage behavior data are used to compare the relative performance of a linear discriminant analysis and several multinomial classification methods. The potential shortcomings of each of the procedures investigated are cited, and a new method for determining the contribution of a variable to discrimination in the context of the multinomial classification problem also is presented. [ABSTRACT FROM AUTHOR]

Minority individuals are disproportionately charged and convicted of crimes in this country. Making matters worse is the fact that many housing providers use criminal history housing applications that disparately impact minority housing applicants. In 2016, after the U.S. Supreme Court held in 2015 that disparate impact liability was cognizable under the Fair Housing Act, the Department of Housing and Urban Development (HUD) issued legal guidance to address how disparate impact liability specifically applies in situations involving housing providers' use of criminal history in housing applications. While the legal guidance could, and should, have significantly impacted the housing market and formerly incarcerated individuals' ability to obtain fair housing HUD's avoidance of notice-and-comment rulemaking when issuing its legal guidance creates an administrative dilemma that will diminish the legal guidance's impact. In light of this, I propose recommendations for HUD moving forward. HUD should either promulgate a proposed rule that is substantively similar to the 2016 legal guidance or, alternatively, promulgate a proposed rule that implements the ideas of the ban-the-box movement from the employment context into the housing context. In either situation, HUD should follow notice-and-comment rulemaking to promulgate the new rule. [ABSTRACT FROM AUTHOR]

Background: Previous research has demonstrated that cancer survivors often fail to receive recommended care and also undergo unnecessary care; this reduces care quality and increases costs.Methods: This phase 2 trial randomized 100 stage 0 to IIIa breast cancer patients who had primary care providers within a large Massachusetts-based hospital network (with accessible online records) to either coordinated follow-up care (CC), which entailed a tailored survivorship care plan (SCP) and patient navigator calls every 3 months, or standard care (SC), which did not include an SCP or patient navigation, for 1 year after the completion of their last chemotherapy, surgery, or radiation treatment. The primary endpoint was the frequency of redundant examinations (>1 breast/chest wall examination per patient within any 30-day period in the absence of a new breast or chest wall complaint) over the year of follow-up. The total number of non-plastic surgery visits in the year of follow-up was a secondary endpoint.Results: Two patients (both on CC) were ineligible, and 2 patients (1 per arm) had a recurrence or died during follow-up; this left 96 for analysis (47 in the CC arm and 49 in the SC arm). Twenty-two of the 47 CC patients (47%; 95% confidence interval, 32%-62%) and 19 of the 49 SC patients (39%; 95% confidence interval, 25%-54%) had 1 or more redundant breast/chest wall examinations during the year. The median number of non-plastic surgery visits was 12 for CC patients and 8 for SC patients.Conclusions: Early-stage breast cancer patients visit health care providers very frequently during their first year of follow-up and often receive unnecessary breast/chest wall examinations. An SCP and patient navigator calls did not reduce this surrogate for redundant care. Cancer 2016;122:3546-3554. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

A 55-year-old male patient presented after a single shock caused by oversensing of isolated nonphysiologic signals on both the distal HV and pace-sense channels. No other abnormalities were found. He subsequently returned complaining of device 'vibration' and his St. Jude implantable defibrillator (ICD; St. Jude Medical, St. Paul, MN, USA) was found to be in VVI backup mode and could not be interrogated. Direct testing in the electrophysiology lab showed normal lead impedances and thresholds with an inability to reproduce the abnormal signals. Detailed cine fluoroscopy of the leads found no abnormalities. A new ICD was connected and successfully delivered a 20-joule shock but failed to deliver a maximum output (39-joule) shock. The new ICD was again found to be in backup mode. A new Endotak Reliance G lead (Boston Scientific, Natick, MA, USA) was implanted and a maximum-output shock was successful using a new Fortify DR ICD. This case likely represents a Durata lead insulation defect in the form of an inside-out abrasion under the distal HV coil. Increased awareness of this defect is warranted, particularly since routine interrogation and submaximum-output shocks may fail to detect the problem. [ABSTRACT FROM AUTHOR]

Reoperation of cardiac surgery (RCS) is linked to higher mortality and morbidity than the first operation partially due to increased technical difficulties and the risk of injuring vital structures during the surgical reentry. The use of contrast-enhanced electrocardiogram (ECG)-gated cardiac computed tomographic (CT) angiography can mitigate the risk of surgical reentry during RCS by providing a detailed preoperative structural evaluation. As a result, in 2010 the Appropriate Use Criteria of the American College of Cardiology rated this application of cardiac CT angiography as an appropriate use of this technology. In the present manuscript we reviewed the current role of cardiac CT for surgical guidance in patients undergoing redo of cardiac surgery. [ABSTRACT FROM AUTHOR]

While multi-detector cardiac computed tomography angiography (MDCCTA) prior to reoperative cardiac surgery (RCS) has been associated with improved clinical outcomes, its impact on hospital charges and length of stay remains unclear. We studied 364 patients undergoing RCS at Washington Hospital Center between 2004 and 2008, including 137 clinically referred for MDCCTA. Baseline demographics, procedural data, and perioperative outcomes were recorded at the time of the procedure. The primary clinical endpoint was the composite of perioperative death, myocardial infarction (MI), stroke, and hemorrhage-related reoperation. Secondary clinical endpoints included surgical procedural variables and the perioperative volume of bleeding and transfusion. Length of stay was determined using the hospital's electronic medical record. Cost data were extracted from the hospital's billing summary. Analysis was performed on individual categories of care, as well as on total hospital charges. Data were compared between subjects with and without MDCCTA, after adjustment for the Society of Thoracic Surgeons score. Baseline characteristics were similar between the two groups. MDCCTA was associated with shorter procedural times, shorter intensive care unit stays, fewer blood transfusions, and less frequent perioperative MI. There was additionally a trend towards a lower incidence of the primary endpoint (17.5 vs. 24.2 %, p = 0.13) primarily due to a lower incidence of perioperative MI (0 vs. 5.7 %, p = 0.002). MDCCTA was also associated with lower median recovery room [$1,325 (1,250-3,302) vs. $3,217 (1,325-5,353) p < 0.001] and nursing charges [$6,335 (3,623-10,478) vs. $6,916 (3,915-14,499) p = 0.03], although operating room charges were higher [$24,100 (22,300-29,700) vs. $23,500 (19,900-27,700) p < 0.05]. Median total charges [$127,000 (95,000-188,000) vs. $123,000 (86,800-226,000) p = 0.77] and length of stay [9 days (6-19) vs. 11 days (7-19), p = 0.21] were similar. Means analysis demonstrated a strong trend towards lower mean total hospital charges [$163,000 (108,426) vs. $192,000 (181,706), p = 0.06] in the MDCCTA group. In conclusion, preoperative MDCCTA is associated with a number of improved perioperative outcomes and does not significantly effect the length of stay or total hospital charges during the index hospitalization. [ABSTRACT FROM AUTHOR]

In this article, the authors focus on changes to U.S. export controls and economic sanctions in 2012. They inform that the U.S. Department of Commerce Bureau of Industry and Security (BIS) has issued the Transition Rule in order to harmonize Export Administration Regulations (EAR) license exceptions for government uses. Other topics include the U.S. Department of State Directorate of Defense Trade Controls (DDTC) and the 2012 National Defense Authorization Act (NDAA).

The article presents information on the significant developments in the laws related to economic sanctions and export controls of the U.S. that took place in the year 2011. The proposed and final rules published in the Export Control Reform Initiative by the U.S. President Barack Obama and the licensing agency based on single information technology platform are discussed. The problems due to political unrest in Middle East North Africa and Middle East are also discussed.

The aim of cancer immunotherapy is to induce immune cells to kill tumor and promote immunological memory that protects against tumor recurrence. Most current immunotherapies, such as monoclonal antibodies (mAb), target the tumor cells directly. Advances in our understanding of the immune system such as the role of co-stimulatory and co-inhibitory receptors, and the advent of new immunomodulatory agents provide new opportunities to target the immune system and enhance anti-tumor immune responses. These promising agents include immunomodulating mAbs, Toll-like receptor agonists, IMiDs, and cytokines. In this review, we discuss the current results of immunomodulating agents in the treatment of hematological malignancies and propose applications that include targeting of the innate and adaptive immune systems as well as combinations with tumor-specific mAbs. [ABSTRACT FROM AUTHOR]

The renin-angiotensin-aldosterone system (RAAS) is a major regulator of blood pressure. The octapeptide angiotensin II (AII) is proteolytically processed from the decapeptide AI by angiotensin-converting enzyme (ACE), and then acts via angiotensin type 1 and type 2 receptors (AT1R and AT2R). Inhibitors of ACE and antagonists of the AT1R are used in the treatment of hypertension, myocardial infarction, and stroke. We now show that the RAAS also plays a major role in autoimmunity, exemplified by multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Using proteomics, we observed that RAAS is up-regulated in brain lesions of MS. AT1R was induced in myelin-specific CD4+ T cells and monocytes during autoimmune neuroinflammation. Blocking AII production with ACE inhibitors or inhibiting All signaling with AT1R blockers suppressed autoreactive TH1 and TH17 cells and promoted antigen-specific CD4+FoxP3+ regulatory T cells (Treg cells) with inhibition of the canonical NF-κB1 transcription factor complex and activation of thealternative NF-κB2 pathway. Treatment with ACE inhibitors induces abundant CD4+FoxP3+ T cells with sufficient potency to reverse paralytic EAE. Modulation of the RAAS with inexpensive, safe pharmaceuticals used by millions worldwide is an attractive therapeutic strategy for application to human autoimmune diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: β-Blockers reduce mortality in patients with systolic chronic heart failure (CHF), yet prescription rates have remained low among primary care providers. OBJECTIVE: To determine the β-blocker prescription rate among patients with systolic CHF at primary care Veterans Affairs (VA) clinics, its change over time; and to determine factors associated with nonprescription. DESIGN: Retrospective chart review. SUBJECTS: Seven hundred and forty-five patients with diagnostic codes for CHF followed in primary care clinics at 3 urban VA Medical Centers. MEASUREMENTS: Rate of β-blocker prescription and comparison of patient characteristics between those prescribed versus those not prescribed β-blockers. RESULTS: Only 368 (49%) had documented systolic CHF. Eighty-two percent (303/368) of these patients were prescribed a β-blocker. The prescription rate rose steadily over 3 consecutive 2-year time periods. Patients with more severely depressed ejection fractions were more likely to be on a β-blocker than patients with less severe disease. Independent predictors of nonprescription included chronic obstructive pulmonary disease, asthma, depression, and age. Patients under 65 years old were 12 times more likely to receive β-blockers than those over 85. CONCLUSION: Primary care providers at VA Medical Centers achieved high rates of β-blocker prescription for CHF patients. Subgroups with relative contraindications had lower prescription rates and should be targeted for quality improvement initiatives. [ABSTRACT FROM AUTHOR]

The setting for this study is the two-group multinomial classification problem. Based on a measure of the log odds in favor of one particular group, a large sample confidence interval for a measure of separability is derived. The asymptotic result employed assumes that all states have positive observed frequencies. Realizing that this assumption is often violated, we consider a method based upon log-linear representation of state frequencies to first remove any random zeros before attempting to effect a classification. The method is illustrated in a data set dealing with the behavioral consequences following hypoxic trauma. [ABSTRACT FROM AUTHOR]

A two-group classification procedure for multivariate binary data is presented and discussed for the case of independent samples. The rule utilizes an orthogonal series expansion for state probabilities and introduces a method to achieve parsimony in modeling in accordance with a condition of optimality. In addition, the classification procedure gives a method for dealing with the difficult problem of sparseness, a condition which frequently causes problems in applying discrete methods to frequency data. [ABSTRACT FROM AUTHOR]